External beam radiation therapy (EBRT) plus brachytherapy and androgen deprivation therapy (ADT) may offer the best outcomes for patients with localized Gleason 9 to 10 prostate cancer, according to a new study.

In these high-risk patients, treatment with the triple regimen was associated with significantly lower rates of distant metastasis and cancer-specific and all-cause mortality compared with EBRT plus ADT and radical prostatectomy (RP), investigators reported in the Journal of the American Medical Association (2018;319:896-905).

Amar U. Kishan, MD, of the University of California Los Angeles, and colleagues compared clinical outcomes among 1809 men with biopsy Gleason score 9 to 10 disease receiving definitive treatment at 12 centers from 2000 to 2013. Of these patients, 639 underwent RP, 734 received EBRT with ADT, and 436 received EBRT plus brachytherapy boost (EBRT+BT) and ADT. Median ages were 61, 67.7, and 67.5 years, respectively. Within 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died.

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The 5-year prostate cancer-specific mortality (PCSM) rates, adjusted by propensity score, were lowest for EBRT+BT+ADT at 3% vs 12% and 13% for RP and EBRT+ADT, respectively, the investigators reported. EBRT+BT was associated with a significant 62% and 59% lower risk of PCSM compared with RP and EBRT+ADT, respectively.

Adjusted 5-year rates of distant metastasis also favored dose-escalated radiation therapy: 8% for EBRT+BT vs 24% for RP and 24% for EBRT. EBRT+BT was associated with a significant 73% and 70% decreased risk of distant metastasis, respectively, compared with RP and EBRT+ADT.

The investigators also examined time to all-cause mortality over 7.5 years of follow-up. The adjusted 7.5-year rate was 10% for EBRT+BT compared with 17% for RP and 18% for EBRT. EBRT+BT was associated with a significant 34% and 39% decreased risk for all-cause mortality, respectively, compared with RP and EBRT+ADT. After 7.5 years, results were similar between groups. “It is possible that this is reflective of a prostate cancer–specific mortality benefit to EBRT+BT emerging early, only to eventually dissipate as other-cause mortality increases over time,” Dr Kishan and his colleagues suggested.

No significant differences in PCSM, distant metastasis, or all-cause mortality were found between men treated with EBRT or RP before or after 7.5 years of follow-up.

“The robust association of EBRT+BT with better outcomes compared with both EBRT and radical prostatectomy is, to our knowledge, a novel finding,” Dr Kishan and colleagues stated. “EBRT+BT potentially offers improved local control over EBRT, which may prevent a ‘second wave’ of metastases. EBRT+BT is unlikely to offer improved local control over radical prostatectomy, yet it was still associated with improved distant metastasis and prostate cancer–specific mortality. Outcomes in the radical prostatectomy cohort may have been improved had a rigorous postoperative radiotherapy protocol been in place.” In this study, 43% of RP patients had postoperative radiation therapy, they noted.

The researchers acknowledged that they could not control for all treatment selection biases, such as comorbidities. They also could not examine toxicity.

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Kishan AU, Cook RR, Ciezki JP, et al. Radical prostatectomy, external beam radiotherapy, or external beam radiotherapy with brachytherapy boost and disease progression and mortality in patients with Gleason score 9-10 prostate cancer. JAMA. 2018;319(9):896-905. doi:10.1001/jama.2018.0587