The Response of Male Erectile Tissues to Androgen Deprivation Therapy and Radiation

Abstract

Androgen deprivation therapy (ADT) plays an important role in the treatment of men undergoing radiation therapy (RT) for high-risk prostate cancer. Erectile dysfunction (ED) is a common side effect after combined RT and ADT. Both RT and ADT may have cardiovascular effects, thus we hypothesized that penile vascular tissue contracts in response to ADT and RT, and that this change correlates with worsening ED. Penile bulb (PB) volume and corpus cavernosum (CC) width were measured retrospectively on computed tomography (CT) scans obtained pre and post-neoadjuvant ADT (but prior to RT) in a cohort of prostate cancer patients treated with prostate RT+ADT. The same measurements were also obtained from a cohort of male cancer patients treated with RT alone using two CT image sets obtained with similar chronologic spacing. PB volume was measured based on RTOG contouring guidelines. CC width was measured at the position of the anterior border of the inferior pubic ramus. To confirm these findings with a separate image modality and to allow analysis of post-RT changes, we evaluated penile tissue changes with pre-treatment, post-neoadjuvant ADT, and post-RT Magnetic Resonance Imaging (MRI) in prostate cancer patients treated with RT+ADT. Sexual Health Inventory for Men (SHIM) scores were obtained pre-treatment and at least 18 months (range 18-30 months) after discontinuing ADT. Worsening ED was defined as an escalation in SHIM severity classification or initiation of medication for ED. Two-tailed paired t-tests were used to compare differences between cohorts and time points. In the prostate cancer RT+ADT cohort (n=41), both the PB (-3.28 cm3, 95%CI: -4.097 to -2.469; p<0.0001) and the CC (-0.12 cm, 95%CI: -0.1554 to -0.0909; p<0.0001) underwent significant reductions in size in response to neoadjuvant ADT. In the cohort not exposed to ADT (n=20), there was no significant change in PB (+1.38 cm3, 95%CI: -0.9424 to 3.709; p=0.2283) and CC (+0.04 cm, 95%CI: -0.0669 to 0.1510; p=0.4298). Findings from the MRI cohort (n=25) with imaging at three time points confirmed a significant PB reduction after neoadjuvant ADT (-104.4 mm2, 95% CI -137.6 to-71.22, p<0.0001), but not after subsequent treatment with RT (-18.34 mm2. 95% CI -49.81 to 13.13, p=0.2407). In the subset of RT+ADT patients with available SHIM data at late follow up (n=17), there was a nonsignificant trend toward worsening of ED with greater reductions in the percent volume of the PB (p=0.4346) and the percent width of the CC (p=0.112) with neoadjuvant ADT. This retrospective series demonstrates a significant reduction in the volume of erectile tissue with short-term neoadjuvant ADT, and no significant change with the addition of RT. Additional work is needed to determine if these changes persist at later time points or correlate to late ED in larger cohorts.