Serum Testosterone Changes In Patients Treated With Radiation Therapy Alone For Prostate Cancer On Rtog 9408

In light of studies suggesting that radiation therapy (XRT) may influence serum testosterone (ST) levels for patients treated for localized prostate cancer, we reviewed data on testosterone changes for patients treated with XRT alone on RTOG 9408. Patients enrolled on RTOG 9408 (T1b-T2b, PSA < 20 ng/mL) were randomized between XRT alone and XRT plus 4 months of total androgen ablation. XRT consisted of either whole pelvic radiation therapy to 46.8 Gy plus a 19.8 Gy prostate boost for a total dose of 66.6 Gy (WPRT) or treatment to the prostate alone for a total dose of 68.4 Gy (PORT). Most patients received WPRT. Only patients with the lowest risk features (PSA < 10 ng/mL and Gleason score ≤5 or a negative lymph node dissection) were assigned to receive PORT. XRT was delivered at 1.8 Gy per fraction. For this analysis, ST levels were investigated at the following collection periods: at study enrollment; completion of XRT; and at first follow-up 3 months after completion of XRT. The Wilcoxon signed rank test was used to compare change in pre and post treatment ST levels in patients who were randomized to the XRT alone arm. Two thousand twenty-eight patients were enrolled on RTOG 9408. Nine hundred ninety-two were randomized to receive XRT alone. Nine hundred four (91%) of these patients had baseline ST values available and completed XRT. Of these 904, immediate and 3 month post XRT testosterone levels were available for 768 and 553 respectively. Excluding 10 patients who received hormonal therapy off protocol, 766 and 543 respectively, were analyzed. Pre-treatment median testosterone level for all patients was 370 ng/dL (P5-P95 = 167 to 926) which did not differ significantly between the WPRT and PORT groups. For the entire group, at completion of XRT (median = -26 ng/dL, P5-P95 = -310 to 360; p < 0.01) and at the 3 month follow-up (median = -33 ng/dL, P5-P95 = -300 to 238; p < 0.01), median change in ST showed a statistically significant trend, indicating a decrease in ST level from baseline. For evaluable patients treated with WPRT (679 at end of XRT and 476 at 3-month follow-up), median change in ST is -29 ng/dL (P5-P95 = -365 to 452; p < 0.01) and -33 ng/dL (P5-P95 = -313 to 245; p < 0.01), respectively. Patients treated with PORT (87 at end of XRT and 67 at 3-month follow-up), median change in ST is -12 ng/dL (P5-P95 = -202 to 101; p = 0.01) and -37 ng/dL (P5-P95 = -240 to 110; p < 0.01), respectively. XRT for prostate cancer, as delivered on RTOG 9408, was associated with statistically significant change in ST, indicating a decline. This may be secondary to scatter radiation to the Leydig cells. We have no evidence that these changes in ST have any direct impact on PSA control rates or on post treatment quality of life.