ASCO 2020: Short-Term Adjuvant Versus Neoadjuvant Hormone Therapy in Localized Prostate Cancer: A Pooled Individual Patient Analysis of Two Phase III Trials

( Intermediate and high-risk localized prostate cancers can be treated with surgery or the combination of radiotherapy and hormonal therapy. The optimal timing of hormonal therapy in relation to radiotherapy for localized prostate cancer is an area of active study. In this poster, Daniel E Spratt, MD, and colleagues pool data from prostate-only radiation in the RTOG9413 trial and data from a phase 3 trial of neoadjuvant versus adjuvant hormonal therapy relative to radiation therapy to further explore the optimal timing of hormonal therapy with prostate-only radiotherapy.

In RTOG9413, patients who received prostate-only radiation were randomized to either androgen-deprivation therapy (ADT) for two months prior (neoadjuvant) to the start of radiation therapy, or ADT starting after radiation (adjuvant) and continuing for four months. Patients on this trial who received prostate-only radiation and adjuvant hormonal therapy had numerically higher progression-free survival than patients getting neoadjuvant hormonal therapy. In the other phase 3 trial published by Malone et al of patients undergoing prostate-only radiotherapy, patients were randomized to ADT starting 4 months before radiation (neoadjuvant), or ADT starting with radiation therapy and continuing for 6 months after (adjuvant). The Malone study did not detect any difference in biochemical recurrence rates, overall survival, or late toxicities between either group.

In their pooled analysis, patients from both trials and either neoadjuvant or adjuvant hormonal therapy were combined. This combination gave a cohort of 531 neoadjuvant treated patients, and 534 adjuvantly treated patients. Baseline characteristics were well-balanced between arms. The authors examined the relationship between hormonal therapy timing and various parameters including biochemical failure, progression-free survival, distant metastasis, overall survival and prostate cancer-specific mortality.

The results from this poster show statistically superior rates of biochemical failure (15yr: 33% vs 43%, HR: 1.37 (95%CI: 1.12-1.68), p=0.002), distant metastasis  (15yr: 12% vs 18%, HR: 1.40 (95%CI: 1.00-1.95), p=0.04),  and progression-free survival (15yr: 36% vs 29%, HR: 1.25 (95%CI: 1.07-1.47), p=0.01) with adjuvant hormonal therapy. While numerically better, there was no statistically significant difference in prostate cancer-specific mortality between the arms (15yr: 15% vs 20%, HR: 1.29 (95%CI: 0.95-1.75), p=0.10). There was also no difference in late toxicities between either method.

From this posthoc analysis, the authors suggest that adjuvant hormonal therapy may be preferable to neoadjuvant hormonal therapy when given with prostate-only radiation for the management of localized cancer.

Presented by: Daniel E Spratt, MD, Associate Professor and Chair of Genitourinary Clinical Research, Rogel Cancer Center, University of Michigan, Ann Arbor, MI

Written by: Alok Tewari, MD, PhD, Medical Oncology Fellow at the Dana-Farber Cancer Institute, at the 2020 ASCO Annual Meeting, Virtual Scientific Program #ASCO20, May 29-31, 2020.