Prostate cancer screening, diagnosis, and treatment present challenges to internists, urologists, and oncologists. For the internist, there is the ongoing debate about when and how often to screen with prostate-specific antigen (PSA) testing, as well as about how to interpret the results. For urologists and oncologists, there is no consensus on how to treat prostate cancer with the growing array of options, from surgery to cryoablation. Most therapies have not been compared in head-to-head trials, and anxious patients often approach their internist for help in navigating the maze of options.
This review summarizes current American Urological Association (AUA) guidelines,1 as well as current practice patterns at the Glickman Urological and Kidney Institute of Cleveland Clinic regarding screening, diagnosis, risk assessment, treatment, and posttreatment management of prostate cancer. We try to explain the approved and the experimental treatments, outlining what we know about their advantages and disadvantages.
SCREENING: WHEN AND HOW
Screening for prostate cancer should involve both a digital rectal examination (DRE) and measurement of the serum PSA level. But when should screening start?
The AUA recommends annual screening with DRE and serum PSA test starting at age 40 for all men with a life expectancy of more than 10 years.1
The American Cancer Society2 and the American College of Physicians,3 in contrast, recommend that men who choose to undergo screening should begin at age 50, or at age 45 if they are black or have a family history of prostate cancer in a primary relative diagnosed before age 65. They also recommend that screening with PSA and DRE be stopped at age 75, given the low likelihood of death from de novo prostate cancer after this age. The AUA recommends that screening be stopped at age 75, but may be continued beyond age 75 if the patient has a life expectancy of 10 years or more.
Before being screened, patients should understand the benefits and the risks of testing. While a small subset of prostate cancers behave aggressively, the majority are slow-growing and pose minimal risk for the development of fatal disease.
A discussion of the rationale for these guidelines and their differences is beyond the scope of this review. Differences stem from the observation that most men treated for prostate cancer will likely not die from prostate cancer, but rather from another condition.
Digital rectal examination’s role and limitations
The utility of DRE is limited to the detection of nodules, gross asymmetry, and gland fixation. DRE is not highly specific: only 40% to 50% of men who have abnormal findings on DRE have prostate cancer on biopsy.5 Anyone who has an abnormal finding on DRE should undergo prostate biopsy. However, if a rectal mass is palpated or if the prostate is exquisitely sensitive, biopsy is not indicated.
DRE is highly inaccurate for estimating gland volume; it should not be used to gauge cancer risk.
Prostate-specific antigen: Caveats
PSA measurement was introduced as a clinical screening test for prostate cancer in the early 1990s, and it serves as the foundation for early detection.
PSA, a protein involved in seminal coagulation, is produced by the prostate epithelium and is mostly confined within the prostatic ducts. Cancer cells secrete PSA into the bloodstream at increased levels via a disrupted basement membrane in tumor-affected areas of the gland. Elevated PSA can also result from benign prostatic hypertrophy, prostatitis, and prostate biopsy.
PSA levels represent a continuum of prostate cancer risk, and no single PSA value is sensitive and specific enough to predict the presence of cancer.6 Abnormal PSA cutoffs have been defined from 2.5 μg/L to 4 μg/L, and much debate surrounds this topic. Men who present with an elevated PSA (ie, > 2.5 μg/L) should be tested again. If the value remains high, then prostate biopsy should be considered. An elevated PSA level in older men with benign prostatic hypertrophy is not unexpected, and in these patients observation of the PSA value over time may prove valuable to assess the need for biopsy.
A useful adjunct in men with elevated PSA and benign prostatic hypertrophy is the percentage of serum PSA that is free rather than bound.7 PSA produced by prostate cancer binds more avidly with serum proteins (alpha-1 chymotrypsin and alpha-2 macroglobulin), resulting in a lower percentage of free PSA. In men with an elevated PSA (ie, 4.1–10.0 μg/L), the percentage of free PSA provides an indication of whether the elevation is due to benign prostatic hypertrophy or to cancer: the lower the percent free PSA, the more likely an elevated total PSA represents cancer and not benign prostatic hypertrophy. The sensitivity of a free PSA less than 15% to detect prostate cancer is about 85%, and its use as a screening tool is under study.
Much attention has also been given to other PSA indices, namely, the PSA density (the PSA level divided by the prostate volume), the PSA velocity (the rate of increase in the PSA level over time), and the PSA doubling time. While these nuanced PSA measures are useful to predict disease severity and behavior, they are not routinely used in screening.