Efficacy of Systemic Treatment in Prostate Cancer Patients With Visceral Metastasis: A Systematic Review, Meta-analysis, and Network Meta-analysis

Abstract

Purpose:There are limited pooled data showing the impact of visceral metastasis on oncologic outcomes in metastatic prostate cancer patients treated with combination systemic therapies. We aimed to analyze and compare the efficacy of combination systemic therapies in metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer with or without visceral metastasis.Materials and Methods:Three databases were queried in July 2022 for randomized, controlled trials analyzing metastatic prostate cancer patients treated with combination systemic therapy (androgen receptor signaling inhibitor and/or docetaxel plus androgen deprivation therapy) to standard of care. We analyzed the association between presence of visceral metastases and efficacy of systemic therapies in metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer patients. The main and secondary outcomes of interest were overall survival and progression-free survival, respectively. Formal meta-analysis using fixed-effect model and network meta-analysis using random-effect model were conducted. We followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) and AMSTAR (A MeaSurement Tool to Assess systematic Reviews) guidelines.Results:Overall, 12 and 8 randomized, controlled trials were included for systematic review and meta-analyses/network meta-analyses, respectively. In metastatic hormone-sensitive prostate cancer patients, adding androgen receptor signaling inhibitor to standard of care improved overall survival in patients with visceral metastasis (pooled HR: 0.77, 95% CI: 0.64-0.94) as well as in those without (pooled HR: 0.66, 95% CI: 0.60-0.72; no differences in both across- and within-trial approach; P = .13 and P = .06, respectively). On the other hand, the progression-free survival benefit from androgen receptor signaling inhibitor + androgen deprivation therapy was significantly lower in patients with visceral metastasis using across-trial approach (P = .03), while it did not reach statistical significance using within-trial approach (P = .14). Analysis of treatment ranking in metastatic hormone-sensitive prostate cancer showed that darolutamide + docetaxel + androgen deprivation therapy had the highest likelihood of improved overall survival irrespective of visceral metastasis. In post-docetaxel metastatic castration-resistant prostate cancer patients, adding androgen receptor signaling inhibitor to androgen deprivation therapy significantly improved overall survival in both patients with visceral metastasis (pooled HR: 0.79, 95% CI: 0.63-0.98) and those without (pooled HR: 0.63, 95% CI: 0.55-0.72). No randomized, controlled trials reported the differential oncologic outcomes stratified by lung vs liver metastases.Conclusions:Despite aggressive clinical behavior and worse trajectory of metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer with visceral metastasis, the effectiveness of novel systemic therapies...

Prostate Cancer Liver Metastasis: An Ominous Metastatic Site in Need of Distinct Management Strategies

“…To date, there are no standard treatments specifically for patients with PCLM, who generally derive little benefit from systemic therapies that are otherwise effective in non-LM mCRPC patients. For instance, a systematic review by Yanagisawa et al highlights the results of select mCRPC clinical trials, such as PREVAIL (Enzalutamide), PROfound (Olaparib), and CARD (Cabazitaxel), which do not suggest an OS benefit for patients with VM [21,29,33,91]. Consequently, there is a growing interest in locally ablative therapies, notably in patients with limited LM.…”

Editorial Comment

“…Yanagisawa et al conducted a systematic review, meta-analysis, and network meta-analysis focused on treatment intensification among patients with both metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer to examine whether the benefit of treatment intensification varied based on the presence of VM. 1 While previous work has examined the same research question by disease burden (which encompasses VM), none has separately focused on VM. Importantly, the authors found that the relative magnitude of benefit from treatment intensification using androgen receptor signaling inhibitors and/or docetaxel is similar in these patients, regardless of VM.…”

Survival Patterns Based on First-site–specific Visceral Metastatic Prostate Cancer: Are Outcomes of Visceral Metastases the Same?

“…Of the men with PCa, 5% present with de novo metastatic disease, and approximately 17% of those diagnosed with localized PCa will eventually develop metastases [3] , [4] , [5] . In the context of metastatic disease, systemic treatment emerges as fundamental for patients, whether in a hormone-sensitive or a hormone-resistant state, showing reported enhancements in survival outcomes [6] .…”