Stereotactic Prostate Cancer Ablative Re-Irradiation: A Systematic Review and Meta-Analysis (SPARE)

Stereotactic ablative radiotherapy (SABR) is emerging as an alternative treatment for patients with locally recurrent prostate cancer after previous radiation. This approach allows for precise target coverage while limiting toxicity to surrounding organs. However, reported outcomes following re-irradiation of the prostate with SABR remain variable. This systematic review and meta-analysis therefore evaluated the efficacy and toxicity of prostate re-irradiation with SABR.

A systematic review and meta-analysis compliant with PRISMA guidelines was conducted to evaluate studies of SABR for local re-irradiation of prostate cancer. Random-effects models were employed to pool biochemical recurrence-free survival (BRFS), local relapse-free survival (LRFS), metastasis-free survival (MFS), and gastrointestinal (GI) and genitourinary (GU) toxicities after SABR re-irradiation. Outcomes were pooled as proportions using the Freeman-Tukey double arcsine transformation, and heterogeneity was assessed using I². Statistical analyses were performed using Stata version 19.5.

A total of 30 treatment cohorts from 29 studies, including 1099 patients, were analysed. The pooled rates for 2-year BRFS, LRFS, and MFS were 62.5% (95% CI, 54.1-70.6%; I² = 81.9%), 89.9% (95% CI, 80.6-96.5%; I² = 85.5%), and 84.6% (95% CI, 77.3-90.7%; I² = 77.8%), respectively. Acute severe side effects were rare, with pooled rates of grade 3-4 GI toxicities of 0.7% (95% CI, 0.3-1.4%; I² = 0%) and grade 3-4 GU toxicities of 1.1% (95% CI, 0.6%-1.9%; I² = 0%). Late grade 3-4 toxicity also remained low, with pooled GI and GU rates of 1.0% (95% CI, 0.5-1.7%; I² = 0%) and 3.3% (95% CI, 2.0-5.0%; I² = 46.1%), respectively.

Prostate re-irradiation with SABR is associated with favourable short- and intermediate-term oncologic outcomes, including high local control and metastasis-free survival, with acceptable toxicity. The heterogeneity observed across studies and the very low certainty of evidence encourage the inclusion of these patients in prospective trials or registries to improve patient selection, dose-fractionation strategies, and long-term outcomes.