Optimal timing of radiotherapy in high risk prostate cancer: Do missed days matter?

Abstract

Introduction: High-risk prostate cancer is associated with poorer overall survival (OS) and biochemical control compared to more favorable risk groups. External beam radiation therapy (EBRT) is widely used; however, outcomes data are limited with respect to time elapsed between diagnosis and initiation of EBRT.

Methods: The National Cancer Database was queried from 2004 to 2015 for patients diagnosed with high-risk adenocarcinoma of the prostate who received androgen deprivation therapy (ADT) and definitive EBRT. Logistic regression was utilized to determine covariates associated with missing EBRT treatments. OS was analyzed using multivariate cox proportional hazards models and propensity score matching.

Results: 9,610 patients met inclusion criteria with median follow-up of 40.6 months and median age of 72 years. Median PSA was 8.7 and median EBRT dose was 78 Gy. ADT was initiated at a median of 36 days and EBRT at a median of 63 days post-diagnosis. Median number of prolonged treatment days was 2.2. Black race (OR: 1.40; p < 0.01), treatment at a community clinic (OR: 1.32; p < 0.01), and living in an urban/densely populated area were associated with prolonged treatment. Time elapsed between ADT and EBRT > 74 days (HR: 1.20; p = 0.01) and prolonged treatment>3 days of EBRT (HR: 1.26; p = 0.005) were associated with an increased hazard of death. The 5-year OS was 79.6% and 82.9% for patients with prolonged treatment of 3 days or more of EBRT and those missing 3 days or less, respectively (p = 0.0006).

Conclusion: In this hypothesis-generating study, prolonged treatment delays and missing three or more EBRT treatments was associated with poorer OS in patients with high-risk adenocarcinoma of the prostate.

Keywords: Androgen deprivation therapy; External beam radiation therapy; Prostate cancer; Radiation oncology; Survival; Urology.

Fig. 1

CONSORT diagram of patient selection. CONSORT diagram depicting our stepwise implementation of exclusion criteria. A total of 282,220 patients from 2004 to 2015 were recorded in the NCDB with T1-3N0M0 adenocarcinoma of the prostate in the NCDB. Ultimately, 9,610 patients met inclusion criteria and were included in this analysis.

Fig. 2

Kaplan Meier survival curve for all patients completing EBRT within and beyond 3 missed treatment days. Kaplan Meier curves for overall survival among patients who missed 3 days of less of EBRT (blue) and over 3 days of EBRT (green), where the x-axis represents the time in months and the y-axis represents the survival probability. At 6-years, the OS was 79.5% for the former and 72.5% for the latter (p = 0.0006). Abbreviations: EBRT: external beam radiation therapy, OS: overall survival. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)