185 - Hypofractionated, Dose-Escalated Radiation vs. Conventionally Fractionated Radiation for Localized Prostate Cancer: Long-Term Update of a Phase 3, Prospective, Randomized Controlled Trial

C. J. Hassanzadeh¹, D. A. Kuban¹, S. Pasyar², R. Bassett Jr.³, P. Troncoso³, M. A. Ansari¹, P. J. Schlembach¹, S. E. McGuire⁴, Q. N. Nguyen¹, S. J. Frank², H. Mok¹, O. Mohamad¹, R. J. H. Park³, S. J. Shah¹, L. L. Mayo⁵, C. Tang⁴, W. Du⁶, R. Kudchadker¹, S. Choi⁴, and K. E. Hoffman²; ¹Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ²The University of Texas MD Anderson Cancer Center, Houston, TX, ³MD Anderson Cancer Center, Houston, TX, ⁴Department of Genitourinary Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁵Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁶Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX

Purpose/Objective(s): The initial report of a prospective phase 3 randomized trial of dose-escalated, moderately hypofractionated versus conventionally fractionated radiation therapy for localized prostate cancer demonstrated superior cancer control with hypofractionated radiation. We analyzed the long-term outcomes to determine if this benefit was maintained given limited long-term data. Materials/

Methods: Between January 2001 to January 2010, men with localized prostate cancer were randomized to 75.6Gy in 1.8-Gy fractions delivered over 8.4 weeks (CIMRT) or 72Gy in 2.4-Gy fractions delivered over 6 weeks (HIMRT) using intensity modulated radiotherapy (IMRT) (IRB approved protocol ID00-381). Men were stratified at randomization by receipt of ADT and PSA = 10 ng/mL. Modified RTOG criteria were used to grade late gastrointestinal (GI) and genitourinary (GU) toxicity. Primary outcome was failure defined as PSA failure (nadir + 2 ng/mL) or initiation of salvage therapy. Time to failure was calculated from the start of radiation while time to toxicity was measured from the end of radiation. Kaplan-Meier curves were generated to estimate rates of failure, survival, and toxicity. The log-rank test was used to compare the treatment arms. Characteristics were compared using Chi-square or Fisher’s exact test. Statistical analyses were performed using a data management and decision management software.
Results: 206 patients with mostly NCCN intermediate risk (71%), Gleason grade group 2 (48%), and PSA = 10 ng/mL (90%) prostate cancer were enrolled and randomized. 102 patients received CIMRT and 104 received HIMRT. Androgen deprivation therapy was administered to 24%. Median follow-up was 11 years. Patient and cancer characteristics were well balanced between treatment groups. Treatment failure occurred less frequently in men undergoing HIMRT (n=13) compared to CIMRT (n=22) but did not meet statistical significance (P= 0.077). 10-year failure rate was 21% (95% CI, 13-30.5%) for CIMRT versus 11% (95% CI, 5.5-18.1%) for HIMRT. In the subgroup of men not receiving ADT, the 10-year failure rate was significantly less for HIMRT (13%) versus CIMRT (26%) (P=0.039). Overall survival (OS) was similar between CIMRT and HIMRT (median OS, 20 years vs not reached) (P=0.076). Also, 15-year distant metastasis rate (DM) was similar between CIMRT (4%) and HIMRT (8%) (P=0.22). 10-year cumulative late GU grade = 2 toxicity was similar for HIMRT (26%) versus CIMRT (23%) (P=0.54). The incidence of 10-year late GI grade = 2 toxicity was similar between CIMRT (5%) and HIMRT (13%) (P=0.08). No grade 4 toxicities were observed.
Conclusion: Long-term outcomes suggest a benefit in terms of treatment failure to dose-escalated, hypofractionated radiation, especially among patients not receiving ADT, without worse late toxicity.