PD17-10 BOOSTING IMMUNE RESPONSE OPTIMIZES PRIMARY CRYOTHERAY FOR THE TREATMENT OF PROSTATE CANCER: A PROSPECTIVE RANDOMIZED CLINICAL TRIAL

Abstract

INTRODUCTION AND OBJECTIVE: The association of focal therapy and immunotherapy has not been tested widely. The aim of this study was to determine the effect of cryoablation (CA) in the generation of detectable specific anti-prostate T and B cell responses, and to identify the differences in the immune response with the use of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) as an adjuvant therapy METHODS: Randomized pilot study of patients who elected to undergo whole-gland cryotherapy. Patients were assigned to either CA alone or CA followed by GM-CSF. The Impact of therapy on the development of T and B cell responses against tumor-related antigens was studied using Elispot (frequency of T cell specific for prostate specific antigens) and Serametrix (ELISA) assays, respectively. Fold changes in response to treatment were calculated by normalization of post-treatment ELISPOT values against the mean pre-cryoablation response. Student t-tests were used to determine if there was a difference in the pre-procedure baseline measures for each biomarker. Subsequently, we then ran two t-tests between all the treatment patients and all the controls at 4 weeks and at 12 weeks across all the biomarkers. Patient-specific fold changes (decrease) in serum PSA were determined by normalizing postsurgery PSA to pre-surgery levels RESULTS: A total of 20 patients were randomized to either CA alone or CA + GM-CSF. At 4 weeks after surgery, patients receiving GMSCF demonstrated an average fold change in cancer antigenrelated antibodies of 2.8% above their mean baseline values, whereas controls averaged an 18% fold-change below mean baseline (p< 0.05). At 12 weeks post-surgery, the mean for all GMCSF-treated patients increased to 25% above baseline, while the average of control group patients remained 9% below baseline (p< 0.05). Patients treated with GMCSF displayed, on average, higher ELISPOT readings for the 4 and 12 week times points (527 vs 481 for PSA and 748 vs 562 for PAP). Although not statistically significant, a trend towards a higher magnitude of PSA fold change was observed in the treatment arm compared to the control group at 180-days after surgery (p=0.1) CONCLUSION(S): GMCSF appeared to broadly elevate antibodies against prostate-specific and nonspecific antigens. Prostate antigen specific T cell responses were more enhanced over nonprostate specific responses, preferentially in the group who received GMCSF. Our findings are early indicators of the potential therapeutic effect of immunotherapy in association with cryotherapy for the treatment of PCa.