• Andrea Cercek, RoxburghCampbell S DCSDDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, England., Paul Strombom, J Joshua Smith, TempleLarissa K FLKFDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Garrett M Nash, Jose G Guillem, Philip B Paty, Rona Yaeger, Zsofia K Stadler, Kenneth Seier, Mithat Gonen, Neil H Segal, Diane L Reidy, Anna Varghese, Jinru Shia, Efsevia Vakiani, Abraham J Wu, Christopher H Crane, Marc J Gollub, Julio Garcia-Aguilar, Leonard B Saltz, and Martin R Weiser.
• Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
• JAMA Oncol. 2018 Jun 14; 4 (6): e180071.

ImportanceTreatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases.ObjectiveTo compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC.Design, Setting, And ParticipantsA retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified.ExposuresOf the 811 patients, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT).Main Outcomes And MeasuresTreatment and outcome data for the 2 cohorts were compared. Dosing and completion of prescribed chemotherapy were assessed on the subset of patients who received all therapy at MSK.ResultsOf the 628 patients overall, 373 (59%) were men and 255 (41%) were women, with a mean (SD) age of 56.7 (12.9) years. Of the 308 patients in the TNT cohort, 181 (49%) were men and 127 (49%) were women. Of the 320 patients in the chemoRT with planned adjuvant chemotherapy cohort, 192 (60%) were men and 128 (40%) were women. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with planned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort.Conclusions And RelevanceOur findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation.

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