Toxicity after three-dimensional radiotherapy for prostate cancer with RTOG 9406 dose level IV.

PURPOSE This is the first report of the toxicity outcomes using dose level IV (74 Gy) on Radiation Therapy Oncology Group (RTOG) study 9406 for Stage T1-T2 prostate adenocarcinoma. METHODS AND MATERIALS A total of 262 patients were entered in this cooperative group, Phase I-II, dose-escalation trial of three-dimensional conformal radiotherapy for localized prostate carcinoma treated to a dose of 74 Gy (Level IV); 256 patients were analyzable for toxicity. A minimal dose of 2 Gy/fraction was prescribed to the planning target volume (PTV). Patients were stratified according to the risk of seminal vesicle invasion on the basis of the Gleason score and presenting prostate-specific antigen level. Group 1 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of <15%. Group 2 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk of >/=15%. Patients in Group 1 were prescribed 74 Gy to a prostate PTV. Patients in Group 2 were prescribed 54 Gy to the prostate and seminal vesicles (PTV1) followed by a boost to the prostate only (PTV2) to 74 Gy. PTV margins between 5 and 10 mm were required. Elective pelvic radiotherapy was not used. The frequency of late effects of Grade 3 or greater was compared with that for a similar group of patients treated in RTOG studies 7506 and 7706, with length of follow-up adjustments made for the interval from therapy completion. A second comparison was made with 206 patients treated to dose level II (73.8 Gy in 1.8-Gy fractions) to see whether the fraction size affected toxicity. RESULTS The average months at risk for late Grade 3+ toxicity after therapy completion were 28.9 and 23.9 months for Group 1 and 2, respectively. Acute toxicity at dose level IV (74 Gy) was remarkably low, with Grade 3 acute effects reported in only 1% of Group 1 and 3% of Group 2 patients. No Grade 4 or 5 acute toxicities were reported. Late toxicity continued to be low compared with RTOG historical controls. One patient in Group 1 and 4 patients in Group 2 experienced Grade 3 bladder toxicity. Two patients in Group 2 experienced Grade 3 bowel toxicity. No Grade 4 or 5 late effects were reported. The rate of late Grade 2 toxicity (any type) was 23% and 16% in Group 1 and 2, respectively. The observed rate of Grade 3 or greater late effects for Group 1 (1 case) was significantly lower (p <0.0001) than the 18.5 cases that would have been expected from the historical control data. The observed rate for Group 2 (6 cases) was also significantly lower (p = 0.0009) than the 21.3 cases expected. No statistically significant difference was noted in the rate of acute or late toxicity in patients who were treated to 73.8 Gy at 1.8 Gy/fraction or 74 Gy at 2.0 Gy/fraction. Patients treated with the larger 2.0-Gy fractions tended to have more Grade 3 or greater toxicity than patients treated with 1.8-Gy fractions (2% vs. 1%, p = 0.09). The results after the longer follow-up with dose level II suggest these differences may increase with additional follow-up. CONCLUSION Tolerance to three-dimensional conformal radiotherapy with 74 Gy in 2-Gy fractions remains better than expected compared with historical controls. The magnitude of any effect from fraction size requires additional follow-up.