Background: The standard treatment for patients diagnosed with rectal cancer is surgery, and, depending on the clinical stage of the tumor, it is frequently combined with preoperative chemo-radiation therapy (CRT). Preoperative CRT results in pathologic complete response (pCR) in about 10-30% of patients. Accurate prediction of that response could avoid surgery. The aim of this study was to identify clinical and histopathological predictors of pCR as well as the association between pre-treatment CEA levels and pCR in non-smoking and smoking patients receiving preoperative CRT for rectal cancer.
Methods: One thousand and two hundred and thirty patients diagnosed between 1998 and 2009 with primary rectal adenocarcinoma without any evidence of distant metastasis and operated with a radical total mesorectal excision (TME) resection were identified. A total of 449 patients remained for inclusion in the study after excluding patients with any of the following: no neoadjuvant CRT (n=720) history of pelvic radiation treatment (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, MRI, CT, flexible sigmoidoscopy/colonoscopy, chest X-ray and PET-CT. 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 5.6 weeks.
Results: Ninety-one patients (20%) achieved pCR and 85 patients (19%) had only microscopic residual disease left at the time of surgery. In patients with pCR, pretreatment tumor size was smaller, 4.2 cm (95% C.I 3.8-4.6 cm) vs. 4.8 cm (95% C.I 4.6-5.0 cm), and pretreatment CEA was significantly lower, 3.4 ng/ml (95% C.I 2.3-4.6 ng/mL) vs. 10.0 ng/mL (95% C.I 7.5-12.5 ng/ml), when compared to the group with no pCR. When stratifying for smoking status, CEA was significantly associated with pCR only in the group with non-smokers (p=0.018). When adjusting for number of cigarettes smoked per week in the multivariate analysis, CEA was no longer significantly associated with pCR.
Conclusions: In non-smokers a low CEA level are significantly associated with pCR. The predictive value of CEA in smokers can be limited and further studies needs to evaluate the impact of smoking on the predictive value of CEA for pCR in rectal cancer.