Patterns of Care for Patients with Locally Advanced Rectal Cancer Treated with Total Neoadjuvant Therapy between 2016-2020: An NCDB Analysis

Abstract

Treatment for locally advanced rectal cancer (LARC), defined as T3/4 or any T with N+ disease, typically requires multi-modality management consisting of radiation (RT), chemotherapy (CHT), and surgery. Despite emerging evidence that total neoadjuvant therapy (TNT) is the preferred treatment of LARC, it remains unknown what proportion of patients are receiving TNT in the United States. Our objective was to (1) determine the proportion of patients with LARC receiving TNT over time, (2) determine the most common method in which TNT is being delivered, and (3) determine what factors are associated with a lower likelihood of receiving TNT in the United States. Retrospective data was obtained from the National Cancer Database (NCDB) for patients diagnosed with rectal cancer between 2016-2020. Patients were excluded if they had M1 disease, T1-2 N0 disease, incomplete staging information, non-adenocarcinoma histology, received RT to a non-rectum site, or received a non-definitive RT dose. Patients were determined to have received TNT if they (1) received RT and multi-agent (MA)-CHT prior to surgery, (2) had an interval of >180 days from the onset of neoadjuvant therapy to surgery if they received long course (LC)-chemoradiation (CRT) (based on 35 days for LC-CRT + 112 days for 8 cycles of MA-CHT + 30 days to surgery), or (3) had an interval of >150 days from the onset of neoadjuvant therapy to surgery if they received short course (SC)-RT (based on 5 days for SC-RT + 112 days for 8 cycles of MA-CHT + 30 days to surgery). Data were analyzed using linear regression, Chi-square test, and binary logistic regression. Of the 26,375 patients included, the median age was 60 (range 21-90) years, with the majority of patients being <65 years old (65.6%), male (62.1%), and non-Hispanic white (77.0%). A total of 5,003 (19.0%) patients received TNT, and 21,372 (81.0%) patients received classical combined modality therapy (CMT). The proportion of patients receiving TNT increased significantly over time, from 6.1% in 2016, 9.0% in 2017, 15.3% in 2018, 25.8% in 2019, to 34.6% in 2020 (slope = 7.36, 95% CI 4.58-10.15, R2 = 0.96, p = 0.040). The most common TNT regimen was MA-CHT followed by LC-CRT (73.2% of cases from 2016-2020). The proportion of patients receiving SC-RT as part of TNT significantly increased from 2.8% in 2016, 1.7% in 2017, 4.6% in 2018, 7.3% in 2019, to 13.7% in 2020 (slope = 2.74, 95% CI 0.37-5.11, R2 = 0.82, p = 0.035). On multivariate analysis, factors associated with a lower likelihood of TNT use included age >65 (OR 0.66, 95% CI 0.61-0.71, p<0.001), female gender (OR 0.92, 95% CI 0.86-0.98, p = 0.014), Black race (OR 0.87, 95% CI 0.77-0.98, p = 0.024), and T3 N0 disease (OR 0.60, 95% CI 0.52-0.70, p<0.001). TNT utilization rates have significantly increased in recent years, from 6.1% in 2016 to 34.6% in 2020. The observed trend appears to be in line with the recent National Comprehensive Cancer Network (NCCN) guidelines recommending TNT as the preferred approach.