There are a series of androgen deprivation therapy (ADT) neoadjuvant trials including those conducted at DF/BWH Cancer Center, University of Washington, BIDMC, Johns Hopkins, University of British Columbia, Princess Margaret Cancer Centre, and MD Anderson. The neoadjuvant treatment paradigm has focused on intermediate- and high-risk localized disease based on biopsy volume, Gleason score (>= Gleason grade group 3), high PSA, or T3 disease by MRI. Patients have traditionally received ADT in standard and intense doses followed by radical prostatectomy (RP), and the primary outcomes have included tissue androgen levels and rates of minimal residual disease (MRD) and cure rates (CR).
The Targeted Androgen Pathway Suppression (TAPS) trial evaluated the above-mentioned primary endpoints after LHRH agonist + bicalutamide, LHRHA + dutasteride, LHRHA + bicalutamide + dutasteride, and LHRHA + bicalutamide + dutasteride + ketoconazole then RP. TAPS reported improved tissue androgen endpoints but relatively low pathologic CRs, 8% in the maximal blockade arm. When the level of ablation was increased, tissue DHT levels accordingly decreased.
A second study evaluated maximal androgen blockade with abiraterone prior to RP by comparing ADT alone to ADT + abiraterone prior to RP and again found significantly lower tissue levels of all androgens, but 10% CR in the 24-week arm. The study did find that the CR/MRD rates improved from 4% to 12% when the treatment duration was doubled from 12 to 24 weeks. Thus, intensification of therapy, through increasing androgen ablation and/or treatment duration, does have a significant impact on tumor response to treatment.
The question then becomes whether recurrence rates are affected by MDR or CR. Evaluating 72 patients from DFCI/BWH, University of Washington or BIDMC showed that the 3-year BCR-free rate was 70% (95% CI 57-80%), 3-year MFS was 95% (95% CI 86-98%), and 3-year DSS was 98% (95% CI 88-100%). Only 1 patient who had MDR/CR had BCR, suggesting that MRD and CR have a significant impact on recurrence. Indeed, eradicating the local tumor does have a significant impact on overall outcomes.
Presented by: Adam S. Kibel, MD, Chief of Urology at Dana-Farber/Brigham and Women’s Cancer Center, Elliott Carr Culter Professor of Surgery at Harvard University School of Medicine and chairman of the Harvard Urology Residency Program, Boston, Massachusetts
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