• Choose a category
• All
• Classic-Fiction

By Root 992 0

76,693 men between the ages of fifty-five and seventy-four who were randomly assigned to annual screening with PSA and a digital rectal examination or to “usual care.” The indications for biopsy were a PSA cutoff of 4 or an abnormal rectal examination. A very high proportion of the men in the “usual care” control group, more than 50 percent, underwent PSA testing. After seven years of follow-up, there was no reduction in death between the two groups. This negative result of the trial could be attributed to the high rate of PSA testing in the control group, the higher PSA cutoff of 4 compared with the European cutoff of 2.5 to 4, or the relatively short follow-up period; see Gerald L. Andriole et al., “Mortality results from a randomized prostate-cancer screening trial,” NEJM 360 (2009), pp. 1310–1319.

There was considerable expectation in the medical community that these two large, randomized studies would yield results that would resolve the controversy about screening through PSA testing, but that proved not to be the case. It is unlikely the issue will be settled soon.

Another way to assess PSA testing is to ask how accurately it predicts prostate cancer in a man with no symptoms. This performance statistic is called the “positive predictive value,” meaning the proportion of men with a PSA above the often used cutoff of 4 who will be found to have cancer. Overall, the positive predictive value for a PSA level greater than 4 is approximately 30 percent, meaning that a proportion slightly smaller than one in three men with this PSA level will have prostate cancer detected on biopsy. For PSA levels between 4 and 10, the positive predictive value is about the same, 25 percent. Only when PSA levels rise above 10 does the test better predict the presence of cancer, in 42 to 64 percent of men depending on the study: Michael K. Brawer et al., “Screening for prostatic carcinoma with prostate specific antigen,” Journal of Urology 147 (1992), pp. 841–845. This relatively poor degree of prediction is offset by the fact that nearly 75 percent of cancers detected within the “gray zone” of PSA values between 4 and 10 are confined to the gland and thus potentially curable. Less than half of the prostate cancers detected when PSA values rise above 10 are confined to the gland. To complicate matters even more, these studies indicate some 15 percent of men above the age of sixty who had consistently normal PSA levels (less than 4) and normal rectal examinations will be found to have prostate cancer over seven years of annual screening. This observation shows that there is not a clear cutoff between what is a “normal” and an “abnormal” PSA. See Scott M. Gilbert et al., “Evidence suggesting PSA cutpoint of 2.5 ng/mL for prompting prostate biopsy: Review of 36,316 biopsies,” Urolog y 65 (2005), pp. 549–553; William J. Catalona, Deborah S. Smith, David K. Ornstein, “Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination,” JAMA 277 (1997), pp. 1452–1455; Mary McNaughton Collins, David F. Ransohoff, Michael J. Barry, “Early detection of prostate cancer,” JAMA 278 (1997), pp. 1516–1519.

Autopsy studies of men who died in accidents like car crashes show that a significant proportion had small nests of prostate cancer that hadn’t been causing symptoms and in all likelihood wouldn’t have contributed to any impairment during life. Overall, prostate cancer was incidentally found in between a third and a half of middle-aged or older men; see N. Breslow et al., “Latent carcinoma of prostate at autopsy in seven areas: The international agency for research on cancer, Lyons, France,” International Journal of Cancer 20 (1977), pp. 680–688.

There is clear concern that prostate cancer may be detected by screening at a stage that would never become clinically significant but, because of detection, prompts treatment; see William J. Catalona et al., “Detection of organ-confined prostate cancer is increased through prostate-specific antigen-based screening,” JAMA 270 (1993), pp. 948–954; Peter H.