Figure. PSA frequency distributions in men with and without prostate cancer sorted by grade group (GG) and patient age. Reprinted with permission from Albertsen PC et al, BJU Int. 2024;133(1):104-111.¹⁰

I am honored to receive this year’s AUA Distinguished Contribution Award. The award validates my lifetime efforts to understand the public health implications of testing for PSA. I began working at UConn Health on January 1, 1987, 9 months before Stamey published his classic article on PSA and 4 years before Catalona published his article promoting prostate cancer screening.^1,2 Most urologists at the time supported the Halsted theory that cancer began as a localized disease that could be cured by surgery if disease was confined to the prostate.³ Shortly after my arrival at UConn, I performed a radical prostatectomy on a faculty member and informed him that he was cured when the postoperative pathology revealed negative margins and his PSA was undetectable. He returned to my office 2 years later with widespread metastatic disease and eventually died of prostate cancer 16 years later following a course of antiandrogen therapy. After a thorough search of the literature, I discovered that there was surprisingly little data concerning the natural history of screen-detected prostate cancer and the impact of treatment. This patient stimulated my quest for answers.

By 1990 several serendipitous but critical factors had fallen into place for me at UConn Health. I spent the previous 2 years completing a master’s degree in epidemiology and statistics from the University of Wisconsin. I learned that the Connecticut Department of Health ran the oldest tumor registry in the country and that the registry was an integral part of the National Cancer Institute’s (NCI’s) SEER (Surveillance, Epidemiology, and End Results) system. One of the nation’s leading health services researchers, Dr Jack Wennberg, was located at Dartmouth, which is just a 2-hour drive from Hartford. I traveled to Hanover one day asking if I could join his research team. They were primarily researching the management of benign prostate hypertrophy, but the team had promised the Agency for Health Care Research and Quality a deliverable on prostate cancer. I presented a Markov model of prostate cancer progression that I had developed on the spreadsheet Lotus 1-2-3. Dr Wennberg’s team confirmed the findings and published them in JAMA in 1993.⁴ At the time the model was heavily criticized by the academic community. This encouraged me to obtain funding from the NIH to gather data on the outcomes of men with newly diagnosed localized prostate cancer in Connecticut in the 1970s and early 1980s. The tumor registry identified 767 men. I tracked their clinical courses through hospital-based records and located most of their original pathology slides. Dr Donald Gleason agreed to read these slides to standardize grading of the biopsy specimens. This led to another widely cited publication in JAMA concerning the natural history of prostate cancer, highlighting the fact that many men with low-grade disease could survive decades without disease progression.⁵ My work with the Connecticut tumor registry led to collaborations with researchers at the NCI and other SEER sites. Together we published several manuscripts concerning clinical outcomes based upon population-based cohorts as compared to more traditional tertiary level case series data. Collectively these manuscripts were entitled the Prostate Cancer Outcomes Studies. My work with the NCI led to an invitation to chair the Cause of Death Committee of the PLCO trial. In 2000, Dr Freddie Hamdy, chair of Surgery at Oxford University, asked me to serve as an external advisor to the CAP and PROTECT trials.^6,7 For the next 20 years I worked with this study team to ensure the quality of the largest randomized trial conducted concerning screening and treatment of prostate cancer. I was honored to serve as the chair of the Cause of Death Committee for both trials and still work with Dr Hamdy as associate editor of BJU International.

Throughout the past 2 decades I have debated many prostate cancer researchers and clinicians concerning the relative public health impact of PSA testing. While PSA testing has prevented many prostate cancer deaths, this has come at an enormous public health cost. The US Preventive Services Task Force argued against routine PSA testing in 2012 because the public health impact of treatment complications was greater than the number of years gained from decreasing prostate cancer mortality.⁸ PSA testing remains controversial worldwide. Screening is strongly supported in North America, but in Europe only 1 country, Lithuania, supports population-based PSA screening. Recent advances in prostate imaging using magnetic resonance have significantly improved PSA testing performance.⁹ The increasing acceptance of active surveillance for men with low-grade disease has also decreased the negative impact of PSA testing and prostate cancer interventions; I was honored to receive the Chodak Award last year from Active Surveillance Patients International.

Despite these advances, many urologists still do not understand why PSA testing poses such a difficult public health problem. To help understand these concepts, I worked with a Norwegian research group last year to map PSA distribution curves by age for men with and without localized prostate cancer.¹⁰ PSA can discriminate men aged 50 to 60 years with and without prostate cancer with reasonable accuracy. Unfortunately, as men age, benign prostatic hyperplasia becomes an increasingly important confounder leading to considerable overlap in the PSA distributions (Figure). Prostate cancer, especially high-grade disease, is relatively rare at age 50. By age 70 the incidence of all grades increases, and false negative and false positive values become a significant problem no matter where one sets the biopsy threshold.

Throughout my career I have been blessed with multiple serendipitous events that have led to collaborations with researchers from around the world working in many different fields of health services research. In 2016 the AUA awarded me the triennial Eugene Fuller Prostate Award. Receiving the 2024 AUA Distinguished Contribution Award further confirms that my research efforts have helped shape contemporary prostate cancer management. I am grateful to the AUA for the recognition.