Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features
Amar U Kishan 1 2 , R Jeffrey Karnes 3 , Tahmineh Romero 4 , Jessica K Wong 4 , Giovanni Motterle 3 , Jeffrey J Tosoian 5 , Bruce J Trock 6 , Eric A Klein 7 , Bradley J Stish 8 , Robert T Dess 9 , Daniel E Spratt 9 , Avinash Pilar 10 , Chandana Reddy 11 , Rebecca Levin-Epstein 1 , Trude B Wedde 12 , Wolfgang A Lilleby 12 , Ryan Fiano 13 , Gregory S Merrick 13 , Richard G Stock 14 , D Jeffrey Demanes 1 , Brian J Moran 15 , Michelle Braccioforte 15 , Hartwig Huland 16 , Phuoc T Tran 17 , Santiago Martin 18 , Rafael Martínez-Monge 19 , Daniel J Krauss 19 , Eyad I Abu-Isa 9 , Ridwan Alam 6 , Zeyad Schwen 6 , Albert J Chang 1 , Thomas M Pisansky 8 , Richard Choo 8 , Daniel Y Song 17 , Stephen Greco 17 , Curtiland Deville 17 , Todd McNutt 17 , Theodore L DeWeese 17 , Ashley E Ross 20 21 , Jay P Ciezki 11 , Paul C Boutros 2 22 , Nicholas G Nickols 1 23 , Prashant Bhat 1 , David Shabsovich 1 , Jesus E Juarez 1 , Natalie Chong 1 , Patrick A Kupelian 1 , Anthony V D'Amico 24 , Matthew B Rettig 25 26 , Alejandro Berlin 10 , Jonathan D Tward 27 , Brian J Davis 8 , Robert E Reiter 2 , Michael L Steinberg 1 , David Elashoff 28 , Eric M Horwitz 4 , Rahul D Tendulkar 11 , Derya Tilki 16 29
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.
CITATION JAMA Netw Open. 2021 Jul 1;4(7):e2115312. doi: 10.1001/jamanetworkopen.2021.15312