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Importance: The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown., Objective: To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment., Design, Setting, and Participants: This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020., Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT)., Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression models., Results: A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer-specific mortality; there was no difference in prostate cancer-specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer-specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P < .001)., Conclusions and Relevance: These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guideline-concordant multimodal therapy, prostate cancer-specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, although distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT. Optimal multimodality treatment is critical for improving outcomes in patients with high-risk prostate cancer.

Purpose: Salvage radiotherapy (SRT) is the standard of care offered when postprostatectomy prostate-specific antigen (PSA) levels are ≥ 0.2 ng/mL. However, emerging evidence suggests that early SRT (ie, SRT delivered at PSA values < 0.2 ng/mL, but generally ≥ 0.05 ng/mL) improves oncologic outcomes. We evaluated the feasibility of improving referral rates for discussion of early SRT by using a dynamic registry that identifies through the electronic medical record patients with rising postprostatectomy PSA levels., Methods: We developed an iteratively updated registry that identifies patients who fall within two postoperative PSA strata: ≥ 0.05 to < 0.1 ng/mL and ≥ 0.1 to < 0.2 ng/mL. We compared referral rates to radiation oncology during a 3-year period before use of this registry with those during a 1-year period after promotion of the registry in multidisciplinary tumor board settings., Results: Before promotion of the registry, referral rates for patients with PSA values ≥ 0.05 to < 0.1 ng/mL and ≥ 0.1 to < 0.2 ng/mL were 35% and 65%, respectively. After promotion of the registry, referral rates within each stratum increased significantly to 82% and 94%, respectively ( P < .05 for both by Fisher's exact test). The overall rate of referral for patients with PSA values ≥ 0.05 to < 0.2 ng/mL rose from 48% to 90% ( P < .001)., Conclusion: The creation of a registry of patients with rising postprostatectomy PSA values can facilitate increased referral rates for early SRT without burdening providers with a clinical support tool embedded within the EMR itself. This is true even in the case of already high baseline rates of referral for early SRT. The changes reported herein most likely reflect a Hawthorne effect wherein the ability to track referrals rather than a direct function of the registry influenced practice patterns. Nonetheless, the registry provided an integral framework to allow for tracking.