The Determinants of Toxicity in the Treatment of Prostate Cancer with a Focal, Intraprostatic "Microboost".

Purpose: A single phase III trial has demonstrated that prostate radiotherapy with a focal, intra-prostatic "microboost" can improve disease control without an overall increase in toxicity. It is unclear how these results generalize to other treatment schedules and protocols.

Methods: A systematic search of PubMed and the Cochrane Review was performed for studies published on or before September 1, 2023. A random-effects meta-analysis was used to pool the cumulative incidence of grade ≥2 (≥G2) acute and late genitourinary (GU) and gastrointestinal (GI) toxicity. Heterogeneity was assessed, and the association of trial-level covariates with toxicity were examined via subgroup analyses and meta-regression. Odds ratios (ORs) for dose metrics were reported per Gy EQD2.

Results: Thirty-eight patient cohorts were included. The pooled estimate of the cumulative incidence of ≥G2 acute and late GU toxicity was 25.3% (95% confidence interval [CI]: 19.1%-32.8%) and 21.1% (95% CI: 16.7%-26.3%), respectively. Late ≥G2 GI toxicity was less frequent, estimated at 5.6% (95% CI: 3.5%-8.7%) and 6.9% (95% CI: 4.6%-10.1%), respectively. Subgroup factors associated with at least one ≥G2 toxicity category were treatment technique, imaging used for boost volume definition, intrafraction motion management, trial phase, and toxicity grading. Rectal D was associated with acute ≥G2 GI toxicity (OR: 1.05 [95% CI: 1.02-1.08], p < 0.001). Additionally, urethral D was associated with late ≥G2 GU toxicity (OR: 1.02 [95% CI: 1.01-1.03], p < 0.001), and a stronger relationship was observed with the average plan urethral D (OR: 1.05 [95% CI: 1.03-1.07], p < 0.001). No association of toxicity with any bladder dose metric examined was observed.

Conclusions: The utilization of a microboost appears tolerable across treatment protocols; however, subgroup factors, including the use of intrafraction motion management and the type of imaging modality utilized, may influence the probability of toxicity. Attention to rectal D constraints and urethral D dose constraints may help to mitigate GI and GU toxicity, respectively. No association between toxicity and bladder dose constraints was observed.