Undertreatment of Elderly Men With High-Risk Prostate Cancer

Abstract

Treatment of high risk prostate cancer (PCa) with androgen deprivation therapy (ADT) alone is inferior to radiation therapy (RT) plus ADT. Elderly men with high-risk PCa are often undertreated. To assess for an age-dependent bias, we examined patterns of care and compared overall survival (OS) between men treated with ADT or RT+ADT. We queried the National Cancer Database between 2004-2013 and identified men ≥75 years of age with clinically localized high-risk PCa (Gleason 8-10, prostate specific antigen [PSA] >20 to 40 ng/ml, or T3a) treated with ADT alone or ADT+RT. Univariate (UVA), multivariate (MVA) and subset OS analyses were completed using chi-squared test, logistic regression, log-rank, Kaplan-Meier methods and cox-proportional hazards models. Propensity score matching was completed using significant variables from logistic regression. Among 17,636 patients treated with ADT, 14,254 (81%) were treated with RT and 3,382 (19%) with ADT alone. Median follow up was 71 months. Between 2004-2013, the proportion of men ≥75 treated with ADT alone remained unchanged (21% in 2004 and 20% in 2013). Factors independently associated with increased use of ADT alone were older age, African American race (vs. caucasian), uninsured and Medicaid insurance type (vs. Medicare), treatment in the South, Midwest and West (vs. Northeast), academic facility type (vs. non-academic), Charlson-Deyo comorbidity score (CCS) 1 and 2 (vs. 0), Gleason score 6 (vs. 7 and 8-10), and PSA of 10-20 and >20 (vs. <10). On UVA, ADT alone was associated with increased risk of death (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: 2.4-2.7, p<0.001) when compared to RT+ADT. Five year OS for ADT alone and RT+ADT were 51% vs 78%, respectively (p<0.0001). On MVA, after controlling for age, race, insurance type, treatment location, facility type, CCS, PSA and clinical T-stage, ADT alone remained independently associated with increased risk of death (HR: 1.9, 95%CI: 1.7-2.0, p<0.001). Propensity score matching identified 4,216 patients and confirmed an increased risk of death associated with ADT alone (HR: 1.8, 95%CI: 1.7-2.0, p<0.001). On subset analysis, the increased risk of death associated with ADT alone persisted when stratified by CCS and age group (75-79, 80-84 and 85 years or greater) when compared to RT+ADT, except for those 85 years and older with CCS of 2 or greater. Despite randomized evidence to support the use of RT+ADT for men with high-risk PCa, approximately 1 in 5 men who are 75 years and older are treated with ADT alone. This approach is associated with a 2-fold risk of death when compared to RT+ADT in most men. Careful consideration of life expectancy and comorbidity status should be given before omitting RT in the elderly.