The Prognostic Value of Liquid Biopsies for Benefit of Salvage Radiotherapy in Relapsed Oligometastatic Prostate Cancer

Simple Summary Around 30% of patients with oligometastatic prostate cancer relapse will benefit from local PET/CT-guided ablative radiotherapy (RT) with improved progression-free and ADT (Androgene Deprivation Therapy)-free survivals. Therefore, there is an urgent need for predictive testing for therapeutic benefits prior to initiation. Various tests have already been established on tumor specimens for the prediction of prostate cancer's behavior or therapy outcome. However, in imaging-proven relapse tumor tissue from the local recurrence or metastases is often not available. Hence, there is a need for a liquid biopsy-based testing. We aimed to assess the prognostic value of CTCs- associated mRNA and blood-derived RNA for the benefit of PSMA PET-guided salvage RT in oligometastatic prostate cancer relapses. Significant correlations were found between the relative transcript levels of several investigated genes and clinicopathological parameters. Furthermore, distinct "transcriptional signatures" were found in patients with temporary and long-term benefits from RT. To assess the prognostic value of "liquid biopsies" for the benefit of salvage RT in oligometastatic prostate cancer relapse, we enrolled 44 patients in the study between the years 2016 and 2020. All the patients were diagnosed as having an oligometastatic prostate cancer relapse on prostate-specific membrane antigen (PSMA)-targeted PET-CT and underwent irradiation at the Department of Radiotherapy at the Hannover Medical School. Tumor cells and total RNA, enriched from the liquid biopsies of patients, were processed for the subsequent quantification analysis of relative transcript levels in real-time PCR. In total, 54 gene transcripts known or suggested to be associated with prostate cancer or treatment outcome were prioritized for analysis. We found significant correlations between the relative transcript levels of several investigated genes and the Gleason score, PSA (prostate-specific antigen) value, or UICC stage (tumor node metastasis -TNM classification of malignant tumors from Union for International Cancer Control). Furthermore, a significant association of MTCO2, FOXM1, SREBF1, HOXB7, FDXR, and MTRNR transcript profiles was found with a temporary and/or long-term benefit from RT. Further studies on larger patients cohorts are necessary to prove our preliminary findings for establishing liquid biopsy tests as a predictive examination method prior to salvage RT.