Patients diagnosed with rectal cancer often face the possibility of complete organ loss, and 25 percent of patients with stage II/III rectal cancer require a permanent colostomy. Improvements in systemic therapy and use of neoadjuvant treatment have encouraged efforts to avoid radical resections. This trend has been seen with other solid malignancies including breast, anal, and head and neck cancers. For rectal cancer, there is ongoing investigation regarding whether preoperative chemotherapy along with less aggressive surgical resection will allow preservation of the rectum and rectal function and avoid the need for a stoma.
The NEO Trial (CCTG CO28)
The CCTG (Canadian Clinical Trials Group) CO28 Neoadjuvant chemotherapy, Excision and Observation (NEO) Trial has been activated at designated centers in the U.S. and Canada. It aims to treat patients diagnosed with T1-T3a/b, low- to mid-rectal tumors with neoadjuvant chemotherapy followed by minimally invasive transanal surgery. Study objectives are to establish the feasibility and safety of this approach to allow sphincter preservation.
Current treatment of T1-T3 rectal tumors includes radical surgery with an open or laparoscopic total mesorectal excision (TME), while preoperative chemoradiation is added for patients with T3-T4 or N+ tumors. Population-based studies in the U.S. have documented an increasing use of local excision/transanal surgery in the treatment of T1 or T2 rectal tumors.1 However, a significant proportion of T1-T2 tumors are pathologically node-positive and the literature demonstrates an increased rate of local relapse when patients are treated with transanal local excision alone.2-4
Staging and treatment
Patients enrolled in CO28 are staged with pelvic magnetic resonance imaging (MRI) and endoscopy (see Figure 1). Clinically node-negative tumors that are eligible for the NEO trial must meet the following criteria: T1, T2, or T3a/b but extend less than 5 mm beyond the muscularis propira; amenable to minimally invasive transanal excision; and exhibit no high-risk pathology features.
Figure 1. Study schema of the NEO Trial, CO28
The primary endpoint is the rate of downstaging to pT0 or pT1 upon excision after neoadjuvant chemotherapy. The study will be considered successful if at least 65 percent of patients are managed with rectal organ preservation.
Patients are treated with three months of neoadjuvant chemotherapy with FOLFOX (Oxaliplatin, Leucovorin, and 5-Fluorouracil) or CAPOX (Capecitabine and Oxaliplatin). If evidence of tumor regression is found on rectal endoscopy and MRI, patients proceed to tumor excision by surgeons experienced in transanal endoscopic microsurgery (TEMS) or transanal minimally invasive surgery (TAMIS). Participating surgeons must have performed at least 20 TEMS/TAMIS procedures and must submit an unedited video of the first patient they enroll.
Local excision is permitted for very low tumors when appropriate. Subsequent treatment is determined on the basis of tumor pathology on the resected specimen. Completely resected tumors downstaged to pT0 or pT1 without any histologic high-risk factors have a low risk of nodal involvement and are treated with observation.5,6 Endoscopic and cross-sectional imaging is repeated every four to six months for 36 months and annually in years four and five.
It is recommended that patients with tumors that do not achieve downstaging to pT1 after systemic chemotherapy proceed directly to standard TME surgery. Preoperative pelvic radiation is recommended only for patients with ypT3+ or node-positive tumors.
Study leads are Hagen Kennecke, MD, MHA, FRCPC, co-author of this column, and Carl J. Brown, MD, FACS, colon and rectal surgeon, Providence Health Care, Vancouver, BC. The study will be run by the Canadian Clinical Trials Group at select Canadian and U.S. cancer centers. Per-case funding will be provided and chemotherapy supply is expected to be commercially available. Contact Hagen.Kennecke@virginiamason.org for study information and participation.
- Stitzenberg KB, Sanoff HK, Penn DC, Meyers MO, Tepper JE. Practice patterns and long-term survival for early-stage rectal cancer. J Clin Oncol. 2013;31(34):4276-4282.
- Salinas HM, Dursun A, Klos CL, et al. Determining the need for radical surgery in patients with T1 rectal cancer. Arch Surg. 2011;146(5):540-543.
- Sajid MS, Farag S, Leung P, Sains P, Miles WF, Baig MK. Systematic review and meta-analysis of published trials comparing the effectiveness of transanal endoscopic microsurgery and radical resection in the management of early rectal cancer. Colorectal Dis. 2014;16(1):2-14.
- You YN, Baxter NN, Stewart A, Nelson H. Is the increasing rate of local excision for stage I rectal cancer in the United States justified?: A nationwide cohort study from the National Cancer Database. Ann Surg. 2007;245(5):726-733.
- Monson JR, Weiser MR, Buie WD, et al. Standards practice task force of the American Society of Colon and Rectal Surgeons. Dis Colon Rectum. 2013;56(5):535-550.
- Greenberg JA, Shibata D, Herndon JE 2nd, Steele GD Jr, Mayer R, Bleday R. Local excision of distal rectal cancer: An update of cancer and leukemia group B 8984. Dis Colon Rectum. 2008;51(8):1185-1191.