Overview
Immunotherapy is currently revolutionizing the field in oncology. However, prostate cancer until now fails to respond to classical IO, like PD-1 and CTLA-4 inhibitors. Radiotherapy (RT) delivered to the primary tumor impacts both tumor cells and surrounding stromal cells. Radiation damage to cancer cells exposes tumor-specific antigens leading to increased visibility to the immune system by improved priming and activation of cytotoxic T cells. RT-induced modulation of the tumor microenvironment may also facilitate the recruitment and infiltration of immune cells by increasing the expression or T-cell attracting chemokines and by increasing T-cell docking molecules on the endothelial cells like VCAM-1. The main-hypothesis is that HDR-brachytherapy will turn an immunologically "cold" (no T-cell infiltrations) prostate cancer into an immunologically "hot" (CD4 and CD8-cell infiltrations) tumor, creating leverage points for different forms of IO.
Description
Prospective analysis of biopsies from 10 patients with local recurrence in the prostate selected for salvage HDR brachytherapy in MAASTRO Clinic, Maastricht. HDR treatment is standard in Maastro Clinic for local relapses of prostate cancer after previously irradiation (internal or external).
Biopsies will be taken at 4 different time points (before and after the 1st fraction; before the 2nd and 3rd fraction of the salvage treatment).
Several immunotyping (expression of PD-(L)-1, CXCL12, IL-23 receptor, etc.) and HLA class I expression will be performed on the biopsies. In addition, HLA genotypes will be determined on DNA isolated from pheripheral blood.
The plasma and the biopsies will be stored for eventually additional research.
Eligibility
Inclusion Criteria:
- Local relapse of prostate cancer, who is candidate for a salvage HDR treatment:
- Biochemical relapse (PSA increase)
- Local relapse on imaging: PSMA scan, mp-MRI
- Pathology proven relapse
- Willing and able to comply with the study prescriptions.
- 18 years or older
- Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.
Exclusion Criteria:
- Not eligible for proposed (HDR brachytherapy) treatment:
- Life expectancy < 10 years
- Distant Metastasis
- Recently TURP with big urethral defect
- Not able to stop anticoagulants
- Flow < 10 ml/sec No compliance to study procedure