Abstract
The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown. To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment. 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. 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). 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. 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). 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.
Highlights
High-risk localized prostate cancer, which is characterized by initial prostate-specific antigen (PSA) level greater than 20 ng/mL, biopsy Gleason grade group 4 or 5 disease, and/or lesions at clinical T stage of T3 or greater,[1] can be treated definitively with radiotherapy or radical prostatectomy (RP)
Compared with RP, treatment with external beam radiotherapy (EBRT) with BT or with EBRT alone 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
Treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP. These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guidelineconcordant multimodal therapy, prostate cancer–specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT
Summary
High-risk localized prostate cancer, which is characterized by initial prostate-specific antigen (PSA) level greater than 20 ng/mL (to convert to micrograms per liter, multiply by 1), biopsy Gleason grade group 4 or 5 (formerly Gleason score 8-10) disease, and/or lesions at clinical T stage of T3 or greater,[1] can be treated definitively with radiotherapy or radical prostatectomy (RP). Two recent studies focusing exclusively on patients with Gleason grade group 5 (formerly Gleason score 9-10) high-risk localized prostate cancer underscored the importance of enriching for modern treatment paradigms and highlighted the importance of multimodality therapy.[7,8] while Gleason grade group 5 disease is uncommon, many patients with the considerably more heterogeneous entity of high-risk localized prostate cancer[9,10,11] have added clinicopathologic factors that are associated with an added risk of treatment failure, including primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, 50% of cores or more with biopsy results positive for prostate cancer, or at least 2 high-risk features. To comprehensively evaluate the associations between prostate cancer–specific mortality, distant metastasis, and the 3 standard treatments for high-risk prostate cancer while accounting for clinical heterogeneity and delivery of guideline-concordant multimodality care, we established a large consortium of patients treated for high-risk localized prostate cancer with at least 1 adverse clinicopathologic feature across 16 tertiary centers from 2000 to 2014
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