Predictive factors of pathological complete response after long-course neoadjuvant chemoradiation therapy for rectal cancer

Abstract

Background: Preoperative chemoradiation therapy (CRT) in patients with rectal cancer results in pathologic complete response (pCR) in about 10-30% of patients. Predictive factors for obtaining pCR may influence the selection of patients for this therapy. The aim of this study was to evaluate the impact of tumor size, stage, location, circumferential extent, patient characteristics and pretreatment CEA levels on development of pCR after CRT. Methods: 530 patients treated with preoperative CRT and radical surgery for rectal adenocarcinoma 1998-2011 were identified. A total of 469 patients remained after excluding patients with a history of pelvic radiation (n=2), previous transanal endoscopic microsurgery or polypectomy of the primary lesion (n=15), concurrent malignant tumor (n=14), and no information about pre- or post-treatment T stage in the chart (n=30). The clinical tumor stage and size were assessed by endorectal ultrasound (90%), MRI (10%), pelvic CT (5%), flexible sigmoidoscopy/colonoscopy (100%), chest X-ray (100%) and PET-CT (1%). Pathologic complete response was defined as absence of viable tumor cells in the rectal wall and in any of the resected lymph nodes. CRT consisted of a 5-fluorouracil-based regimen and external beam radiation with a mean radiation dose of 50 Gy given over a mean of 5.7 weeks. Mean time between completion of CRT and surgery was 8.7 weeks (SD, ±7,4). Results: Ninety-six patients (20%) were found to have pCR in the operative specimen. Low pretreatment CEA (3.4 vs. 9.6 ng/ml; p<0.008) and smaller mean tumor size (4.2 vs. 4.7 cm; p<0.02) were significantly associated with pCR, but only low CEA level remained a significant predictor of pCR in the multivariate analysis. When stratifying for smoking status, low CEA was significantly associated with pCR only in the group of non-smokers (p=0.02). Conclusions: The current study indicates that non-smoking rectal cancer patients with a low CEA level have an improved chance to obtain pCR after CRT. Further studies are necessary to determine whether a low CEA level can aid in identifying patients who are candidates for close follow-up rather than surgery after CRT.