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

Abstract

ObjectiveApproximately 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.MethodsPatients 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.ResultsComplete 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.ConclusionCEA 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.

Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer

“…Another RCT 59 corroborated these findings. Two previous meta-analyses 10,60 found that the length of the interval between nCRT and surgery was an independent predictor of pCR. Kalady et al 61 even demonstrated that a longer waiting time between nCRT and surgery was the single most important determinant of pCR.…”

“…Another RCT corroborated these findings. Two previous meta‐analyses found that the length of the interval between nCRT and surgery was an independent predictor of pCR. Kalady et al .…”

Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer

“…Clinical factors, including tumor size, clinical T and N stages, distance of tumor from the anal verge, and interval from nCRT to surgery, are associated with response to nCRT in rectal cancer [19,20,21,22,23]. In addition, some pathological features have been shown to predict the response to nCRT.…”

“…In addition, some pathological features have been shown to predict the response to nCRT. Tumor differentiation, circumferential tumor, mucinous histology and the presence of macroscopic ulceration are associated with poor response to nCRT [20,21,22,23,24]. Imaging modalities including positron emission tomography-computed tomography, magnetic resonance imaging (MRI) and endoscopic ultrasound are currently used for pretreatment staging, assessment of response to nCRT, and restaging after nCRT [25,26,27,28,29,30,31,32].…”

Case Report of a Clinically Complete Response in a Rectal Cancer Patient after Chemoradiotherapy with a 2-year Watch and Wait Approach

“…The NCCN has a guideline for locally advanced rectal cancer proposing that CRT be followed by total mesorectal excision (TME) 1) . Pathological complete response (pCR) rates have been reported to range from 10 to 40% 2) . Maas et al demonstrated that achievement of pCR is associated with an improved outcome 3) .…”