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

Background And Purpose: 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.

Materials And Methods: 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.

Results: 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 D0.1 cm3 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.

Conclusion: 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.