There is limited pooled data showing the impact of visceral metastasis on oncologic outcomes in metastatic prostate cancer (mPCa) patients treated with combination systemic therapies. We aimed to analyze and compare the efficacy of combination systemic therapies in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) with or without visceral metastasis.
Three databases were queried in July 2022 for RCTs analyzing mPCa patients treated with combination systemic therapy (androgen receptor signaling inhibitor [ARSI] and/or docetaxel [DOC] plus androgen deprivation therapy [ADT]) to standard of care [SOC]. We analyzed the association between presence of visceral metastases and efficacy of systemic therapies in mHSPC and mCRPC patients. The main and secondary outcomes of interest were overall survival (OS) and progression-free survival (PFS), respectively. Formal meta-analysis using fixed-effect model and network meta-analysis using random-effect model with a frequentist approach were conducted. We followed PRISMA and AMSTAR guidelines.
Overall, 12 and 8 RCTs were included for systematic review and meta-analyses/network meta-analyses, respectively. In mHSPC patients, adding ARSI to SOC improved OS in patients with visceral metastasis (pooled hazard ratio [HR]: 0.77, 95% confidence interval [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 PFS benefit form ARSI + ADT 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 mHSPC showed that darolutamide + DOC + ADT had the highest likelihood of improved OS irrespective of visceral metastasis. In post-docetaxel mCRPC patients, adding ARSI to ADT significantly improved OS 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 RCTs reported the differential oncologic outcomes stratified by lung versus liver metastases.
Despite aggressive clinical behavior and worse trajectory of mHSPC and mCRPC with visceral metastasis, the effectiveness of novel systemic therapies is similar in both mHSPC and mCRPC patients with and without visceral metastasis. Further well-designed studies with detailed visceral metastatic sites and number will enrich the clinical decision-making.
The Journal of urology. 2023 Jun 20 [Epub ahead of print]
Takafumi Yanagisawa, Pawel Rajwa, Tatsushi Kawada, Keiichiro Mori, Wataru Fukuokaya, Patrik Petrov, Fahad Quhal, Ekaterina Laukhtina, Markus von Deimling, Alberto Bianchi, Muhammad Majdoub, Benjamin Pradere, Gero Kramer, Takahiro Kimura, Shahrokh F Shariat
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan.