Umbrella review of photodynamic therapy for cancer: efficacy, safety, and clinical applications.

Background: Photodynamic therapy (PDT) can target cancers, while causing little damage to surrounding healthy tissues. Objective: To systematically evaluate the efficacy, safety, and clinical applications of PDT across cancer types. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were searched to April 7, 2024 for systematic reviews and meta-analyses of PDT in patients with cancer. Quality assessment was performed using Assessment of Multiple Systematic Reviews 2, overlapping meta-analyses were handled using Corrected Covered Area, and data re-synthesized using a random-effects model. Results: Eighteen publications met the inclusion criteria. There is weak evidence that PDT combined with biliary stenting improves overall survival (OS) relative to stenting alone (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.33-0.73), while PDT with chemotherapy improved OS (HR 0.36, 95% CI 0.15-0.87), without increasing adverse events. Weak evidence indicated lower clearance and complete response rates and higher recurrence rates of non-melanoma skin cancers, particularly basal cell carcinoma (BCC), after PDT than following surgery. In squamous cell carcinoma (SCC), complete response rates (relative risk 2.75; 95% CI 2.19-3.45) were higher for laser-assisted than conventional PDT; PDT provided better cosmetic outcomes than other therapies. Single-arm meta-analyses demonstrated some efficacy of PDT for treating cutaneous metastatic SCC, oral SCC, prostate cancer, and bladder cancer. Conclusion: PDT shows potential benefits in several cancers, especially for non-melanoma skin cancer and unresectable cholangiocarcinoma. While newer PDT strategies may improve outcomes, more high-quality trials are needed to confirm its role across cancer types. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024538243, identifier CRD42024538243.