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Original Investigation
June 14, 2018

Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

Author Affiliations
  • 1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
  • 3Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, England
  • 4Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
  • 5Department of Pathology, Memorial Sloan Kettering Cancer Center, New York
  • 6Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
  • 7Department of Radiology, Memorial Sloan Kettering Cancer Center, New York
JAMA Oncol. 2018;4(6):e180071. doi:10.1001/jamaoncol.2018.0071
Key Points

Question  What are the advantages of total neoadjuvant therapy (preoperative systemic chemotherapy in combination with chemoratiation [TNT]) compared with the traditional approach of preoperative chemoradiation and postoperative adjuvant chemotherapy in patients with locally advanced (T3/4 or node-positive) rectal cancer?

Findings  In this retrospective cohort analysis, 308 patients treated with TNT were compared with 320 patients treated with chemoRT with planned adjuvant chemotherapy. Patients in the TNT cohort received greater percentages of the planned systemic chemotherapy, had higher rates of complete response (pathologic and sustained clinical), and were more likely to have temporary ileostomy reversed within 15 weeks of proctectomy.

Meaning  Total neoadjuvant therapy appears to have short-term advantages over the traditional chemoRT and adjuvant chemotherapy regimen for locally advanced rectal cancer; long-term follow-up will be required to determine if this translates into improved overall survival.

Abstract

Importance  Treatment 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.

Objective  To compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvant chemotherapy with the more recent TNT approach for LARC.

Design, Setting, and Participants  A 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.

Exposures  Of 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 Measures  Treatment 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.

Results  Of 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 Relevance  Our 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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