Abstract 5142: Clinical and genomic correlates of survival outcomes in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) receiving intensified androgen deprivation therapy (ADT) in a real-world population
Authors: Sayegh Nicolas , Peterson Bennet , Tripathi Nishita , Chigarira Beverly , Li Haoran , Sahu Kamal Kant , Sirohi Deepika , Nussenzveig Roberto , Maughan Benjamin L. , Agarwal Neeraj , Swami Umang 
Published: June 2022

Abstract
Introduction: Use of upfront chemotherapy or novel hormonal therapy (NHT) in patients (pts) with mCSPC has been approved based on improved outcomes. Baseline clinical and genomic correlates associated with inferior outcomes on intensified therapy would help identify pts at high risk for early progression or death, may improve patient counselling and guide drug development.
Methods: In this IRB-approved study, pt-level data were collected retrospectively. Eligibility: mCSPC pts undergoing ADT plus NHT or docetaxel with available pre-treatment tumor comprehensive genomic profiling from a CLIA-certified lab. Study endpoint: progression-free survival (PFS) per PCWG-2, is defined as PSA, or radiographic, or clinical progression or death whichever occurred first. Variants of unknown significance and mutated genes present in ≤5% pts were excluded. Cox proportional hazards was used to evaluate the relationship between PFS and age at diagnosis, Gleason score, volume of disease (per CHAARTED), presence of visceral mets, PSA at baseline and genomic alterations. Significance was pre-set at p ≤ 0.05.
Results: 106 pts with mCSPC were included: median follow-up was 20 months. Median age at diagnosis was 62 yrs (58 - 68); 85 pts (80%) had a Gleason score ≥8; 67 pts (63%) had de-novo metastatic disease; 69 pts (56%) had high-volume disease; and 20 (19%) had visceral metastases at time of diagnosis of metastatic disease. Most frequently mutated genes: TP53 (28%, n=30), TMPRSS2 (27%, n=29), and PTEN (21%, n=22). See table for COX regression results.
Conclusion: In this real-world cohort of mCSPC pts undergoing intensified ADT we identify clinical and genomic markers that are significantly associated with a an inferior PFS. These hypothesis-generating data need external validation.
Hazard Ratio (95% CI) P Age 0.98 (0.94-1.02) 0.40 De Novo 1.28 (0.61-2.62) 0.52 Gleason Score ≥8 2.61 (0.98-6.93) 0.05 Log-PSA at Baseline 1.17 (1.03-1.33) 0.02 High Vol of Disease 2.47 (1.23-4.99) 0.01 Visceral Mets 1.25 (0.54-3.92) 0.60 Mutated Genes MYC 5.17 (1.39-19.27) 0.01 KDM6A 0.97 (0.20-4.52) 0.97 RB1 3.14 (0.97-10.17) 0.06 PTEN 1.07 (0.48-2.36) 0.87 TMPRSS2 1.09 (0.55-2.14) 0.81 TP53 0.89 (0.47-1.74) 0.74
Citation Format: Nicolas Sayegh, Bennet Peterson, Nishita Tripathi, Beverly Chigarira, Haoran Li, Kamal Kant Sahu, Deepika Sirohi, Roberto Nussenzveig, Benjamin L. Maughan, Neeraj Agarwal, Umang Swami. Clinical and genomic correlates of survival outcomes in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) receiving intensified androgen deprivation therapy (ADT) in a real-world population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5142.