Salvage low-dose vs high-dose brachytherapy for radio-recurrent prostate cancer

Objective To summarise the efficacy and toxicity of salvage low-dose-rate brachytherapy (LDR-BT) and compare these findings with the published data on salvage high-dose-rate brachytherapy (HDR-BT). Methods We reviewed PubMed and EMBASE for studies published up to May 2024, mainly focusing on recurrence-free survival (RFS) with salvage LDR-BT across subgroups. We also compared RFS and adverse events with HDR-BT as a secondary objective. We reconstructed survival curves using a semi-automated tool called WebPlotDigitizer, along with a new shiny application integrated with R. Results A total of 31 studies (891 patients) met the inclusion criteria for salvage LDR-BT. The median RFS of patients treated with salvage LDR-BT was 131.6 months, with 2-, 3- and 5-year rates of 84.6%, 74.3% and 63.5%. Lower median age (65-70 years vs 72.3-75 years, hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.35-0.70; P < 0.0001) and higher adjuvant androgen deprivation therapy (ADT) proportion (83.8%-100% vs 0%-47%, HR 0.60, 95% CI 0.55-0.65; P = 0.036) were positive RFS factors. Compared to HDR-BT, salvage LDR-BT demonstrated improved RFS for all patients (HR 0.67, 95% CI 0.55-0.81; P < 0.0001). Specifically, salvage LDR-BT exhibited superior RFS (P < 0.05) for patients with a median age <= 70 years at recurrence, a median time from primary treatment to salvage therapy (TPTS) of >= 70 months, a median pre-salvage prostate-specific antigen level of >= 5 ng/mL, and a proportion of adjuvant ADT of >= 53%, compared to HDR-BT. However, LDR-BT was associated with a higher rate of severe gastrointestinal (GI; 3.5% vs 0.3%, odds ratio [OR] 0.08, 95% CI 0.03-0.28; P < 0.0001) and genitourinary (GU) toxicities (12.7% vs 5.8%, OR 0.42, 95% CI 0.30-0.60; P < 0.001) compared to HDR-BT. Conclusions In specific cohorts, salvage LDR-BT appears to yield superior RFS but entails a higher incidence of severe GI/GU toxicities compared to HDR-BT.