Recommended definitions of aggressive prostate cancer for etiologic epidemiologic research.

In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research.

Among prostate cancer cases diagnosed in 2007 in the U.S. SEER-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV).

In our case population (n = 55,900), 3,073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM stage and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of stage T4 or N1 or M1 or Gleason score ≥8 prostate cancer, as this definition had one of the higher PPVs (0.23, 95% confidence interval [CI] 0.22-0.24) and reasonable sensitivity (0.66, 95% CI 0.64-0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses.

We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced stage (T4 or N1 or M1), high grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.

Journal of the National Cancer Institute. 2020 Oct 03 [Epub ahead of print]

Lauren M Hurwitz, Ilir Agalliu, Demetrius Albanes, Kathryn Hughes Barry, Sonja I Berndt, Qiuyin Cai, Chu Chen, Iona Cheng, Jeanine M Genkinger, Graham G Giles, Jiaqi Huang, Corinne E Joshu, Tim J Key, Synnove Knutsen, Stella Koutros, Hilde Langseth, Sherly X Li, Robert J MacInnis, Sarah C Markt, Kathryn L Penney, Aurora Perez-Cornago, Thomas E Rohan, Stephanie A Smith-Warner, Meir J Stampfer, Konrad H Stopsack, Catherine M Tangen, Ruth C Travis, Stephanie J Weinstein, Lang Wu, Eric J Jacobs, Lorelei A Mucci, Elizabeth A Platz, Michael B Cook, Prostate Cancer Cohort Consortium (PC3) Working Group

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA., Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA., Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA., Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Department of Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA., Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia., Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom., School of Public Health, Loma Linda University, Loma Linda, CA, USA., Department of Research, Cancer Registry of Norway, Oslo, Norway., Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA., Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA., Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA., Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, GA, USA.