Clinical Efficacy and Survival Outcomes of Targeted Radioisotope Therapy Across Cancer Types (2015–2026): A Systematic Review and Meta-Analysis

The clinical landscape of targeted radioisotope therapy (TRT) has expanded rapidly across multiple oncologic indications, yet no comprehensive cross-cancer meta-analysis has synthesized the survival evidence spanning diverse tumor types and radiopharmaceutical agents. The purpose of this systematic review and meta-analysis was to evaluate the clinical efficacy and survival outcomes of TRT across five cancer types—metastatic castration-resistant prostate cancer (mCRPC), gastroenteropancreatic neuroendocrine tumors (GEP-NETs), hepatocellular carcinoma (HCC), differentiated thyroid carcinoma, and lymphoma—using five radioisotopes (Lu-177, Ra-223, Ac-225, I-131, and Y-90) from January 2015 through December 2026. Following PRISMA 2020 guidelines, a systematic search of PubMed/MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov identified 16 eligible clinical trials encompassing 4,632 participants. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled using DerSimonian–Laird random-effects models. For OS (k = 7), the pooled HR was 0.788 (95% CI: 0.629–0.986, p = .037), indicating a statistically significant 21.2% reduction in the risk of death, with GRADE-rated moderate certainty of evidence. Substantial heterogeneity was observed (I² = 82.9%), driven primarily by divergent HCC trial outcomes. Subgroup analysis revealed consistent OS benefit in mCRPC (HR = 0.664, 95% CI: 0.592–0.744, I² = 0.0%) and a remarkable PFS benefit in GEP-NETs (HR = 0.227, 95% CI: 0.150–0.345, k = 2, GRADE moderate certainty). Cancer type emerged as the most important moderator of heterogeneity (Q_between = 5.16, p = .076), while personalized dosimetry was identified as a critical determinant of efficacy in HCC, with the DOSISPHERE-01 trial demonstrating a median OS of 26.6 versus 10.7 months under personalized versus standard dosimetry (HR = 0.421). Publication bias assessment via trim-and-fill yielded an adjusted HR of 0.728, confirming robustness. Sensitivity analyses demonstrated stability across leave-one-out iterations (HR range: 0.737–0.828). These findings establish TRT as a viable and effective therapeutic modality with meaningful survival benefits, while underscoring the necessity of cancer-type-specific treatment selection, personalized dosimetric approaches, and expanded clinical trial programs to optimize patient outcomes across the oncologic spectrum.