Uncoupling anatomical barriers from radiotherapy toxicity: a two-part hurdle analysis of sexual function in gynecologic cancer

BACKGROUND: Pelvic radiotherapy (RT) is essential for gynecological cancer; however, it often causes chronic, under-recognized sexual toxicity in survivorship care. AIM: We applied a two-part hurdle model to separately evaluate predictors of sexual activity and function in women receiving RT for gynecological cancers. METHODS: We conducted a retrospective cohort study involving 120 women treated with definitive or adjuvant pelvic RT (external beam radiotherapy EBRT-inclusive or vaginal brachytherapy VBT-only) for gynecological cancer at a single medical center. OUTCOMES: The primary outcome was post-treatment sexual function quantified via the 19-item Female Sexual Function Index, while the secondary outcomes included the predictors of sexual activity (binary status defined as any non-zero score on physiological domains) and functional quality (total score) among active women, analyzed using a two-part hurdle model consisting of logistic and beta regressions with a Smithson-Verkuilen transformation. RESULTS: The cohort exhibited a severe floor effect, with 64.2% (77/120) of patients classified as sexually inactive. In the activity hurdle, lubricant use (OR 12.2; 95% CI: 1.66-88.9; P = .01) and multiparity (OR 12.6; 95% CI, 1.74-91.8; P = .01) were associated with continued sexual engagement, whereas age demonstrated an independent negative association (OR 0.89 per year; 95% CI, 0.81-0.99; P = .04). In the functional hurdle, sexually active patients treated with EBRT-inclusive regimens demonstrated significantly lower functional scores compared to the VBT-only cohort (the exponentiated coefficient of β = 0.17; P = .001). Historical comparisons revealed significant deficits across all domains, especially orgasm (P < .001), within the EBRT-inclusive cohort relative to published healthy controls. CLINICAL IMPLICATIONS: The management of RT-induced sexual dysfunction requires a tiered approach that prioritizes mechanical lubricants to overcome initial activity barriers, while necessitating rehabilitation strategies to mitigate profound functional deficits and to improve the quality of life for patients requiring EBRT. STRENGTHS AND LIMITATIONS: The main strength is the methodological separation of uncoupling of behavioral engagement hurdles from inherent tissue radiation toxicity; limitations comprise the retrospective design, baseline clinical imbalances between cohorts, and the small number of sexually active patients receiving brachytherapy. CONCLUSION: Sexual dysfunction following pelvic RT presents as a complex bifurcated phenomenon, wherein sexual engagement is strongly associated with parity-related anatomical factors and mechanical lubricative support, whereas overall functional quality is constrained by exposure to EBRT.