A Phase III Trial of the Use of Long Term Androgen Suppression Following Neoadjuvant Hormonal Cytoreduction and Radiotherapy in Locally Advanced Carcinoma of the Prostate.

Jason Lee, MD
OncoLink Assistant Editor
Last Modified: May 22, 2000

Presenter: Gerald E. Hanks
Affiliation: Fox Chase Cancer Center


  • Radiation therapy is a long-standing treatment option for prostate cancer

  • Previous studies by the RTOG and the EORTC have demonstrated improved disease-specific survival using the combination of adjuvant hormone therapy and radiation therapy

  • The duration of hormone therapy has varied in these previous studies

  • The optimal duration of hormone therapy with definitive radiation therapy was studied in this trial.

Materials and Methods:

  • The RTOG conducted a phase III randomized trial of short-term hormone therapy with radiation therapy versus long-term hormone therapy alone in localized but poor-prognosis patients with adenocarcinoma of the prostate

  • Eligibility criteria included patients with T2c- T4 disease, PSA <150, and KPS >=70

  • Patients were treated with definitive external beam radiation therapy; quality assurance was performed on treatment fields

  • All patients received two months of Zoladex and Flutamide before radiation therapy and during the two months of radiation therapy

  • The experimental arm received two additional years of Zoladex and Flutamide

  • Patients were assessed for PSA response, disease-specific survival, overall survival and toxicity


  • Median followup for 1554 enrolled patients was 4.9 years

  • For the entire cohort, the experimental arm with long-term hormone therapy experienced improved disease-specific survival (54% compared with 34%)

  • Biochemical control measured by a rising PSA was also improved with long-term hormone therapy (79% compared with 54%)

  • Overall survival for the entire cohort, however, was similar in the two arms (78% compared with 79%)

  • Grade 3 and 4 bowel toxicity was slightly higher in the long-term hormone therapy arm (8% compared with 5%)

  • 8% of patients in the long-term hormone therapy arm did not complete treatment due to toxicity compared with 1% of patients in the short-term hormone therapy arm

  • In the subgroup with Gleason 8-10 disease, the use of long-term hormone therapy resulted in improved survival (80% vs. 69% at 5 years)

  • In the subgroup with less advanced disease comparable to patients enrolled in a trial by Bolla et al (NEJM 1998), there was no survival difference
Authors' Conclusions

  • Patients with nonmetastatic prostate cancer and Gleason score 8-10 should be considered for long- term hormone therapy before, during, and after radiation therapy

  • Patients with nonmetastatic but locally advanced prostate cancer and lower Gleason scores still experience better biochemical control and better disease-specific survival with long-term hormone therapy
Clinical/Scientific Implications:
    Long-term hormone therapy appears to be beneficial for patients with higher grade disease