Association between neoadjuvant chemoradiation and survival for patients with locally advanced rectal cancer (original) (raw)

To examine the overall survival differences of neoadjuvant therapy modalities: no therapy, chemotherapy alone, radiation alone, and chemoradiation in a large cohort of patients with locally advanced rectal cancer. METHOD: Adults with clinical stage II and III rectal adenocarcinoma were selected from the National Cancer Database and grouped by type of neoadjuvant therapies received: no therapy, chemotherapy only, radiotherapy only, or chemoradiation. Multivariable regression methods were used to compare adjusted differences in perioperative outcomes and overall survival. RESULTS: Among 32978 patients included, 9714 (29.5%) received no neoadjuvant therapy, 890 (2.7%) chemotherapy only, 1170 (3.5%) radiotherapy only, and 21204 (64.3%) chemoradiation. Compared to no therapy, chemotherapy or radiotherapy alone was not associated with any adjusted differences in surgical margin positivity, permanent colostomy rate, or overall survival (all p > 0.05). With adjustment, neoadjuvant chemoradiation vs. no therapy was associated with a lower likelihood of surgical margin positivity (OR 0.74, p < 0.001), decreased rate of permanent colostomy (OR 0.77, p < 0.001), and overall survival Accepted Article This article is protected by copyright. All rights reserved. (HR 0.79, p < 0.001). When compared to chemotherapy or radiotherapy alone, chemoradiation remain associated with improved overall survival (vs. chemotherapy alone: HR 0.83, p = 0.04; vs. radiotherapy alone: HR 0.83, p < 0.019). CONCLUSIONS: Neoadjuvant chemoradiation, not chemotherapy or radiotherapy alone, is important for sphincter preservation, R0 resection, and survival for patients with locally advanced rectal cancer. Despite this finding, one-third of patients in the United States with locally advanced rectal cancer fail to receive stage-appropriate chemoradiation. SIGNIFICANCE STATEMENT: While neoadjuvant chemoradiation improves local control and results in a higher rate of sphincter-sparing surgery for patients with locally advanced rectal cancer compared radiotherapy alone, the association between chemoradiation and survival has been inconsistent. Our analysis demonstrates chemoradiation to be superior to monotherapy for sphincter preservation, R0 resection, and survival. Introduction: Over the past four decades, combined multi-modality treatments have significantly reduced morbidity and mortality for rectal cancer patients. 1 Following Heald's pioneering work demonstrating that local recurrence could be lowered by intact removal of the mesorectum, 2 randomized data have supported the efficacy of radiotherapy and fluorouracilbased chemotherapy in reducing the risks of local recurrence and improving long-term survival. 3-6 In particular, preoperative delivery of chemoradiation for rectal cancer improves tumor response, downstages advanced tumors, increases R0 resection rates, and reduces local recurrence. 7-10 Based on these benefits, national guidelines in the United States have supported use of concomitant neoadjuvant chemoradiation for all stage II and III rectal cancer Accepted Article This article is protected by copyright. All rights reserved. patients since 2002. 11 However, several groups have shown that adherence to neoadjuvant chemoradiation for rectal cancer continues to be suboptimal, varying by hospital volume, cancer center accreditation status, and geographic region. 12, 13 Lack of adherence to guidelines may be driven, in part, by conflicting data regarding the impact of neoadjuvant chemoradiation on patient survival. Existing randomized studies have not consistently demonstrated improved survival with neoadjuvant chemoradiation compared to radiotherapy alone, 3, 5, 14 which may be due to an inadequately powered study design. The largest randomized data from the European Organization on Research and Treatment of Cancer (EORTC) 22921 trial only included 250 patients per group, which may not be sufficient to detect differences in outcomes. 4 Therefore, we evaluated the effect of various neoadjuvant therapies on perioperative outcomes and long-term survival in rectal cancer using contemporary data from a nationwide dataset in the United States. Method Data Source and Study Population We queried the National Cancer Data Base (NCDB), which represents a joint collaboration between the American College of Surgeons and the American Cancer Society and captures approximately 70% of newly diagnosed cancer cases from more than 1500 Commission on Cancer-accredited hospitals in the United States and Puerto Rico. 15 The 2006 to 2012 Participant Use File for rectal tumors was used for analysis due to completeness of treatment data and reflection of current clinical management trends. The Duke University Institutional Review Board reviewed and granted exempt status for this retrospective study.