Outcomes Post Neoadjuvant Intense Hormone Therapy and Surgery for Patients with High-Risk Localized Prostate Cancer: Results of a Pooled Analysis of Contemporary Clinical Trials.

We report on the post-radical prostatectomy (RP) outcomes of patients enrolled on three randomized, multicenter, clinical trials of intense neoadjuvant androgen deprivation therapy (ADT) therapy prior RP.

All patients included were enrolled on trials evaluating intense ADT followed by RP. The primary endpoint was time to biochemical recurrence (BCR), defined as the time from RP to prostate specific antigen (PSA) >0.1 ng/mL or start of first post-RP therapy, stratified by pathologic response at RP (presence or absence of exceptional pathologic response defined as residual tumor at RP measuring 0-5 mm). Secondary endpoints included metastasis-free survival, overall survival, and time to testosterone recovery.

Overall, 117 patients were included in the analysis of whom 78.6% (n=92) had high-risk disease. Following neoadjuvant therapy, 21.4% (n=25) had 0-5 mm of residual tumor [including 9.4% (n=11) with a pathologic complete response). Overall, 49 patients (41.9%) experienced BCR and the 3-year BCR-free rate was 59.1% (95% CI 49.0-67.9). Of the 25 patients with an exceptional pathologic response, two patients (8.0%) developed BCR; while 51.1% of nonresponders (n=47/92) developed BCR. Testosterone recovery was observed in 93.8% of patients (n=106/113). PTEN loss and intraductal carcinoma were associated with shorter time to BCR.

In this pooled analysis of prospective trials, we demonstrate that exceptional pathologic response following neoadjuvant therapy is associated with a favorable impact on BCR. PTEN loss and intraductal carcinoma were associated with BCR. Additional follow-up is warranted to evaluate the impact on long-term outcomes.

The Journal of urology. 2021 Jan 27 [Epub ahead of print]

Rana R McKay, Jacob Berchuck, Lucia Kwak, Wanling Xie, Rebecca Silver, Glenn J Bubley, Peter K Chang, Andrew Wagner, Zhenwei Zhang, Adam S Kibel, Mary-Ellen Taplin

University of California San Diego, La Jolla, California., Dana-Farber Cancer Institute, Boston, Massachusetts., Beth Israel Deaconess Medical Center, Boston, Massachusetts.