Predictors of Complete Response and Disease Recurrence Following Chemoradiation for Rectal Cancer.

Danielle S Bitterman,Nicholas J Sanfilippo,Ping Gu,Lucas Resende Salgado,Harvey G Moore,Ioannis Hatzaras,Kevin L Du

doi:10.3389/fonc.2015.00286

Danielle S Bitterman, Nicholas J Sanfilippo + Show 5 more

Open Access

https://doi.org/10.3389/fonc.2015.00286

Copy DOI

Abstract

Approximately 10-40% of rectal patients have a complete response (CR) to neoadjuvant chemoradiation (CRT), and these patients have improved survival. Thus, non-operative management ("watch-and-wait" approach) may be an option for select patients. We aimed to identify clinical predictors of CR following CRT. Patients treated with definitive CRT for T3-T4, locally unresectable T1-T2, low-lying T2, and/or node-positive rectal cancer from August 2004 to February 2015 were retrospectively reviewed. Most patients were treated with 50.4 Gy radiation and concurrent 5-fluoruracil or capecitabine. Patients were considered to have a CR if surgical pathology revealed ypT0N0M0 (operative management), or if they had no evidence of residual disease on clinical and radiographic assessment (non-operative management). Statistical analysis was carried out to determine predictors of CR and long-term outcomes. Complete records were available on 138 patients. The median follow-up was 24.5 months. Thirty-six patients (26.3%) achieved a CR; 30/123 operatively managed patients (24.5%) and 6/15 (40%) non-operatively managed patients. None of the 10 patients with mucinous adenocarcinoma achieved a CR. Carcinoembryonic antigen (CEA) ≥5 μg/L at diagnosis (OR 0.190, 95% CI 0.037-0.971, p = 0.046), tumor size ≥3 cm (OR 0.123, 95% CI 0.020-0.745, p = 0.023), distance of tumor from the anal verge ≥3 cm (OR 0.091, 95% CI 0.013-0.613, p = 0.014), clinically node-positive disease at diagnosis (OR 0.201, 95% CI 0.045-0.895, p = 0.035), and interval from CRT to surgery ≥8 weeks (OR 5.267, 95% CI 1.068-25.961, p = 0.041) were independent predictors of CR. The CR group had longer 3-year distant metastasis-free survival (DMFS) (93.7 vs. 63.7%, p = 0.016) and 3-year disease-free survival (DFS) (91.1 vs. 67.8%, p = 0.038). Three-year locoregional control (LRC) (96.6 vs. 81.3%, p = 0.103) and overall survival (97.2 vs. 87.5%, p = 0.125) were higher in the CR group but this did not achieve statistical significance. CR was not an independent predictor of LRC, DMFS, or DFS. CEA at diagnosis, tumor size, tumor distance from the anal verge, node positivity at diagnosis, and interval from CRT to surgery were predictors of CR. These clinical variables may offer insight into patient selection and timing of treatment response evaluation in the watch-and-wait approach.

Highlights

The standard treatment of locally advanced rectal cancer consists of chemoradiation (CRT), followed by total mesorectal excision (TME) 4–8 weeks later
We found carcinoembryonic antigen (CEA)
While we reported similar median distance from the anal verge as Restivo et al, our interquartile range (IQR) was wider and it is possible that very distal tumors are more susceptible to CRT

Summary

Introduction

The standard treatment of locally advanced rectal cancer consists of chemoradiation (CRT), followed by total mesorectal excision (TME) 4–8 weeks later. Other studies have reported a pCR rates ranging from ~10 to 40% [1,2,3,4,5]. Maas et al demonstrated that achievement of a pCR is associated with an improved outcome [2]. These findings raised interest in the possibility of a nonoperative treatment strategy, the “watch-and-wait” approach, for rectal cancer. Recent studies have reported rectal preservation rates of up to 78% and similar survival to patients treated operatively [7,8,9,10]

Methods

Results

Discussion

Conclusion