Neoadjuvant chemotherapy allowed 79% of patients with early-stage I/IIA rectal cancer to pursue organ-sparing excision surgery, potentially preserving their quality of life and bowel function.
Three months of neoadjuvant chemotherapy may allow patients with early-stage rectal cancer to significantly downstage their tumors and undergo organ-preserving surgery without the toxicities associated with preoperative chemoradiation, according to findings from the NEO trial published in the Journal of Clinical Oncology.
Ultimately, the organ preservation rate among patients with stage I or IIA rectal cancer who underwent neoadjuvant treatment was 79%. This included patients who declined recommended total mesorectal excision (TME). Enrolled patients experienced limited postoperative complications and although the transanal excision surgery initially had negative effects on bowel function, these symptoms subsequently improved.
In addition, the mean low anterior resection syndrome (LARS) score, though initially dipping within the 6 months post-excision, improved to baseline-like levels after 1 year.
“Three months of induction chemotherapy with mFOLFOX6/CAPOX may successfully downstage a significant proportion of patients with favorable-risk, early-stage rectal cancer, allowing well-tolerated organ-preserving surgical therapy with minimal effect on organ function,” wrote Hagen F. Kennecke, MD, medical oncologist with the Providence Cancer Institute and Earle A. Chiles Research Institute, and coinvestigators. “The approach offers a much-desired organ-sparing option and warrants further investigation.”
Many patients with select T1N0 of T2N0 rectal tumors undergo transanal excision surgery; however, there is an increased rate of local relapsed with local excision compared with surgical resection because of the pathologically node-positivize nature of many cT1-2N0 tumors. Multiple single-arm and randomized phase 2 studies have been conducted to explore the effect of pelvic chemoradiation prior to transanal excision surgery, and the organ preservation is reported to be between 50% to 68% with this technique. Preoperative radiation is linked to wound-healing complications, as well as sexual and sphincter dysfunction.
Neoadjuvant chemotherapy represents 1 approach to reduce the risk of relapse, although there are no data capturing the prospective experience of neoadjuvant chemotherapy and transanal surgery for patients with stage I rectal tumors. Therefore, the Canadian Cancer Trials Group designed a phase 2 trial with the intention of determining the outcomes and organ preservation rate associated with patients who received mFOLFOC6 or CAPOX.
The nonrandomized, open-label trial, enrolled patients with invasive, well-moderately differentiated rectal adenocarcinoma. Therapy included 6 cycles of mFOLFOX6 or 4 cycles of CAPOX per investigator choice. A 14-day cycle of mFOLFOX6 comprised leucovorin 400 mg/m2 and oxaliplatin 85 mg/m2 in one 2-hour infusion, bolus fluorouracil 400 mg/m2 once on day 1, and one 46-hour infusion of fluorouracil 2400 mg/m2. A 21-day cycle of CAPOX consisted of capecitabine 1000 mg/m2 twice daily for 14 days and oxaliplatin 130 mg/m2 once on day 1.
Ultimately, 56 out of 58 patients who commenced chemotherapy went on to receive excision surgery. One patient proceeded to receive TME. Patients underwent excision surgery within 2 to 6 weeks of completing their final cycle of chemotherapy. The surgery involved a minimum of 1 cm gross margin.
The protocol-specified organ preservation rate (psOPR) or the proportion of patients who had significant tumor downstaging and were able to avoid radical surgery, was 57% (n = 33/58; 90% CI, 45%-68%) among patients. This psOPR rate was similar among subset of patients with ct1, T2, or t3ab stage tumors at 63%, 54%, and 62%, respectively. The 23 remaining patients were advised to proceed with TME surgery based on protocol requirements; 13 declined and instead chose observation.
During the follow-up period, the 1-year and 2-year locoregional relapse-free survival rates were 98% (95% CI, 86%-100%) and 90% (95% CI, 58%-98%), respectively. Throughout that time, 2 locoregional recurrences were documented. There were no distant recurrences or deaths.
Lastly, an analysis of the EORTC QLQ-C30 analysis showed that, 12 months post-surgery, quality-of-life and rectal function scores showed almost no change compared with baseline scores.
“This is the first published study to describe organ-sparing outcomes of patients with stage I and early-stage II rectal cancer treated with induction chemotherapy and transanal surgical excision,” study authors concluded. “More than half of the enrolled patients experienced complete or near-complete pathologic downstaging and met the protocol criteria for organ-sparing therapy [and] no unexpected toxicities were encountered.”
Kennecke HF, O’Callaghan CJ, Loree JM, et al. Neoadjuvant chemotherapy, excision, and observation for early rectal cancer: the phase II NEO trial primary end results. J Clin Oncol. Published online August 18, 2022. doi:10.1200/JCO.22.00184