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, 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.
Highlights
Prostate cancer (PC) is the most common cancer type in senior males worldwide [1]
10 randomized controlled trials (RCTs) with 11,194 participants were included in our analysis
We assumed that the transitivity assumption was satisfied in our study, this was difficult to validate owing to the paucity of the baseline data in several of the included trials
Summary
Prostate cancer (PC) is the most common cancer type in senior males worldwide [1]. In the last few decades, androgen deprivation therapy (ADT) has been the standard of care for metastatic PC. The STAMPEDE trial demonstrated that combining docetaxel (DOC) or abiraterone (ABI) with ADT conferred a clinically meaningful survival advantage in patients with mHSPC [2, 3]. In addition to systemic therapies, local treatment of the prostate combined with ADT was shown to prolong survival in mHSPC patients. Results from two randomized clinical trials revealed a potential survival benefit with local radiotherapy (RT) complementary to ADT in certain subgroups of mHSPC patients [8, 9]. Many combined treatment approaches have been shown to be effective, there are no data on the comparative efficacy of systemic and local therapies combined with ADT. 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
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