Translational exploratory endpoints
toxicity, tumor, prostate cancer, prostate
TUMOR, DNA DAMAGE, PROSTATE, BLOOD, PROSTATE CANCER
At the time of the second HDR treatment for cohort 1 and the HDR treatment for cohort 2, patients will receive a research prostate biopsy via a transperineal approach under ultrasound guidance. Targeted biopsies of PSMA PET/MR defined lesions will be obtained along with systematic biopsies of the whole gland. These tissue samples are obtained for further translational studies and will assess the effects of HDR brachytherapy in cohort 1 and Lu-177 PSMA RLT in cohort 2 on the prostate cancer ILF.Blood and urine samples will be collected prior to the first treatment, prior to the second treatment, at 6 weeks after the second treatment and at 6 months after the second treatment, in both cohorts 1 and 2. Patients will have serum PSA, marrow function, renal function and hepatic function bloodwork at 6 months after the second treatment in both cohorts. CTCAE v4.0 toxicity scores and EPIC QoL scores will be done at 6 weeks and 6 months after the second treatment as well.Regarding the translational biomarkers, the research biopsy specimens will undergo panel-based deoxyribonucleic acid (DNA) sequencing analysis of commonly altered DNA repair pathway and prostate cancer genes, tumor-associated T-cell receptor deep-sequencing (TCR-seq), as well as PSMA expression and gamma-H2A histone family member X (gamma-H2AX) expression, a marker of radiation-induced DNA damage, by immunohistochemistry. Blood plasma will also undergo circulating tumor DNA (ctDNA) sequencing as well as peripheral blood mononuclear cell (PBMC) analysis with TCR-seq and flow cytometry assessing markers of immune activation and radiation-induced DNA damage (e.g., gamma-H2AX). Finally, urine will be collected for urine tumor DNA (utDNA) sequencing.