The Association between Acute and Late Genitourinary and Gastrointestinal Toxicities: An Analysis of the PACE B Study

Simple Summary: Several studies have shown the association between significant short-term and long-term side-effects after prostate radiotherapy using older techniques. Our study, tests whether there is an association between short- and long-term bowel and urinary side-effects with modern prostate radiotherapy techniques such as stereotactic body radiotherapy (SBRT) and intensity modulated radiotherapy (IMRT). We use CTCAE clinical assessments of patient symptoms for radiotherapy side-effects in the PACE-B study to answer this question. We show that patients who develop short-term urinary and bowel side-effects are at higher odds of developing long-term side-effects, after conventional fractionated radiotherapy and SBRT. This association remains even after adjusting for patient, treatment and tumour factors. We show that patients who have significant urinary symptoms before radiotherapy are also at higher odds of developing long-term side-effects. We suggest that patients who experience significant short-term side-effects should be closely monitored and potentially have their symptoms treated earlier. Several studies have demonstrated the association between acute and late radiotherapy toxicity in prostate cancer using older radiotherapy techniques. However, whether this association is present with newer techniques such as stereotactic body radiotherapy (SBRT), remains unclear. We use univariable and multivariable logistic regression to analyse the association between grade 2 or worse acute gastrointestinal (GI) and genitourinary (GU) toxicities with equivalent late toxicities in patients treated with SBRT and conventional or moderately fractionated radiotherapy (CRT) within the PACE-B study. 842 patients were included in this analysis. Common Terminology Criteria for Adverse Events (CTCAE) was the primary clinician reported outcome measure used in this analysis. In univariable analysis, experiencing a grade 2+ acute GU toxicity was significantly associated with developing a grade 2+ late GU toxicity after SBRT (OR 4.63, 95% CI (2.96-7.25), p < 0.0001) and CRT (OR 2.83, 95% CI (1.69-4.71), p < 0.0001). This association remained significant in multivariable analysis. In univariable analysis, experiencing a grade 2+ acute GI toxicity was also associated with developing a grade 2+ late GI toxicity after SBRT (OR 3.67, 95% CI (1.91-7.03), p < 0.0001) and CRT (OR 4.4, 95% CI (2.04-9.47), p < 0.0001). This association also remained significant in multivariable analysis. Grade 2+ baseline GU symptoms were also associated with grade 2+ late urinary toxicity in both univariable and multivariable analysis. Overall, acute toxicity is an important predictor variable for late GU/GI toxicity after localised prostate radiotherapy using SBRT and CRT. Future work should test whether optimising symptoms pre-treatment and early intervention in those with significant acute toxicities could mitigate the development late of toxicity.