STRATOS-P clinical model for prognosis and selection of patients with metastatic hormone sensitive prostate cancer (mHSPC) for intermittent therapy.

5106 Background: Current trials use prostate-specific antigen (PSA) response of ≤0.2 ng/mL at 6-12 months as a prognostic marker and identify patients for intermittent therapy. Clinico-genomic assessment can increase prognostic accuracy and patient selection for intermittent therapy, which would improve quality of life and decrease adverse events associated with mHSPC combination therapies without impacting survival. Methods: Retrospective study of veterans diagnosed with mHSPC between 2018-2024. PSA response at 6-12 months and volume of disease were determined. DNA alterations were classified by Somatic Tumor Risk Assessment for Overall Survival-Prostate (STRATOS-P) genomic system, a validated method of risk stratification. PSA response was grouped into ≤0.2, >0.2-<2, 2-<10, and ≥10 ng/mL. Charlson comorbidity index (CCI) high was defined as ≥3. PSMA-PET based staging was determined if PSMA-PET performed within 100 days of mHSPC diagnosis. Multivariable Cox model-based weights were used to create the STRATOS-P mHSPC clinical risk score to prognosticate overall survival and select patients for intermittent therapy. Kaplan-Meier analysis was used to estimate Overall Survival (OS) and time to death or castration resistance from diagnosis, a real-world progression-free survival (rwPFS) surrogate. Results: In 3094 Veterans identified, 937 (30.3%) had DNA-based genomic testing within 6 months of diagnosis. There were 1349 patients (43.6%) with a PSA of ≤0.2 who had a median OS of 74.6 months. Of patients with genomic testing, 459 (49.0%) were STRATOS-P Clinical low risk with a median OS that was not reached and rwPFS of 72.1 months, moderate risk with median OS of 37.1 months and rwPFS of 21.6 months, and high risk with median OS of 19.1 months and rwPFS of 12.1 months. There were 66 (13.0%) patients that were STRATOS-P Clinical low risk but did not achieve ≤0.2% and 116 (22.8%) patients that achieved PSA ≤0.2 but were considered STRATOS-P clinical moderate risk. Approximately 497 patient (53%) could be considered for intermittent therapy and had a median OS of 77.9 months and rwPFS of 56.2 months, similar to patients with PSA≤0.2. Conclusions: STRATOS-P Clinical model in mHSPC is prognostic for OS and rwPFS and can identify patients for intermittent therapy to achieve similar OS and rwPFS compared to selection using PSA ≤0.2 at 6-12 months. Future trials should incorporate clinico-genomic assessments to improve risk stratification and selection of therapy. STRATOS-P clinical model (n=937). n HR 95.0% CI CCI High 397 1.62 1.34-1.95 High Volume 608 1.53 1.31-1.78 STRATOS-P Genomic risk* Intermediate 470 1.53 1.23-1.92 Unfavorable 132 2.39 1.80-3.17 Non-PSMA-PET staging 708 1.62 1.23-2.14 >0.2 - 2 210 1.60 1.25-2.04 PSA Response# >2 - <10 131 2.98 2.30-3.84 10+ 87 5.64 4.26-7.47 *STRATOS-P genomic risk favorable is referent, n=335. #PSA Response ≤0.2 is referent, n=509.