Update of Toxicity Following 3D Radiation Therapy for Prostate Cancer on RTOG 9406

Todd Doyle, MD
OncoLink Assistant Editor
Last Modified: October 25, 2000

Presenter: J.M. Michalski
Affiliation: Radiation Therapy Oncology Group


Randomized data have been reported that show improvements in biochemical outcomes for high risk prostate cancer patients treated with 3D conformal dose escalation. However, the therapeutic window has yet to be defined regarding the perceived benefits of conformal treatment with dose escalation versus the potential risk of increased late morbidity. This prospective, dose escalation trial (RTOG 9406) was initiated to test the feasibility of dose escalation and define the MTD as well as the rate of long term morbidities.

Materials and Methods:

  • -Four hundred and twenty four patients with prostate cancer have been entered at the first two dose levels and are the subject of this presentation.

  • The dose levels are as follows: I. 68.4 Gy, II. 73.8 Gy, III. 79.2 Gy.

  • All doses are prescribed to the minimum isodose line covering the PTV.

  • Patients were stratified prior to entry on the study by clinical stage and risk of seminal vesical invasion as determined by PSA and biopsy gleason score.

  • Group 1 consisted of patients with T1/2 tumors with SVI risk less than 15%.

  • Group 2 consisted of patients with T1/2 tumors with SVI risk greater than or equal to 15%.

  • Group 3 patients had clinical stage T3 tumors.

  • The average months at risk after completion of radiation ranged from 33-37 for patients at dose level 1 and 19-29 for patients at dose level 2.

  • The frequency of greater than or equal to grade 3 late effects was compared to a similar group of patients treated on RTOG 7506 and 7706.


  • Greater than or equal to grade 3 acute toxicity is very low for all patients: less than 1% for group 1, less than 3% for group 2, and less than 10% for group 3 patients.

  • The highest incidence of acute toxicity was in the group 3 patients treated to 73.8 Gy: 7% grade 3 and 3% grade 4 acute toxicities.

  • Late toxicity is low compared to historical controls: 2 patients have demonstrated late grade 3 GU toxicity. No patients have been reported with greater than or equal to grade 3 late rectal complications.

  • Late grade 2 toxicity ranged from 16-21% for group 1 and 2 patients to 25-31% for group 3 patients.

  • All acute and late complications were significantly less than predicted by comparable patients from previous RTOG studies.

Authors' Conclusions

  • Tolerance to 3D conformal radiation therapy in RTOG 9406 remains better than expected despite dose escalation.

  • Patients in group 3 (clinical T3) have low rates of grade 3 or 4 acute and late toxicities similar to patients in groups 1 and 2.

  • Grade 2 acute and late complications appear to be higher in group 3 patiens than in group 1 and 2 patients.

  • Dose-volume analysis of the bladder and rectum to predict the risk of grade 3 or 4 acute and late toxicity is planned.

Clinical/Scientific Implications:

  • This analysis confirms the feasibility and safety at 2 to 3 years followup of modest dose escalation with 3D conformal radiation therapy for both early stage and locally advanced prostate cancer.

  • Rigorous quality assurance and experience are desirable in attempting to duplicate these low rates of complication with 3D dose escalation.

  • Further followup and reports of the third level of dose escalation (79.2 Gy) are awaited.