Lower urinary tract sub-structures as predictors of late urinary toxicity in concurrent chemo-radiotherapy for anal cancer.

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Late toxicity is substantial after chemotherapy for anal cancer. This study aimed to investigate the relationship between radiation dose to lower urinary tract sub-structures and the risk of late urinary toxicities, in patients with anal cancer treated with chemoradiotherapy or radiotherapy. From 2015 to 2021, 314 patients with localized anal cancer were included in a national prospective registration study. Urinary toxicity (CTCAE) was scored during treatment (acute toxicity) and at one- and three-years follow-up (late toxicity). Lower urinary tract sub-structures (bladder, bladder neck, bladder trigone, and urethra) were contoured post-hoc on the planning-CT and dosimetric variables extracted. Logistic regression was used to evaluate the association between clinical and dosimetric variables and registered toxicity. There was an increase in late toxicity from baseline of 15% for both urgency and frequency, and 25% for incontinence. The most common late toxicity was urinary frequency, with 40% of patients experiencing grade 1 and 2% experiencing grade 2 toxicity. A dose-effect relationship was found for late urinary urgency and increasing D0.1cm3 of the urethra (p=0.01). Increased late urinary frequency was correlated to increasing D2cm3 of the urethra (p=0.007), and bladder neck V30Gy (p=0.03). Patients with acute toxicity had up to three times increased risk of corresponding late toxicity. We found a significant dose-effect relationship between radiation dose to urethra and bladder neck and late urinary toxicity. These findings warrant more focus on these structures when optimizing radiotherapy for anal cancer. Furthermore, a strong association between having acute toxicity and developing late toxicity was shown.