Practice patterns and outcomes by genomic risk in octogenarians with high-risk localized prostate cancer: A national real-world data analysis.

Abstract

1660 Background: Chronologic age and traditional clinical-pathologic prostate cancer (PCa) risk factors (e.g. PSA, Gleason Score) are useful but incomplete predictors of prognosis. While some octogenarians may benefit from watchful waiting for clinically high risk (HR) and very high risk (VHR) PCa due to competing risks, others may survive more than a decade with curative prostate-directed treatment. We examined real-world data (RWD) on practice patterns and outcomes for octogenarians with HR PCa stratified by genomic classifier (GC) scores. Methods: A retrospective cohort study was conducted using a national database of clinical–genomic linkage of Decipher GC with longitudinal RWD (Veracyte, South San Francisco, CA). The cohort included 1,519 patients, ≥80-years-old with HR/VHR PCa who underwent GC testing with >1 year of follow-up. Patients were stratified by low (GC-Low) compared to intermediate or high (GC-High/Int) GC scores. Observational management was determined by absence of treatment with evidence of prostate cancer–related services (e.g. GC-High/Int-Obs). Freedom from distant metastases (FFDM), metastasis-free survival (MFS), and overall survival (OS) were modeled using Kaplan-Meier analysis and log-rank tests. Results: Most patients (88%, n=1,341) had GC-High/Int. The rate of observational management was significantly lower in the GC-High/Int compared to GC-Low cohorts (26% vs 38%, p=0.001). Among treated patients, there were similar rates of ADT only use (52% GC-Low vs 54% GC-High/Int) but amongst those who were treated with radiotherapy, concurrent ADT use was lower in GC-Low compared to GC-High/Int (55% vs 69%, OR 0.83, 95% CI 0.73-0.95, p=0.007). There were significant differences between groups for FFDM (p=0.003), MFS (p<0.001), and OS (p<0.001) (Table). Among observed patients, GC-Low had significantly better FFDM than GC-High/Int (HR 0.11, 95% CI 0.02–0.80; p=0.03). Conclusions: Geriatric patients with aggressive, localized PCa decide between potentially morbid, curative treatments and heterogeneous risk of distant metastases in the setting of limited life expectancy. We present RWD that patients ≥80 years old with NCCN HR/VHR PCa with low GC scores have <5% rate of metastatic disease within 5 years with observation alone. This hypothesis generating data suggests GC score may be a useful prognostic tool in addition to standard clinical-pathologic factors for elderly patients. Patient-specific risk calculators for cancer and non-cancer specific mortality may help this underserved but growing population. NCCN HR (%) NCCN VHR (%) FFDM Hazard Ratio (95% CI) 5-yr FFDM 5-yr MFS 5-yr OS GC-Low-Obs 58 (85%) 10 (15%) 0.11 (0.02-0.80) 98% 70% 71% GC-Low-Treat 90 (82%) 20 (18%) 0.76 (0.36-1.59) 82% 75% 91% GC-High/Int-Obs 250 (71%) 104 (29%) Reference 83% 37% 43% GC-High/Int-Treat 633 (64%) 354 (36%) 1.35 (0.93-1.98) 81% 59% 64%