Clinically, prostate cancer ranges from an asymptomatic slow-growing tumor to an aggressive cancer with painful metastases. Treatment may be unnecessary at one end of the spectrum and palliative at the other.
The goal of screening is to identify slow-growing tumors destined to extend beyond the prostate while they are confined to the prostate and amenable to treatment, thereby decreasing the risk of prostate cancer morbidity and death.
Usually low morbidity. For a 50-year-old man, the risk of being diagnosed with prostate cancer by age 80 years is 15%; however, the same man has a 1.4% chance of dying of prostate cancer over that 30-year period.7 This 10-fold difference shows that prostate cancer usually is not a fatal illness. Another indication of the often benign nature of the disease is the high percentage of prostate cancers identified at surgery for bladder cancer; up to 40% of specimens contain unsuspected prostate cancer (level of evidence [LOE]: 2c).10,11
Most clinical diagnoses (80%) and prostate cancer deaths (90%) occur among men older than 65 years;6 the median age at diagnosis is 72 years.12 More than 75% of men older than 85 years will have histological prostate cancer (LOE: 2c).13 Many men live with their disease for more than 10 years, but do not die of it (LOE: 2c).12 Additionally, a review of several decision analyses indicates that men 75 years of age and older are not likely to benefit from screening and aggressive treatment (LOE: 2a).14
Hence the recommendation: if performing prostate cancer screening, limit to men with greater than 10 years life expectancy.15
Details of screening tests
Digital rectal examination insufficient
Digital rectal examination (DRE)—palpating the prostate gland to determine size and consistency—is one screening tool for prostate cancer, usually performed in conjunction with PSA testing.15 It is not a difficult or expensive test, but its reproducibility is only fair, even among experienced urologists (LOE: 2b).16
The sensitivity and specificity of DRE can only be estimated because men with a normal finding on DRE are not routinely biopsied in any studies (TABLE 1).17,18 One of two pertinent meta-analyses18 included studies that followed men with a negative DRE finding for development of prostate cancer (LOE: 2a). Both meta-analyses of DRE as a screening tool found that the included studies were heterogeneous in their study populations and definition of abnormal DRE test result (LOE: 2a). The positive predictive value (PPV) of DRE was 28% in one meta-analysis and 18% in the other.
Characteristics of screening tests for prostate cancer
|TEST/SOURCE||DESCRIPTION (LEVEL OF EVIDENCE)||SN ESTIMATE (%)||SP ESTIMATE (%)||LIKELIHOOD RATIO||PPV (%)|
|Abnormal DRE18||Meta-analysis of studies that performed biopsies for abnormal DRE (2a)||59 (51%–67%)||94 (91%–96%)||+ 9.8|
|Abnormal DRE17||Meta-analysis of studies that performed biopsies for abnormal DRE or PSA (2a)||53.2||83.6||+ 3.24|
|PSA >4 ng/mL12||Review of multiple cohort studies with diverse populations, not systematic||Mean = 71||Mean = 75||+ 2.8|
|PSA >4 ng/mL19||Longitudinal retrospective study of prostate cancers that developed within 2 years of PSA test (3b)||73.2||85.4||+ 5.0|
|PSA >4 ng/mL20||Nested case-control study of prostate cancers that developed within 5 years of PSA test in a cohort study (3b)||86||94||+ 14.3|
|PSA > 4 ng/mL17||Meta-analysis of studies that performed biopsies for abnormal PSA or DRE (2a)||72.1||93.2||+ 10.2|
|Sn, sensitivity; Sp, specificity; PPV, positive predictive value;|
|PSA, prostate-specific antigen; DRE, digital rectal examination.|
Prostate-specific antigen: Improving its clinical usefulness
Prostate-specific antigen (PSA), first detected in serum in 1979, is a protein produced by prostate epithelial cells. It was originally used to follow men treated for prostate cancer for evidence of recurrence. In the late 1980s, it became widely used in the US to screen for prostate cancer.
An elevated PSA level is suggestive but not diagnostic of prostate cancer. Elevated levels also occur with advancing age, increased prostate size, and prostatitis, and following ejaculation. Prostate manipulation such as biopsy and surgery (but not digital examination) also elevates PSA.
Customary cutpoint. An abnormal serum PSA level is commonly regarded as 4 ng/mL or greater. At this cutpoint, most studies report sensitivity for cancer of around 70%, with more variability in specificity (TABLE 1). Again, in most studies that report sensitivity and specificity, men with a PSA level less than 4 ng/mL did not undergo prostate biopsy; therefore, the number of false negatives and true negatives are only estimates.
In nested case-control studies of longitudinal cohorts, eligible cases were defined by the length of time between an abnormal PSA result and prostate cancer diagnosis, while controls were men who were not diagnosed with prostate cancer during the same time period (however, a biopsy was not usually performed). The PPV of an abnormal PSA level is estimated at 25% to 37%. As a comparison, the PPV of a positive mammogram finding for women 50 to 59 years is 4% to 9%, and 10% to 19% for women age 60 to 69.21