Wild Iris Medical Education
COURSE PRICE: $37.50
CONTACT HOURS: 5.5
This course is available until September 5, 2012.
ACCREDITATION / APPROVAL
Wild Iris Medical Education, Inc., has been pre-approved by the Commission for Case Manager Certification to provide continuing education credit to Certified Case Managers (CCMs). Course approval number 790003248.
The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.
Copyright © 2009 Wild Iris Medical Education, Inc. All Rights Reserved.
COURSE OBJECTIVE: The purpose of this course is to review the epidemiology, diagnosis, and treatment of prostate cancer and update health professionals on recent approaches for screening and preventing the disease.
Upon completion of this course, you will be able to:
Whereas prostate cancer is unequivocally lethal in some patients, most men do indeed die with, rather than of, their cancer.
—EASTHAM & SCARDINO, 2007
Prostate cancer is the most common non–skin cancer in American men, and it is the second leading cause of men’s cancer deaths (Kung et al., 2008). Prostate cancer is relatively slow growing, and it is a disease of older men. As many as three-quarters of men older than 80 years have at least microscopic evidence of prostate cancer, but the disease is detected in only 1 in 6 men during their lifetimes and only 1 in 28 men die of it (Gronberg, 2003; Catalona & Han, 2007).
Today, most prostate cancers are discovered by noninvasive screening, a combination of a blood test for the enzyme prostate-specific antigen (PSA) and a digital rectal examination (DRE). Most of the detected tumors grow slowly and do not cause death. On the other hand, some tumors are aggressive, metastasize to bone, and eventually prove fatal.
Early treatment is usually successful. Treating prostate cancer when it is small and confined inside the prostate can often cure the disease. The three main treatments for prostate cancer are:
The side effects of these treatments can be significant, and quite frequently, it is not clear whether to treat a small tumor immediately or to postpone the treatment until there is evidence that the tumor is progressing (Catalona & Han, 2007).
As with all diseases, the ideal treatment for prostate cancer is prevention, and a number of potential preventatives are being studied. Dietary additions may have a small role in reducing the risk of prostate cancer, and soy, green tea, and a variety of fresh fruits and vegetables are safe additives that may be helpful. Not long ago it had been hoped that supplementing a man’s diet with selenium and vitamin E would reduce his risk of developing prostate cancer; these hopes have proved to be unfounded, and selenium and vitamin E supplements are no longer recommended.
Medications may be more effective preventatives than dietary supplements. Studies of 5α-reductase inhibitors, such as finasteride (a treatment for male pattern baldness), suggest that taking these drugs daily for many years may reduce a man’s chances of developing prostate cancer by as much as 30%.
The prostate is a gland that is part of the male reproductive system. Its function is to add fluid to semen.
The prostate is a dense, muscular, secretory organ the size and shape of a chestnut. Internally, the prostate is filled with branching tubular glands embedded in a fibrous muscular meshwork (Ramey et al., 2007).
The prostate surrounds the first segment of the urethra and sits between the base of the bladder and the urogenital diaphragm of the pelvic floor. (See “Anatomy of the Male Urogenital System” below.) The portion of the prostate against the bladder is called the base. The other end is called the apex, and this end follows the urethra, tapering toward the pelvic floor. In the anterior-posterior axis, the prostate lies behind the pubic symphysis and in front of the rectum.
Anatomy of the Male Urogenital System. (National Cancer Institute, © 2005 Terese Winslow.)
Functionally, the prostate lies along the line of travel for sperm, which leave the testes, pass through the deferens ducts, and are squirted out through the urethra of the penis. Each deferens duct enters the base of the prostate laterally near the bladder. Before entering the prostate, the ducts of the neighboring seminal vesicles merge with the deferens ducts to form the ejaculatory ducts; these combined ducts open into the prostatic urethra as longitudinal slits on either side of the midline. More distally, although still inside the prostatic segment of the urethra, a number of smaller ducts empty into the urethra carrying the secretions from the glands that are directly a part of the prostate.
The bulk of the prostate is found behind and on both sides of the urethra. The front, or anterior, segment of the prostate is filled with transverse muscle that is continuous with the urethral sphincter underneath. The back, or posterior, surface of the prostate is just in front of the rectum. This surface of the prostate has two lateral bulges separated by a furrow, and these external landmarks and the consistency of the prostate can be felt through the anterior wall of the rectum.
The lateral bulges of the prostate are sometimes called prostatic lobes, but they do not correlate with specific internal structures. Instead, the inner architecture of the prostate comprises three concentric ovoid tissues surrounding the urethra. Each of the three tissue zones contains its own characteristic type of glands.
The innermost core of prostate tissue is called the transition zone. This small, spherical region surrounds the urethra just proximal to the entry of the ejaculatory ducts. Normally, the transition zone makes up 5 to 10% of the prostate. In benign prostatic hypertrophy (BPH), the transition zone expands, and it often impinges on the urethra or the base of the bladder. Approximately 1 in 5 prostate cancers begin in the transition zone (Ramey et al., 2007).
The middle tissue of the prostate is called the central zone. This zone is shaped like an indented cone. The central zone surrounds the ejaculatory ducts as they run behind the transition zone and empty into the urethra. Normally, the central zone makes up 25% of the prostate. Fewer than 1 in 20 prostate cancers begin in the central zone.
The outermost tissue of the prostate is called the peripheral zone. It encloses the transition and central zones. The peripheral zone tapers along the urethra and ends by merging with the surface of the external urethral sphincter. Normally, the peripheral zone makes up 65 to 70% of the prostate. Between two-thirds and three-quarters of all prostate cancers begin in the peripheral zone (Nelson WG et al., 2008).
Blood is supplied to the prostate mainly from the inferior vesical artery, a branch of the anterior division of the internal iliac artery. Most of the lymph nodes that drain the prostate are found along the internal iliac blood vessels and the neighboring obturator muscles.
The prostate is innervated by both sympathetic and parasympathetic autonomic axons. These axons come from the prostatic plexus, a collection of autonomic nerves and neurons that are trunks of the superior hypogastric plexus. (The superior hypogastric plexus is a meshwork of nerves that lies anterior to the bifurcation of the aorta.)
During sexual arousal, there is parasympathetic stimulation; then, during orgasm, there is sympathetic stimulation. Stimulation of parasympathetic axons causes the prostate glands to secrete fluid. Subsequent stimulation of the sympathetic axons causes the smooth muscle in the prostate to contract and push the fluid into the semen.
In men with benign prostatic hyperplasia, the prostate often squeezes the urethra continuously. Alpha-adrenergic sympathetic blockers will relax the smooth muscle inside the prostate, and these drugs will usually improve urinary flow through the prostatic region of a urethra that has been narrowed by BPH.
The prostate’s main function is secretory. The prostate is composed of 30 to 50 compound tubuloalveolar glands. (Tubuloalveolar describes glands in which the ducts of clusters of secretory cells are arranged like branches on a tree merging into a few main trunks.) In the prostate, the clusters of secretory cells create fluid that is added to other components of the seminal fluid of the ejaculate.
The prostatic glands are packed in a fibrous mesh that contains a significant amount of smooth muscle. Approximately one-third of the prostate is muscle, and during ejaculation the prostate contracts, squeezing its glandular secretions into the urethra (Veltri & Rodriguez, 2007).
An ejaculate consists of spermatozoa immersed in seminal fluid. The total volume of an average human ejaculate is approximately 3 ml. Spermatozoa make up only about 0.03 ml of the ejaculate, and the other 2.97 ml is seminal fluid.
Seminal fluid is produced in a number of glands along the male reproductive tract. The seminal vesicles contribute 2 ml to the seminal fluid of an ejaculate, the prostate contributes 0.8 ml, and the bulbourethral (Cowper’s) gland and the Littre’s glands together contribute less than 0.2 ml. The fluid contributed by the prostate contains citric acid, zinc, lipids, and a variety of polyamines (such as spermidine and spermine), which are small, positively-charged molecules.
Prostate-specific antigen (PSA) is a protease enzyme made in the prostate’s epithelial cells. PSA is a prostate-specific member of the kallikrein enzyme family. PSA is added to seminal fluid, where it helps to liquefy the ejaculate, which on its own would form a gel. In the process of producing seminal fluid, some prostate proteins, including PSA, leak into the blood stream. The amount of PSA leaking into the blood rises with increased prostatic growth, either benign or malignant, and with injury to the prostate.
During puberty, the prostate grows rapidly. When it reaches its adult size, the normal prostate then maintains a balance of cell growth and cell death, in which the scales are tipped slightly in favor of growth. Over the years, most men have a gradual increase in their total number of prostate cells. This increase is a condition known as benign prostatic hyperplasia, or BPH. Eventually, as men reach their 60s, the slowly enlarging prostate often impinges sufficiently on the urethra and the bladder to give urinary symptoms (Epstein, 2005; Kirby & Lepor, 2007).
The single most significant stimulant for prostate growth, differentiation, and maintenance is the sex hormone dihydrotestosterone, an androgen that the prostate produces from testosterone that has been circulating in the bloodstream. Testosterone is made by the Leydig cells in the testes, and the signals to make testosterone come from the pituitary. Requests to manufacture more testosterone are relayed from the pituitary by the luteinizing hormone. (See “Androgen-Deprivation Therapy” below for additional details.)
Dihydrotestosterone is the quintessential male hormone. It plays a critical role in prostate growth, and it is the key stimulant of the growth of facial hair, acne, and male pattern baldness. To produce dihydrotestosterone, testosterone is modified by an intracellular enzyme called 5α-reductase, found mainly in the prostate, skin, and liver.
Humans have at least three isoforms of 5α-reductase. Type I is characteristic of nonprostate tissues; type II is the main form found in the prostate, seminal vesicles, and epididymis; and type III is newly discovered and still being studied.
In prostate cancer, the levels of types I and II 5α-reductase are both increased in prostate cells. The inhibition of 5α-reductase is one promising avenue being explored for prevention and control of prostate cancer (Klein et al., 2007; Crawford, 2009; Kramer et al., 2009). (See “Prevention of Prostate Cancer” below.)
Cancer is not a single disease. Cancers differ in cause, behavior, and sensitivity to treatment. On the other hand, some general similarities can be seen in cancers that derive from similar tissue types, and one of the useful categorizations of cancers groups them according to the type of cell from which they have developed.
Like the breast and the pancreas, the prostate is a glandular organ, yet prostate cancers differ in their cellular origins from major cancers of the breast or the pancreas. In the breast and the pancreas, cancers tend to develop from the duct cells of the glands. In contrast, cancers of the prostate usually develop from the secretory cells of the glands.
One early stage of abnormality seen in the prostate is called prostatic intraepithelial neoplasia (PIN). In PIN, the prostatic glands have normal architecture but the cells in the glands appear abnormal. Mild or low-grade PIN does not seem to foreshadow cancer. On the other hand, severe or high-grade PIN may be a precursor to prostatic adenocarcinomas. PIN does not cause elevated PSA blood levels, and PIN can only be diagnosed by needle biopsy.
Most prostate cancers are adenocarcinomas. Carcinomas are cancers that develop from epithelial cells, and adenocarcinomas are cancers that develop from the types of epithelial cells that form glands (Epstein, 2007). Prostatic adenocarcinomas usually arise from the secretory cells at the ends of ducts in the peripheral zone of the prostate.
Prostate adenocarcinomas develop quietly. By the time they are discovered, adenocarcinomas can usually be found at more than one site in the prostate. Later, after a protracted asymptomatic growth, some prostatic cancers metastasize, usually to lymph nodes or bones. Lymph node metastases show up first; the most common nodes involved are the obturator, perivesical, hypogastric, and iliac lymph nodes. The most common sites for bone metastases are the lumbar spine, proximal femurs, and pelvic bones.
Prostate cancers occasionally originate from cell types other than secretory and in prostatic zones other than the peripheral.
Infrequently, prostatic carcinomas develop from duct cells. Malignant duct cells do not leak PSA into the bloodstream, and men with ductal cancers can have normal PSA blood levels. For this reason, ductal prostate cancers are not picked up by routine blood-screening tests, which measure PSA blood levels. Ductal prostate cancers tend to be diagnosed at an advanced stage, and they have a poor prognosis.
Another type of prostate carcinoma with a relatively poor prognosis develops from cells in the transition zone. Transition zone carcinomas account for fewer than 1 in 5 prostate cancers. They tend to infiltrate the neck of the bladder and the surrounding tissues, and by the time of diagnosis, 20% of transition zone carcinomas have metastasized.
Rarely, small cell carcinomas develop in the prostate, often in conjunction with adenocarcinomas. Like the small cell carcinomas of the lung, small cell carcinomas of the prostate are aggressive, with a patient’s average survival time being less than 1 year.
The steps leading from the development of cancerous cells to the appearance of a clinically recognizable tumor are not known for prostate cancer. Similarly, researchers still have only a sketchy idea of what actually happens as an untreated tumor progresses after it has been clinically recognized.
As a rule, prostate cancers grow slowly, with doubling times for local tumors estimated at 2 to 4 years. However, individual cancers show a wide range of progressions. Slow-growing prostate cancers present little risk to the overall health of elderly patients, but aggressive prostate cancers cause significant morbidity and mortality. Currently, it is difficult to identify many of the aggressive cancers at an early stage in which treatment would be most effective (Eastham & Scardino, 2007).
In very general terms, however, tumor grade can be a guide. (See “Tumor Grade” below.) High-grade prostate cancers progress to death more often and more quickly than low-grade cancers. One major study found that men with low-grade prostate cancers had a 10-year survival rate of 87%. With intermediate-grade prostate cancers, the 10-year survival rate was 58%. With high-grade prostate cancers, the 10-year survival rate was only 25%. When prostate cancer has metastasized, the average survival rate is less than 5 years (Meng & Carroll, 2007).
The instigators of prostate cancer include a list of culprits. Because the detailed progression from initial trigger to clinical disease appears to involve a varying number of factors, the potential contributing agents are often called risk factors rather than causes.
Microscopically, cancerous cells can be identified in the prostates of fewer than 33% of men older than 50 years. In contrast, the chance of a man ever being diagnosed with clinical prostate cancer is less than 18%. It is thought that the transition from latent to clinical cancer requires the participation or contribution of additional risk factors after the initial trigger (Klein et al., 2007).
One class of prostate cancer risks is carried in the genomes of some men. A propensity for developing prostate cancer can be inherited, and men are more likely to get prostate cancer if close relatives have the disease. Evidence that this effect is genetic and not environmental comes from the observation that monozygotic twins show the effect more than do dizygotic twins (Gronberg, 2003).
Some families are plagued by particularly “strong” prostate cancer propensity genes. In these families, not only is there a greater tendency than usual for men to get prostate cancer, the disease also strikes at a younger age (under 55 years). To date, more than 8 “strong” prostate cancer susceptibility genes have been identified; their mechanisms of action are currently being worked out (Gretzer & Partin, 2007).
About 15% of cases of prostate cancer are governed by strong prostate genes. These are called familial or hereditary prostate cancers. The remaining 85% of prostate cancers are called sporadic because they occur in patients whose families show no clustering of cancer cases and in which prostate cancers usually develop later, in men aged 70 years and older.
Many outside influences have been linked to prostate cancer. Even in men with a genetic susceptibility to prostate cancer, certain environmental factors seem to play a role in causing the cancers to become clinically apparent.
Cancers tend to develop in tissues with high rates of proliferation. Chronic inflammation stimulates cell proliferation as part of its continuous repair processes, and this may be one reason that chronic inflammation increases the risk of cancers of the bladder, colon, esophagus, prostate, and stomach (Klein et al., 2007). In addition, for prostate cancer, sexually transmitted infections and prostatitis are specific risk factors.
Oxidants are chemicals that injure DNA and cause mutations. Chronic exposure to oxidants appears to lead to the development of cancer, and antioxidant drugs have been suggested as protectants that may lessen a man’s risk of developing prostate cancer.
Normally, the body defends against damage from oxidants through a collection of mechanisms. The protective mechanisms include antioxidant enzymes, DNA repair enzymes, and the triggered suicide (apoptosis) of cells with excessively damaged DNA. Genetic or acquired defects in these protective mechanisms are likely to be risk factors for prostate cancer.
Certain growth-stimulating hormones have been indirectly linked to prostate cancer. These hormones include androgens and insulin-like growth factor 1.
Population studies have implicated certain habits and lifestyle-related issues as potential influences on the chances of developing prostate cancer.
Prostate cancer is the most common non-skin cancer in American men. In the United States, more than 1 in 6 men will be diagnosed with prostate cancer during their lifetimes. Many cases of prostate cancer go unrecognized, and the disease statistics suggest that prostate cancers are slow-growing tumors.
The National Cancer Institute estimates that 192,280 new cases of prostate cancer will be diagnosed during 2009 (National Cancer Institute, n.d.). Prostate cancer is rarely diagnosed in men younger than 45 years, and the 192,280 new cases represent a yearly rate of approximately 250 new cases per 100,000 men over the age of 45 years. In other words, an American man older than 45 years has an approximately 0.25% chance of being diagnosed with prostate cancer this year.
Prostate cancers account for about one-third of all visceral malignancies in men (Klein et al., 2007). Prostate cancer is about twice as common as lung and bronchial cancers, the next most common malignancies in men. Going down the list, the third most common malignancies to be diagnosed in men are colon and rectal cancers.
In 2009, 27,360 American men are expected to die of prostate cancer (National Cancer Institute, undated); this will be about 2.4% of all male deaths. While more common than most other cancers in men, prostate cancers are less lethal than lung and bronchial cancers or lymphomas and leukemias. When a newly diagnosed prostate tumor is localized within the prostate, the 5-year survival rate in the United States is 100%. In contrast, when a newly diagnosed prostate tumor has already metastasized, the 5-year survival rate is 32% (Crawford, 2009).
The following table compares the death rates from prostate cancer to death rates from other diseases.
| Cause of Death | Percent of All Male Deaths |
|---|---|
| Source: Kung et al., 2008. | |
| Cardiovascular (all types) | 34 |
| Cancers (all types) | 24 |
| Lung & bronchial | 7.5 |
| Lymphomas & leukemias | 2.5 |
| Prostate | 2.4 |
| Colon & rectum | 2.2 |
| Pancreas | 1.3 |
In the United States, it is estimated that about 18% of white males and about 20% of African American males will be diagnosed with prostate cancer during their lifetimes. In addition, the death rate from prostate cancer for African American males is twice the rate for white males. It is not clear what portion of these disparities is due to genetic factors and what portion is due to social factors, such as differences in the rate of prostate screening between whites and African Americans.
| Racial / Ethnic Group | Percent of Men Developing Prostate Cancer Annually |
|---|---|
| Source: Crawford, 2009. | |
| Black | 0.25% |
| White | 0.16% |
| Hispanic | 0.14% |
| Asian/Pacific | 0.09% |
As men age, many of them develop small foci of prostate cancer. Clinical diagnoses of prostate cancer peak for men in their late 60s and early 70s, with the median age at diagnosis being 68 years (National Cancer Institute, n.d.).
Each year in the United States, 7 times more men are diagnosed with prostate cancer than die from the disease. Most deaths from prostate cancer occur in men who are in their late 70s or early 80s, and the median age of prostate cancer death is 80 years (National Cancer Institute, undated).
The time span between the median age of diagnosis (68 years) and the median age of death (80 years) suggests that even among the approximately 1 in 7 cases of all prostate cancer that directly cause death, the cancer tends to be a slowly progressing disease that takes more than 10 years to become fatal.
| Age Group (years) | Total Prostate Cancer Diagnoses | Total Prostate Cancer Deaths |
|---|---|---|
| Source: National Cancer Institute, n.d. | ||
| <20 | 0% | 0% |
| 20–34 | 0% | 0% |
| 35–44 | 0.6% | 0.1% |
| 45–54 | 8.7% | 1.4% |
| 55–64 | 29.0% | 7.2% |
| 65–74 | 35.6% | 20.1% |
| 75–84 | 21.4% | 40.9% |
| >84 | 4.7% | 30.3% |
Prostate cancers can be small and slow-growing, and many occurrences of prostate cancer go unrecognized during men’s lifetimes. From autopsy studies, Coley and colleagues (1997) give the following estimates of the percent of men who have unrecognized prostate cancer in each age group.
| Age Group (years) | Percent with Unrecognized Prostate Cancer |
|---|---|
| Source: Coley et al., 1997. | |
| 40–49 | 12% |
| 50–59 | 15% |
| 60–69 | 22% |
| 70–79 | 39% |
| >79 | 43% |
Overall, it is estimated that 1 in 3 men older than 50 years have prostate cancer that is currently unsuspected.
Early prostate cancer rarely gives symptoms. If physicians wait until patients come to them with complaints, the prostate cancers will be advanced. To catch prostate cancers at early stages, physicians must proactively screen their patients.
The two widely used screening methods are digital rectal examination (DRE) and measurement of blood levels of the protein prostate-specific antigen (PSA). Using PSA blood tests, most prostate cancers can be diagnosed early, before they are palpable. DRE screening is added to PSA testing because DRE picks up about 17% of the prostate cancers that would be missed when using the blood test alone (Gretzer & Partin, 2007).
Neither technique can provide a reliable diagnosis of prostate cancer, but together they give enough information to recommend whether an asymptomatic prostate should be biopsied. A biopsy after abnormal DRE and PSA screens gives the best available diagnosis (Carter et al., 2007).
Most adenocarcinomas develop in the peripheral zone of the prostate, where they initially cause no symptoms. Today, because of DRE and PSA screening, greater than 80% of prostate cancers are detected in the asymptomatic stages.
In their later stages, prostate cancers expand locally and often metastasize. The local infiltrative growth and the metastases are directly responsible for most of the symptoms of advanced prostate cancer.
The most useful physical findings for diagnosing prostate cancers come from a digital rectal examination. By itself, DRE can detect 50 to 60% of prostate cancers, usually, however, only when the cancers are relatively advanced.
DIGITAL RECTAL EXAM TECHNIQUE
For a digital rectal exam, the patient can be in a lithotomy position, a knee-chest position, a left lateral prone position, or standing and bent prone over an exam table. Lubricate the forefinger of your gloved hand. Put the pad of your lubricated forefinger on the anal orifice and press gently anteriorly until the anal sphincter relaxes.
Next, ease your finger into the anal canal with the finger pad facing forward (anteriorly). Past the anal canal, you will feel the posterior surface of the prostate, a firm rounded organ the size of a chestnut. Usually, there is a lateral bulge on either side of a midline, top-to-bottom furrow.
Illustration: Digital Rectal Examination (DRE). (National Cancer Institute, 2009b.)
Source: Modified from DeGowin & DeGowin,1969.
| Condition | DRE Impression |
|---|---|
| Normal | Rounded, symmetric, roughly heart-shaped |
| Infection (prostatitis) | Enlarged, tender, warm, surrounded by edematous tissue |
| BPH (benign prostatic hypertrophy) | Symmetrically enlarged, smooth, midline furrow obliterated, rubbery or firm, rectal mucosa slides over prostate smoothly |
| Cancer | Irregular, asymmetric, areas of hardness, stony nodules, less mobile, rectal mucosa adheres to prostate, anal sphincter may be found to be relaxed |
No tumor marker has had as great an impact on the diagnosis, management, and treatment of a disease as prostate-specific antigen (PSA) has had on prostate cancer.
—MORRIS & SCHER, 2007.
The main laboratory test used to diagnose and to follow prostate cancer is a blood test for PSA levels.
PSA
Prostate-specific antigen (PSA) is an enzyme made in the glands of the prostate and secreted in the seminal fluid. A small amount of PSA regularly leaks into the blood stream. When in the blood, 65 to 95% of the PSA is bound to specific circulating proteins (alpha1-antichymotrypsin, alpha2-macroglobulin, and alpha1-protease inhibitor), while 10 to 35% circulates unbound. Commercial assays are available for measuring the blood concentrations of both forms of PSA (Gretzer & Partin, 2007).
Most men of all ages have a blood PSA level <2.6 ng/ml. In the general population, the average PSA blood level increases as men age, and levels ≥2.6 are more common in older men. In the sixth decade of life, 4% of men have a PSA blood level >4 ng/ml, in the seventh decade 11% have a PSA >4 ng/ml, and in the eighth and ninth decades 21% have a PSA >4 ng/ml. (See graph below.)
Source: Carter et al., 2007.
The likelihood that a man has prostate cancer increases as his blood level of PSA increases. However, the information learned from a PSA level is probabilistic: some men with low PSA levels have prostate cancer, while some men with high levels do not.
For single blood readings, a total PSA blood level greater than 4 ng/ml is often used as the threshold for suspicion of prostate cancer, and when PSA levels are lower than 4 ng/ml, a prostate biopsy is usually recommended. In younger men, the threshold is lower, usually 2.5 ng/ml; however, there is disagreement as to whether the lower threshold should be applied to men younger than 60 years or to men younger than 50 years (Carter al., 2007). These particular PSA levels—i.e., 2.5 ng/ml for younger men and 4 ng/ml for older men—are commonly used, but “the PSA threshold that most efficiently balances the dual goal of reducing cancer mortality and reducing unnecessary testing ([i.e., repeated] PSA measurements and biopsies) is not known” (Gretzer & Partin, 2007).
Many additional factors must be considered when interpreting the meaning of PSA values (Gretzer & Partin, 2007). Important points include:
The challenge to physicians today is to identify the minority of men with an aggressive, localized prostate cancer with a natural history that can be altered by definitive local therapy while sparing the remainder the morbidity of unnecessary treatment.
—EASTHAM & SCARDINO, 2007.
Even when using the results of a concurrent digital rectal examination, a PSA threshold greater than 4 ng/ml misses some prostate cancers. At the same time, a PSA threshold less than 4 ng/ml leads to biopsies for men without prostate cancer. These false negatives and false positives have caused scientists to search for blood tests that are both more sensitive and more specific. Current proposals include:
For each of these proposals, there is now a usable recipe and evidence demonstrating that it is more accurate than using a universal PSA threshold greater than 4 ng/ml, and many clinicians have added one or more of these techniques to their diagnostic arsenal (Gretzer & Partin, 2007).
The early stages of prostate cancer can only be recognized microscopically. None of the current noninvasive imaging techniques has the resolution to match direct histologic studies of a tissue biopsy. At the same time, however, the precision of getting a biopsy has been improved dramatically by use of one particular imaging technology, transrectal ultrasound (Carter et al., 2007).
Transrectal ultrasound (TRUS) creates pictures using an ultrasound probe that is put in the rectum directly against the posterior surface of the prostate. The images from TRUS accurately show the locations and relative densities of parts of the prostate (Ramey et al., 2007).
Most nonpalpable prostate cancers do not show up distinctly in TRUS images. In ultrasound images, detectable cancers of the prostate tend to be hypoechoic, that is, they appear darker than the normal tissue of the region. The majority of hypoechoic changes in the prostate, however, are not cancer. Therefore, by itself, TRUS is not useful for diagnosing or staging prostate cancers.
On the other hand, TRUS images are effective for measuring the volume of the prostate. TRUS is also the best way to visually guide physicians during nonsurgical procedures, and it is commonly used to localize needle biopsies and radiation treatments.
Radionuclide bone scanning is another imaging technology that is important for managing prostate cancer. Radionuclide scans are used to search a patient’s body for metastases, which take up certain radioactive compounds more avidly than healthy tissues do (Dotan, 2008).
For low-risk patients, CT and MRI images are not sufficiently sensitive to identify prostate cancer or to determine the extent of limited local spread. CT and MRI are more effective at imaging prostate tumors with nodules that can already be detected by digital rectal examination and prostate tumors with extensive local spread. CT and MRI images are also used to make internal body maps to guide radiation therapy and other physical treatments (Ramey et al., 2007).
The diagnosis and characterization of a prostate cancer is determined by studying tissue samples. Typically, the samples are obtained using a needle biopsy that has been carried out under visual guidance with transrectal ultrasonography. Biopsies are usually taken in sets that sample many areas of the prostate (Carter et al., 2007; Ramey et al., 2007).
A prostate biopsy is commonly recommended for men under 85 years old who have any of these conditions:
CONTROVERSY 1: AT WHAT PSA LEVEL TO BIOPSY?
Sufficient data is not available to make firm recommendations for many aspects of the diagnosis and management of prostate cancers (Dahm et al., 2008). Even the usefulness of routine screening is debated (see “Controversy 3”, under “Routine Screening of Prostate Cancer”, below).
One current controversy concerns the threshold PSA blood level at which to recommend a prostate biopsy. Although a PSA threshold of 4 ng/ml has been the most commonly used, the PSA threshold that most efficiently balances the two goals of reducing cancer mortality and reducing unnecessary biopsies is not known (Gretzer & Partin, 2007). The overall probabilities shown below for men over 50 years illustrate the dilemma.
| PSA Level (ng/ml) | Probability of Having Cancer |
|---|---|
| (Gretzer & Partin, 2007.) | |
| <2.5 | <2% |
| 2.5–4 | 18% |
| 4–10 | 25% |
| >10 | 67% |
On the one hand, a substantial proportion of cancers are missed when prostate biopsies are recommended only for patients with PSA levels above 4 ng/ml. On the other hand, recommending lower PSA thresholds (for men older than 50 years) raises the following concerns:
Source: Carter et al., 2007.
When the Initial Biopsy Was Benign: Biopsies can miss areas of tumor. When a biopsy has found only benign tissue, a repeat biopsy is advised when 1) the DRE discovered hard areas or asymmetry of the prostate or 2) repeat PSA measurements are suspiciously high.
To improve the sensitivity of the biopsy, some doctors recommend taking a set of ten or more samples during the second biopsy. Even with increased sampling, when the first PSA values were under 10 ng/ml, the likelihood of finding cancerous tissue decreases with each successive biopsy (Ramey et al., 2007).
When the Initial Biopsy Found Atypical Cells or Atypical Gland Structures: A diagnosis of “atypical” has a high chance of being changed to “cancer,” and atypical readings are often referred for a second opinion. Whenever the final decision remains “atypical,” a biopsy should be repeated. Cancer will be diagnosed in 40% of these repeat biopsies (Epstein, 2007).
When the Initial Biopsy Showed High-Grade PIN: When a biopsy shows prostatic intraepithelial neoplasia (PIN)—even high-grade PIN—it can be treated as a benign diagnosis, and a repeat biopsy is not necessary during the next year unless DRE or PSA results are suspicious. It is still unknown whether a diagnosis of high-grade PIN should trigger a repeat biopsy later, perhaps after several years.
The most common condition from which prostate cancer must be distinguished is benign prostatic hyperplasia (BPH). Both BPH and prostate cancer are prostatic diseases of elderly men. Although the two conditions are distinct, it is important to remember that men diagnosed with BPH can also have prostate cancer, and men diagnosed with prostate cancer often have BPH (Kirby & Lepor, 2007).
BPH, also called nodular prostatic hyperplasia, is a slowly progressing, noncancerous condition that causes enlargement of the prostate. It is a common disorder in men over the age of 50 years. BPH develops slowly, and it is rare in men under 40 years old. The prevalence increases with age, and BPH can be found in 70% of men in their 60s and in 90% of men in their 80s.
Benign Prostatic Hyperplasia (BPH). (National Cancer Institute, 2004.)
BPH can cause obstructive and irritative lower urinary tract problems, such as:
BPH increases the number of cells (hyperplasia) in the transition zone of the prostate surrounding the urethra. Both glandular and interglandular (i.e., stromal) cells increase in number, there are more branches on each of the prostatic glands, and the glands become tightly packed into large, discrete nodules. The microscopic hallmark of BPH is the nodularity of the prostate. When sufficiently large, these nodules will compress and narrow the urethral canal and will cause obstruction of the urethra (Epstein, 2005). The underlying causes of BPH are not completely understood.
On digital rectal examination, a prostate with BPH usually feels uniformly enlarged, and the prostate’s midline furrow is sometimes gone. BPH does not produce palpably hard or asymmetric nodules, and the prostate does not become fixed to the surrounding tissue (Kirby & Lepor, 2007).
BPH, like most other prostate diseases and injuries, increases the blood level of PSA. In BPH, the PSA increase is directly related to the increase in the volume of the prostate. In older men, BPH is more common than prostate cancer, and PSA levels less than 10 ng/ml are more likely to be caused by BPH than by cancer when the DRE gives no suspicion of cancer. Nonetheless, for PSA values greater than 2.5 ng/ml in men younger than 50 years and greater than 4 ng/ml in men 50 years or older, a prostate biopsy is usually recommended, even without a suspicious DRE (Carter et al., 2007).
A variety of additional measurements, including volume-based PSA parameters, comparisons of complexed and free PSA, PSA velocity, and specialized cell markers, are being studied with the goal of more definitively distinguishing BPH from cancer and thereby reducing the number of biopsies that are currently being recommended.
Biopsies are used to recognize prostate cancer. Usually, a diagnosis of BPH cannot be made from a needle biopsy because the typical architecture of BPH nodules cannot be clearly recognized in samples of such small volume. Moreover, needle biopsies do not usually sample the transition zone where BPH occurs.
On the other hand, two histologic changes associated with BPH are sometimes seen in needle biopsies: 1) foci of squamous metaplasia and 2) small infarcts. The metaplastic foci in BPH are usually found along the edges of the infarcts, and the metaplastic squamous cells can be confused with adenocarcinomas (Epstein, 2005).
To suggest a prognosis and to plan a treatment, physicians put prostate cancers into subcategories. There are two commonly used classification scales. Tumor grade classifies the degree of differentiation of the cancer cells, and tumor stage classifies the spread of the cancer.
Grading and staging tumors are both based on histological information, and except for prostates studied after they have been surgically removed, the histological information comes from biopsies (Epstein, 2005).
Cancers are graded according to the degree of differentiation of the tumor cells. This feature correlates with the aggressiveness of the tumor: well-differentiated cells tend to be less aggressive than poorly differentiated cells. For prostate adenocarcinomas, the most widely used tumor grading system is the Gleason system.
The Gleason system ranks the architecture of a prostate tumor as seen under low-power magnification. Prostate cell patterns are graded from 1 (a normal-looking glandular architecture) to 5 (no recognizable glandular pattern). Because prostate cancers are not always uniformly distributed in the prostate, the Gleason grading system uses information from more than one area. Specifically, the Gleason score is calculated by adding together the grades of the two most common patterns seen in the tissue sections. Gleason grades range from 1 to 5, while Gleason scores range from 2 (for the most differentiated tumors) to 10 (for the least differentiated tumors) (Epstein, 2007).
Cancers are staged according to the size of the primary lesion, its extent of spread to regional lymph nodes, and the presence or absence of distant metastases. A widely used cancer staging classification describes the stage of a cancer with three terms: T for the primary tumor, N for any local lymph nodes that are involved, and M for any distant metastases.
TNM STAGING SYSTEM FOR PROSTATE CANCERS
T0 = no evidence of primary tumor
T1 = nonpalpable tumor that is not evident from radiographic imaging
T2 = palpable tumor confined to the prostate
T3 = palpable tumor extending beyond the prostate
T4 = palpable tumor that is fixed or that invades adjacent structures
N0 = no lymph node metastases
N1 = metastases in one regional lymph node that is ≤2 cm wide
N2 = metastases in one or more regional lymph nodes, each ≤5 cm wide
N3 = metastases in at least one regional lymph node >5 cm wide
M0 = no evidence of distant metastases
M1 = at least one distant metastasis
(There are subsets for many of these classes; for instance, stage T1 is currently subdivided into T1a, T1b, and T1c.)
Source: Epstein, 2005.
For example, using the TNM nomenclature, a prostate cancer of stage T2N1M0 is a cancer in which:
Diagram of a Stage T2 Tumor of the Prostate. (National Cancer Institute, 2006.)
For prognostic and treatment decisions, the tumor grade and stage are considered along with details of the DRE assessment, the PSA blood level, and all other available information, such as pelvic lymph node histology from a pelvic lymphadenectomy, results of a seminal vesicle biopsy, TRUS images, or bone scans. Tables have been compiled collating these forms of information to make as accurate an assessment as possible (Carter et al., 2007; Eisenberger & Carducci, 2007).
For most men, prostate cancer is a slowly progressing disease. One in 6 men is diagnosed with the disease, but only 1 in 28 die of it. The major treatments used for prostate cancer are surgery, radiation, and reduction of the body’s androgens. Because of the slow growth and spread of many prostate cancers, another option is to monitor the cancer and to delay treatment until the cancer shows that it is progressing (Epstein, 2005).
Active monitoring and watchful waiting are almost unique to prostate cancer.
—CATALONA ET AL., 2007.
Prostate cancer is relatively slow growing, with doubling times for most local tumors estimated at 2 to 4 years. Some prostate cancers prove to be so small, low-grade, and noninvasive that they appear to pose little risk to a person’s life. With active treatments producing a variety of discomforts and side effects, some people with low-risk prostate cancer elect conservative therapy, in which they wait until there is evidence that the cancer is progressing before beginning any interventions (Eastham & Scardino, 2007).
At one end of the spectrum of conservative therapies is watchful waiting. Here, the goal is to avoid any treatments that might degrade the patient’s quality of life, and if the cancer progresses, treatments are chosen to maintain the patient’s quality of life, even when those treatments are only palliative.
Watchful waiting is most often chosen by patients either who are older than 70 years or who have a life expectancy of less than 10 to 15 years and tumors that are still fairly well differentiated, with Gleason scores below 8. After the initial diagnosis, watchful waiting patients are monitored only by their symptoms.
At the other end of the spectrum of conservative therapies is active surveillance or active monitoring. Here, the goal is to avoid unnecessary treatment by delaying active intervention until a tumor has “revealed” its aggressiveness. Cancers are watched carefully, and once they begin to progress, treatments are chosen with the aim of curing the disease.
Under active surveillance, patients need annual biopsies because PSA blood tests do not reliably identify progressing cancers. In the few available studies of patients electing active surveillance, approximately one-third of those patients who began with low-stage, low-volume prostate cancer showed progression of the disease in less than 5 years.
Both watchful waiting and active surveillance are commonly chosen by patients who have low-risk cancers. Currently, it is difficult to predict whether a given tumor is actually “low-risk,” and classifying a specific cancer as low-risk is somewhat of a gamble for the patient. Because treatment is more successful when it is instituted early, many physicians recommend direct, aggressive treatment even for small cancers, except in the elderly or in other individuals with short life spans (Catalano et al., 2007).
For low-grade tumors, a radical prostatectomy can often slow or stop the cancer and avoid distant metastases. In addition, the removed prostate can be thoroughly examined, and the grade and stage of the cancer can be determined accurately (Catalona et al., 2007).
Performing a radical prostatectomy while sparing (preserving) the adjacent nerve bundles and the external urinary sphincter is a difficult operation. Nevertheless, radical prostatectomy is often preferred over technically easier treatments, such as radiation therapy or androgen-deprivation therapy, because these are not as uniformly successful across the full range of locally confined prostate cancers. Mortality from radical prostatectomy is approximately 0.5% (Michaelson et al., 2008).
Two approaches have been used for open prostatectomies: surgery from the bottom (the perineal approach) and surgery from the front (the retropubic approach). Radical prostatectomies can also be done laparoscopically, directly or by remote control (robotic). The efficacy of the various surgical techniques are difficult to compare, and as with many operations, a skilled surgeon who is experienced in the specific technique appears to be the key factor in determining the success of any prostatectomy (Walsh & Partin, 2007).
Typical hospital stays for a prostatectomy are 1 to 3 days. The urinary catheter can be removed about a week after surgery, and Kegel exercises will help to regain full urinary control. The two main complications of radical nerve-sparing prostatectomy are erectile dysfunction and urinary incontinence.
After successful surgery, PSA levels should be undetectable in about 1 month. The long-term success of the operation is monitored by continuing to follow PSA blood levels. Regular digital rectal examinations will occasionally pick up recurring tumors before they are evident by their PSA values.
Radiation treatments are an important tool for slowing or killing many forms of cancer. Radiation kills cells mainly by damaging their DNA, and cells are most sensitive to radiation damage in the G2 and M phases of their cell cycle, that is, when the cells are preparing to divide or while they are dividing.
For prostate cancers, radiation is delivered in one of two forms: beams of radiation from a machine outside the patient or continuous radiation from radioactive materials implanted directly into the prostate. Treatment with x-ray beams generated by a linear accelerator is called external beam radiation; implantation of radioactive sources directly into the tumor is called brachytherapy (Catalona et al., 2007).
External beam radiation therapy shoots gamma rays at the prostate from outside the body, requiring the radiation to pass through surrounding tissues to reach the prostate. To minimize collateral injury, especially to the bladder and the rectum, the ionizing gun rotates around the patient and directs the beam from many different angles. The rotating beam is focused using a computer in techniques called three-dimensional conformal radiation therapy and intensity-modulated radiation therapy. Beam positions are mapped from CT images (Catalona et al., 2007; Michaelson et al., 2008).
When external beam radiation is combined with androgen-deprivation therapy (see “Androgen-Deprivation Therapy” below), patients’ outcomes can sometimes be improved. For example, the combined therapy gives men with locally advanced or with high-grade, high-risk prostate cancers longer survival times than when either therapy is used alone. The advantage of adding androgen-deprivation does not generalize: combining it with radical prostatectomy or with brachytherapy does not significantly change patients’ outcomes (Catalona et al., 2007).
Brachytherapy (also called interstitial brachytherapy) is mainly used to treat small, low-risk prostate cancers. The treatment involves implanting high-dose radioactive sources called seeds directly into the prostate. The radioactive materials are positioned with visual guidance from transrectal ultrasound images; afterward, the position and the actual dosage of the seeds are checked with a post-treatment CT scan. Brachytherapy concentrates high doses of radiation in focal areas without the need for the radiation to first pass through surrounding tissues, although these tissues do receive damaging radiation.
When the radioactive sources are low-dose emitters—such as radioactive iodine or radioactive palladium—the seeds are implanted permanently, and the therapy is called low-dose-rate brachytherapy. When the radioactive sources are more powerful—such as radioactive iridium—the seeds are implanted temporarily and are later removed; this therapy is called high-dose-rate brachytherapy. The implantation and removal procedures can be performed under general or regional anesthesia (Pisansky et al., 2008).
Both external beam radiation therapy and brachytherapy cause irradiation of the penile bulb, the neurovascular bundles, the anterior rectal wall, the prostatic urethra, and the neck of the bladder. Urinary problems are more common after brachytherapy than after external beam therapy (Catalona et al., 2007). (See “Side Effects and Their Management” below.)
Other physical treatments for prostate cancer are being studied, including cryotherapy and high-intensity focused ultrasound.
The response of prostate cancer to androgen ablation is among the most reproducible, durable, and profound of any systemic therapy for a solid tumor.
—J.B. NELSON, 2007.
Throughout a man’s life, androgens stimulate prostate growth, maintenance, and secretory functioning. By reducing the amount of androgen that is available, the growth of prostate cancers can be slowed. Androgen-deprivation therapy does not cure prostate cancer, but for many patients it gives a long remission (Catalona et al., 2007; Veltri & Rodriguez, 2007).
The androgen that has the greatest effect on the prostate is dihydrotestosterone, which is made in the prostate from circulating testosterone (Veltri & Rodriguez, 2007). The brain controls the amount of testosterone that circulates in the body. The first in a chain of androgen signals, luteinizing hormone-releasing hormone (LHRH) travels from the hypothalamus in the brain to the pituitary gland. In response, the pituitary gland releases the second signal, luteinizing hormone(LH), into the general circulation. When luteinizing hormone reaches the testes, it stimulates the synthesis and release of testosterone. Circulating testosterone is then taken up by the prostate, which transforms the testosterone into dihydrotestosterone using the intracellular enzyme 5α-reductase type II (5α-RII).
Androgens can be reduced in men either 1) surgically, by removing both testes, or 2) chemically, by blocking androgen synthesis, by competitive blocking of androgen receptors, or by blocking the hormonal stimulation of androgen production.
Both testes can be removed under local anesthesia in an outpatient procedure. This reduces testosterone levels by greater than 90% within 24 hours. Over a 10-year period, the cost of bilateral orchiectomy is less than one-tenth the cost of other forms of androgen-deprivation therapy. However, patients tend to avoid orchiectomy for psychological reasons such as the disfigurement and the permanence of the surgery (Nelson JB, 2007).
Medicines can also reduce the effect or the availability of androgens.
These drugs block steps in the metabolic pathways that build testosterone molecules. Two blockers used in androgen-deprivation therapy are aminoglutethimide and ketoconazole. These compounds also interfere with steps in the synthesis of adrenal steroids, so patients taking these drugs need cortisol supplements.
Antiandrogens block androgen receptors, either extracellularly (i.e., at the uptake level) or intracellularly (i.e., at the activity level). Antiandrogens include cyproterone acetate, flutamide, bicalutamide, and nilutamide. Nonsteroidal antiandrogens will cause luteinizing hormone and testosterone levels to increase. Serious liver toxicity is a possible side effect of taking antiandrogens.
Androgen-deprivation (shutting down the prostate’s supply of dihydrotestosterone) is very effective at slowing the growth of prostate cancer. After a time, however, patients on androgen-deprivation therapy usually develop rising PSA levels. This indicates that the cancer is becoming androgen resistant.
When androgen resistance develops, discontinuing androgen-deprivation therapy will sometimes produce a PSA decline. Therefore, one therapeutic protocol involves intermittently using and discontinuing androgen-deprivation techniques. Eventually, this technique will also fail to slow the cancer’s progression.
When intermittent androgen-deprivation therapy fails and PSA levels continue to rise, chemotherapy with docetaxel can be tried. Docetaxel can sometimes give a longer and more comfortable survival (Fitzpatrick et al., 2008) than stopping therapies altogether.
After it has become unresponsive to androgen-deprivation therapy, prostate cancer will usually have produced metastases. Two common problems from metastases are bone pain and symptoms from spinal cord compression.
Metastatic prostate cancer usually progresses to a point where further cancer treatments only offer increased problems and discomfort. Now, the physician and patient can move into the palliative care mode. Palliative treatment is not giving up on patient care; it is only shifting the care goals and tasks.
In palliative care, physical, emotional, and spiritual comfort become the physician’s goals, and completing unfinished tasks and resolving uncompleted relationship problems become the patient’s goals. Palliative care and end-of-life medicine are recognized medical subspecialties, and trained professionals are available to coordinate this phase of patient treatment. Hospices are some of the best environments for palliative treatment (Abrahm, 2008).
Regularly measuring PSA blood levels is the standard method for monitoring the status of prostate cancer patients.
After a radical prostatectomy, PSA blood levels should be undetectable (<0.1 ng/ml) within a month. When PSA levels remain over 0.1 ng/ml, it is likely that some cancer is still present.
Even after PSA levels have become undetectable, prostate cancer can recur. These recurrences raise PSA blood levels and are called biochemical recurrences. After radical prostatectomy for local cancer, 50% of the biochemical recurrences appear within 3 years, 80% within 5 years, and 88% within 10 years (Catalona et al., 2007).
Each year, approximately 50,000 American men are diagnosed with a biochemical recurrence after radical prostatectomy. Typically, these recurrences are slow-growing cancers. Only one-third form metastases, and the metastases take, on average, 8 years to develop (Nelson WG et al., 2008). The strategy for optimally managing biochemical recurrences after radical prostatectomy is still an unsettled issue (Morris & Scher, 2007).
After radiation therapy, PSA blood levels gradually decline as the damaged cells begin to die, and it can take 2 to 3 years for PSA levels to bottom out. When PSA levels have reached their lowest values, they can then be followed to monitor the state of the tumor. If the PSA values begin to rise, recurrence of the cancer is a possibility and a biopsy is taken to provide a more definitive evaluation (Epstein, 2007).
After beginning androgen-deprivation therapy, most prostate cancer patients will have lower PSA blood levels. Those patients showing a significant (>80%) and rapid (<1 month) drop in PSA values are likely to continue responding well to the therapy. Patients whose PSA values become undetectable (<0.1 ng/ml) have the longest survival times.
Usually, there is more than one type of treatment that could be considered for any particular prostate cancer patient, and choosing between available treatments is rarely simple.
Treatments affect the patient’s quality of life as well as the quality of life of his family (Gomella et al., 2009). Many factors figure into the equation that balances the potential benefits of each treatment against its side effects. Choosing the most acceptable treatment plan almost always requires a number of back-and-forth discussions between a patient and his doctor.
Treatments are planned from a list of data specific to each patient. The data includes:
As men age, their remaining years steadily decrease. The two ends of the life-expectancy spectrum pose quite different scenarios for men with prostate cancer. Young men, those under 50 years old, have expected life spans of 30 or more years. Thus, young men are most likely to face the full consequences of a newly diagnosed prostate cancer. In contrast, old men, those over 85 years old, have expected life spans of 5 or fewer years. Prostate cancers tend to progress slowly, and old men are likely to die of causes other than a newly diagnosed prostate cancer (Fitzpatrick et al., 2008). Source: Graph drawn with data for the year 1998 from Eastham, 2007.
With the tumor data, patients can be assigned to risk groups.
| Risk Group | Tumor Stage | PSA Level | Gleason Score | Other Biopsy Data |
|---|---|---|---|---|
| Source: Catalona et al., 2007. | ||||
| Low | T1a, T1c | <10 ng/ml | 2 to 5 | Unilateral tumor or <50% of prostate involved |
| Intermediate | T1b, T2a | <10 ng/ml | 6 or (4+3)=7 | Bilateral tumor |
| High | T2b,T3 | 10–20 ng/ml | 4+3=7 | >50% of prostate involved or perineural invasion or ductal differentiation |
| Very high | T4 | >20 ng/ml | 8 to 10 | Lymphovascular invasion or neuroendocrine differentiation |
The patient’s risk group is next set in the context of his estimated life span. Together, these two characterizations usually offer the most useful perspective when discussing which treatments are best for a particular patient. Although decisions must be individualized, there are some hard-won suggestions.
Currently, there are some differences between the major clinical guidelines on the specifics of treatment for those prostate cancers that are entirely contained within the prostate (Dahm et al., 2008). Nonetheless, for nonmetastatic prostate cancer, recommended options usually include:
High- and very high-risk patients have what is called locally advanced prostate cancer and constitute about 10% of all initial prostate cancer diagnoses. A locally advanced prostate has not yet metastasized, but it is stage T3 or T4, meaning that it has grown through the prostate capsule and into neighboring tissue.
Appropriate treatment for locally advanced cancer usually requires systemic measures, such as androgen-deprivation therapy or chemotherapy in addition to any local surgery or radiation that might be given. There are recommended treatment options for these patients, but there is currently no consensus on the best general way to manage locally advanced prostate cancer (Meng & Carroll, 2007; Fitzpatrick et al., 2008).
CONTROVERSY 2: AT WHAT POINT TO BEGIN ANDROGEN-DEPRIVATION THERAPY?
Androgen-deprivation therapy can delay the progression of prostate cancer of any stage, but it is not an innocuous treatment. Androgen-deprivation therapy produces side effects that significantly diminish a person’s quality of life, and for prostate cancers that show no evidence of distant metastases, it is not clear when to recommend beginning this therapy (Nelson JB, 2007).
Androgen-deprivation therapy (ADT) is always recommended for symptomatic metastatic disease, but the question of whether to begin androgen-deprivation therapy earlier is made difficult by a host of complexities. These complexities include:
Patients with metastatic prostate cancer are usually treated with androgen-deprivation therapy. Once prostate cancer patients develop metastases, the median time until death is 5 years; and historically, androgen-deprivation therapy for advanced prostate cancer has also included palliative care, with special attention to relieving pain.
During constant androgen-deprivation therapy, patients can develop androgen resistance. When the next step, intermittent androgen-deprivation therapy, also fails, chemotherapy can be tried. Chemotherapy—specifically, treatment with docetaxel—has been shown to increase the survival and the comfort of some patients (Fitzpatrick, 2008).
All active treatments for prostate cancer have costs as well as benefits. Because the prostate is an integral part of the genitourinary tract, physical treatments tend to cause genitourinary problems. In addition, radiation will damage neighboring tissues, the most sensitive of which is the rectum, so radiation often gives bowel as well as genitourinary problems. In contrast, androgen-deprivation therapy is a systemic treatment, and its side effects can be whole body problems, either metabolic, physiologic, or psychological.
The ability to have erections that are sufficient for penetration and intercourse are lost for a few months after a nerve-sparing radical prostatectomy. Partial erections return in 3 to 6 months, and improvements continue for up to 3 years (Catalona et al., 2007). The recovery of sexual function occurs slowly: at 3 months post-operatively 38% of patients are potent, at 6 months 54%, at 12 months 73%, and at 18 months 86%. When preoperative erections have been normal, younger men are more likely to recover their ability to have erections than are older men. In favorable situations, erections sufficient for intercourse were recovered in the following percent of the cases (see table) (Michaelson et al., 2008).
| Patient Age (years) | Recovery of Potency |
|---|---|
| Source: Michaelson et al., 2008. | |
| 40–50 | 95% |
| 50–60 | 85% |
| 60–70 | 75% |
| 70–80 | 50% |
With the use of phosphodiesterase 5 inhibitors, such as sildenafil, 80% of patients who become impotent can achieve erections sufficient for intercourse (Michaelson et al., 2008). Besides phosphodiesterase 5 inhibitors, available postoperative treatments for erectile dysfunction include intraurethral and intracorporal administration of vasodilators, vacuum erection devices, venous flow constrictors, and implantable penile prostheses (Catalona et al., 2007).
After prostatectomy by an experienced surgeon, urinary continence returns in most men. Eventual urinary continence ranges from 95% for men under 50 years old to 85% for men over 70 years old (Michaelson et al., 2008).
For incontinence, Kegel exercises and biofeedback have helped some patients. Urinary incontinence tends to improve slowly during the first 2 years after a radical prostatectomy; for this reason, any invasive treatments for incontinence are usually delayed for at least 1 year after prostatectomy (Michaelson et al., 2008).
To treat the prostate adequately with external beam radiation, radiation must pass through adjacent normal structures. The bladder neck, penile bulb, and the anterior rectal wall all receive significant doses of radiation. The prostatic urethra and the local neurovascular bundles are also irradiated. When it has been decided to irradiate the pelvic lymph nodes, the bladder, rectum, sigmoid colon, and small bowel receive extra radiation. For these reasons, external beam radiation therapy can lead to problems in all the surrounding tissues, including a decline of sexual abilities, obstructive and irritative urinary symptoms, and rectal urgency and bleeding (Michaelson et al., 2008).
With radiation therapy there is inescapable radiation to the neurovascular bundles and to the penile bulb. This leads to decreased potency in treated men compared with age-matched controls. It is thought that there are three contributors to the impotence (erectile dysfunction) that follows radiation therapy:
Patients develop erectile dysfunction beginning about 1 year after radiation treatment. By 2 years after treatment, half of the patients are unable to have an erection sufficient for intercourse; by 5 years after treatment, almost two-thirds of the patients have impotence. Younger patients are less likely to develop impotence, while the problem is more likely to develop in patients who enter treatment with partial potency or diabetes or who receive even a brief course of androgen-deprivation therapy (Michaelson et al., 2008).
Another study found that 14% of patients had erectile dysfunction at 15 months, 50% at 6 years, and a total of 70% were eventually impotent. Sildenafil succeeded in reversing impotence in 74% of these cases (Nelson WG et al., 2008).
External beam radiation therapy causes inflammation and cell destruction at the bladder neck and inside the prostatic urethra. Symptoms begin 2 to 3 weeks after treatment, when the mucosa first becomes denuded. The symptoms then continue for several weeks until the epithelium has regrown, usually by 2 months post treatment
Both irritative and obstructive urinary symptoms may occur, although men with large prostates are more likely to develop obstructive urinary symptoms. After external beam radiation, one-third of patients have dysuria or symptoms of urinary obstruction.
Months or even years after external radiation, a variety of late sequelae may develop. These problems are the result of destructive changes in the small vessels of the irradiated tissues, resulting in chronic hypoxia, mucosal thinning, and the growth of aberrant blood vessels. The symptoms can include painless hematuria, urinary frequency, and dysuria.
Obstructive and irritative urinary symptoms from radiation can often be managed effectively with alpha-blockers, such as tamsulosin or terazosin, or by anticholinergics. Anticholinergics must be used with caution in men with pre-existing benign prostatic hypertrophy because there is a risk of causing acute urinary retention.
Rectal tissue is quite sensitive to radiation, and bowel symptoms are often seen after radiation therapy (Michaelson et al., 2008). After external beam radiation, a third of the patients have temporary irritable bowel syndrome, rectal bleeding, or bladder irritability. Intermittent continuations of these symptoms happen in 5% to 10% of patients (Catalona et al., 2008).
Men receiving radiation to the pelvic lymph nodes have a larger volume of bowel irradiated and, consequently, an increased rate of side effects involving the intestines, such as cramping, diarrhea, and adhesions (Michaelson et al., 2008).
The majority of mild to moderate bowel symptoms are treated effectively by dietary changes (e.g., the addition of fiber) or by the use of hydrocortisone suppositories or foam. Late rectal complications peak during the first 3 years and then resolve slowly over time.
Brachytherapy produces a somewhat different mix of side effects than external beam radiation therapy.
As with external beam radiation therapy, brachytherapy has a significant risk of inducing impotency. The appearance of erectile dysfunction begins a few months after the procedure, and by 6 months after treatment, one-quarter of patients will develop impotence. Approximately half of all men treated with brachytherapy will eventually become impotent. Again, sildenafil allowed almost 80% of these patients to achieve erections sufficient for intercourse (Michaelson et al., 2008).
Urinary problems are common side effects of brachytherapy. Urinary symptoms include frequency, urgency, dysuria, incomplete emptying, and a weak urine stream. The initial trauma of the implants causes some of these symptoms within 24 hours, but the direct effects of the radiation begin later, in about 2 to 3 weeks. These direct effects result from radiation-induced inflammation.
Urinary incontinence or urinary retention occurs in approximately 1 of 5 brachytherapy patients. Either problem can occur immediately after the radioactive seeds have been implanted or 2 to 3 weeks later. These urinary complications may require catheterization. Obstructive and irritative symptoms tend to be mild after brachytherapy and can usually be treated effectively with alpha-blockers. A post-treatment course of corticosteroids will decrease the likelihood of urinary retention (Michaelson et al., 2008).
A smaller volume of outside tissue is irradiated by brachytherapy compared to external beam radiation; therefore, bowel problems are much less common with brachytherapy.
Diarrhea can be managed with antidiarrheal agents such as loperamide. Proctitis and urgency can be treated with dietary modifications or with psyllium to add bulk. For those patients with significant rectal irritation, cramping, or tenesmus, hydrocortisone suppositories can provide relief.
In addition to its role as an adjunct to external beam radiation, androgen-deprivation therapy is used as an initial treatment, and it is the primary treatment for recurrent prostate cancer. For recurrent cancer, androgen therapy is typically continued until the patient’s death, a period that may last for many years. On androgen-deprivation therapy, patients with metastatic prostate cancer live, on average, for 2 to 3 years.
Although it does not cure prostate cancer, androgen deprivation is very effective at slowing tumor growth and at relieving symptoms. On the other hand, decreasing a man’s androgens leads to a host of undesirable and debilitating side effects, although the likelihood of developing some of these problems varies with the specific type of androgen-deprivation therapy that is used (Meng & Carroll, 2007).
Long-term androgen deprivation has another complication. Many prostate tumors treated with androgen-deprivation therapy eventually become less dependent on androgens. The tumors then become androgen resistant, they begin to grow even during androgen-deprivation treatment, and the patient’s PSA blood levels rise again. When prostate cancer becomes androgen resistant, systemic chemotherapy can be instituted. Chemotherapy can improve the quality of a patient’s life and sometimes it will lengthen the patient’s life span (Eisenberger & Carducci, 2007).
The changes in circulating sex hormones that are brought about by androgen-deprivation therapy lead to significant changes in a patient’s metabolism of bone, fat, muscle, and blood cells.
All elderly men tend to lose bone mineral density. Androgen deprivation increases this loss, causing an immediate and sustained decrease in bone mineral density. During therapy, a patient’s bone mineral density continues to drop 2% to 3% each year. The osteoporosis caused by androgen-deprivation therapy can lead to bone fractures, and the risk of fractures increases while a patient is on the therapy (Nelson JB, 2007).
Treatments for osteoporosis include smoking cessation and increased weight-bearing exercises. For all older men, the National Institutes of Health recommends daily supplements of 1200–1500 mg of calcium and 400 IU of vitamin D. However, these supplements are insufficient to prevent the excess loss of bone mineral density in patients treated with androgen-deprivation therapy. Therefore, bisphosphonates (typically, pamidronate or zoledronic acid) are often added to the calcium and vitamin D supplements for androgen-deprivation patients (Nelson JB, 2007).
Androgen-deprivation therapy markedly changes the fat-to-muscle balance in the overall composition of a man’s body. Men on androgen-deprivation therapy increase their fat mass about 10% during the first year, and they decrease their muscle mass by about 3%. The increased fat tends to be subcutaneous rather than intra-abdominal (Michaelson et al., 2008; Saylor & Smith, 2009).
Androgen deprivation also increases levels of total blood cholesterol, circulating low-density lipoprotein cholesterol, circulating triglycerides, and insulin resistance (Saylor & Smith, 2009). Thus, men on androgen-deprivation therapy tend to become overweight and to have dyslipidemia and elevated fasting plasma glucose levels (Michaelson et al., 2008).
Loss of muscle mass and an increase in body fat can both be helped by vigorous exercise of more than 3 hours/week. The best counter measures are still being worked out, but exercise, weight loss, diet changes, and, if necessary, statins will likely be parts of the recommended treatment (Nelson JB, 2007; Saylor & Smith, 2009).
Normochromic, normocytic anemia is common on androgen-deprivation therapy, although the anemia is usually mild and asymptomatic. Giving patients erythropoietin will increase hemoglobin concentrations in men receiving LHRH agonists for prostate cancer, but the degree of anemia is usually small and does not require treatment (Michaelson et al., 2008).
The changes in circulating sex hormones caused by androgen-deprivation therapy distort or debilitate the functioning of a number of systems in a patient’s body (Michaelson et al., 2008).
Hot flashes are unpredictable episodes of intense warmth in the upper body and face, sometimes accompanied by sweating. Hot flashes are a common side effect of androgen-deprivation therapy, occurring in 50% to 80% of all patients.
Available drug treatments for hot flashes include transdermal estrogen or megestrol acetate (a progesterone), but these drugs give adverse side effects: estrogens cause gynecomastia and mastodynia, while progesterones cause weight gain. (Gynecomastia is a benign increase in the glandular tissue in the breast; mastodynia is breast or nipple tenderness.) In some women, selective serotonin reuptake inhibitors will reduce hot flashes, and preliminary evidence suggests that venlafaxine and paroxetine may also be effective in some men (Michaelson et al., 2008).
Between 80% and 90% of patients on androgen-deprivation therapy lose the ability to have an erection sufficient for intercourse. However, due to the concurrent loss of libido, most patients accept their inability to have erections.
Some forms of androgen-deprivation therapy lead to gynecomastia and mastodynia. Antiandrogens cause breast problems more often than LHRH agonists or bilateral orchiectomy do.
Prophylactic breast irradiation is an effective physical technique for preventing breast problems. If radiation is given later, after the development of gynecomastia, pain (mastodynia) can be reduced but the enlargement remains. Tamoxifen is the most effective medical therapy for gynecomastia and mastodynia after androgen-deprivation therapy. Breast reduction surgery may benefit the occasional man who develops severe breast symptoms that are refractory to medications (Michaelson et al., 2008).
These three conditions are commonly reported by men on androgen-deprivation therapy.
Androgen-deprivation therapy is associated with a greater risk of developing diabetes, coronary heart disease, and myocardial infarction.
Sex hormones affect mood, motivation, and the cognitive workings of the brain. The changes in circulating sex hormones brought about by androgen-deprivation therapy alter both a patient’s feelings and his mental acuity.
As many as 95% of androgen-deprivation therapy patients find their level of sexual interest has decreased.
Between one-half and three-quarters of men on androgen-deprivation therapy show decreased abilities in at least one cognitive area, such as verbal fluency, memory, or complex information processing. The most common declines are found in visuospatial abilities and in executive functioning (Nelson CJ et al., 2008).
A few studies have attempted to objectively compare prostate cancer patients’ overall quality of life after different therapies. The available data suggest that all treatments produce some decreases in quality of life due to problems with urinary control, bowel control, sexual intimacy, and sexual self-confidence. Broadly speaking, the levels of quality of life were similar after treatment with either radical prostatectomy or radiation (Michaelson et al., 2008).
AN IMPORTANT NURSING ROLE
At every step of a prostate cancer patient’s interaction with the medical system, nurses are central to ensuring that the patient receives full care (Tarnhuvud et al., 2007). Beyond the direct medical evaluation and treatment, a prostate cancer patient needs:
Nurses are uniquely able to provide these forms of help (Doyle-Lindrud, 2007).
One common problem is that the psychological response to prostate cancer and its treatment disrupts the relationship between a patient and his sexual partner. Cancer treatments often hinder a patient’s ability to have an erection. In addition, the patient’s sexual desire can be damped down by feelings of inadequacy and fear of being unable to complete sexual intercourse.
When meeting with patients, physicians point out such underlying psychological barriers. However, working through these difficulties and finding satisfying solutions take time. When they are given the opportunity, nurses can be the team members who guide patients and their partners as they attempt to maintain intimate relationships in the face of prostate cancer. Darst (2007) is an excellent introduction to the ways in which nurses can significantly improve the quality of life for their patients with prostate cancer.
As a rule, prostate cancers progress slowly. Many men develop unnoticed prostate cancers, but few men die of the cancer. For instance, for American men over 50 years old, there’s a 42% chance of developing unnoticed prostate cancer, a 17% chance of being diagnosed with prostate cancer, and a 3.6% chance of dying of prostate cancer (Eastham & Scardino, 2007).
The clinical course of prostate cancer varies, and the future of any particular case is not easily predicted. Two important questions are 1) Will the cancer metastasize? and 2) Will the cancer be fatal? The degree of a cancer’s differentiation is one of the more useful tools when attempting to make these predictions.
For prostate cancers that are entirely inside the prostate at the time of diagnosis, well-differentiated cancers are much less likely to metastasize than poorly differentiated cancers.
| State of Differentiation | Likelihood of Metastasis in 10 Years |
|---|---|
| Source: Meng & Carroll, 2007. | |
| Well-differentiated | 19% |
| Moderately differentiated | 42% |
| Poorly differentiated | 74% |
Similarly, tumor differentiation helps to predict longevity. The graph below shows that the chances of a man dying from prostate cancer within 15 years of its diagnosis increase for poorly differentiated tumors; in other words, longevity is shorter when the initial Gleason score is higher.
Source: Meng & Carroll, 2007.
After approximately 15 years of the disease, however, even quiet prostate cancers tend to lead to problems that are more serious. For men with cancers that were confined entirely within the prostate at diagnosis (i.e., stage T1 and T2 tumors), 21% had died of the disease in the first 15 years after diagnosis. However, 1.35 times as many men died in the next 5 years alone (Meng & Carroll, 2007).
Once prostate cancer patients develop metastases, the median time until death is 5 years (Fitzpatrick et al., 2008). Patients with bone metastases have the poorest prognosis; for them, the median time until death is 1 to 3 years (Dotan, 2008).
Available studies are not always easy to compare because they often differ in the endpoints (such as PSA levels, presence of metastases, or survival times) that were used. Here are some overall statistics for survival times after surgery and after radiation therapies.
| *defined as PSA levels remaining low Source: Catalona et al., 2007; Epstein, 2007. |
|
| RADICAL PROSTATECTORY | |
|---|---|
| 10-year Survival | Postoperative Histology of Resected Prostate |
| 85–90% | Disease confined within prostate |
| 65–70% | Disease extends beyond prostate, but surgical margins are cancer-free |
| 55–60% | Disease extends beyond prostate and surgical margins have cancer |
| 25–30% | Seminal vesicle has been invaded |
| 10–15% | Lymph nodes have metastases |
| EXTERNAL BEAM RADIATION | |
| 10-year Cure* | Pretreatment Characterization of Cancer |
| 50% | Disease confined within prostate |
| BRACHYTHERAPY | |
| 7-year Cure* | Pretreatment Characterization of Cancer |
| 80% | Disease confined within prostate |
Prostate cancer is a disease of older men, and it appears that the disease typically takes decades to develop. Physicians are hopeful that during the many pre-disease years, a thoughtful lifestyle, proper diet, sufficient exercise, and certain supplements or medicines can further delay the clinical appearance of the disease.
There is good indirect evidence that a man can reduce his risk of developing prostate cancer by:
Dietary supplements are popular health aids for all medical problems. Everyone would like to have some control over their own health, and supplements have the attraction that people can buy them without a prescription and take them as they see fit.
For many years, selenium and vitamin E had been considered dietary supplements with possible protective action against prostate cancer (Facompre & El-Bayoumy, 2009). However, new evidence contradicts that hope.
SELENIUM AND VITAMIN E NO LONGER RECOMMENDED
Following the recent publication of results of a large controlled study (Lippman et al., 2009), it has been recommended that men be advised not to take selenium or vitamin E to prevent prostate cancer. In his editorial, Dr. Patrick Walsh, editor of The Journal of Urology and a prostate cancer expert, wrote:
Men should stop taking vitamin E and selenium for the prevention of prostate cancer. They are ineffective and may be dangerous. The SELECT trial, which began to recruit in 2001, was originally scheduled to last for 12 years. However, it was abruptly halted in October 2008 because of two concerning trends: a small but not statistically significant increase in the number of prostate cancer cases among the men taking vitamin E, and a small but not statistically significant increase in the number of cases of adult onset diabetes in men taking selenium….
Men need to know that there is no pill that prevents prostate cancer from developing, and if they take more than 7 vitamin pills a week, they may be more likely to develop advanced disease and die of it.
Source: Lippman et al., 2009.
On the other hand, a number of safe natural foods may offer some reduction in prostate cancer risk (Syed et al., 2008; Van Patten et al., 2008). Soybeans contain isoflavones, which appear to reduce the risk of developing prostate cancer. Similarly, lycopene, a relative of beta-carotene and a component of tomatoes and other red fruits and vegetables, appears to reduce a man’s risk of developing prostate cancer. Indirect evidence suggests that both green tea and pomegranates may also reduce a man’s risk of developing prostate cancer. For all these substances, the results of scientific studies are suggestive but not definitive.
The most encouraging results for a drug that can potentially reduce the risk of developing prostate cancer are for finasteride. Finasteride lowers androgen levels by inhibiting 5α-reductase type II, the enzyme that converts testosterone into dihydrotestosterone in the prostate. Currently, finasteride (Propecia) is used to increase hair growth in men with male pattern baldness (Klein et al., 2007).
In a large trial, finasteride, taken daily for many years, was found to reduce prostate cancers by 25%. Until recently, the American Society of Clinical Oncology and the American Urological Association (Kramer et al., 2009) advised that asymptomatic men with low PSA levels “may benefit from a discussion of both the benefits of 5-ARIs [5α-reductase inhibitors] for 7 years for the prevention of prostate cancer and the potential risks (including the possibility of high-grade prostate cancer [and sexual dysfunction]).” Updated results from the same study are even more encouraging.
5α-REDUCTASE INHIBITORS CAN REDUCE PROSTATE CANCER RISK
Recently published studies are brightening the outlook for chemoprevention of prostate cancer. These updates conclude that finasteride:
From the new results, the authors recommend: “With an excellent safety profile and minimal side effects, men aged 55 years or older should be informed of the opportunity to reduce their risk of prostate cancer with finasteride” (Kramer et al., 2009).
Prostate-specific antigen (PSA) was discovered in 1979. Since the 1980s, PSA blood levels have been used to monitor prostate health and to detect, stage, and follow prostate cancers in situ. Changes in PSA blood levels can often be seen even for small cancers that are asymptomatic and are not palpable by digital rectal examination. The widespread use of PSA blood-level screening has changed the type of prostate malignancies that physicians regularly face: at one time, doctors saw mainly advanced cancers; now, they see mainly early cancers (Gretzer & Partin, 2007).
CONTROVERSY 3: TO SCREEN OR NOT TO SCREEN?
Currently, men are usually offered screening for prostate cancer. As they get older, men are more likely to be screened; for example, in 2006, 48% of men 50 to 59 years and 56% of men 80 years and older were screened for prostate cancer (Carter et al., 2007).
Screening by PSA blood level is used to identify men who may have asymptomatic prostate cancer and to predict which men may get prostate cancer in the future (Fleshner & Lawrentschuk, 2009). Nonetheless, screening for prostate cancer in asymptomatic men remains controversial (Carter et al., 2007; Klein et al., 2007).
At first glance, it would seem that screening for a potentially fatal disease such as prostate cancer would be embraced by healthcare workers. However, screening comes with costs that reduce patients’ quality of life (Gomella et al., 2009).
With these qualifiers in mind, today’s screening recommendations usually suggest that physicians discuss the pros and cons of screening with their patients and then make screening available if the patient is interested (Carter et al., 2007; Carroll et al., 2009).
AMERICAN CANCER SOCIETY’S POSITION ON SCREENING
Because the value of regular screening is still debated among professionals, the American Cancer Society’s recommendations emphasize the shared role of physician and patient in deciding whether to screen. Screening can identify some asymptomatic cases of prostate cancer; however, the available evidence is insufficient to say that treating these early cancers leads to better outcomes than waiting until they become symptomatic. Therefore, the current American Cancer Society position is:
The American Cancer Society recommends that healthcare providers discuss the potential benefits and limitations of prostate cancer early detection testing with men and offer the PSA blood test and the digital rectal examination annually, beginning at age 50, to men who are at average risk of prostate cancer and who have a life expectancy of at least 10 years. Those men who indicate a preference for testing following this discussion should be tested.
Men at high risk of developing prostate cancer (African Americans or men with a close relative diagnosed with prostate cancer before age 65) should have this discussion with their provider beginning at age 45.
Men at even higher risk (because they have several close relatives diagnosed with prostate cancer at an early age) should have this discussion with their provider at age 40.
Source: Smith et al., 2009.
For men who choose to be screened, the examination includes both a measurement of the PSA blood level and a digital rectal examination.
The optimum age at which to begin prostate cancer screening has not been determined. The American Cancer Society (Smith et al., 2009) and the American Urological Association (Carroll et al., 2009) both recommend offering screening to men having an average risk for prostate cancer at age 50 and earlier for men having a higher risk, such as blacks and men with a family history of prostate cancer.
The American Urological Association (Carroll et al., 2009) recommends rescreening every 2 years for men with PSA blood levels under 2 ng/ml and rescreening every year for patients with PSA blood levels over 2 ng/ml. The American Cancer Society (Smith et al., 2009) recommends offering screening annually, beginning at age 50, to men with a life expectancy of over 10 years.
The benefits of screening decline rapidly with age (Carroll et al., 2009). There is no consensus as to when to discontinue screening, although the age of 75 years is often suggested. Some physicians suggest that screening be stopped at the age of 70 years if the patient’s previous PSA levels have remained low and at the age of 65 years if previous PSA levels have remained very low (i.e., <1 ng/ml) (Carter et al., 2007).
In contrast, the American Urological Society points out that information provided by screening can be helpful to men of any age as long as the evidence of a possible prostate cancer does not automatically trigger the need to treat the disease (Carroll et al., 2009).
Prostate cancer is a disease of elderly men. In the U.S., it is estimated that more than a third of the men in their 50s and as many as three-quarters of men over 85 have at least microscopic evidence of cancer in their prostates.
Many fewer men are diagnosed with prostate cancer than actually have microscopic indications of the disease. Prostate cancer usually grows slowly—the doubling time for small tumors is 2 to 4 years—and it is not often a quickly fatal disease. Approximately 232,000 new cases of prostate cancer are diagnosed each year, but prostate cancer causes only about 28,000 deaths each year. The disparity between new cases and deaths from prostate cancer indicates that almost 85% to 90% of the men diagnosed with prostate cancer will die of other causes.
Early stages of prostate cancer usually produce no symptoms. On the other hand, late stages of prostate cancer can present with pelvic pain, urinary obstruction, or bone pain because advanced prostate cancer spreads outside of the prostate and may metastasize to bone (Cookson & Chang, 2008).
In asymptomatic men, prostatic cancer is suspected when either:
The definitive diagnosis is then made from a biopsy.
Prostate cancers are categorized by grade and stage. Tumor grade is an indicator of the aggressiveness of a tumor. The commonly used Gleason grading system assigns prostate cancers a score on a scale of 2 to 10: cancers with scores of 2 to 4 are well differentiated, 5 to 7 are moderately differentiated, and 8 to 10 are poorly differentiated.
Tumor stage is an indicator of the spread of the tumor. Stages T1 and T2 cancers are confined within the prostate, while stages T3 and T4 have spread outside the prostate. When lymph nodes are involved, an N number is added, and when metastases are present, an M number is added. Thus, stage T2N1M0 describes a cancer in which:
Surgical resection of a prostate tumor can potentially cure the disease when the cancer is still confined inside the prostate. Surgical resection is called radical prostatectomy, and it includes removal of nearby lymph nodes. Nerve-sparing radical prostatectomies attempt to preserve the adjacent nerve bundles that are necessary for sexual functioning (Walsh & Partin, 2007).
Radiation therapy is another treatment that can cure or significantly slow the growth of prostate cancers. Radiation can be delivered to the prostate from an external beam that is focused through surrounding tissues. Alternatively, radioactive seeds can be implanted inside the prostate. Both technologies are quite effective on cancers that have not spread beyond the prostate (D’Amico et al., 2007).
Treatments that interfere with a prostate tumor’s supply of androgen (androgen-deprivation therapy) will slow tumor growth and reduce any symptoms. After a time, however, prostate cancers become less sensitive to androgen-deprivation treatments, and the tumors resume their growth.
Aggressive prostate cancers can metastasize to pelvic lymph nodes and then into the bones. Once prostate cancer has metastasized, cures are unlikely. Androgen-deprivation therapy and chemotherapy can reduce the symptoms (such as bone pain) and prolong the patient’s survival. Nonetheless, more than half of the prostate cancer patients with metastases die within 5 years (Crawford, 2009).
Early treatment of small prostate cancers brings the promise of a cure, but the treatments also cause side effects that reduce the patient’s quality of life. For example, surgery and radiation therapy are often followed by urinary problems, bowel problems, or impotence. Given that most men with prostate cancer will not die from the cancer, the challenge to physicians is predicting which patients will, on balance, benefit from treatment (Eastham & Scardino, 2007).
Currently, physicians do not have the ability to identify accurately which early cancers will be most destructive, and more patients are treated than is necessary. Some scientists have suggested that screening for early asymptomatic cancers using the imprecise tools currently available is not always in the patient’s best interest (Carter et al., 2007; Klein et al., 2007; Carroll et al., 2009).
Health professionals who advise patients need to know straightforward answers to basic questions (Ross, 2007). Here are a few important questions and answers about prostate cancer.
What is a prostate?
The prostate is a gland located just below the bladder in men. The urethra—the tube carrying urine from the bladder and out through the penis—runs through the prostate. The prostate’s job is to make some of the seminal fluid that mixes with the sperm when a man ejaculates.
What is prostate cancer?
Prostate cancer is a disease in which new gland cells inside the prostate are made without a stop signal. The new cells are not normal, they crowd out the normal cells, and they block tubes and channels that should be open.
Sometimes the out-of-control cancer cells metastasize, which means that they break away from the prostate and spread into the body. Metastasizing cancer cells often settle in lymph nodes, where they continue to divide and crowd out the normal lymph node cells. Prostate metastases can also settle inside bones, where they cause pain and weaken the architecture, making a person prone to bone fractures.
What does PSA mean?
In medicine, PSA stands for “prostate-specific antigen,” a chemical that is made in the prostate. A small amount of PSA normally leaks into the bloodstream, and the blood level of PSA can be measured using a simple blood test.
A rise in the blood level of PSA is a sign that something unusual is happening to the prostate. More PSA leaks into the bloodstream when the prostate is injured, such as when it becomes infected or when it is biopsied. More PSA also enters the bloodstream when the prostate is growing excessively, such as in benign prostatic hyperplasia (BPH) or in prostate cancer. Even small areas of prostate cancer will sometimes increase the blood level of PSA.
What is a Gleason score?
A Gleason score, or tumor grade, is a number that ranks how aggressive a prostate cancer is. The lowest Gleason score (2) means that the prostate cells look normal, and therefore, if there is any cancer, then it is probably growing slowly. The highest Gleason score (10) means that the prostate cells look quite abnormal, and therefore, there is a prostate cancer that is likely to grow quickly.
Gleason scores are given by a pathologist, who has studied microscope slides of prostate tissues. Usually, the tissue has been obtained by a biopsy. Tissue can also be obtained from a prostate that has been surgically removed in a procedure called a prostatectomy.
I’ve heard that vitamin D prevents prostate cancer. Is that true?
It’s known that if men have a deficiency of vitamin D, then they have a higher risk of developing prostate cancer. However, there is no good evidence that taking extra vitamin D helps to prevent prostate cancer (Klein et al., 2007).
Does having sex make you more likely or less likely to get prostate cancer, or does it have no effect?
Two aspects of sexual activity have an effect on a man’s chances of developing prostate cancer. First, having sexually transmitted diseases appears to increase a man’s risk of developing prostate cancer. This is one of many reasons that men should use condoms when having sex.
Second, having frequent ejaculations appears to decrease a man’s risk of developing prostate cancer. This protection seems to help men who averaged 5 or more ejaculations a week, beginning in their 20s. Ejaculation can be by masturbation or by sexual intercourse (Klein et al., 2007).
I only like to use natural remedies. Are there any herbs that will protect me from prostate cancer?
The medical community is always hesitant about recommending herbal products because they are not standardized and they can come in unmeasured doses and contain a variety of ingredients. Moreover, some components in herbal products can be dangerous or can interact with your regular medicines.
On the other hand, some natural foods may be helpful, and these are known to be safe. There is indirect evidence that soy products, pomegranates, and green tea may have some protective effects against prostate cancer. In addition, many red fruits and vegetables (such as tomatoes, carrots, watermelon, and papaya) contain lycopene, a compound that some people think may reduce the risk of developing prostate cancer. At the moment, though, there is not enough scientific evidence to be certain about the protective claims for these foods (Van Patten et al., 2008).
Where can I get trustworthy information about prostate cancer?
Here are two websites that have accurate and easy-to-understand information about prostate cancer:
I have been diagnosed with prostate cancer, but my doctor keeps giving me choices and not clear advice. I don’t know how to decide these things; what should I do?
You can’t be expected to be a doctor, and it’s reasonable to turn to your physician for guidance, advice, and recommendations. Patients do best with a doctor they trust and with a doctor who understands how to be most helpful to them.
Do you have confidence in your doctor? Has he or she been helpful in other situations? If you have felt comfortable with your doctor in the past, then begin your next visit by explaining how overwhelmed you are with the diagnosis of prostate cancer. Tell him or her that you need help in working through the decisions you are facing. If your doctor doesn’t have the time to spend with you, then ask if there is a nurse, social worker, or psychologist who understands prostate cancer and who can talk with you.
A diagnosis of prostate cancer brings two major decisions. First, should the disease be treated immediately? Second, what form of treatment is best? At the moment, even doctors aren’t sure of the best answers to either of these questions. A critical part of the decision-making process is finding out what choices the patient feels are best under the circumstances. In the end, you—the patient—have to be able to say, “Of all my options, this is the one that is least worrisome.” It can take time to understand your options sufficiently to make peace with one of them.
My doctor just told me that I have prostate cancer, but he is vague about whether this is a death sentence. I want to know the truth: how soon am I going to die?
Being diagnosed with cancer is scary. It makes you and your family face the fact that someday you are going to die. However, prostate cancer is rarely a “death sentence” because prostate cancers tend to grow slowly, and most men with prostate cancer end up dying from some other cause.
Your doctor may sound vague because it is simply not possible to predict how long a person will live after being diagnosed with prostate cancer. Details about your particular cancer can give you some clues, but the available information is statistical and your cancer may behave differently than the statistical averages.
For a general perspective, here are some overall numbers:
My doctor says I have BPH. Is that a kind of cancer?
No. BPH is a common, perhaps even “normal,” enlargement of the prostate in older men.
BPH stands for “benign prostatic hyperplasia.” A man’s prostate grows slowly throughout most of his life. By the time men are in their 60s, the continual enlargement often causes symptoms because the prostate begins to press on the bladder and the urethra, the tube that empties urine from the bladder. Symptoms of an enlarged prostate include having a hesitant, interrupted, or weak stream of urine: having to urinate more frequently, especially at night; and not having complete control so that urine leaks or dribbles.
In BPH, prostate cells do not spread (metastasize) or destroy other tissues, and BPH does not cause death.
American Cancer Society
http://www.cancer.org/docroot/CRI/CRI_2x.asp?sitearea=LRN&dt=36
American Urological Association Patient Guide
http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm
Mayo Clinic
http://www.mayoclinic.com/health/prostate-cancer/DS00043
National Cancer Institute
http://www.cancer.gov/cancertopics/types/prostate
Prostate Cancer Foundation
http://www.prostatecancerfoundation.org
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