Prior to 1992, prostate cancer mortality steadily increased. At the time of diagnosis, approximately 1/3 of patients presented with metastatic disease, and five-year survival for such patients was approximately 29%. In 1987, PSA was first approved by the FDA as a tool for monitoring response to prostate cancer treatment but was not approved for use as a screening tool. In 1989, Dr. Catalona and colleagues pioneered its use as a screening test, and published their results which indicated that many patients with curable prostate cancer could be easily identified using a PSA cutoff of 4 ng/ml.
In 1991, PSA was first shown to be useful as a screening test by Catalona et al (NEJM 1991). The study enrolled 30,000 patients over 12 years and demonstrated that PSA was the superior first-line screening test. The authors concluded that the combination of PSA testing with digital rectal examination (DRE) was superior for identifying prostate cancer compared to DRE alone. PSA screening was subsequently adopted and served as a model for the study that eventually led to the approval of PSA for screening a few years later. Furthermore, the study set the stage for subsequent randomized control trials evaluating the utility and benefits of PSA screening.
The prostate cancer landscape subsequently changed as a result of PSA screening. There was a 53% reduction in cancer specific mortality and notable stage migration resulting in a significantly smaller proportion of patients presenting with metastatic disease (5% from 30%). For patients who do present with metastases, however, the five-year survival remains unchanged and quite poor (29%). Thus, the goal is to identify patients with localized disease early enough to intervene.
The European Randomized Study of Screening for Prostate Cancer (ERSPC) included 162,388 men aged 55-69, and showed that at 13 years follow-up, prostate cancer specific death was 21% lower in the screening arm. In stark contrast to these findings, the Prostate, Lung, Colorectal, Ovarian Screening trial (PLCO) showed no mortality benefit in screened patients, but the study had significant issues, most notably >90% contamination in the control arm (>90% of patients in the “no screening” group had undergone PSA testing). Despite the clear study limitations and contamination bias, the US Preventive Service Task Force (USPSTF) recommended against screening in 2012, concluding that the harms of screening outweigh the benefits. Notably, no urologists were included on the expert panel.
Following the USPSTF recommendations, there was an immediate drop in PSA screening. With this, the incidence rate of localized prostate cancer decreased but the same decrease in metastatic prostate cancer was not observed. The US National Cancer Institute Cancer Intervention and Surveillance Modeling Network (CISNET) concluded that stopping screening would result in twice as many metastatic cases, result in a stage shift back to pre-PSA screening levels, and be associated with a 13-20% increase in preventable prostate cancer deaths by 2025. This report along with significant pushback from the urologic community has led to a revision of the USPSTF recommendations, which now state that clinicians inform men about the potential benefits and harms of screening (Grade C recommendation). Despite the changed recommendations, the original recommendations against screening have unfortunately led to a generation of primary care physicians who do not believe in screening and ongoing education efforts and collaboration are necessary.
Presented by: William J. Catalona, MD, Professor of Urology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois
Written by: Selma Masic, MD, Urologic Oncology Fellow (SUO), Fox Chase Cancer Center, @selmasic at the 20th Annual Meeting of the Society of Urologic Oncology 2019 at the 2019 Society for Urologic Oncology Annual Meeting – December 4-6, 2019 – Washington, DC