CRT indicates chemoradiotherapy.
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Ellis CT, Dusetzina SB, Sanoff H, Stitzenberg KB. Long-term Survival After Chemoradiotherapy Without Surgery for Rectal Adenocarcinoma: A Word of Caution. JAMA Oncol. 2017;3(1):123–125. doi:10.1001/jamaoncol.2016.3424
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Early studies1-5 with small samples from specialized centers report success with nonoperative management (NOM) or the watch-and-wait approach after neoadjuvant chemoradiotherapy for rectal adenocarcinoma. However, it is unknown whether the results are generalizable to the broader population of patients with rectal cancer.1-5 Still, use of chemoradiotherapy without surgery has doubled among individuals with nonmetastatic rectal adenocarcinoma.6 The highest use is observed among those who typically have lower access to innovative care: black patients, uninsured or Medicaid insured patients, and individuals treated at low-volume centers.6 We suspected that this treatment approach in the community setting may often represent a disparity in appropriate care rather than an innovative and intentional treatment strategy. The outcomes for patients who receive chemoradiotherapy only outside a clinical trial are unknown. We hypothesized that this approach is associated with worse overall survival (OS).
The National Cancer Database, a hospital-based cancer registry, was used to identify incident cases of clinical stage II/III rectal adenocarcinoma from January 1, 2004, through December 31, 2008. The cohort was divided into 2 groups: chemoradiotherapy only and chemoradiotherapy plus proctectomy. To construct the cohort in such a way as to maximize the chance that patients in the chemoradiotherapy-only group would have been candidates for surgery, we restricted this group to only patients for whom it was reported that surgery was “not part of the planned first course of treatment.” We calculated OS in months from date of diagnosis to last contact or confirmed death.
We compared OS by treatment group using Kaplan-Meier survival curves and adjusted Cox proportional hazards models, controlling for patient, tumor, and facility characteristics. To account for immortal time bias, we excluded deaths that occurred in the year of diagnosis. The National Cancer Database analyses were each approved by and the need for informed consent waived by the University of North Carolina Institutional Review Board. All data were deidentified.
Throughout the entire follow-up period, individuals receiving chemoradiotherapy only had poorer OS than those receiving chemoradiotherapy and proctectomy (hazard ratio, 1.90; 95% CI, 1.75-2.04) (Figure). These differences persisted after adjusting for race, insurance status, and other factors independently associated with OS (adjusted hazard ratio, 1.69; 95% CI, 1.59-1.84) (Table).
Among a national sample of patients with clinical stage II/III rectal adenocarcinoma, patients treated with chemoradiotherapy only had inferior survival compared with conventional treatment. This finding is contrary to results of previously published single-institution and clinical trial reports on NOM.1-5 This finding is likely because chemoradiotherapy only can be viewed at once as both an innovative treatment paradigm in some settings and low-quality care in others. Although NOM is an intentional approach for some patients, it is likely that many individuals forgoing surgery in the community are doing so as a result of systematic barriers. Our results point to disparities in the process of rectal cancer care where historically disadvantaged groups receive suboptimal care and experience worse outcomes.
The finding that NOM is noninferior to conventional treatment for patients who have a complete response has received much attention. However, intensive follow-up is required for these patients. Although this type of surveillance is feasible with motivated patients in the context of a trial, substantial barriers may exist to ongoing follow-up in real-world settings.
Our study found inferior survival for patients treated with chemoradiotherapy only. From these data, we cannot know whether patients were receiving NOM and had a complete response to chemoradiotherapy or whether patients failed to receive surgery for other reasons. However, the results are concerning. As NOM becomes an increasingly accepted treatment approach, more comparative effectiveness studies evaluating outcomes in the real-world setting will be needed.
Corresponding Author: C. Tyler Ellis, MD, MSCR, Department of Surgery, University of North Carolina at Chapel Hill, 4001 Burnett-Womack Bldg, Campus Box 7050, Chapel Hill, NC 27599 (firstname.lastname@example.org).
Published Online: October 20, 2016. doi:10.1001/jamaoncol.2016.3424
Author Contributions: Dr Ellis had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Ellis, Dusetzina, Stitzenberg.
Acquisition, analysis, or interpretation of data: Ellis, Sanoff, Stitzenberg.
Drafting of the manuscript: Ellis, Stitzenberg.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Ellis, Dusetzina.
Obtaining funding: Ellis.
Administrative, technical, or material support: Ellis, Stitzenberg.
Study supervision: Ellis, Dusetzina, Stitzenberg.
Conflict of Interest Disclosures: Dr Sanoff reported receiving research funding from Novartis, Bayer, and Merck. No other disclosures were reported.
Funding/Support: This research was partially supported by grant T32-HS000032 from a National Research Service Award Pre-doctoral/Post-doctoral Traineeship from the Agency for Healthcare Research and Quality sponsored by The Cecil G. Sheps Center for Health Services Research, The University of North Carolina at Chapel Hill.
Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methods used or the conclusions drawn from these data by the investigator.
Additional Contributions: Tim Carey, MD, MPH, Department of Medicine and Social Medicine, School of Medicine, and Department of Epidemiology, University of North Carolina at Chapel Hill, provided thoughtful review of the manuscript and Allison Deal, MS, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, reviewed the survival analysis. Neither was financially compensated.
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