Cancer and Leukemia Group B 90203 (Alliance): Radical Prostatectomy With or Without Neoadjuvant Chemohormonal Therapy in Localized, High-Risk Prostate Cancer

Abstract

Purpose: Radical prostatectomy (RP) alone is often inadequate in curing men with clinically localized, high-risk prostate cancer (PC). We hypothesized that chemohormonal therapy (CHT) with androgen-deprivation therapy plus docetaxel before RP would improve biochemical progression-free survival (BPFS) over RP alone.

Patients and methods: Men with clinically localized, high-risk PC were assigned to RP alone or neoadjuvant CHT with androgen deprivation plus docetaxel (75 mg/m2 body surface area every 3 weeks for 6 cycles) and RP. The primary end point was 3-year BPFS. Biochemical failure was defined as a serum prostate-specific antigen level > 0.2 ng/mL that increased on 2 consecutive occasions that were at least 3 months apart. Secondary end points included 5-year BPFS, overall BPFS, local recurrence, metastasis-free survival (MFS), PC-specific mortality, and overall survival (OS).

Results: In total, 788 men were randomly assigned. Median follow-up time was 6.1 years. The overall rates of grade 3 and 4 adverse events during chemotherapy were 26% and 19%, respectively. No difference was seen in 3-year BPFS between neoadjuvant CHT plus RP and RP alone (0.89 v 0.84, respectively; 95% CI for the difference, -0.01 to 0.11; P = .11). Neoadjuvant CHT was associated with improved overall BPFS (hazard ratio [HR], 0.69; 95% CI, 0.48 to 0.99), improved MFS (HR, 0.70; 95% CI, 0.51 to 0.95), and improved OS (HR, 0.61; 95% CI, 0.40 to 0.94) compared with RP alone.

Conclusion: The primary study end point, 3-year BPFS, was not met. Although some improvement was seen in secondary end points, any potential benefit must be weighed against toxicity. Our data do not support the routine use of neoadjuvant CHT and RP in patients with clinically localized, high-risk PC at this time.

Trial registration: ClinicalTrials.gov NCT00430183.

Conflict of interest statement

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Figures

FIG 1.

CONSORT diagram of Cancer and Leukemia Group B (Alliance) trial. PSA, prostate-specific antigen.

FIG 2.

Biochemical progression–free survival (BFS) was compared between men treated with neoadjuvant chemohormonal therapy and radical prostatectomy (designated neoadjuvant) versus radical prostatectomy alone (designated surgery alone). Biochemical failure was defined as a serum prostate-specific antigen (PSA) level > 0.2 ng/mL that increased on 2 consecutive occasions that were at least 3 months apart. The time of biochemical failure is measured from the date of randomization to the date of the first PSA level > 0.2 ng/mL.

FIG 3.

(A) Event-free survival (EFS) or the likelihood of not requiring additional treatment after radical prostatectomy in men treated with neoadjuvant chemohormonal therapy plus radical prostatectomy (designated neoadjuvant) versus radical prostatectomy alone (designated surgery alone). An event is defined as death, prostate-specific antigen progression, local or distant progression, initiation of androgen-deprivation therapy, and/or radiation therapy > 6 months after surgery. (B) Metastasis-free survival (MFS; the time from randomization to metastasis) in men treated with neoadjuvant chemohormonal therapy plus radical prostatectomy versus radical prostatectomy alone. (C) Prostate cancer–specific survival (the time from randomization to death from prostate cancer) in men treated with neoadjuvant chemohormonal therapy plus radical prostatectomy versus radical prostatectomy alone. Cause of death was assigned by the treating physician. (D) Overall survival (OS; the time from randomization to death) in men treated with neoadjuvant chemohormonal therapy plus radical prostatectomy versus radical prostatectomy alone.