Dose to penile bulb is not associated with erectile dysfunction 18 months post radiotherapy: A secondary analysis of a randomized trial

BACKGROUND: Erectile dysfunction is a common side effect of prostate cancer (PC) therapy. In this randomized study (The RIC-study) we used patient reported outcomes to evaluate sexual function 18 months after combined endocrine therapy and radical radiotherapy (RT) given with either wide or tight planning target volume (PTV) margins. We also analyzed the impact of radiation dose to penile bulb on sexual function. METHODS: The RIC-study included 257 men with intermediate and high-risk PC. All patients received 6 months of total androgen blockage started 3 months prior to randomization. In high-risk patients, an oral anti-androgen (Bicalutamide) was administered for an additional 2.5 years. Patients were randomized to receive 78 Gy in 39 fractions guided either by weekly offline orthogonal portal imaging or by daily online cone beam computed tomography image-guided RT. Sexual function was evaluated at 18 months after start of RT using the Questionnaire Umeå Fransson Widmark 1994. Ability to have an erection was assessed on an 11-point scale numerical rating scale (0 = no and 10 = very much) as the primary outcome. In addition, the association between penile bulb (PB) radiation dose and erectile function was analyzed. FINDINGS: Of 250 evaluable patients, 228 (mean age 71.8 years) returned the questionnaires. The patients reported a high degree of sexual related problems with mean scores to the primary outcome question (221 respondents) of 7.44 and 7.39 in the 2D weekly IGRT-arm and 3D daily IGRT-arm (p = 0.93) respectively. For four additional questions (scale 0–10) regarding sexual function resulted in mean scores >6.5 with no difference between study arms. The mean dose to PB was substantially larger in the 2D weekly IGRT-arm vs the 3D daily IGRT-arm (mean 59.8 Gy vs mean 35.1 Gy). We found no effect of mean PB-dose on the primary outcome adjusted for study-site, risk-group and age. When adjusting for serum-testosterone level at 18 months in addition, the effect of mean PB-dose remained insignificant. INTERPRETATION: IGRT protocol or PB dose had no effect on ED 18 months after RT in this study population. The low potency rates can partly be explained by the prolonged use of anti-androgen in high risk patients. Longer follow-up is needed to confirm the results from the RIC-study.