Editorials

Screening for prostate cancer

BMJ 2010; 341 doi: http://dx.doi.org/10.1136/bmj.c4538 (Published 14 September 2010) Cite this as: BMJ 2010;341:c4538
  1. Gerald L Andriole Jr, chief of urologic surgery
  1. 1Washington University School of Medicine, 4960 Children’s Place, Campus Box 8242, St Louis, MO 63110, USA
  1. andrioleg{at}wustl.edu

    PSA testing should be tailored to individual risk

    Screening based on prostate specific antigen (PSA) measurement has contributed to a dramatic increase in the number of prostate cancer cases diagnosed. In addition, most tumours are now smaller and clinically localised at diagnosis, whereas before the introduction of screening, tumours were often clinically advanced or overtly metastatic at diagnosis. However, the effects of screening on overall mortality and mortality from prostate cancer were unclear and variable in two large randomised trials.1 2 The American PLCO study found no benefit on mortality, whereas the European ERSPC trial showed a 20% reduction in prostate cancer specific mortality after 10 years in men who underwent PSA based screening.

    In the linked systematic review and meta-analysis (doi:10.1136/bmj.c4543), Djulbegovic and colleagues comprehensively assessed the effects of screening for prostate cancer. The analysis of six randomised controlled trials, including the PLCO and ERSPC studies, found that screening increased the probability of being diagnosed with prostate cancer (relative risk 1.46, 95% confidence interval 1.21 to 1.77) but had no significant effect on mortality from prostate cancer (0.88, 0.71 to 1.09) or overall mortality (0.99, 0.97 to 1.01). The authors concluded that insufficient evidence is available to support the routine use of prostate cancer screening.3

    In addition to the uncertain benefit on mortality, the human and economic costs associated with PSA based screening are substantial, mainly as a result of “overdiagnosis” and “overtreatment.”4 5 This occurs because repetitive PSA based screening detects all types of prostate cancer—indolent small volume tumours as well as aggressive lesions that have a high potential to cause harm. To date, methods of reducing overdiagnosis and overtreatment of indolent tumours have included the use of 5α reductase inhibitors6 7 as an adjunct to PSA testing and “active surveillance”8 programmes for small “low risk” tumours. By eliminating dihydrotesterone, 5α reductase inhibitors reduce the development or growth (or both) of low grade prostate tumours. In clinical trials, about 25% fewer cases of low grade prostate cancers were seen in treated men who were followed for four to seven years. Active surveillance requires close follow-up of men with low grade tumours, with frequent PSA testing and biopsy every year or so. In well selected patients, often elderly men or those with an anticipated short overall survival, this strategy has helped avert aggressive treatment in those who are likely to die of other conditions. Neither of these strategies is widely practised at the moment.

    A second linked study by Vickers and colleagues assessed the potential of another strategy to improve the efficacy and reduce the costs of PSA based screening.9 They correlated PSA concentration at age 60 to the lifetime risk of a clinical diagnosis of prostate cancer, prostate cancer metastasis, and death from prostate cancer. PSA concentration at age 60 was strongly associated with prostate cancer and death from prostate cancer. Men with a PSA concentration below 1 ng/ml (about half of the population studied) had negligible rates of metastasis or death. Although only a minority of men with a PSA concentration greater than 2 ng/ml developed fatal prostate cancer, 90% (78% to 100%) of deaths from prostate cancer occurred in these men. Thus, men with a PSA less than 1 ng/ml could be exempted from repetitive testing, which would reduce overdiagnosis and overtreatment. Conversely, men with higher PSA concentrations at age 60, who have the highest risk for prostate cancer metastases or death, could be followed more intensively and might be more compliant with screening and treatment recommendations and with risk reduction strategies, such as drugs and lifestyle adjustments.

    These findings need to be validated in additional studies. Studies should also look at different racial and ethnic groups, in whom the risk of prostate cancer may correlate with different PSA thresholds, and investigate whether a similar risk stratification can be carried out in a younger cohort—for example, men in their late 40s and early 50s. However, ultimately, early detection of prostate cancer relies on finding more specific biomarkers. Sadly, none has yet emerged, although recently there have been some promising developments.10 11 Identification of cancer specific genes in cells sloughed into the urine after prostatic examination, which is now feasible with the commercially available PCA3 test, may reduce the number of benign biopsies in men whose increased PSA concentration is caused by benign prostatic hyperplasia, and identification of aggressive prostate cancer by its molecular signature should help clinicians decide which prostate cancers need aggressive treatment.

    For now, clinicians are best advised to individualise their approach to PSA based screening. Young men at high risk of prostate cancer, such as those with a strong family history and higher baseline PSA concentrations, should be followed closely and could also be considered for “risk reduction” approaches with 5α reductase inhibitors or dietary and lifestyle modifications (or both). Conversely, elderly men and those with a low risk of disease could be tested less often, if at all. Approaches such as these will hopefully make the next 20 years of PSA based screening better than the first 20.12

    Notes

    Cite this as: BMJ 2010;341:c4538

    Footnotes

    • Research, doi:10.1136/bmj.c4521
    • Research, doi:10.1136/bmj.c4543
    • Competing interests: The author has completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares: no support from any organisation for the submitted work; he has had specified relationships with Aeterna Zentaris, Amgen, Augmenix, Cambridge Endo, Caris, EMD Serono, Envisioneering, Ferring Pharmaceuticals, France Foundation, GenProbe, GlaxoSmithKline, Johnson & Johnson, Myriad Genetics, NCI, NIDDK, Nema Steba, Onconome, Ortho Clinical Diagnostics, Veridex LLC, and Viking Medical in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

    • Provenance and peer review: Commissioned; not externally peer reviewed.

    References