PSA screening halves cancer mortality

Prostate-specific antigen (PSA) testing reduces mortality by half over 14 years, although the risk of overdiagnosis is substantial and the number needed to treat is at least as high as in breast cancer screening, concluded researchers in a Swedish registry-based study.

Beginning in 1994, the ongoing study evenly randomized 20,000 men ages 66 to 80 years old to either a screening group invited for PSA testing every 2 years or to a control group. Men in the screening group were invited every two years up to the upper age limit (median 69 years, range 67 to 71 years) and men with raised PSA concentrations were offered digital rectal exams, trans-rectal ultrasound and laterally directed sextant biopsies. The primary endpoint was prostate-cancer specific mortality, analyzed according to the intention-to-screen principle. Results were published in The Lancet Oncology.

In each group, 48 men were excluded from the analysis because of death, emigration or prevalent prostate cancer. Among the screening group, 7,578 (76%) attended at least once. During a median follow-up of 14 years, 1,138 men in the screening group and 718 in the control group were diagnosed with prostate cancer, resulting in a cumulative prostate-cancer incidence of 12.7% in the screening group and 8.2% in the control group (hazard ratio 1.64; 95% CI, 1.50 to 1.80; P<0.0001). The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0.4% (95% CI, 0.17% to 0.64%), from 0.9% in the control group to 0.5% in the screening group. The rate ratio for death from prostate cancer was 0.56 (95% CI, 0.39 to 0.82; P=0.002) in the screening compared with the control group, which corresponded to “no effect on overall mortality (similar number of men at risk at 14 years, and similar number of total deaths in the study group),” the authors noted. The rate ratio of death from prostate cancer for attendees compared with the control group was 0.44 (95% CI, 0.28 to 0.68; P=0.0002). Overall, 293 (95% CI, 177 to 799) men needed to be invited for screening and 12 needed to be diagnosed to prevent one prostate cancer death.

The authors wrote, “In a programme in which all the men started screening at 50 years of age, some men could instead be diagnosed at a curable stage; therefore, potential for larger mortality reduction exists.” However, they acknowledged, prostate cancer is a slowly developing disease and overdiagnosis and overtreatment are major concerns.

An editorial highlighted the point that study results do not support widespread testing or immediate treatment. “About 40% of men in the screening group were placed on active monitoring protocols; 28% remained on these protocols. Moreover, the results show that in certain circumstances, PSA testing and early diagnosis reduces death from prostate cancer. It does not imply that PSA screening programmes should now be introduced internationally.”