Long-Term Androgen Suppression Slows Progression in Locally Advanced Prostate Cancer

PHILADELPHIA—Significant benefit can be achieved from long-term androgen suppression following neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced prostate cancer.

This finding from a phase III RTOG study was reported at ASCO by Gerald Hanks, MD, of Fox Chase Cancer Center.

According to Dr. Hanks, local progression, biochemical progression, deaths due to prostate cancer, and 5-year survival were all significantly improved in patients who received 24 months of goserelin (Zoladex) after initial goserelin, flutamide (Eulexin), and radiation therapy, compared to patients who did not receive the long-term goserelin.

“This was a study of long-term total androgen suppression following neoadjuvant hormonal cytoreduction,” Dr. Hanks explained. Arm 1 was goserelin and flutamide for 2 months before and roughly 2 months during radiation therapy. Arm 2 was goserelin and flutamide for 2 months before and 2 months during radiation therapy, then goserelin alone for 24 months.

Designated RTOG Protocol 92-02, this study was a prospective randomized trial of androgen suppression and external beam radiation in patients with locally advanced prostate cancer (T2C-T4) with PSA less than 150 ng/mL.

“This was a remarkable study,” Dr. Hanks said. “It opened in June of 1992 and closed less than 3 years later, in April of 1995, with a total accrual of 1,557 patients.” Median follow-up was 4.9 years.

Survival Advantages

Local progression was 12% in short-term vs 6% in long-term androgen suppression. Biochemical progression by 5 years was 47% vs 22%. Deaths due to prostate cancer at 5 years were 7.2% vs 4.3%.

Although there is no difference yet in overall survival, “with every cancer progression indicator including rate of metastasis and cause-specific death being different, overall survival will change with more time,” Hanks predicted.

Subset analysis showed a long-term survival advantage with long-term androgen suppression in patients with Gleason 8–10 tumors. The difference was 69% vs 80% at 5 years (P = .01).

There was a significant increase in RTOG grade 3-4 bowel complications in the long-term androgen suppression group, 42 vs 26.

“This study supports the continued use and study of long-term androgen deprivation in patients with poorly differentiated or locally advanced prostate cancers,” Dr. Hanks commented.

He said that long-term androgen deprivation is superior to short-term in patients with locally advanced prostate cancer. “It is particularly important in patients with Gleason 8–10 tumors,” he said. “All of these patients should have an opportunity to be treated with this combined modality.”

This treatment now becomes the standard against which innovative treatments for this locally advanced disease should be compared in randomized trials, he concluded.