Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features

TY - JOUR

T1 - Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features

AU - Kishan, Amar U

AU - Karnes, R Jeffrey

AU - Romero, Tahmineh

AU - Wong, Jessica K

AU - Motterle, Giovanni

AU - Tosoian, Jeffrey J

AU - Trock, Bruce J

AU - Klein, Eric A

AU - Stish, Bradley J

AU - Dess, Robert T

AU - Spratt, Daniel E

AU - Pilar, Avinash

AU - Reddy, Chandana

AU - Levin-Epstein, Rebecca

AU - Wedde, Trude B

AU - Lilleby, Wolfgang A

AU - Fiano, Ryan

AU - Merrick, Gregory S

AU - Stock, Richard G

AU - Demanes, D Jeffrey

AU - Moran, Brian J

AU - Braccioforte, Michelle

AU - Huland, Hartwig

AU - Tran, Phuoc T

AU - Martin, Santiago

AU - Martínez-Monge, Rafael

AU - Krauss, Daniel J

AU - Abu-Isa, Eyad I

AU - Alam, Ridwan

AU - Schwen, Zeyad

AU - Chang, Albert J

AU - Pisansky, Thomas M

AU - Choo, Richard

AU - Song, Daniel Y

AU - Greco, Stephen

AU - Deville, Curtiland

AU - McNutt, Todd

AU - DeWeese, Theodore L

AU - Ross, Ashley E

AU - Ciezki, Jay P

AU - Boutros, Paul C

AU - Nickols, Nicholas G

AU - Bhat, Prashant

AU - Shabsovich, David

AU - Juarez, Jesus E

AU - Chong, Natalie

AU - Kupelian, Patrick A

AU - D'Amico, Anthony V

AU - Rettig, Matthew B

AU - Berlin, Alejandro

AU - Tward, Jonathan D

AU - Davis, Brian J

AU - Reiter, Robert E

AU - Steinberg, Michael L

AU - Elashoff, David

AU - Horwitz, Eric M

AU - Tendulkar, Rahul D

AU - Tilki, Derya

PY - 2021/7/1

Y1 - 2021/7/1

N2 - 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.

AB - 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.

U2 - 10.1001/jamanetworkopen.2021.15312

DO - 10.1001/jamanetworkopen.2021.15312

M3 - SCORING: Journal article

C2 - 34196715

VL - 4

JO - JAMA NETW OPEN

JF - JAMA NETW OPEN

SN - 2574-3805

IS - 7

M1 - e2115312

ER -