Salvage Radiotherapy Following Nonradiotherapy Ablative Techniques for Primary Prostate Cancer: A Systematic Review and Meta-analysis.

Background and objective: The treatment landscape for localized prostate cancer has evolved with the increasing use of nonradiotherapy ablative interventions (NRAIs) such as high-intensity focused ultrasound (HIFU) and cryotherapy. These minimally invasive therapies promise fewer side effects and quicker recovery but come with a higher risk of recurrence, often necessitating salvage treatments. Salvage radiotherapy (SRT) is a potential option, but its efficacy and safety following NRAIs remain uncertain. Our aim was to conduct a systematic review and meta-analysis of the safety and efficacy of SRT in patients with recurrent prostate cancer after NRAI. The primary objective was SRT safety in terms of acute and late gastrointestinal (GI) and genitourinary (GU) toxicities. The secondary objectives were SRT efficacy in terms of biochemical relapse rates according to prior NRAI type (HIFU vs cryotherapy).

Methods: A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library up to August 2023. Studies were included if they assessed SRT outcomes in patients with prostate cancer recurrence after NRAI, focusing on GI and GU toxicities and biochemical relapse. Data were extracted and pooled using a random-effects meta-analysis model to estimate the incidence of acute and late toxicities and biochemical recurrence rates. Statistical analysis included assessments of heterogeneity and publication bias.

Key findings and limitations: Twenty-one studies involving 817 patients were included. The pooled rate for acute SRT grade 1-2 GI toxicity was 22% (95% confidence interval [CI] 10-34%; p < 0.01) and was higher for prior HIFU versus cryotherapy. The pooled rate for acute SRT grade 1-2 GU toxicity was 37% (95% CI 22-52%) and was higher for prior HIFU. The incidence of late grade 1-2 toxicity was 12% (95% CI 5-19%; p < 0.01) for GI and 26% (95% CI 12-39%; p < 0.01) for GU toxicity. Grade ≥3 toxicities were rare, occurring in less than 5% of patients. The biochemical relapse rate after SRT was ∼20% (95% CI 14-26%; p < 0.01) for both HIFU and cryotherapy, indicating similar efficacy. The odds ratio for biochemical relapse was 0.19 (95% CI 0.12-0.26; p < 0.01) for HIFU and 0.22 (95% CI 0.10-0.35; p < 0.01) for cryotherapy. There was evidence of publication bias and high heterogeneity.

Conclusions and clinical implications: SRT following NRAI for localized prostate cancer has low toxicity rates, particularly following cryotherapy, and reasonable biochemical control. Despite these findings, short follow-up and variability in treatments for patients with varying risk profiles highlight the need for further studies to refine SRT protocols and establish more definitive long-term outcomes.