RTOG 94-06: Is the addition of neoadjuvant hormonal therapy to dose-escalated 3D conformal radiation therapy for prostate cancer associated with treatment toxicity?

Purpose: This study determines the effect on toxicity of adding neoadjuvant hormonal therapy (NHT) to three-dimensional conformal radiation therapy (3D-CRT) in RTOG 94-06. Methods: Between August 1994 and February 2000, 583 eligible prostate cancer patients enrolled on the first 3 dose levels of RTOG 94-06, a Phase I/II dose escalation 3D-CRT trial. Two hundred and seven men initiated hormonal therapy (HT) between 2 to 3 months before 3D-CRT, and completed all HT no longer than 3 months after radiotherapy. Thirty-three patients receiving longer-duration HT were excluded. The 547 patients were treated at dose level 1 (68.4 Gy), level 11 (73.8 Gy), or level 111 (79.2 Gy). All dose prescriptions were to the minimum isodose surface encompassing the planning target volume (dose levels I and 11) or the clinical target volume (dose level III). Men were stratified into three risk groups according to their relative risk of seminal vesicle invasion: < 15% (Group 1) vs. > 15% (Group 2), or to T stage (T1, 2 vs. T3 tumors [Group 3]). In Group 2 patients, there was a clinical target volume reduction to treat only the prostate after delivery of 55.8 Gy to a planning target volume including the seminal vesicles. All HT consisted of a luteinizing hormone-releasing hormone agonist with or without a nonsteroidal anti-androgen. Results: On univariate analysis, NHT significantly increased the likelihood of Grade 2 acute genitourinary (GU) complications (22% to 32%, p = 0.009). Hormonal therapy did not have a significant univariate effect on any other acute or late toxicity. On multivariate analysis, the percent of the bladder (less than or equal to30% vs. >30%) receiving greater than or equal to the reference dose (68.4 Gy, 73.8 Gy, or 79.2 Gy) (p = 0.0009, relative risk = 2.07, confidence interval: 1.88-2.28) was a significant predictor of acute GU effects. Although NHT was not significant in itself, in the multivariate analysis its interaction with baseline urinary status was an important factor (p = 0.011, relative risk = 4.31, confidence interval: 1.68-5.29). Conclusion: Neoadjuvant HT did not show an independent effect on the risk of side effects after 3D-CRT in patients treated on RTOG 94-06. However, this combined modality therapy significantly increased the risk of acute GU effects compared to 3D-CRT alone in men with poor baseline urinary function. (C) 2003 Elsevier Inc.