Screening for prostate cancer (PCa) decreases the risk of dying from the malignancy, researchers concluded based on an analysis of data from 2 randomized trials that came to conflicting conclusions about the survival benefit.
The ERSPC (European Randomized Study of Screening for Prostate Cancer) trial found that screening decreased the risk of PCa mortality by 21%, whereas the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial), which was conducted in the United States, found no survival benefit associated with PCa screening. In the current analysis, a team led by Ruth Etzioni, PhD, of the Fred Hutchinson Cancer Research Center in Seattle attempted to reconcile the effects of screening on PCa mortality in these trials.
After accounting for differences in implementation and practice settings, the investigators found that screening reduced the risk of PCa mortality by an estimated 25% to 31% in the ERSPC trial and 27% to 32% in the PCLO trial, according to a paper published online ahead of print in the Annals of Internal Medicine.
“Our estimation of the common effect of screening suggests that it can significantly reduce the risk for prostate cancer death,” the investigators concluded. “However, as for all interventions, the benefit of screening must be weighed against its potential harms for informed clinical and shared decision making.”
The ERSPC trial included men aged 55 to 69 years at randomization. The trial had 72,473 men in a screening arm and 88,921 in a control arm. The PCLO trial included men aged 55 to 74 years at randomization, with 38,340 men in a screening arm and 38,343 in a control arm. The screening interval was longer in the ERSPC trial compared with the PLCO trial (every 2–4 years vs annually). The PLCO trial had a higher PSA threshold for biopsy than the ERSPC trial (4.0 vs 3.0 ng/mL in most ERSPC centers and screening rounds).
“Rather than comparing the trial groups as if they represented screened and nonscreened populations,” the authors explained, “this study estimated the intensity of screening in each group relative to no screening. This allowed us to formally assess whether screening effects differed between the trials when we accounted for differential screening intensity between groups in each trial.”
Using mean lead times (MLTs), the researchers accounted for increased PCa incidence due to screening and diagnostic work-up in each group. MLTs usually are defined as the average time by which diagnosis is advanced by screening to the date of diagnosis without screening, Dr Etzioni’s team noted. MLTs reflect the magnitude of increased PCa incidence relative to a baseline level expected in the absence of screening, they explained. Dr Etzioni and her colleagues estimated that screening conferred a 7% to 9% reduction in the risk for PCa mortality per year of MLT.
In an editorial accompanying the new study, Andrew J. Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York, said he hopes the researchers “have finally put to rest the question of whether PSA screening reduces prostate cancer mortality. I say this not to close debate but to refocus it. Screening with PSA testing does good by saving lives, but it also causes harm in terms of overdiagnosis and overtreatment. Thus, we need to determine how to screen so that the benefits outweigh the harms.”
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; published online ahead of print. doi: 10.7326/M16-2586
Vickers AJ. Prostate cancer screening: Time to question how to optimize the ratio of benefits and harms. Ann Intern Med 2017; published online ahead of print. doi: 10.7326/M17-2012