Visceral Metastases as Predictors of Response and Survival Outcomes in Patients of Castration-Resistant Prostate Cancer Treated With 177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy A Systematic Review and Meta-analysis

Background The presence of visceral metastases is associated with poor prognosis in patients of metastatic castration-resistant prostate cancer (mCRPC) treated with hormonal therapy and chemotherapy. However, studies evaluating its impact on treatment outcomes with Lu-177-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) are currently limited and show inconsistent results. This systematic review was conducted to precisely evaluate the impact of visceral metastases on biochemical response and survival outcomes in patients of mCRPC treated with Lu-177-PSMA RLT. Methods This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. Searches in PubMed, Scopus, and EMBASE were made using relevant keywords, and articles up to May 2020 were included. Univariate and multivariate odds ratios and hazard ratios (HRs) were extracted from the individual articles, and pooled estimates were generated using meta-analysis. Results Twelve articles comprising 1504 patients were included in this review. Presence of visceral metastases not only predicted low biochemical response rate (pooled univariate odds ratio: 0.38, 95% confidence interval [CI], 0.22-0.66) but was also a significant prognosticator of worse progression-free survival (pooled univariate HR, 1.85; 95% CI, 1.39-2.46; and pooled multivariate HR, 1.48; 95% CI, 1.15-1.92) and overall survival (pooled univariate HR, 1.77; 95% CI, 1.29-2.44; and pooled multivariate HR, 2.22; 95% CI, 1.82-2.70). There was no evidence of publication bias. Conclusions Presence of visceral metastases was associated with poor response and survival outcomes in patients of mCRPC treated with Lu-177-PSMA RLT. The results are clinically significant for pretreatment risk stratification of such patients and to guide optimal treatment strategies.