Intermediate rectal dose exposure as a predictor of late toxicity after prostate stereotactic body radiotherapy: a principal component analysis of dose volume histogram

Background and purposeStereotactic body radiotherapy (SBRT) has become a standard treatment option for localized prostate cancer, with low rates of clinically relevant late toxicity. However, the identification of robust dosimetric predictors of toxicity remains challenging due to the high dimensionality and collinearity of dose-volume histogram (DVH) metrics. This study aimed to explore whether principal component analysis (PCA) of DVHs can identify dose regions associated with late gastrointestinal and genitourinary toxicity after prostate SBRT. Materials and methodsWe analysed a single-institution cohort of patients treated with prostate SBRT. Rectum, rectal wall, bladder and bladder wall DVHs were extracted with a dose bin resolution of 0.5 Gy. PCA was applied separately to each structure to identify dominant patterns of dose-volume variability. PCA-derived dose metrics were subsequently evaluated using Spearman correlation analyses, receiver operating characteristic (ROC) curves, and exploratory logistic regression models. Late toxicity was scored according to CTCAE version 5.0, with grade [≥] 2 events at 12 months as the primary endpoint. ResultsPCA demonstrated that a limited number of components accounted for most DVH variability, with the largest contributions arising from intermediate-dose regions. For the whole rectum, intermediate-dose metrics showed the strongest association with late rectal toxicity. Rectal V18.1 Gy yielded the highest discriminative performance (AUC = 0.87), followed by V29 Gy (AUC = 0.83), whereas low-dose (V1.5 Gy) and high-dose (V42.5 Gy) metrics showed limited or no discrimination. Rectal wall metrics demonstrated weaker and less robust associations, and no clinically meaningful discriminative performance was observed for bladder or bladder wall DVH metrics. Exploratory regression analyses supported the association between intermediate rectal dose exposure and late rectal toxicity. ConclusionIn prostate SBRT, PCA of DVHs highlights intermediate rectal dose exposure as the primary dosimetric determinant of late rectal toxicity. Whole-rectum intermediate-dose metrics outperform both low- and high-dose parameters, as well as rectal wall and bladder-derived metrics. These findings support a parsimonious, data-driven focus on intermediate-dose rectal volumes for toxicity risk assessment and hypothesis generation in prostate SBRT planning.