RESUMO
Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9×10-7 and GAB2, p = 2.0×10-6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% Confidence Interval [CI]= 0.94-1.36); whereas, decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04-1.50). These results suggest that germline genetics may help inform and individualize the decision of AS-or the intensity of monitoring on AS-versus treatment for the initial management of patients with low-risk PC.
RESUMO
Importance: Of patient-reported outcomes for individuals undergoing radical prostatectomy, sexual function outcomes are among the most reported and the most detrimental to quality of life. Understanding variations at the patient and surgeon level may inform collaborative quality improvement. Objective: To describe patient- and surgeon-level sexual function outcomes for patients undergoing radical prostatectomy in the Michigan Urological Surgery Improvement Collaborative (MUSIC) and to examine the correlation between surgeon case volume and sexual function outcomes. Design, Setting, and Participants: This is a prospective cohort study using the MUSIC registry and patient-reported sexual function outcome data. Patient- and surgeon-level variation in sexual function outcomes were examined among patients undergoing radical prostatectomy from May 2014 to August 2019. Sexual function outcome data were collected using validated questionnaires, which were completed before surgery and at 3, 6, 12, and 24 months' follow-up following surgery. All participants were male. Race and ethnicity data were self-reported and were included to examine potential variation in outcomes by race and/or ethnicity. Data were analyzed from January 2021 to March 2021. Main Outcomes and Measures: There were 4 outcomes in this study, including the 26-item Expanded Prostate Cancer Index Composite (EPIC-26) sexual function scores at 3, 6, 12, and 24 months' follow-up; patient-level sexual function recovery at 12- and 24-month follow-up; surgeon-level variation in sexual function outcomes at 12- and 24-month follow-up; and correlation between surgeon case volume and sexual function outcomes. Results: A total of 1426 male patients met inclusion criteria for this study. The median (IQR) age was 64 (58-68) years. A total of 115 participants (8%) were Black, 1197 (84%) were White, 25 (2%) were of another race or ethnicity (consolidated owing to low numbers), and 89 (6%) were of unknown race or ethnicity. Among patients undergoing bilateral nerve-sparing radical prostatectomy, mean (SD) EPIC-26 sexual function scores at 12- and 24-month follow-up (12 months, 39 [28]; 24 months, 63 [29]) did not return to baseline levels. There was wide variation in EPIC-26 sexual function scores at both 12-month follow-up (range, 23-69; P < .001) and 24-month follow-up (range, 27-64; P < .001). Similar variations were found in EPIC-26 sexual function scores and recovery of sexual function by surgeon. Recovery rates ranged from 0% to 40% of patients at 12-month follow-up (18 surgeons; P < .001) and 3% to 44% of patients at 24-month follow-up (12 surgeons; P < .001). Surgeon case volume and sexual function outcomes were not significantly correlated. On multivariable analysis, the following variables were associated with better recovery at 24-month follow-up: younger age (P < .001), lower baseline EPIC-26 sexual function score (P < .001), lower Gleason score (P = .05), and nonobesity (P = .03). Conclusions and Relevance: In this study, there was significant patient- and surgeon-level variation in sexual function recovery over 2 years following radical prostatectomy. Variation in surgeon-level sexual function outcomes presents an opportunity and model for surgical collaborative quality improvement.