As reported in the Journal of Clinical Oncology by Eastham et al, the phase III CALGB 90203/Alliance trial has shown no improvement in 3-year biochemical progression-free survival (BPFS) with the addition of neoadjuvant chemohormonal therapy to radical prostatectomy in patients with localized high-risk prostate cancer.
Study Details
In the trial, 788 men were randomly assigned between December 2006 and October 2015 to receive neoadjuvant chemohormonal therapy with androgen-deprivation therapy plus docetaxel at 75 mg/m2 every 3 weeks for 6 cycles plus radical prostatectomy (n = 391) or surgery alone (n = 397). The primary endpoint was 3-year BPFS. Biochemical failure was defined as a serum prostate-specific antigen level of > 0.2 ng/mL that increased on 2 consecutive occasions at least 3 months apart. Secondary endpoints included 5-year BPFS, overall BPFS, metastasis-free survival, prostate cancer–specific mortality, and overall survival.
Biochemical Progression-Free Survival
Median follow-up was 6.1 years. At 3 years, BPFS rates were 89% in the neoadjuvant chemohormonal therapy group vs 84% in the surgery alone group (95% confidence interval [CI] for difference = -0.01–0.11, P = .11). At 5 years, BPFS was 81% vs 74% (95% CI for difference = -0.01–0.16). BPFS over the entire follow-up was greater in the neoadjuvant group (hazard ratio [HR] = 0.69, 95% CI = 0.48–0.99).
As stated by the investigators, “Our ability to determine BPFS was compromised because 48% of patients (43% in neoadjuvant arm and 52% in the surgery arm) received additional treatment—usually salvage radiation therapy with or without androgen-deprivation therapy—before meeting the primary endpoint; these patients were censored at the time of additional therapy for the BPFS comparison as per U.S. Food and Drug Administration guidance.”
Neoadjuvant chemohormonal therapy was associated with significantly improved metastasis-free survival (HR = 0.70, 95% CI = 0.51–0.95) and overall survival (HR = 0.61, 95% CI = 0.40–0.94) but not prostate cancer–specific survival (HR = 0.69, 95% CI = 0.32–1.07). Overall survival probabilities at 10 years were 80% vs 74%.
Toxicity
Grade 3 and 4 adverse events occurred during chemotherapy in 26% and 19% of the neoadjuvant group, with the most common including neutropenia (23%), hyperglycemia (6%), fatigue (4%), and febrile neutropenia (4%). Intraoperative complications were infrequent in the entire study population (3 rectal injuries and 1 ureteral injury). No deaths were observed within 30 days of radical prostatectomy. The neoadjuvant chemohormonal therapy group had more cases of postoperative grade 3 low hemoglobin and postoperative bleeding.
The investigators concluded, “The primary study endpoint, 3-year BPFS, was not met. Although some improvement was seen in secondary endpoints, any potential benefit must be weighed against toxicity. Our data do not support the routine use of neoadjuvant CHT and radical prostatectomy in patients with clinically localized, high-risk prostate cancer at this time.”
James A. Eastham, MD, of the Department of Surgery, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute and Sanofi. For full disclosures of the study authors, visit ascopubs.org.
