By David Fiore, MD

Professor of Family Medicine, University of Nevada, Reno

Dr. Fiore reports no financial relationships relevant to this field of study.

SYNOPSIS: Using a mathematical model to account for differences in implementation and baseline screening, researchers reassessed mortality data from two major studies and discovered that screening led to a 25-30% reduction of prostate cancer death in both.

SOURCE: Tsodikov A, Gulati R, Heijnsdijk EAM, et al. Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO trials. Ann Intern Med 2017 Sep 5. doi: 10.7326/M16-2586. [Epub ahead of print].

The current recommendation from the U.S. Preventive Services Task Force (USPSTF) cautions against screening for prostate cancer in men (Grade D).1 This recommendation was based largely on results from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening trial.2 The authors of this enormous study found no mortality benefit from prostate cancer screening compared to “usual care.” The recommendation immediately caused a firestorm of criticism, as did the PLCO trial itself. Partly because of this criticism and partly because of new information, the USPSTF is in the process of releasing an updated recommendation for prostate cancer screening. The draft recommendation proposes a Grade C designation and notes that physicians should discuss the pros and cons of prostate cancer screening with men 55-69 years of age.3 After age 70 years, the USPSTF continues to recommend against prostate cancer screening.

As noted, critics blasted the PLCO trial, noting there was significant “contamination” of the control group because many subjects in that group received a prostate-specific antigen (PSA) test prior to or during the study period. In fact, in the editorial accompanying the current study, Vickers stated that approximately 50% of patients in the control arm were subjected to PSA testing before enrollment and 90% were subjected to PSA testing during the study period (others cited much lower PSA testing rates).4 These criticisms have continued in the eight years since the original PLCO data were published. In 2012, Gulati et al published a paper using mathematical models to assess the effect of this contamination. They found that the corrected mortality risk in the screened group would be 0.68-0.77, very similar to the results from the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial.5

Tsodikov et al tried to correct for the PSA screening contamination in the PLCO trial, and then compared it directly to the ERSPC results. The authors calculated “mean length time” (MLT) for prostate cancer in the two trials, defining MLTs as “the average time by which diagnosis is advanced by screening relative to the date of diagnosis without screening.” Tsodikov et al found similar MLTs for the PLCO and ERSPC study groups of about four years. Using these calculations, the authors then concluded that the PLCO study would have revealed a 25-31% reduction in prostate cancer deaths over 11 years compared to an unscreened population, which is similar to the results from the ERSPC trial.

COMMENTARY

This interesting study used some advanced math to attempt to compare the prostate cancer mortality of screened vs. unscreened men in both the PLCO and ERSPC trials. Based on concerns about “screening contamination” of the PLCO trial, Tsodikov et al’s findings on the PLCO have generated much more interest. Unfortunately, their calculations and assumptions are difficult to parse. It will take time for the medical and public health community to fully vet these results. However, given the new USPSTF draft recommendations on prostate cancer screening, it seems the pendulum is swinging toward a more nuanced stance on this challenging issue. This is partly in response to the clarification of the harms and benefits of prostate cancer screening, but also a result of better treatment decisions. No longer are men with prostate cancer reflexively receiving aggressive treatment. As the decision on whether to screen men aged 50-69 years has become more nuanced, so, too, has the decision on whether and how to treat these men. It is hard to argue with the draft recommendations of the USPSTF that “clinicians inform men ages 55-69 years about the potential benefits and harms of PSA-based screening for prostate cancer.”

REFERENCES

  1. Moyer VA; U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012;157:120-134.
  2. Andriole GL, Crawford ED, Grubb RL 3rd, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310-1319.
  3. U.S. Preventive Services Task Force. Draft Recommendation Statement. Prostate Cancer: Screening. Available at: http://bit.ly/2xNqaMI. Accessed Sept. 19, 2017.
  4. Vickers AJ. Prostate cancer screening: Time to question how to optimize the ratio of benefits and harms. Ann Intern Med 2017 Sep 5. doi: 10.7326/M17-2012. [Epub ahead of print].
  5. Gulati R, Tsodikov A, Wever EM, et al. The impact of PLCO control arm contamination on perceived PSA screening efficacy. Cancer Causes Control 2012;23:827-835.