Neoadjuvant Chemotherapy, Excision, and Observation for Early Rectal Cancer: The Phase II NEO Trial (CCTG CO.28) Primary End Point Results

Author(s): Hagen F. Kennecke, MD, MHA1;Chris J. O’Callaghan, PhD, DVM, MSc2;Jonathan M. Loree, MD, MS3;Hussein Moloo, MD, MPH4;Rebecca Auer, MD, MSc4;Derek J. Jonker, MD4;Manoj Raval, MD, MSc5;Reilly Musselman, MD4;Grace Ma, MD6;Antonio Caycedo-Marulanda, MD6;Vlad V. Simianu, MD7;Sunil Patel, MD2;Lacey D. Pitre, MD8;Ramzi Helewa, MD, MSc9;Vallerie L. Gordon, MD10;Katerina Neumann, MSc, PhD, MD11;Halla Nimeiri, MD12;Max Sherry, MSc, MBA2;Dongsheng Tu, PhD2;and Carl J. Brown, MD, MSc5
Source: DOI: 10.1200/JCO.22.00184 Journal of Clinical Oncology 41, no. 2 (January 10, 2023) 233-242.
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

Nice study showing a non-radiation approach to node-negative, earlier stage, low-lying rectal cancer, using FOLFOX/CAPEOX x 3 months followed by local excision for those with downstaging to T0/T1 disease. 79% of patients achieved organ preservation, and 2-year locoregional RFS was 90%. A good option for those who are not good candidates for radiation yet still want to avoid an APR-type surgery.


Organ-sparing therapy for early-stage I/IIA rectal cancer is intended to avoid functional disturbances or a permanent ostomy associated with total mesorectal excision (TME). The objective of this phase II trial was to determine the outcomes and organ-sparing rate of patients with early-stage rectal cancer treated with neoadjuvant chemotherapy followed by transanal excision surgery (TES).


This phase II trial included patients with clinical T1-T3abN0 low- or mid-rectal adenocarcinoma eligible for endoscopic resection who were treated with 3 months of chemotherapy (modified folinic acid–fluorouracil-oxaliplatin 6 or capecitabine-oxaliplatin). Those with evidence of response proceeded to transanal endoscopic surgery 2-6 weeks later. The primary end point was protocol-specified organ preservation rate, defined as the proportion of patients with tumor downstaging to ypT0/T1N0/X and who avoided radical surgery.


Of 58 patients enrolled, all commenced chemotherapy and 56 proceeded to surgery. A total of 33/58 patients had tumor downstaging to ypT0/1N0/X on the surgery specimen, resulting in an intention-to-treat protocol-specified organ preservation rate of 57% (90% CI, 45 to 68). Of 23 remaining patients recommended for TME surgery on the basis of protocol requirements, 13 declined and elected to proceed directly to observation resulting in 79% (90% CI, 69 to 88) achieving organ preservation. The remaining 10/23 patients proceeded to recommended TME of whom seven had no histopathologic residual disease. The 1-year and 2-year locoregional relapse-free survival was, respectively, 98% (95% CI, 86 to 100) and 90% (95% CI, 58 to 98), and there were no distant recurrences or deaths. Minimal change in quality of life and rectal function scores was observed.


Three months of induction chemotherapy may successfully downstage a significant proportion of patients with early-stage rectal cancer, allowing well-tolerated organ-preserving surgery.

Author Affiliations

1Providence Cancer Institute and Earle A Chiles Research Institute, Portland, OR;2Canadian Cancer Trials Group, Queen’s University, Kingston, ON, Canada;3BC Cancer, Vancouver, BC, Canada;4The Ottawa Hospital Research Institute, Ottawa, ON, Canada;5Providence-St. Paul’s Hospital, Vancouver, BC, Canada;6Health Sciences North, Sudbury, ON, Canada;7Virginia Mason Cancer Institute, Seattle, WA;8Juravinski Cancer Center, Hamilton, ON, Canada;9University of Manitoba, Winnipeg, MB, Canada;10CancerCare Manitoba, Winnipeg, MB, Canada;11Nova Scotia Health, Halifax, NS, Canada;12Foundation Medicine, Cambridge, MA

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