To examine sex differences in radiation induced bladder dysfunction following radiotherapy, men and women with storage and voiding dysfunction were prospectively enrolled in an observational cohort, enriched with women undergoing radiotherapy for cervical and endometrial cancer.

There were 205 men and women consented for enrollment over the 6 month study period (May to October 2019). A total of 176 questionnaires [American Urological Association Symptom Score (AUASS), International Consultation on Incontinence Female / Male Lower Urinary Tract Symptoms (ICIQ FLUTS / MLUTS), 12-Item Short Form Health Survey (SF12)] were collected. Participants with complete data were included for analysis. Primary outcome was gender differences in the storage, voiding and incontinence domains of the ICIQ questionnaires. Data were analyzed in Statistical Analysis System software (SAS, Cary, NC) using analysis of variance (ANOVA) with Tukey correction for multiple comparisons.

136 participants completed questionnaires (Non-radiated women n=52, mean age 55.4±18.5 years; Radiated women n=18, age 58.5±15.6; Non-radiated men n=55, age 57.6±18.5; Radiated men n=11, age 64.5±15.6) and had a mean time since radiation of 3,530±3,163 (median 3,142; IQR 544-5,042) days in men, and 2,615±4,171 (median 87; IQR 21-3,215) days in women. There was no significant difference in post void residual, or AUASS overall score (ANOVA p=0.294) between any groups. All domains of the AUASS failed to capture between group differences in storage and voiding dysfunction in radiated individuals, with the exception of difficulty postponing urination (ANOVA p=0.012). Non-radiated women reported significantly higher AUASS QOL score (4±1.6 versus men 2.8±1.6, ANOVA p<0.001), and did not differ significantly compared to radiated women. In the storage domain of the ICIQ there was an increase in urinary urgency (ANOVA p=0.004) after radiotherapy, with male gender protective, and no difference in nocturnal (ANOVA p=0.479) and daytime (ANOVA p=0.193) urinary frequency. In the voiding phase domain of the ICIQ, radiated men had the greatest intermittency (ANOVA p=0.048), radiated women tended to have the lowest hesitancy (ANOVA p=0.075), and there was no difference in straining (ANOVA p=0.177). Across the incontinence domains of the ICIQ, radiotherapy uniformly increased urgency incontinence (ANVOA p<0.001), and nocturnal enuresis (ANOVA p=0.016) in all radiotherapy groups, with more men reporting stress (ANOVA p<0.001) and unawareness incontinence (ANOVA p=0.002) after radiotherapy.

The ICIQ FLUTS and MLUTS are more sensitive than the AUASS at classifying the burden of storage and voiding dysfunction in men and women following radiotherapy.

Further research is needed to better classify gender specific changes in lower urinary tract function following pelvic radiotherapy.