e17075 Background: Chimeric antigen receptor (CAR) T-cell therapies targeting prostate-associated antigens, such as prostate-specific membrane antigen (PSMA), prostate stem cell antigen (PSCA), and six-transmembrane epithelial antigen of the prostate 1 (STEAP1), have demonstrated preliminary antitumor activity in heavily pretreated prostate cancer patients. However, their overall safety and efficacy in prostate cancer remain uncertain. We conducted a systematic review and meta-analysis to evaluate clinical outcomes of CAR-T cell therapy in this setting. Methods: Following PRISMA guidelines, we searched PubMed, Cochrane Library, and Embase from inception to November 21, 2025, using MeSH terms and keywords including “CAR-T,” “chimeric antigen receptor,” and “prostate cancer.” Eligible studies were prospective early-phase open-label, dose-escalation clinical trials reporting safety or efficacy outcomes. Pooled estimates for cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), objective response rate (ORR), and PSA50 response (≥50% PSA decline) were generated using random-effects models with restricted maximum likelihood estimation. Freeman–Tukey transformation and Knapp–Hartung adjustment were applied as appropriate. Heterogeneity was assessed via I² and τ² statistics. Analyses were performed in R version 4.5.2. Results: Seven studies encompassing 69 patients were included. All patients had metastatic castration-resistant prostate cancer (mCRPC) and were heavily pretreated (median prior lines 2–8), with frequent exposure to androgen deprivation therapy, androgen receptor signaling inhibitors, and taxane-based chemotherapy (docetaxel exposure 46%-86% where reported). Median age ranged from 61 to 70 years when reported; baseline performance status (ECOG 0-1) was documented in only one study. Efficacy outcomes (from subset reporting) showed a pooled ORR of 39.0% (95% CI, 24.2%- 54.7%, I 2 = 0.0%) and a PSA50 response rate of 47.8% (95% CI, 15.0%-81.6%, I 2 = 33.9%). The pooled CRS rate was 45.0% (95% CI, 10.9%-81.5%, I 2 = 82.1) for any grade and 9.2% (95% CI, 0.1%-25.4%, I 2 = 42.3%) for grade ≥3. ICANS occurred in 13.2% (95% CI, 4.8%-23.8%, I 2 = 0.0%) for any grade and 4.4% (95% CI, 0.0%-16.8%, I 2 = 9.2%) for grade ≥3. Conclusions: CAR-T cell therapy demonstrates early antitumor activity in mCRPC, with meaningful biochemical (PSA50) responses and a manageable safety profile across various targets and CAR constructs. CRS and ICANS rates are notable but predominantly low-grade. Larger phase II/III trials are essential to confirm efficacy, optimize antigen selection, mitigate toxicities, and evaluate combination strategies to enhance durability in this refractory population.
Zaidi et al. (2026) studied this question.