From the Desk of the Associate Editor: Revisiting Neoadjuvant ADT Prior to Prostatectomy

This compelling study revisits the concept of neoadjuvant adjuvant deprivation therapy (ADT) prior to radical prostatectomy. A small series of randomized clinical trials (RCTs) performed almost 20 years ago failed to demonstrate substantial benefits in patients with localized prostate cancer who received ADT before surgery. Based on these data, the American Urological Association and the European Association of Urology recommend against ADT prior to prostatectomy outside the setting of a clinical trial.

Yet these RCTs employed arguably flawed and underpowered study designs.  Substantial limitations included: 1) small sample sizes (the largest study involved only 110 patients); 2) inclusion of predominately low- and intermediate-risk—rather than high-risk— study populations; 3) a dearth of patients with locally aggressive, node positive disease; 4) lack of Gleason stratification in the randomization allocation; and 5) primary outcomes focused on margin status rather than survival (Kumar, S., et al. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer (Cochrane Database Syst Rev, 2006: CD006019).

There are also convincing contemporary justifications for reconsidering this topic. A pooled Cochrane meta-analysis of the RCT data observed substantial clinical benefits of neoadjuvant ADT including 1) a significant (p < 0.001), 66% reduction in the positive surgical margin rate; 2) a borderline significant (p = 0.05), 26% reduction in disease recurrence rates; and 3) significant decreases in lymph node involvement and extra-capsular disease(Cochrane Database Syst Rev, 2006: CD006019). Moreover, newer, more potent hormonal agents merit further study in these patients.

These investigators undertook an exploratory, pooled analysis of three clinical trials of 72 men with high-risk, localized prostate cancer who received “intense” ADT prior to prostatectomy. “Intense” ADT regimens varied and involved combinations of LHRH agonists or antagonists, bicalutamide, dutasteride, ketoconazole, abiraterone, and enzalutamide. In marked contrast to prior studies, most patients had a Gleason score ≥ 8. The primary endpoint was time to biochemical recurrence (BCR), with BCR defined as a PSA ≥ 0.2 ng/mL or treatment with radiation or ADT for a rising PSA < 0.2 ng/mL. Over a median follow-up of 3.4 years, the 3-year BCR-free rate was 70% (95% CI 57%, 90%). Of the (n = 15) patients with either residual tumor ≤ 0.5 cm or pathologic T down staging—including 6% (n = 4) with a pathologic complete response, no patient experienced a recurrence.

The take-home message is that, in patients with unfavorable intermediate and high-risk localized and loco-regional prostate cancer, neoadjuvant ADT prior to prostatectomy may decrease recurrence rates; and while neoadjuvant ADT should not be routinely administered outside the setting of a clinical trial, these data warrant further study with contemporary RCTs focused on longer-term clinical outcomes.

Written by: J. Kellogg Parsons, MD, MHS, a board-certified urologist and Professor of Urology who specializes in treating prostate cancer, benign prostatic hyperplasia (BPH), bladder cancer, and kidney cancer.  J. Kellogg Parsons is an expert in cryosurgery, laser surgery, robotic surgery, and magnetic resonance imaging (MRI) of the prostate, and is internationally recognized for his work in prostate disease and urologic oncology. He has published over 130 scientific research articles, edited four medical textbooks, and received research grants from the NIH/National Cancer Institute (NCI), NIH/National Institute of Diabetes and Digestive and Kidney Diseases, and Department of Defense. Dr. Parsons currently serves as a consulting editor for European Urology and European Urology Focus, and is an associate editor for Prostate Cancer and Prostatic Diseases.

PCAN Full-Text Article Post Prostatectomy Outcomes of Patients with High-risk Prostate Cancer Treated with Neoadjuvant Androgen Blockade McKay et al. Prostate Cancer and Prostatic Diseases 2017 Dec 20. doi: 10.1038/s41391-017-0009-6. [Epub ahead of print]

Further Related Content:
Watch: Neoadjuvant Therapy for Men with High-Risk Disease Prior to Prostatectomy - Mary-Ellen Taplin
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