Methods and Materials: A total of 225 patients were entered in this cooperative group, Phase I-II dose-escalation trial of three-dimensional conformal radiotherapy for localized carcinoma of the prostate treated to a dose of 78 Gy (Level V). Of these patients, 219 were analyzed for acute and 218 for late toxicity. A minimum of 2 Gy/fraction was prescribed to the planning target volume (PTV). Patients were stratified according to the risk of seminal vesicle invasion as determined by Gleason score and presenting prostate-specific antigen level. Group 1 patients had clinical Stages T1-T2 tumors with a seminal vesicle invasion risk of <15%. Group 2 patients had clinical Stages T1-T2 tumors with a seminal vesicle invasion risk of ≥15%. Patients in Group 1 were prescribed 78 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 78 Gy. PTV margins of between 5 and 10 mm were required. The average time at risk for late Grade 3+ toxicity after therapy completion was 23.2 and 23.1 months for Groups 1 and 2, respectively. The frequency of Grade 3 or worse late effects was compared with a similar group of patients treated in Radiation Therapy Oncology Group (RTOG) studies 7506 and 7706, with length of follow-up adjustments made for the interval from therapy completion. A second comparison was made with 170 patients treated to dose Level III (79.2 Gy in 1.8 Gy/fraction) to see whether the fraction size affected toxicity. Unlike other dose levels, patients treated at dose Level III had treatment prescribed as a minimum to the gross tumor volume. This effectively lowered the volume of the rectum treated to the study dose.
Results: Acute toxicity at dose Level V (78 Gy) was remarkably low, with Grade 3 acute effects reported in only 4%of Group 1 and 2%of Group 2 patients. No Grade 4 or 5 acute toxicity was reported. There was no statistically significant difference in rates of acute toxicities in patients who were treated to 79.2 Gy at 1.8 Gy/fraction or 78 Gy at 2.0 Gy/fraction. Late toxicity continues to be low compared with RTOG historical controls. The observed rate of Grade 3 or worse late effects for Group 1 (6 cases) was significantly lower (p = 0.0042) than the 18.2 cases that would have been expected from the historical control. The observed rate for Group 2 (8 cases) was lower than the 15.5 cases expected, but this difference was not statistically significant (p = 0.06). A trend was noted that Group 2 patients treated on dose Level V had more late Grade 3 or worse toxicity than patients treated to a similar dose on Level III (7%vs. 1%, p = 0.06). A significantly (p < 0.0001) greater incidence of late Grade 2 or greater toxicity occurred in patients treated at dose Level V (30%and 33%for Groups 1 and 2, respectively) than at dose Level III (13%and 9%for Groups 1 and 2, respectively). The longer follow-up at dose Level III suggests these differences may increase with additional follow-up.
Conclusion: Tolerance to three-dimensional conformal radiotherapy with 78 Gy in 2-Gy fractions remains better than expected compared with historical controls. The magnitude of any effect from fraction size and treatment volume requires additional follow-up.