Volume 199 - Issue 9
The dilemmas of prostate cancer screening
Authors: Jonas Hugosson and Sigrid V Carlsson
Med J Aust 2013; 199 (9): 583-584. || doi: 10.5694/mja13.10905
Published online: 4 November 2013
Published online: 4 November 2013
In reply: We wish to make some comments in response to Haines’s point that the PIVOT (Prostate Cancer Intervention Versus Observation Trial) failed to show any benefit from radical prostatectomy (RP) over surveillance.
First, in the PIVOT, a benefit of RP in terms of reduced all-cause mortality was suggested in men with a prostate-specific antigen (PSA) level > 10 ng/mL and in men with intermediate- and high-risk prostate ...
In reply: We wish to make some comments in response to Haines’s point that the PIVOT (Prostate Cancer Intervention Versus Observation Trial) failed to show any benefit from radical prostatectomy (RP) over surveillance.
First, in the PIVOT, a benefit of RP in terms of reduced all-cause mortality was suggested in men with a prostate-specific antigen (PSA) level > 10 ng/mL and in men with intermediate- and high-risk prostate cancer (PC).1
Second, the PIVOT is not the only randomised controlled trial of RP versus observation. The large, well conducted, SPCG-4 (Scandinavian Prostate Cancer Group Trial Number 4) showed a clear benefit from RP over watchful waiting (relative risk, 0.62; 95% CI, 0.44–0.87; P = 0.01) after a median of 12.8 years.2
Third, even though most of the tumours were palpable (non-PSA-detected) in the SPCG-4, the conceptual idea of screening is to allow early detection and stage migration within the window of opportunity where early treatment can affect the natural history of the disease. Recent trends in treatment point to the importance of focusing on treating high-risk and more advanced disease.
Fourth, the Göteborg trial showed a 44% PC mortality reduction after 14 years of follow-up. As screening per se does not reduce mortality, it must be related to treatment. If the treatment administered was not effective, we would not have observed any difference. As RP was the dominant treatment in the Göteborg trial, it gives an indirect support for the efficacy of RP.3
Fifth, other studies are still ongoing, eg, the PROTECT (Prostate Testing for Cancer and Treatment) trial in the United Kingdom and the National Cancer Institute’s START (Surveillance Therapy Against Radical Treatment) trial in North America.
Further, RP is not the only treatment for PC. Management of this disease involves strategic individualised therapy that aims at postponing PC death long enough for the patient to die from unrelated causes. This is especially important, since overdiagnosis and overtreatment of PSA-detected low-risk tumours is a major concern that needs to be avoided to every possible extent.
We agree with Miklos’s point that heterogeneity exists in the ERSPC (European Randomized Study of Screening for Prostate Cancer) due to differences in the centres’ study designs (eg, randomisation, screening interval and PSA cut-off) — the effects of which are, and have been, studied within our group. We regard this heterogeneity as a strength of the study; it gives us an opportunity to analyse how differences in screening algorithms relate to the screening effect. To claim that some ERSPC centres showed results congruent with the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) is incorrect; all centres within ERSPC showed an effect in favour of screening.
It is a common misunderstanding to believe that screening trials could show any effect on all-cause mortality; this is not possible because of the low statistical power at early follow-up.4 Miklos’s statement about differential treatment is another false apprehension of our trial. In the ERSPC, as well as in the Göteborg trial, the proportion that had curative treatment (RP or radiotherapy) was similar among men with low- and moderate-risk tumours in the screening groups compared with those in the control groups.3,5
Finally, we agree that the focus of PSA screening should be on maximising benefits and minimising harms, especially minimising long-term side effects from treatment that substantially affect quality of life.6 Future screening calls for a risk-stratified approach that focuses on the benefit for the individual.
Competing interests
No relevant disclosures.
References
- Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012; 367: 203-213.
- Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2011; 364: 1708-1717. 0_pgfId-2887897
- Hugosson J, Carlsson S, Aus G, et al. Mortality results from the Göteborg randomised population-based prostate-cancer screening trial. Lancet Oncol 2010; 11: 725-732. 0_pgfId-2887905
- Carlsson S, Vickers AJ, Roobol M, et al. Prostate cancer screening: facts, statistics, and interpretation in response to the US Preventive Services Task Force Review. J Clin Oncol 2012; 30: 2581-2584. 0_pgfId-2887914
- Wolters T, Roobol MJ, Steyerberg EW, et al. The effect of study arm on prostate cancer treatment in the large screening trial ERSPC. Int J Cancer 2010; 126: 2387-2393. 0_pgfId-2887923
- Heijnsdijk EA, Wever EM, Auvinen A, et al. Quality-of-life effects of prostate-specific antigen screening. N Engl J Med 2012; 367: 595-605. 0_pgfId-2893410