Androgen Deprivation May Improve Outcomes in Locally Advanced Prostate Cancer

Laurie Barclay, MD
January 2, 2008 — The addition of 4 months of androgen deprivation therapy (ADT) to external beam radiotherapy (EBRT) seems to have a dramatic impact on clinically meaningful endpoints in men with locally advanced prostate cancer without significantly increasing the risk for fatal cardiac events, according to the results of the Radiation Therapy Oncology Group (RTOG) 8610 study reported in the January 2 Early Release issue and will appear in the February 1 print issue of the Journal of Clinical Oncology.
"RTOG 8610 was the first major, phase III randomized trial to test the hypothesis that short-term neoadjuvant ADT combined with EBRT would improve treatment outcomes compared with EBRT alone," write Mack Roach III, MD, from the University of California San Francisco, and colleagues. "With relatively short follow-up, the addition of ADT was associated with an improvement in local control, a reduction in distant metastases, and cause-specific mortality. Herein, we update the long-term results of RTOG 8610 and confirm the important clinical benefits of adding short-term ADT to EBRT in patients with high-risk, locally advanced disease."
RTOG 8610 enrolled 456 assessable patients between 1987 and 1991. Median age was 70 years. Inclusion criteria, based on the 1988 American Joint Committee on Cancer Tumor, Node, Metastasis (TNM) staging system, were bulky (5 x 5 cm) tumors, stage T2-4, with or without pelvic lymph node involvement.
Patients were randomized to receive EBRT alone or with combined ADT, which consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg 3 times daily for 2 months before and during EBRT. The main outcome measures were overall survival, disease-specific mortality, distant metastases, disease-free survival, and biochemical failure.
At 10 years, estimates of overall survival (43% vs 34%) and median survival (8.7 vs 7.3 years) favored the combination of ADT plus EBRT vs EBRT alone. However, these differences were not statistically significant (P = .12). With the addition of ADT, improvements were observed in 10-year disease-specific mortality (23% vs 36%; P = .01), distant metastases (35% vs 47%; P = .006), disease-free survival (11% vs 3%; P < .0001), and biochemical failure (65% vs 80%; P < .0001).
The risk for fatal cardiac events was similar in both groups.
"The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events," the study authors write. "These updated findings of RTOG 8610 suggest that patients with high-risk, locally advanced disease who decline or who, for medical reasons, are not considered candidates for long-term ADT should be offered short-term neoadjuvant and concurrent ADT in combination with EBRT. The biologic rationale for using ADT with EBRT includes a reduction in the tumor volume and enhanced biologic effects."
The National Cancer Institute supported this study. Two of the study authors have disclosed various financial relationships with Astra-Zeneca.
J Clin Oncol. Published on January 2, 2008.2008;26:1-7.