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

Abstract

Purpose: 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).

Methods: 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.

Results: 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.

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

Trial registration: ClinicalTrials.gov NCT03259035.

Conflict of interest statement

Carl J. Brown

Honoraria: Ethicon/Johnson & Johnson

Other Relationship: Medtronic (Inst)

No other potential conflicts of interest were reported.

Figures

FIG 1.

Flow diagram of 58 patients enrolled in the study. aRepresents ypT, cN0 stage. bRepresents yp stage. c, clinical; CAPOX, capecitabine-oxaliplatin; mFOLFOX, modified folinic acid–flurouracil-oxaliplatin 6; N, node; oOPR, observed organ preservation rate; psOPR, protocol-specified organ preservation rate; T, tumor; TES, transanal excision surgery; TME, total mesorectal excision; yp, pathologic stage following systemic or radiation therapy prior to surgery.

FIG 2.

Tumor genotype by FoundationOne CDx analysis in 53 patients with sufficient archival tumor tissue. MSI, microsatellite; TMB, tumor mutation burden.

FIG 3.

(A) EORTC QLQ-C-30 scores at baseline, pre-excision, 6 months, and 12 months after TES. Functioning and global scales were scored from 0 to 100, with higher scores indicating better QoL. Observed/expected sample size was 58/58 at baseline, 53/58 at pre-excision, 37/43 at 6 months after TES, and 23/26 at 12 months after TES. (B) LARS mean total scores at baseline, pre-excision, 6 months, and 12 months after excision. Scores of 0-20 correspond to no LARS, 21-29 to minor LARS, and 30-42 to major LARS. Observed/expected sample size was 58/58 baseline, 50/58 pre-excision, 36/43 at 6 months after TES, and 21/26 at 12 months after TES. (C) FIQL mean scores at baseline, pre-excision, 6 months, and 12 months after excision. FIQL was scored with a range from 1 to 5 with 1 indicating a lower functional status of QoL. Observed/expected sample size was 52/58 at baseline, 52/58 at pre-excision, 37/43 at 6 months after TES, and 23/26 at 12 months after TES. EORTC QLQ-C-30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–C30; FIQL, Fecal Incontinence Quality of Life; LARS, Low Anterior Resection Syndrome; QoL, quality of life; TES, transanal excision surgery.

FIG A1.

Kaplan-Meier curve for LRR-free survival among 58 patients enrolled in the study. LRR, locoregional recurrence.