Authors J, Carlsson S, Aus G, Bergdahl S, Khatami A, Lodding P, Pihl C-G, Stranne J, Holmberg E, Lilja H.
Review Date Jul 2010
Citation Lancet Oncology 2010 DOI: 10.1016/S1470-2045(10)70152-2 (published online 30 June)
Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world. One strategy to decrease the risk of death from this disease is screening with prostate-specific antigen (PSA); however, the extent of benefit and harm with such screening is under continuous debate.
To assess the benefits and harms of PSA screening from the Goteborg randomised prostate-cancer screening trial.
In December 1994, 20,000 men born between 1930 and 1944, randomly sampled from the population register, were randomised by computer in a 1:1 ratio to either a screening group invited for PSA testing every 2 years (n=10,000) or to a control group not invited (n=10,000). Men in the screening group were invited up to the upper age limit (median 69, range 67-71 years) and only men with raised PSA concentrations were offered additional tests such as digital rectal examination and prostate biopsies. The primary endpoint was prostate-cancer specific mortality, analysed according to the intention-to-screen principle. The study is ongoing, with men who have not reached the upper age limit invited for PSA testing.
In each group, 48 men were excluded because of death or emigration before the randomisation date or prevalent prostate cancer. In men randomised to screening, 7578 (76%) of 9952 attended at least once. During a median follow-up of 14 years, 1138 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 1.50-1.80; p<0.0001).
The absolute cumulative risk reduction of death from prostate cancer at 14 years was 0.40% (95% CI 0.17-0.64), from 0.90% in the control group to 0.50% in the screening group. The rate ratio for death from prostate cancer was 0.56 (95% CI 0.39-0.82; p=0.002) in the screening compared with the control group. The rate ratio of death from prostate cancer for attendees (those invited for screening who attended at least once) compared with the control group was 0.44 (95% CI 0.28-0.68; p=0.0002). Overall, 293 (95% CI 177-799) men needed to be invited for screening and 12 to be diagnosed to prevent one prostate cancer death.
This study shows that prostate cancer mortality was reduced by almost half over 14 years. However, the risk of over-diagnosis is substantial and the number needed to treat is at least as high as in breast-cancer screening programmes. The benefit of prostate-cancer screening compares favourably to other cancer screening programs.
Points to Note
- The study is relatively small compared to studies published in 2009 (a European and an American study) but showed greater reductions in mortality (RR=0.8 in the European study and no effect in the American).
- Possible explanations for differences in study findings are: the follow-up time in this study was longer; the median age was 4 years younger; the screening interval was every 2 years rather than 4 in the European study; there was a higher rate of biopsy in men with a positive screening result (93%); a lower rate of PSA testing in the population before the study started; and a probable lower rate of contamination of the control group (i.e. low rates of PSA testing in the control group). (Contamination was an important issue in the American study).
- Although not a primary outcome of the study, an interesting finding was that 40% of men in the screening group were placed on active surveillance following diagnosis of prostate cancer, potentially avoiding risks of over-treatment.
- The benefit from prostate cancer screening takes a long time to achieve suggesting that the benefit of screening older men (over 70 years) is questionable.
- The ability to differentiate intermediate and high-risk prostate cancers from those that are indolent remains elusive and is the subject of considerable research.