Apoptosis and Senescence in Localized Prostate Cancer Tissues Treated With HDR-BT Boost With Radiotherapy (EBRT) and ADT

Abstract

High dose rate brachytherapy HDR-BT boost with external beam radiotherapy (EBRT) and adjuvant Androgen Deprivation Therapy (ADT) is an effective treatment of localized prostate cancer (PCa). Ionizing radiation (IR) delivered by BT or by EBRT induce DNA damage leading to cell death by activation of apoptosis. On the other hand, ADT can also induce apoptosis or senescence depending on the duration of treatment. The goal of this study is to determine which signaling pathway is activated in PCa cells in response to the DNA damage induced by HDR-BT boost with EBRT and ADT.22 patients with localized PCa signed an informed consent to participate in this clinical pilot study. Ten patients were treated with only HDR-BT / EBRT alone (no ADT group) and twelve patients also received additional ADT (ADT group). The expression of Ki-67 and p53, pro-apoptotic markers Bax and PUMA and p16 as a senescence marker were analyzed by immunohistochemistry in the biopsies taken from all patients before and post-treatment.Our results show an up-regulation of pro-apoptotic markers and reduction of senescence marker expression in the tissues treated by HDR-BT/ EBRT. However, we noticed an increase expression of senescence marker p16 and no change in pro-apoptotic markers receiving additional ADT.HDR-BT/ EBRT treatment alone induces apoptosis in PCa cells while additional ADT appears to promote their senescence. This could explain the mitigated benefit of ADT to improve radiation treatment combined with BT. These results need to be validated in a larger cohort of patients.