Overall Survival Outcomes with Brachytherapy Based Dose Escalation for Gleason 8 versus 9-10 Prostate Cancer: An NCDB Analysis

Abstract

Some data suggests an overall survival (OS) benefit with a brachytherapy (BT) boost in Gleason score (GS) 8-10 prostate cancer patients compared with dose escalated external beam radiation therapy (EBRT). It is unclear whether all GS 8-10 patients derive the same benefit from a BT boost. Our hypothesis was GS 8 patients might benefit more from intensified local therapy, as their risk of distant disease is generally less compared with GS 9-10 patients. We utilized the National Cancer Database (NCDB) to investigate OS differences between GS 8 and GS 9-10 patients treated with either EBRT only or BT +/- EBRT. We included definitively treated localized prostate adenocarcinoma patients between 2004-2012 who received EBRT and/or BT with or without the addition of androgen deprivation therapy (ADT). Patients who underwent surgery or local ablative therapies were excluded. Dose escalated EBRT (DE-EBRT) was defined as 75.6-86.4 Gy, while dose deescalated EBRT (DD-EBRT) was defined as 59.4-75.4 Gy. All EBRT patients also received ADT. BT could have been monotherapy or in combination with EBRT, with or without the addition of ADT. Both high dose rate and low dose rate BT were included. A multivariable Cox proportional hazard model was used to assess OS. Furthermore, a test of interaction was used to assess differences in the effect of BT versus EBRT among subgroups of patients with Gleason 8 and Gleason 9-10 disease. Median survival was determined based on Kaplan-Meier survival curves. 24,842 pts were included (median follow up, 5.7 years). Among GS 8 patients, BT was associated with improved OS compared to DE-EBRT (HR – 0.83 (0.75 - 0.91, p < 0.001) and DD-EBRT (HR – 0.76 (0.67 – 0.84), p < 0.001). The median OS in GS 8 patients receiving BT, DE-EBRT, and DD-EBRT was 12.7, 10.4, and 9.8 years, respectively. A similar association was seen in GS 9-10 patients for BT compared to DE-EBRT (HR – 0.88 (0.79 – 0.99), p < 0.03) and DD-EBRT (HR – 0.78 (0.69 – 0.89, p < 0.001). The median OS in GS 9-10 patients receiving BT, DE-EBRT, and DD-EBRT was 10.6, 9.1, and 8.7 years, respectively. A test of interaction showed no difference in the effect of BT versus EBRT among subgroups of Gleason 8 (p=0.41) and Gleason 9-10 pts (p=0.37). In patients who received BT, there was no difference in OS in Gleason 8 (HR – 0.88 (0.73 to 1.06), p = 0.17) or Gleason 9-10 disease (HR – 0.99 (0.76 to 1.30), p = 0.96) with ADT versus no ADT. BT based dose escalation was associated with improved OS when compared to DE-EBRT and DD-EBRT in patients with GS 8-10 disease. The magnitude of benefit from BT was similar for Gleason 8 and Gleason 9-10, suggesting BT should be considered as a treatment option for these patients irrespective of Gleason group. Despite improved outcomes with BT, OS is still worse for GS 9-10 versus 8 disease suggesting the need for improvements beyond intensifying local treatment.