Volume 199 - Issue 9
The dilemmas of prostate cancer screening
Author: Chris B Del Mar*
Med J Aust 2013; 199 (9): 584. || doi: 10.5694/mja13.10923
Published online: 4 November 2013
Published online: 4 November 2013
In reply: We thank Lawrentschuk and colleagues for the critical response. We would like to respond to several wrong assertions:
We did not give equal weighting to the results of the ERSPC (European Randomized Study of Screening for Prostate Cancer) and the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Standard meta-analysis practice is to weight studies by the inverse variances of their effect estimates.1 ...
In reply: We thank Lawrentschuk and colleagues for the critical response. We would like to respond to several wrong assertions:
We did not give equal weighting to the results of the ERSPC (European Randomized Study of Screening for Prostate Cancer) and the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Standard meta-analysis practice is to weight studies by the inverse variances of their effect estimates.1 Accordingly, the results of the ERSPC were weighted about double those of the PLCO.
We adjusted the Cochrane review for contamination of the non-screened arm of studies (see Del Mar et al, Box2).
We included the updated data of the ERSPC (published between our original submission and its accepted revision).
We do not misrepresent the positive effects of prostate-specific antigen (PSA) testing: the observed 30% reduction in prostate cancer mortality is based on selected data, and can be credibly explained by many possible confounders (including improved treatment), reinforcing the need for randomised controlled trials (RCTs) to evaluate screening.
So, we do not agree that our perspective is unbalanced. Rather, we believe that the proposal by Lawrentschuk et al, that surveillance be used as an alternative to full screening — without mentioning the potential harms of surveillance itself3 — suggests imbalance. Surveillance is a management option after screening, and is in urgent need of critical evaluation.
We also thank Miklos for pointing out the difficulties associated with heterogeneity of studies. We agree that careful assessment of trials is important.
We thank Haines for pointing out an RCT that showed radical prostatectomy to be ineffective compared with watchful waiting for early prostate cancer4 (now supported by a cost-effectiveness analysis5). However, this study was possibly underpowered, and many men were not referred from PSA screening (so more men may have had microscopic metastases than in a screening trial).
We thank McKenzie and colleagues for drawing attention to different prevalence estimates of latent prostate cancer.6,7 There have been many similar studies. One summary of these suggests that rates vary by as much as 31%–83% in those aged older than 80 years and by 5%–46% in those aged 51–60 years8 (with some of this variation no doubt originating from different diagnostic thresholds, but also different sampling rates: by race, higher in African Americans than in Caucasian Americans; and by geography, higher in developed economies such as Australia than in developing economies such as in Africa). These latent prostate cancers in developed economies8 are so much more prevalent than the incidence identified by PSA testing that they must be contributing to overdiagnosis. The observation by McKenzie et al, that pathologists now rarely report prostate carcinoma with a Gleason score less than 6, begs an explanation. One possibility is diagnostic drift, in which what was once low-grade is now reported as higher to be on the safe side.
Competing interests
No relevant disclosures.
* On behalf of Del Mar CB, Glasziou PP, Hirst GH, Wright RG, Hoffmann TC.
References
- Higgins JPT, Green SE. Cochrane handbook for systematic reviews of interventions. Version 5.1.0. www.cochrane-handbook.org (accessed Oct 2013).
- Del Mar CB, Glasziou PP, Hirst GH, et al. Should we screen for prostate cancer? A re-examination of the evidence. Med J Aust 2013; 198: 525-527. 0_i1142859
- Bergman J, Litwin MS. Quality of life in men undergoing active surveillance for localized prostate cancer. J Natl Cancer Inst Monogr 2012; 2012: 242-249. 0_i1142861
- Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012; 367: 203-213. 0_pgfId-2888348
- Hayes JH, Ollendorf DA, Pearson SD, et al. Observation versus initial treatment for men with localized, low-risk prostate cancer: a cost-effectiveness analysis. Ann Intern Med 2013; 158: 853-860. 0_i1142865
- Yin M, Bastacky S, Chandran U, et al. Prevalence of incidental prostate cancer in the general population: a study of healthy organ donors. J Urol 2008; 179: 892-895; discussion 895. 0_i1142867
- Sakr WA, Haas GP, Cassin BF, et al. The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. J Urol 1993; 150: 379-385. 0_i1142869
- Haas GP, Delongchamps N, Brawley OW, et al. The worldwide epidemiology of prostate cancer: perspectives from autopsy studies. Can J Urol 2008; 15: 3866-3871. 0_pgfId-2888384