Abstract

Neal Andruska¹, Benjamin Fischer-Valuck ², Ruben Carmona ³, Temitope Agabalogun¹, Randall Brenneman¹, Hiram Gay⁴, Jeff Michalski⁴, Brian Baumann⁴

¹Washington University School of Medicine, Radiation Oncology, St Louis, USA; ²Emory University School of Medicine, Radiation Oncology, Atlanta, USA; ³University of Miami, Radiation Oncology, Miami, USA; ⁴Washington University School of Medicine, Radiation Oncology, St. Louis, USA

The NCCN currently recommends several definitive radiotherapy options for men with unfavorable intermediate-risk prostate cancer (UIR-PCa) including external beam radiotherapy (EBRT) ± brachytherapy boost ± androgen deprivation therapy (ADT). However, brachytherapy alone (BT) ± ADT is not currently recommended by the NCCN for UIR-PCa. Given that BT allows for significant dose-escalation relative to EBRT, we hypothesized that men treated with BT±ADT have comparable survival to men treated with EBRT±ADT.

A total 32,246 men diagnosed between 2004-2015 with UIR-PCa treated with EBRT±ADT (≥ 72 Gy in 1.8-2.0 Gy per fraction) or BT±ADT (HDR-BT or LDR-BT) were identified in the National Cancer Database (NCDB). Patients with a Charlson-Deyo comorbidity index (CDCI) score > 1, who received systemic therapy other than ADT, or missing key information were excluded. Inverse propensity of treatment weighting (IPTW) was used to adjust for covariable imbalances and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. Covariables included age, race, ethnicity, year of diagnosis, CDCI score, insurance status, educational and socioeconomic metrics, treatment at an academic center, PSA as diagnosis, Gleason score, clinical T-stage, and receipt of ADT.

Patients were stratified into four groups: (i) EBRT (n=12,985), (ii) EBRT+ADT (n=12,960), (iii) BT (n=4,535), or (iv) BT+ADT (n=1,303). Relative to EBRT alone, the following treatments were associated with improved OS: EBRT+ADT (Hazard Ratio (HR): 0.92 [95% Confidence Interval (95% CI): 0.87-0.97], P=.002), BT alone (HR: 0.90 [0.83-0.98], P=.01), and BT+ADT (HR: 0.78 [0.69-0.88], P=.00006). In men receiving ADT, brachytherapy correlated with improved OS relative to EBRT (HR: 0.84 [0.75-0.95]. P=.004) (Figure 1A). In men who were not treated with ADT, brachytherapy correlated with improved OS relative to EBRT (HR: 0.92 [0.84-0.99]. P=.03) (Figure 1B). At 10 years follow-up, 56% and 63% of men receiving EBRT and brachytherapy were alive, respectively (P<.0001). IPTW was used to determine the average treatment effect of definitive brachytherapy. Relative to EBRT, definitive brachytherapy was associated with improved OS (HR: 0.90 [0.84-0.97, P=.009) on weight-adjusted MVA. The addition of ADT was associated with a similar improvement in OS (HR: 0.90 [0.83-0.97], P=.004).

Definitive brachytherapy was associated with improved OS compared to EBRT for UR-PCa. The addition of ADT was associated with improved OS for patients treated with EBRT and those treated with BT.  BT+ADT was associated with improved OS vs. EBRT+ADT, an NCCN standard-of-care treatment. This study provides additional evidence to support incorporating BT+ADT into the NCCN guidelines for UIR-PCa.