PSOR6 Presentation Time: 11:55 AM: A Scoping Review of Immune Changes After Prostate Brachytherapy

Abstract

<h3>Purpose</h3> Prostate brachytherapy (BT), with either low-dose-rate (LDR) or high-dose-rate (HDR), delivers a highly conformal and heterogeneous dose, allowing for dose escalation beyond external beam radiotherapy (EBRT). Whether this different dose deposition results in opportunistic biological changes that could be harnessed to improve outcomes is not well studied. Given the increasing interest in incorporating immunotherapy into prostate cancer treatment, we sought to investigate the impact of prostate BT on the immune system. <h3>Materials Methods</h3> A scoping review was performed using PubMed and Scopus for papers published between 2011-2021. Search terms used were "brachytherapy" AND "immune" AND "prostate". A total of 62 records were identified. After review, 6 studies were identified for review that included information an immune assessment on patient samples (tissue and/or blood) after prostate BT. <h3>Results</h3> 2 LDR studies (N=68) evaluated changes in the peripheral blood following I-125 BT monotherapy. Both studies demonstrated significant increases in peripheral CD3+ T cells and CD4+ T cells post-BT. However, increased circulating CD8+ T cells were observed in only one study. One study also demonstrated significant increases in Treg subsets up to 150 days post-treatment, which may be compensatory to increased cytotoxic T cell titers. 4 HDR studies (N=37) were identified (HDR fraction sizes 10-15 Gy), and all were done in combination with EBRT. Androgen deprivation therapy was included, for select patients, and one study included nivolumab. Three looked at changes in tissue immune infiltrates seen in post-BT biopsies and 1 looked at changes in both tissue and blood. The largest study (N=24) showed a single 10 Gy fraction of HDR converted 80% of "cold" tumors into an "intermediate" or "hot" state, based on a tumor inflammation signature, when comparing a pre-BT biopsy to a biopsy done prior to HDR fraction 2. In another study (N=6) a significant correlation between increased pathologic response (no tumor in ≥ 4/6 cores) and increased CD4+ and CD8+ T cells in prostate tissue as well as CD4+ T cells in the blood was seen (p values not reported). Tumor infiltrating lymphocyte recruitment may be context dependent given a case report demonstrated decreased T cell infiltration post BT+EBRT. Finally, in a separate study (N=6), peripheral blood analysis demonstrated increased CD8+ T cells with an activated phenotype, decreased CD4+/CD8+ T ratio, decreased CD4+ helper T cells, and increased CD4+PD1+ cells at 3 months post-treatment when compared to baseline levels EBRT. Patients with PSA<0.02 at 3 months were also more likely to have increased CD4+ PD1+ T cells. <h3>Conclusion</h3> Both LDR and HDR BT can invoke an immune activating phenotype in prostate cancer; however, changes in immunosuppressive cells are also seen. Additional data is needed to understand how to better promote synergy between these changes and improving clinical outcomes.