10 Year Follow-Up of RTOG 92-02: A Phase III Trial of the Duration of Elective Androgen Deprivation in Locally Advanced Prostate Cancer

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 10, 2006

Presenter: G. Hanks
Presenter's Affiliation: Fox Chase Cancer Center
Type of Session: Scientific

Background

Multiple large randomized trials have demonstrated a clinical benefit with the addition of androgen deprivation to external beam radiotherapy for treatment of locally advanced prostate cancer
This report represents long-term follow-up of RTOG 92-02, which evaluated different durations of hormone withdrawal in prostate cancer patients treated with external beam radiotherapy

Materials and Methods

Patients with cT2c-4 prostate cancer with no extrapelvic nodal involvement, KPS >70, and PSA values <150 ng/mL were randomized to 4 months vs. 28 months of hormone treatment along with external beam radiotherapy
All patients received approximately 4 months of total androgen suppression via flutamide and goserelin, and the 28 month group received an additional 2 years of goserelin therapy
Radiation treatment consisted of 45 Gy delivered to the whole pelvis, followed by a boost to the prostate for a total dose of 65-70 Gy

Results

1,554 patients were enrolled into the study
The median follow-up duration was 9 years for all patients, and >11 years for surviving patients
The 10-year biochemical failure rate was found to be significantly decreased in the 28 month arm vs. the 4 month arm (32% vs. 48%, p<0.0001)
The 10-year distant metastasis (DM) rate was found to be significantly decreased in the 28 month arm vs. the 4 month arm (15% vs. 23%, p<0.0001)
The 10-year disease-specific survival (DSS) was found to be significantly increased in the 28 month arm vs. the 4 month arm (88% vs. 84%, p=0.0042)
The 10-year disease-free survival (DFS) was found to be significantly increased in the 28 month arm vs. the 4 month arm (22% vs. 13%, p<0.0001)
There was no difference between the 2 arms with respect to 10-year overall survival (OS)
for the Gleason score (GS) 8-10 subgroup:
- There was a significant decrease in the 10-year DM rate in the 28 month arm vs. the 4 month arm (26% vs. 40%, p=0.0019)
- There was a significant increase in the 10-year DSS rate in the 28 month arm vs. the 4 month arm (80% vs. 66%, p=0.0072)
- There was a significant increase in the 10-year OS rate in the 28 month arm vs. the 4 month arm (45% vs. 32%, p=0.0061)
There was a significant increase in both grade 3 GI toxicity (2% vs. 1%, p=0.0231) and grade 4 GI toxicity (3% vs. 1%, p=0.0037) in the 28 month arm vs. the 4 month arm

Author's Conclusions

The long-term androgen ablation arm proved superior to the short-term androgen ablation arm in all endpoints studied, with the exception of OS
When considering only the subgroup of patients with higher risk disease (GS 8-10), all endpoints were found to be improved in the long-term androgen ablation arm, including OS
Serious GI toxicity was found to be significantly increased in the long-term androgen ablation arm
The consistency of results between the 5- and 10-year follow-up periods confirms the value of 5-year analyses of RTOG phase III prostate cancer trials

Clinical/Scientific Implications

The updated results of this trial support long-term androgen ablation and radiation as the standard of care in higher risk prostate cancer patients. It is an overstatement, however, to say that the consistency of the results throughout the 5- and 10-year follow-up periods is evidence that 5 years of follow-up is adequate time for a phase III trial. As in breast cancer, late relapses of prostate cancer are certainly not uncommon, and follow-up periods of at least 10 years should be considered necessary before drawing definitive conclusions from any given prospective prostate cancer study.