Comparative Efficacy of Combined Radiotherapy, Systemic Therapy, and Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer: A Network Meta-Analysis and Systematic Review

Abstract

Background: Recent randomized clinical trials have examined the efficacy of different combinations of systemic and local treatment approaches for metastatic hormone-sensitive prostate cancer (mHSPC). We compared the efficacy of these combined regimens in order to identify the optimal therapy for specific patient subgroups.Methods: The treatments were abiraterone (ABI), apalutamide (APA), docetaxel (DOC), enzalutamide (ENZ), and radiotherapy (RT) combined with androgen-deprivation therapy (ADT). Five electronic databases were searched up to May 7, 2020 for relevant trials. The risk of bias in the included trials was evaluated with the Cochrane tool. The hazard ratio (HR) with 95% confidence interval (CI) was determined for the included trials and indirect comparisons were performed using the R software.Results: In total, 10 randomized, controlled trials with 11,194 patients were included in the meta-analysis. ADT + RT was superior to ADT monotherapy in terms of overall survival (HR = 0.96, 95% CI: 0.85-1.1) and conferred a survival benefit in a subgroup of low-volume patients (HR = 0.68, 95% CI: 0.54-0.87). Combined systemic treatments were significantly superior to ADT monotherapy in comparisons of survival and prostate-specific antigen response, including in the high-volume subgroup; meanwhile, in the low-volume subgroup only ADT + ENZ (HR = 0.38, 95% CI 0.21-0.69) showed a significant clinical benefit. In the Gleason score <8 subgroup, all combined systemic treatments were superior to ADT monotherapy, but the results were only significant for ADT + APA (HR = 0.56, 95% CI: 0.33-0.95) and ADT + DOC (HR = 0.71, 95% CI: 0.54-0.92). In the Gleason score ≥8 subgroup, ADT monotherapy was inferior (albeit not significantly) to combined treatments. In a ranking of performed comparisons, Wang et al.Combined Therapies for Prostate Cancer ADT + ENZ was the optimal regimen, although this was non-significant. Combined therapies also demonstrated superiority in quality-of-life indicators such as time to skeletal events and pain progression. Conclusion:ADT + radiotherapy led to superior outcomes in mHSPC patients with low-volume disease. While all combined systemic regimens confer a survival advantage over ADT monotherapy, the optimal treatment approach for certain mHSPC patient subgroups remains to be determined.

Abiraterone Acetate for Metastatic Castration-Sensitive Prostate Cancer

“…Of these 5 SRs, 3 were published in 2020, 13,16,17 1 in 2019, 14 and 1 in 2018. 15 The literature searches ranged from database inception to May 15, 2020.…”

“…The primary author for 3 of the SRs were from China. 13,15,17 One SR was authored by an investigator in the US 16 and 1 from France. 14 Two primary studies were authored by investigators in Japan 18,19 and 1 by an investigator in Canada.…”

“…All SRs included patients with mCSPC. One study 17 limited study inclusion to those with patients18 years and older, another limited to patients older than 70 years, 14 and 3 studies had no age restrictions. 13,[15][16][17] The number of mCSPC patients included in each SR ranged from 499 to 11,494.…”

Treatment Strategies for Metastatic Castration-Sensitive Prostate Cancer: From “All-Comers” to “Personalized” Approach

“…The same results were also obtained in another meta-analysis. 28 This meta-analysis included seven RCTs (ENZAMET, TITAN, GETUG-AFU-15, CHAARTED, STAMPEDE, LATITUDE, HORRAD) with 8820 patients. In the low-volume subgroup, ENZ, APA, docetaxel, AAP, and external beam radiation therapy (EBRT) to the prostate had superior OS than ADT alone; however, statistical significance was only observed for ENZ (HR, 0.38; 95% CI, 0.21–0.69) and EBRT (HR, 0.68; 95% CI, 0.54–0.87).…”

“…Meta-analysis of 2 RCTs that involved 2493 patients suggested that ADT plus EBRT to the prostate was associated with improved OS as compared to ADT alone in men with low-volume metastatic burden (HR, 0.68, 95% CI, 0.54–0.87); however, this result was not observed in those with high-volume disease (HR, 1.1, 95% CI, 0.92–1.2). 28 Prostatectomy may also improve the oncologic outcomes in patients with oligometastatic prostate cancer. 31 The definitive treatments, either radiation or prostatectomy, may be associated with survival benefit in patients with low metastatic burden.…”