Phase III Randomized Study of Adjuvant Radiation Therapy versus Observation in Patients with Pathologic T3 Prostate Cancer (SWOG 8794)

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 17, 2005

Presenter: G. P. Swanson
Presenter's Affiliation: UT San Antonio
Type of Session: Plenary

Background

Prostate cancer patients with adverse findings at surgery have an increased risk of local failure. Although radiation in the post-prostatectomy setting has been shown to improve local control, its long-term benefit is unclear. The Southwest Oncology Group initiated a randomized study comparing immediate radiation versus observation following surgery in those patients with pathologic T3 disease.

Materials and Methods

473 patients prospectively randomized between 6/15/88 and 1/1/97 to immediate radiation versus observation following prostatectomy
Eligibility and stratification of patients based on presence of pathologically proven extracapsular extension, positive surgical margins, and/or seminal vesicle invasion
Patients followed with PSA measurements until death, and biochemical failure was defined as PSA >0.4 ng/ml
Radiation consisted of 60 to 64 Gy in 200 cGy fractions
Primary endpoint was metastasis-free survival (MFS)

Results

410 patients eligible for follow-up
Median follow-up of 9.7 years for all patients
68% of patients with extracapsular extension +/- positive margins, 12% with seminal vesicle invasion, and 20% with both
Approximately half of patients with detectable PSA following surgery and half with no detectable PSA following surgery
Biochemical disease-free survival (bDFS) was significantly improved with radiation, and metastatic-free and overall survival were non-significantly improved

	5Y bDFS	10Y bDFS	5Y MFS	10Y MFS	5Y OS	10Y OS
XRT	61%	47%	87%	83%	91%	74%
OBS	38%	23%	71%	61%	89%	63%

median OS of 14.7 versus 13.8 years (p=NS) favoring radiation group
radiation benefits observed in all pathologic risk groups
in patients with seminal vesicle involvement, 5Y bDFS was 57% with radiation (n=22) versus 22% with observation (n=21)
32% of patients in the observation group eventually received radiation treatment
84 patients (39%) in the radiation group received hormone therapy at a median of 12.4 years, while 106 patients (50%) in the observation group received hormone therapy at a median of 9.9 years
GI and GU toxicity worse in the radiation group during radiotherapy, though no significant difference in quality of life measures between the radiation and observation groups at 2 years from randomization

Author's Conclusions

Adjuvant radiation significantly improved 5 and 10Y bDFS and non-significantly improved 5 and 10Y MFS and OS
Radiation decreased the need for androgen ablation and delayed the use by 2.5 years in those patients who did require ablation
Long-term quality of life not adversely impacted by adjuvant radiotherapy
Patients with adverse findings at prostatectomy should be given option to receive immediate radiation treatment

Clinical/Scientific Implications

This study provides level I evidence of the benefit of immediate radiation following prostatectomy in those patients with adverse pathologic features. Radiation was found to significantly improve biochemical survival at both 5 and 10 years, and eliminated or delayed the need for androgen ablation. These findings have been confirmed by an identical EORTC study (protocol 22911) which yielded similar progression-free survival curves. Although some investigators have argued for delayed radiation at time of recurrence in this population, no prospective randomized evidence exists supporting this position. Due to the superior results of the radiation arm and the abatement by 2 years of adverse toxicity related to hormone use, post-prostatectomy radiation should be considered standard of care in patients with adverse pathologic features.