Baseline Frailty, Treatment Intensity, and Clinical Outcomes Among Older Adults with Locally-advanced Prostate Cancer.

BACKGROUND AND

OBJECTIVE

The addition of prostate radiation (RT) to androgen deprivation therapy (ADT) improves oncologic outcomes in patients with locally-advanced prostate cancer (PCa). However, this approach remains underutilized in older adults. We therefore emulated the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) PR3/MRC PR07 clinical trial of ADT + RT versus ADT alone to examine clinical outcomes and the role of frailty as an effect modifier.

METHODS

We included adults aged 66-89 yr with locally-advanced PCa (cT3-T4, N1, T2 + PSA ≥ 40, or Gleason ≥ 8 + prostate-specific antigen [PSA] ≥ 20) treated with ADT + RT or ADT alone in Surveillance, Epidemiology, and End Results (SEER)-Medicare from 2004-2017. Frailty was assessed using the claims-based frailty index (CFI). We evaluated oncologic outcomes adjusted using stabilized inverse probability of treatment weights (sIPW), and explored the association of treatment intensity with CFI.

KEY FINDINGS AND LIMITATIONS: A total of 5494 patients were included, of whom 3378 were treated with ADT + RT. Baseline characteristics were balanced after sIPW reweighting. Median follow-up was 64.0 mo. ADT + RT was associated with reduced cancer-specific mortality (hazard ratio [HR] 0.61; p < 0.01) and all-cause mortality (HR 0.84; p < 0.01) in the overall cohort. Findings were consistent across CFI, T stage, N stage, Gleason score, and PSA. However, increasing frailty was associated with a reduced probability of receiving ADT + RT (adjusted odds ratio [OR] 0.81 per unit CFI).

CONCLUSIONS AND CLINICAL IMPLICATIONS: In observational analyses designed to emulate a real-world target trial in older adults, increasing frailty was associated with a reduced likelihood of receiving more intensive treatment, despite a consistent benefit in cancer-specific mortality. These findings underscore the need to re-evaluate treatment disparities in older adults with locally-advanced PCa.