Washington, DC (UroToday.com) At the 20th Annual Meeting of the Society of Urologic Oncology, Dr. James Eastham reviewed updates on study outcomes for CALGB 90203 (Alliance) randomized trial comparing neoadjuvant chemohormonal therapy (CHT) with radical prostatectomy (RP) to RP alone in patients with clinically localized high-risk prostate cancer (CLHRPC). Men with CLHRPC have significant risk of BCR after RP. Prior studies have failed to demonstrate improved outcomes with neoadjuvant ADT, but docetaxel chemotherapy has been associated with improved survival in patients with castrate resistant metastatic prostate cancer (mCRPC). The investigators hypothesize that the combination of the two in a neoadjuvant setting, or neoadjuvant CHT, may improve outcomes.
Eligibility criteria for the Alliance trial include cT1-3a by DRE, PSA <=100 ng/ml, adenocarcinoma on pathology, no radiographic evidence of metastases, Kattan pre-operative nomogram probability of <60% biochemical progression-free survival (bPFS) at 5 years after RP or Gleason score 8-10. The patients were randomized to 6 cycles of CHT (docetaxel + LHRH) followed by RP with extended pelvic lymphadenectomy or RP with extended lymphadenectomy alone. The primary endpoint was 3-year bPFS; PSA failure was defined as PSA >0.2 ng/ml on two consecutive tests at least 3 months apart. Secondary endpoints included overall bPFS, overall survival (OS), freedom from treatment failure.
To date, the authors have observed a favorable adverse event profile, with no deaths or grade 5 events within the CHT group. They found that the trial was negative for the primary endpoint of freedom of PSA failure at 3 years, but the results were distorted because, during the timecourse of the study, many patients (approximately 50%) received earlier salvage RT or ADT before actually reaching the BCR definition at 3 months. With the exception of the primary endpoint, all other endpoints had positive results including overall bPFS, OS, and freedom from treatment after RP.
In conclusion, the study did not demonstrate a bPFS difference at 3 years based on a planned 12% benefit with neoadjuvant CHT, but some of this may be a function of the definition of BCR employed by the investigators. There was a statistically significant improvement in bPFS over the course of the study and a survival benefit associated with neoadjuvant CHT. These data support neoadjuvant CHT prior to RP as a standard option for men with CLHRPC, but further study may be necessary.
Presented by: James A. Eastham, MD, FACS, Professor and Chief of the Urology Service, Department of Surgery, Memorial Sloan- Kettering Cancer Center, New York, New York, USA.
Written by: Selma Masic, MD, Urologic Oncology Fellow (SUO), Fox Chase Cancer Center, @selmasic at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DC
Read: AUA 2019: CALGB 90203: Radical Prostatectomy with or without Neoadjuvant Chemohormonal Therapy in Men with Clinically Localized, High-Risk Prostate Cancer