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Nodal Disease in Rectal Cancer Patients With Complete Tumor Response After Neoadjuvant Chemoradiation

Danger Below Calm Waters

Baucom, Rebeccah B., M.D.1; Maguire, Lillias H., M.D.2; Kavalukas, Sandra L., M.D.1; Geiger, Timothy M., M.D.1; Ford, Molly M., M.D.1; Muldoon, Roberta L., M.D.1; Hopkins, M. Benjamin, M.D.1; Hawkins, Alexander T., M.D., M.P.H.1

doi: 10.1097/DCR.0000000000000947
Original Contributions: Colorectal Cancer
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BACKGROUND: A subset of patients with rectal cancer who undergo neoadjuvant chemoradiation therapy will develop a complete pathologic tumor response. Complete nodal response is not universal in these patients and is difficult to assess clinically. Quantifying the risk of nodal disease would allow for targeted therapy with either radical resection or “watchful waiting.”

OBJECTIVE: This study aimed to identify risk factors for residual nodal disease in ypT0 rectal adenocarcinoma.

DESIGN: This is a retrospective case control study.

SETTINGS: The National Cancer Database 2006 to 2014 was used to identify patients for this study.

PATIENTS: Patients with stage II/III rectal adenocarcinoma who completed chemoradiation therapy followed by resection and who had ypT0 tumors were included. Patients with metastatic disease and <2 lymph nodes evaluated were excluded. Patients were divided into 2 groups: node positive and node negative.

MAIN OUTCOME MEASURES: The main outcome was nodal disease. The secondary outcome was overall survival.

RESULTS: A total of 42,257 patients with stage II/III rectal cancer underwent chemoradiation therapy and radical resection; 4170 (9.9%) patients had ypT0 tumors and 395 (9.5%) were node positive. Of patients with clinically node-negative disease (ie, pretreatment imaging), 6.2% were node positive after chemoradiation therapy and resection. In multivariable analysis, factors predictive of nodal disease included increasing (pretreatment) clinical N-stage, high tumor grade (3/4), perineural invasion, and lymphovascular invasion. Higher clinical T-stage was inversely associated with residual nodal disease. Overall 5-year survival was significantly different between patients with ypN0, ypN1, and ypN2 disease (87.4%, 82.2%, and 62.5%, p = 0.002).

LIMITATIONS: This study was limited by the lack of clinical detail in the database and the inability to assess recurrence.

CONCLUSIONS: Ten percent of patients with ypT0 tumors had positive nodes after chemoradiation therapy and resection. Factors associated with residual nodal disease included clinical nodal disease at diagnosis and poor histologic features. Patients with any of these features should consider radical resection regardless of tumor response. Others could be suitable for “watchful waiting” strategies. See Video Abstract at

1 Division of General Surgery, Vanderbilt University Medical Center, Nashville, Tennessee

2 Division of Colon and Rectal Surgery, University of Minnesota, Minneapolis, Minnesota

Funding/Support: None reported.

Financial Disclosures: None reported.

Disclaimer: The data used in the study are derived from a deidentified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data by the investigator.

Podium presentation at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, WA, June 10 to 14, 2017.

Correspondence: Alexander T Hawkins, M.D., M.P.H., Section of Colon & Rectal Surgery, Vanderbilt University, 1161 21st Ave South, Rm D5248 MCN, Nashville, TN 37232. E-mail:

© 2017 The American Society of Colon and Rectal Surgeons