Summary
Background
Local excision is an organ-preserving treatment alternative for patients with stage I rectal cancer. However, local excision alone is associated with a high risk of local recurrence and inferior survival compared to transabdominal rectal resection. Here we investigate the oncologic and functional outcomes of neoadjuvant chemoradiotherapy and local excision for T2N0 rectal cancer.
Methods
This was a prospective, multi-institutional, single arm phase 2 trial for patients with clinically-staged T2N0 distal rectal cancer, treated with neoadjuvant chemoradiotherapy consisting of capecitabine (original dose 825mg/m2, twice daily, on days 1-14 and 22-35) , oxaliplatin (50mg/m2 weeks 1, 2, 4, 5), and radiation (5 days/week at 1.8 Gy/day for 5 weeks to a dose of 45 Gy, then a boost, for a total dose of 54 Gy) followed by local excision. Due to adverse events during chemoradiotherapy, the dose of capecitabine was reduced to 725 mg /m2, twice daily, 5 days/week, for 5 weeks, and the total dose of radiation to 50.4 Gy. Patients were followed at scheduled intervals and evaluated for recurrence and survival. Anorectal function (ARF) and quality of life (QOL) were assessed at baseline and one year after surgery, using validated instruments. The primary endpoint was 3-year disease-free survival for all eligible patients and for patients who completed chemotherapy and radiation, and had ypT0, ypT1, or ypT2 tumors, and negative resection margins. This trial is registered with ClinicalTrials.gov, number NCT00114231.
Findings
Seventy-nine eligible patients were accrued to the trial, and started nCRT. Three patients did not complete nCRT or LE per-protocol. Four additional patients completed protocol treatment, but one had a positive margin and three had ypT3 tumours. Median follow-up was 56 months. Of the 79 patients, five (6%) developed distant recurrence, and three (4%) recurred locally. All but two underwent salvage surgery. Three-year disease-free survival and overall survival for the entire group were 88% (0.88 (95% CI: 0.81, 0.96) and 95% (95% CI: 0.90, 1.00), respectively. Overall 14 (29%) of 79 patients had grade 3-4 gastrointestinal adverse events, 12 (16%) of 79 patients had grade 3-4 pain as an adverse event, 12 (16%) of 79 patients had grade 3-4 hematological adverse events, and 9 (11%) of 79 patients had grade 3 dermatologic adverse events during chemoradiation. Six (8%) of the 77 patients who had surgery had grade 3 pain, 3(4%) of 77 patients had grade 3-4 hemorrhage, 3 (4%) of 77 patients had gastrointestinal adverse events, 2 (3%) of 77 patients had infectious/febrile neutropenia, 2 (3%) of 77 patients had hematological adverse events, and one (1%) had neurological adverse events. The rectum was preserved in 72 of the 79 (91%) patients. ARF and QOL were unchanged one year after surgery compared to baseline.
Interpretation
Most patients with T2N0 rectal cancer treated with nCRT and LE achieved organ preservation without deterioration of their quality of life. The estimated 3-year DFS rate wa...
