Single PSA screening tests make no significant difference in prostate cancer mortality, according to a new study.
As part of the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP), Richard M. Martin, PhD, from the University of Bristol in the United Kingdom, and colleagues randomly assigned 573 primary care practices in the United Kingdom to offer men aged 50 to 69 years an invitation to a single PSA test (271 practices) and a control group that did not offer PSA testing (302 practices). After a median follow-up of 10 years, 549 of the 189,386 men in the PSA screening group (0.30 per 1000 person-years) and 647 of 219,439 men in the control group (0.31 per 1000 person-years) died from PCa, a non-significant between-group difference in mortality rate, Dr Martin’s team reported in JAMA (2018;319:883-895).
A significantly higher proportion of patients in the screening arm than control arm were diagnosed with PCa (4.3% vs 3.6%), however.
With respect to all-cause mortality, 25,459 deaths occurred in the screening group (13.74 per 1000 person-years) and 28,306 deaths occurred in the control arm (13.51 per 1000 person-years), a non-significant difference in death rate.
“Among practices randomized to a single PSA screening intervention vs standard practice without screening, there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased,” the authors concluded. “Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening.”
Of the 189,386 men in the screening arm, 75,707 (40%) attended a PSA testing clinic and 67,313 (36%) underwent PSA testing. Of 64,436 men with a valid PSA test result, 6857 (1150 had a PSA level of 3 to 19.9 ng/mL. Among these men, 5850 underwent a prostate biopsy.
The study provides new evidence that complements published trials such as the (European Randomized Study of Screening for Prostate Cancer (ERSPC) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) trial, the authors noted. Both trials involved repeated PSA testing at intervals of 1, 2, or 4 years. The CAP trial was designed to determine the effects of a low-intensity, single invitation PSA test and standardized diagnostic pathway on PCa-specific and all-cause mortality while minimizing overdetection and overtreatment.
“It was an interesting and well-conducted study with unsurprising results,” commented Eric Klein, MD, Chairman of the Glickman Urological and Kidney Institute at Cleveland Clinic, who was not involved in new study.
The main concern it raised is that even a single PSA results in overdetection of low-grade cancers, but the trial did not account for the substantial increase in active surveillance for such patients, which substantially reduces the harms of overdetection, Dr Klein told Renal & Urology News.
“One of the limitations of the study was that it was analyzed on an intent-to-screen basis, just as the initial analysis of the PLCO was done,” Dr Klein pointed out. “A recent reanalysis of the PLCO comparing men who actually got screened vs those not screened showed the same value to screening that was demonstrated in the ERSPC. It would be interesting to look at the data in this trial in the same fashion. There is also a lot of data showing that a single PSA at age 50 predicts lifetime risk of prostate cancer. It would be interesting to see if that held true in this trial as well.”
The negative results of the PLCO trial, he said, are negated by the high drop-in rate in the control arm. A re-analysis of screened vs unscreened men in the PLCO trial showed a similar benefit to screening as in the ERSPC. Furthermore, he noted, the benefit of screening should not only be measured in reductions in mortality, but also in reductions in the rate of metastatic disease, which has a significant treatment burden in terms of morbidity and cost. “The benefit in reducing metastatic disease demonstrated in those screened in the ERSPC was substantial – around 30% – and is often overlooked in the debate on screening,” Dr Klein said. “The weight of the data supports that regular PSA screening both reduces the risk of dying of prostate cancer and the risk of getting metastatic disease. Much of the harm from screening is mitigated by the use of active surveillance for low-grade cancers; newer modalities such as genomic testing, which allows for direct assessment of the biological potential of the tumor, and mpMRI [multiparametric magnetic resonance imaging], which reduced the risk of biopsy under sampling, promise the development of more precise management strategies for each patient.”
Martin RM, Donovan JL, Turner EL, et al. Effect of low-intensity PSA-based screening intervention on prostate cancer mortality. JAMA. 2018;319:883-895. Doi: 10.1001/jama.0154.