Prognostic value of PSMA radio-genomics in hormone sensitive synchronous metastatic prostate cancer.

Abstract

e17116 Background: Molecular characterization of prostate cancer (PCa) has allowed development in targeted therapies design; with molecular imaging as PSMA-PET, they both determine precision oncology and personalized medicine. Currently, genomic advancements have lead to mayor prognostic and predictive implications in oncologic outcomes, aim in this study was to evaluate and describe PSMA-PET quantitative parameter patterns in de novo metastatic hormonosensitive prostate cancer (mHSPC) and the associations with somatic pathogenic variants. Methods: We conducted a retrospective analysis of 45 patients referred to the nuclear medicine’s department in Mexico’s National Cancer Institute for a staging PSMA-PET/CT, with confirmed PCa histopathological results and with new generation sequency (NGS) testing of the primary tumour. Results: 28.89% (n=13) of patients had confirmed pathogenic (or likely pathogenic) variant (PV) mutations in HRR or TS genes; 35.56% (n=16) had variants of unknown significance (VUS) mutations, and 35.56% (n=16) of patients had a negative NGS test. PV and VUS detected are described in table 1, Coexisting PV (≥2) were found in 23% and 37.5% in VUS group. Differences between group 1 and 3 were statistically significant (Mann Whitney’s U p=0.0056). In the mutational status analysis, group 1 and group 2 did not have any significant difference in overall survival ( p=0.731 ); opposed to statistical results from group1 and 2 (altogether) compared to group 3 ( p=0.055 ). We defined TTV cutoff value at 94 ml, for worse overall survival by ROC curves, and was used to stratify patients according to TTV (>94 ml vs <94 ml) and mutational status (VP carriers + VUS carriers vs non-mutated); where VP and VUS carriers with >94 ml TTV exhibited a worse molecular and clinical prognostic behavior, resulting in a markedly decreased overall survival (p =0.0218 ) Log-rank Mantel Cox’s. Conclusions: Mutations in the HRR gene are associated with increased metabolic substrate requirements for DNA base pairs as a compensatory mechanism for the effects of such mutations. Folate hydrolase and glutamate carboxypeptidase are core functions of PSMA and play a role as a molecular marker in cellular adaptive mechanisms to genomic alterations. Our findings suggest that the integration of molecular imaging and genomic profiling has an impact on overall survival. Mutational and PSMA SUVmax characteristics. Group PV carriers (Group 1) VUS carriers (Group 2) Non-mutated (Group 3) SUVmax (Median) SUVmax (Range) 16.5 (8.2-39.9) 9.3 (3.1-28.86) 9.75(4.1-16.6) Genes p53(n=4) 30.8% ATM 18.75%(n=3) CHECK2(n=2) 15.4% p53 12.5%(n=2), ATM(n=2) 15.4% RAD54D 6.25% (n=1) FANCA(n=1) 7.7% CHECK2 6.25% (n=1) RADB51(n=1) 7.7% CDK12 6.25% (n=1) FANCL 6.25% (n=1) BRCA1 6.25% (n=1)