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Recommended definitions of aggressive prostate cancer for etiologic epidemiologic research

  • 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,
  • the Prostate Cancer Cohort Consortium (PC3) Working Group

Publication: Journal of the National Cancer Institute, October 2020

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.