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