Long‐Term Oncologic Outcomes of Neoadjuvant Tumor‐Directed Immunotherapy (PROSTVAC) Before Radical Prostatectomy for Localized Prostate Cancer: A Secondary Analysis of a Neoadjuvant Trial

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ABSTRACT Background Biochemical recurrence (BCR) following radical prostatectomy (RP) occurs in 20%–40% of patients with localized prostate cancer. Neoadjuvant PROSTVAC has been shown to enhance T‐cell infiltration into the tumor immune microenvironment, but whether these immunologic changes translate into improved long‐term oncologic outcomes remains unknown. Patients and Methods This secondary analysis evaluated 26 patients from a Phase II neoadjuvant PROSTVAC trial who underwent RP. Patients received recombinant vaccinia‐PSA‐TRICOM priming followed by three fowlpox‐PSA‐TRICOM boosts before surgery. Tumor immune responses (CD4 + /CD8 + T‐cell infiltration) and peripheral antigen‐specific T‐cell responses to PSA, MUC‐1, and brachyury were previously assessed. Primary outcomes included BCR‐free survival (BCR‐FS) and metastatic progression at extended follow‐up. Results From May 2014 to June 2017, 26 patients were enrolled, received neoadjuvant PROSTVAC, and subsequently underwent RP. Eighteen (69.2%) patients had NCCN® unfavorable‐intermediate, high, or very high‐risk disease at baseline. At a median follow‐up of 8.9 years (range 7.0–10.1), BCR occurred in six patients (23.1%), and none developed metastatic disease. Comparing pre‐ and post‐PROSTVAC peripheral antigen‐specific T‐cell responses, patients with PSA‐specific immune responses had 100% 8‐year BCR‐FS, compared with 70.0% in nonresponders ( p = 0.247). Those with any tumor‐associated antigen response demonstrated 85.7% versus 66.7% 8‐year BCR‐FS ( p = 0.149). Patients with CD4+ or CD8 + T‐cell responses at the tumor site or invasive margin had 86.2% versus 58.9% 8‐year BCR‐FS ( p = 0.257). Conclusion Neoadjuvant PROSTVAC may have oncologic activity in localized prostate cancer, as we observed a longer BCR‐FS in immune responders and no metastatic progression in a small cohort. Further investigation of the biological mechanism by which therapeutic immunotherapy may establish durable antitumor immunity in localized prostate cancer is warranted.