Preliminary evaluation of low-grade toxicity with conformal radiation therapy for prostate cancer on RTOG 9406 dose levels I and II

Purpose: To evaluate the rates of low-grade late effects in patients treated for prostate cancer on Radiation Therapy Oncology Group (RTOG) 9406. Methods and Materials: Between August 1994 and September 1999, 424 patients were entered on this dose escalation trial of three-dimensional conformal radiation therapy (3D-CRT) for localized adenocarcinoma of the prostate at doses of 68.4 Gy (level I) and 73.8 Gy (level II). We have previously reported Grade 3 or greater late toxicity of patients treated on the first two dose levels of this trial. This analysis examines the distribution of all late toxicities in these patients. All radiation prescriptions were a minimum dose to a planning target volume (PTV). Patients were stratified according to clinical stage and risk of seminal vesicle invasion (SVI) based upon Gleason score and presenting prostate-specific antigen. Group 1 includes patients with T1,2 disease with SVI risk < 15%, and Group 2 includes patients with T1,2 disease with SVI risk > 15%. Group 3 patients had T3 disease. Average months at risk after completion of therapy ranged from 21.4 to 40.1 months for patients treated at dose level I and 10.0 to 34.2 months for patients at dose level II. The frequency of all grades of late effects was compared with a similar group of patients treated in RTOG studies 7506 and 7706 with adjustments made for the interval from completion of therapy. The RTOG toxicity scoring scales for late effects were used for grading. Results: The rate of Grade 3 or greater late toxicity continues to be low compared with RTOG historical controls. No Grade 4 or 5 late sequelae were reported in any of the 393 evaluable patients during the period of observation. The frequency of patients free of any complications was lower in RTOG 9406 than in historical controls. In the 73 Group 1 patients treated on dose level 1, there were 24 patients without sequelae compared with an expected rate of 39.7 (p = 0.013), and in 80 Group 3 patients at dose level II there were 24 patients without sequelae when 56.2 were expected (p < 0.0001). Other groups treated at these dose levels demonstrated a nonsignificant reduction in the rate of patients free of any side effects. These data suggest that the reduction in high-grade morbidity may be related to a shift of complications to lower grades. Conclusion: Morbidity of 3D-CRT in the treatment of prostate cancer is low. It is important to continue to closely examine late effects in patients treated in RTOG 9406. The primary objective of dose escalation without an increase rate of ≥ Grade 3 sequelae has been achieved. However, the reduction in Grade 3 complications may have resulted in a higher incidence of Grade 1 or 2 late effects. Because Grade 2 late effects may have a significant impact on a patient's quality of life, it is important to reduce these complications as much as possible. Clinical trials should use quality-of-life measures to determine that trade-offs between severity and rates of toxicity are acceptable to patients.