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

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 is similar in both metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer patients with and without visceral metastasis. Further well-designed studies with detailed visceral metastatic sites and number will enrich the clinical decision-making.

Positive family history as a predictor for disease outcomes after radical prostatectomy for nonmetastatic prostate cancer.

Background: While family history (FHx) of prostate cancer (PCa) increases the risk of PCa, comparably less is known regarding the impact of FHx on pathologic and oncologic outcomes after radical prostatectomy (RP). Methods: We retrospectively reviewed our multicenter database comprising 6,041 nonmetastatic PCa patients treated with RP. Patients with a FHx of PCa in one or more first-degree relatives were considered as FHx positive. We examined the association of FHx with pathologic outcomes and biochemical recurrence (BCR) using logistic and Cox regression models, respectively. Results: In total, 1,677 (28%) patients reported a FHx of PCa. Compared to patients without FHx, those with, were younger at RP (median age of 59 vs. 62 years, p < 0.01), and had significantlymore favorable biopsy and RP histopathologic findings. On multivariable logistic regression analysis, positive FHx was associated with extracapsular extension (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.66-0.90, p < 0.01; model AUC 0.73) and upgrading (OR 0.70, 95% CI 0.62-0.80, p < 0.01; model AUC 0.68). Incorporating FHx significantly improved the AUC of the base model for upgrading (p < 0.01). Positive FHx was not associated with BCR in pre- and postoperative multivariable models (p = 0.1 and p = 0.7); c-indexes of Cox multivariable models were: 0.73 and 0.82, respectively. Conclusions: We found that patients with clinically nonmetastatic PCa who have positive FHx of PCa undergo RP at a younger age and have more favorable pathologic outcomes. Nevertheless, FHx of PCa did not confer better BCR rates, suggesting that FHx leads to potentially early detection and treatment without impact on BCR.