Recommended Definitions of Aggressive Prostate Cancer for Etiologic Epidemiologic Research

Abstract

Background 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. Methods 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). Results 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. Conclusions 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.

Rare Germline Pathogenic Variants Identified by Multigene Panel Testing and the Risk of Aggressive Prostate Cancer

“…The literature, including reports from epidemiological studies, have used various combinations of clinical parameters, making it difficult to compare and combine studies. In this study, we used the definition recently published by Hurwitz et al, and the hard end point of prostate cancer death to facilitate further elucidation of prostate cancer etiology, including its genetic risk factors, and advance the prevention strategies specifically targeting aggressive prostate cancer [ 20 ].…”

“…Cases were men diagnosed with aggressive prostate cancer, which was defined to be fatal prostate cancer or prostate cancer that met the criteria described by Hurwitz et al [ 20 ]: cancers that are clinical or pathologic category T4, N1, or M1 or Gleason score greater than or equal to 8. In this definition, missing criteria were assumed to be equal to the lower risk category, e.g., a missing Gleason score was taken to be 7 or lower.…”

“…In this study, we performed targeted sequencing of 26 genes commonly included on panel tests for cancer predisposition. We defined aggressive prostate cancer as fatal prostate cancer or prostate cancer that met criteria described by Hurwitz et al [ 20 ], i.e., diagnosis of prostate cancer of category T4, N1, or M1 or a Gleason score of 8 or greater. Controls in our study were men who had not been diagnosed with aggressive prostate cancer, i.e., men unaffected with prostate cancer and men with prostate cancer that was not aggressive by the above definition (effectively treating aggressive and non-aggressive prostate cancer as separate diseases).…”

Marital Status and Prostate Cancer Incidence: A Pooled Analysis of 12 Case-Control Studies From the PRACTICAL Consortium

“…The degree of aggressiveness of prostate cancer was de ned using the Gleason score, which re ects cell differentiation [33]. Following a recent recommendation [34], a tumour with a Gleason score ≥ 8 was considered as high-grade [35] whereas a score ≤ 7 indicated a low-grade cancer. We also used an alternate de nition of high-grade tumours (Gleason scores ≥7 [4 + 3]) [35], but as results were similar to those based on scores ≥ 8, only the latter are presented here.…”

Identification of Germline Genetic Variants that Increase Prostate Cancer Risk and Influence Development of Aggressive Disease

“…These updated classifications of aggressive PrCa may consider varying combinations of Gleason score (typically one of Gleason score ≥7, Gleason score ≥8 or Gleason grade group ≥3), T stage (generally either T4 or ≥T3), nodal invasion, metastatic spread, extreme PSA measurements, young age at diagnosis (generally defined as diagnosis at age < or ≤55 years, with ages 60 or 65 also frequently used as cut-offs), and death from PrCa. A recent analysis considering the sensitivity and positive predictive value of different definitions of aggressive disease with respect to discriminating patients that experience death from PrCa within 10 years of diagnosis has proposed the adoption of a standardised definition of aggressive PrCa in etiological research as being any one or more of stage T4 or N1 or M1 or Gleason score ≥8 disease at diagnosis [ 12 ].…”