As reported in the Journal of Clinical Oncology by Hagen F. Kennecke, MD, MHA, and colleagues, the Canadian Cancer Trials Group phase II NEO trial has shown that 3 months of neoadjuvant chemotherapy resulted in tumor downstaging and avoidance of radical surgery in a high proportion of patients with early rectal cancer.
Study Details
In the study, 58 patients from sites in Canada and the United States with clinical T1–T3abN0 low- or mid-rectal adenocarcinoma eligible for endoscopic resection were enrolled between August 2017 and May 2020. Patients received 3 months of neoadjuvant chemotherapy with mFOLFOX6 (modified folinic acid, fluorouracil, oxaliplatin; n = 32) or CAPOX (capecitabine/oxaliplatin; n =26). Those with evidence of response proceeded to endoscopic transanal excision surgery (TES) 2 to 6 weeks later; those without sufficient downstaging were recommended for total mesorectal excision (TME).
Hagen F. Kennecke, MD, MHA
The primary endpoint was organ preservation rate in the intention-to-treat population, defined as the proportion of patients with tumor downstaging to ypT0/T1N0/X and who avoided radical surgery.
Key Findings
Among the 58 patients, all started chemotherapy and 56 proceeded to TES. A total of 33 of the 58 patients had tumor downstaging to ypT0/1N0/X on surgery specimens, representing an organ preservation rate of 57% (90% confidence interval [CI] = 45%–68%). Of the 23 patients recommended for TME, 13 chose to proceed directly to observation, resulting in an overall organ-preservation rate of 79% (90% CI = 69%–88%). Among the 10 patients undergoing TME, 7 had no histopathologic residual disease.
Median follow-up was 15.4 months. Among all patients, locoregional relapse-free survival at 1 and 2 years was 98% (95% CI = 86%–100%) and 90% (95% CI = 58%–98%). No distant recurrences were observed. No deaths were reported.
The proportion of patients with major low anterior resection syndrome at 6 months postexcision was 22%, decreasing to 14% at 12 months. At all time points, there was little change from baseline in the lifestyle and depression/self-perception scales of the Fecal Incontinence Quality of Life instrument.
The investigators concluded, “Three months of induction chemotherapy may successfully downstage a significant proportion of patients with early-stage rectal cancer, allowing well-tolerated organ-preserving surgery.”
Dr. Kennecke, of the Providence Cancer Institute and Earle A. Chiles Research Institute, Portland, Oregon, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Canadian Cancer Society. For full disclosures of the study authors, visit ascopubs.org.
