Combined Cryoablation and GM-CSF Treatment for Metastatic Hormone Refractory Prostate Cancer

Abstract

A total of 12 patients with metastatic hormone refractory prostate cancer were treated by combining cryoablation and granulocyte macrophage colony-stimulating factor administration. Besides prostate-specific antigen (PSA) measurements, peripheral blood mononuclear cells were also obtained; the frequency of tumor-specific T cells was tested ex vivo in an interferon-gamma enzyme-linked immunospot assay after stimulating with autologous prostate cancer-derived protein lysates. To assess cytolytic activity, T cells were coincubated with human prostate cancer cells (LNCaP) or renal cancer cells (GRC-1), and release of cytosolic adenylate kinase was measured by a luciferase assay. The median PSA decline percentage was 69.4% (range: 30.5% to 92.5%) and the median time to the nadir PSA was 4 months after therapy (range: 3 to 6). The median time to disease progress was 18 months, and 1 patient obtained a 92.5% PSA decline and a greater than 50% reduction of lung disease and survived 31 months. Four or 8 weeks after treatment, the tumor-specific T-cell responses were increased in peripheral blood mononuclear cell. The cytolytic activity against LNCaP was also increased significantly whereas no response was found against GRC-1. It seemed that there was no direct correlation between the degree of T-cell response and decline in PSA. Combined cryoablation with granulocyte macrophage colony-stimulating factor treatment was suggested to be an alternative approach for metastatic hormone refractory prostate cancer and could induce tumor-specific immunologic response.