Recurrence and survival in patients with uT2uN0 rectal cancer treated with neoadjuvant chemoradiation and local excision: Results of the acosog Z6041 trial

Purpose: LE alone is an effective treatment for selected uT1uN0 RCs; however, for uT2uN0 RCs LE results in a higher local recurrence rate and lower survival compared to total mesorectal excision (TME). The Z6041 phase II trial (NCT00114231) investigates the efficacy of CRT and LE for treating uT2uN0 RC. Here we report the oncologic outcomes. Methods: Patients (pts) with ultrasound-staged T2N0, ≤4 cm diameter, RC located within 8 cm of the anal verge, and ECOG PS ≤2 were treated with capecitabine (825 mg/m2 days 1-14 and 22-35) and oxaliplatin (50 mg/m2 weeks 1, 2, 4 and 5) during radiation (RT) (total dose 54 Gy) followed by LE. Due to toxicity, the dose of RT was reduced to 50.4 Gy and capecitabine to 725 mg/m2 (5 days/week/5 weeks). Local and distant recurrences were recorded. Disease-free survival at 3 years was calculated using Kaplan-Meier analysis. Results: Of the 90 pts accrued, 11 were considered ineligible or withdrew consent. Of the 79 eligible pts, 1 had TME and 2 had no surgery. Of the 76 pts who had LE, 3 had ypT3 tumors and 1 had positive margins. They were considered inevaluable from primary endpoint analysis per study protocol. The 72 evaluable pts were followed for a mean 4.2 (0.5 - 6.4) years. At the end of follow-up 2 (3%) pts had developed local recurrence after LE; both were salvaged with an R0 abdominoperineal excision (APE) of the rectum, but 1 developed recurrence after APE. Five (7%) pts have developed distant metastasis (lung 3, liver 1, uterus 1). Six pts have died from unrelated causes during follow-up. The 3-year disease-free survival for the evaluable pts was 0.87 (0.79-0.95, 95% CI). Conclusions: The treatment of uT2uN0 rectal cancer with CRT and LE is associated with a low rate of local recurrence, but a higher rate of distant metastasis. The 3- year disease-free survival falls above the unacceptable level and close to levels deemed promising as defined by the study design. Therefore, CRT and LE may be considered as an alternative to TME for selected patients with uT2uN0 distal RC.