Risk of Sexual Dysfunction in Men Treated with Pelvic Radiation Therapy for Locally Advanced Rectal Cancer: 20 Years of Experience with 451 Patients

Abstract

Radiation therapy (RT) is commonly used in the treatment of locally advanced rectal cancer (LARC), but data on its impact on men's sexual health is limited. Given the rising incidence of rectal cancer in younger men, sexual function is an important quality of life factor. We hypothesized that men with LARC treated with RT would be at increased risk of sexual dysfunction compared to men who did not receive RT. This is a single institution retrospective analysis of outcomes of men ≤50 years diagnosed with LARC between 1999 and 2019. Primary outcomes of erectile dysfunction (ED), ejaculatory dysfunction (EjD), and testosterone deficiency (TD) were assessed via ICD-9/10 codes, and TD was captured with free testosterone <300 ng/dL. Cumulative incidences were calculated with death as a competing risk and p values were calculated using Gray's test. Subdistribution hazard ratios from competing risk regression models were used. The combined study sample included 451 men: 347 received RT as part of their multimodality treatment, and 104 did not. Median time to last follow up was 5.6 years (IQR 3.3-8.7). Age at diagnosis, stage, and medical comorbidities for sexual dysfunction were similar between the two groups (p>0.05). Cumulative incidence estimates are shown in Table 1, showing a higher cumulative incidence of ED in the RT group, but no difference in EjD or TD between the 2 groups. On univariable analysis, RT, smoking, dyslipidemia, peripheral artery disease, depression, prostate cancer/hyperplasia, closed or current ileostomy, and undergoing rectal cancer surgery were all independent risk factors for ED (p<0.05). On multivariable analysis, RT maintained statistical significance as an independent risk factor for ED (HR 3.87, 95% CI 1.93-7.75, p<0.001). Within the RT group, IMRT compared to 3D (HR 1.54, 95% CI 1.02-2.32, p = 0.040) and groin RT (HR 2.60, 95% CI 1.21-5.59, p = 0.014) were independent risk factors for ED. Within the RT group, groin RT also approached significance as a risk factor for TD (HR 3.61, 95% CI 0.98-13.3, p = 0.054). No RT dose thresholds to external genitals or penile bulb were identified that increased risks of ED, EjD, or TD. RT for LARC independently increases risk of ED but not EjD or TD. IMRT might increase the risk of ED due to increased scatter dose to the genitals and including the inguinal nodes in the target volumes increases the dose to the genitals/testicles, which could translate into a higher risk for ED and TD. Future research on proton RT and prophylactic sildenafil is needed in men ≤50 to decrease the risk of ED.