Molecular testing for prostate cancer in Greek patients.

170 Background: Molecular testing for mutations in genes related to homologous recombination repair (HRR) and microsatellite instability (MSI) is suggested for patients with advanced prostate cancer by international guidelines. Recently, olaparib has been approved for patients with metastatic castration resistant prostate cancer patients that bear mutations in BRCA1/2 genes in Europe. In Greece, molecular testing for prostate cancer patients is not reimbursed. In this setting we describe our experience from investigating the molecular profile of patients with advanced/metastatic disease. Methods: We retrospectively collected clinicopathological data of patients treated in our center for advanced/metastatic prostate cancer whose tumours were subjected to whole exome sequencing analysis for a panel of 58 genes including BRCA1/2. All patients provided written informed consent and the study was approved by the local ethics committee. Results: Tumor samples from 37 patients with advanced or metastatic prostate cancer were analyzed. Median age of the patients was 60.2 years (25th-75th percentile 54.4-63.9 years) and most of them (19/37, 51.4%) were presented with de novo metastatic disease. Clinicopathological characteristics of the patients are presented in the table. Eight samples (21.6%) were evaluated as inadequate to perform further analysis. In the remaining 29 cases, no BRCA1/2 mutations were detected. Instead, 7 patients had mutations in HRR-related genes, including 3 patients with ATM mutations, two in CHEK2, one in CHEK1 and one in RAD50. TP53 mutations were found in 8 patients (21.6%) and PTEN mutations in 2 (5.4%). Newer Hormonal Treatments were used as first-line treatment in mCRPC in 24 patients (64.9%), while 6 received docetaxel. Median PFS in first-line mCRPC was 12.0 months (95% CI 9.7-14.3) in the whole population and did not differ significantly in patients with HRD mutations (11.8 months) or TP53 mutations (11.8 months). Two patients with ATM mutations received olaparib as fourth and fifth line of treatment respectively with stable disease as best response. Conclusions: Biomarker driven targeted therapies are currently available for mCRPC patients. In our cohort, molecular testing was negatively affected by the poor quality of archival tissues in a significant percentage of patients. However, mutations in HRR-related genes were found in almost 20% of patients with possible therapeutic implications. Therefore, it is necessary to have a reimbursed molecular testing for prostate cancer patients in Greece.[Table: see text]