Evaluating the relationship between carcinoembryonic antigen levels and response to neoadjuvant therapy and tumor regression degree in patients with localy advanced rectal cancer

OBJECTIVEIn our study we, in patients who received the diagnose of advanced-stage local cancer and were decided to undergo neoadjuvant chemoradiotherapy, aimed to assess the relationship between pre-neoadjuvant therapy CEA levels and response measures to neoadjuvant therapy and tumor regression degrees established in histopathologic examination and to reveal those factors which can be used in predictting the response to neoadjuvant therapy.MATERIALS AND METHODSPatients who received the diagnose of advanced-phase local cancer and were followed up in Dokuz Eylül University Hospital between 1993 and 2009 and whose data were recorded prospectively, have been screened in Colorectal Cancer database retrospectively. A total of 138 patients whose data were accessed completely were enrolled in study.Pathologic stages of patients were scrutinized in accordance with `?Collage of American Pathologist?? criteria. Wheeler scoring system was used for tumor regression rating.Preoperative radiotherapy was applied as a dose of 45-50 Gy for 20-25 days. A concurrent chemotherapy of 5FU 225/m2/day was applied through central venous catheter.All the patients underwent an operation by a total mezorectal excision technique for a period of 6-8 weeks post-neoadjuvant therapy. A sphincter protective surgery was applied for patients for whom a clear surgical border of 2 cm was provided at distal and abdominoperineal resection was applied for others. In statistical analysis SPSS for Windows version 15.0 was used.FINDINGSOf the patients included in study 89 (64.5 %) were males, 49 (35.5 %) were women, their mean age was 58 ±13 years (ranging; 21-87 years). Tumor was localized at lower rectum at 92 (66.7 %) patients, middle rectum at 31 (22.5 %) and upper rectum at 15 (10.8 %). When preoperative stages were examined 24 (17.4 %) were at stage II and 114 (82.6 %) at stage III. 83 (60.1 %) patients underwent sphincter protective surgery and 55 (39.9 %) abdominoperineal resection.A complete pathological response observed in 8 patients (5.8 %) postoperatively. A regression in stage was detected in 86 patients (62.3 %) after neoadjuvant therapy. In series, 39 (28.2 %) patients with TRG1, 70 (50.7 %) with TRG2 and 29 (21.1 %) with TRG3 were detected. A response to adjuvant therapy was observed in 27 (69.2 %) patients with TRG1 (p>0.05).Patients? mean CEA value was 11.1 ± 23.6 ng/ml (ranging; 0.32-202ng/ml). CEA level was ?5 ng/ml in 53.6 % (74 patients) and >5 ng/ml in 46.4 % (64 patients). The regression in T stage was significantly higher in patients with CEA ?5 ng/ml, compared to the group with CEA>5 (p=0.004). Regression in stage was also significantly higher in the CEA ?5 ng/ml-group (p=0.002). A significant relationship was found between CEA levels ve TRG groups.The mean duration of follow-up was 42 months. When the patients with positive peripheral resection limit were excluded in 11 (8.1 %) patients a locoregional relapse was detected. A significant relationship was established between response to neoadjuvant therapy and locoregional relapse. Locoregional relapse was observed significantly infrequent in patients who respond to neoadjuvant therapy (p=0.025). There was no relationship between TRG and locoregional relapse.The overall survival rate in patients who respond to neoadjuvant therapy was found as 127 ± 13 months. In the same group disease-free survival was 99.9 ± 11.2 months (p<0.001). Any relationship between disease-free survival and TRG could not be found.DISCUSSION AND CONCLUSIONWhile a complete pathological response was seen in some of the patients who received neoadjuvant therapy, resistance to chemoradiotherapy was observed in others. To predict the responses of patients to chemoradiotherapy will lead to changes in treatment plan and prevent resistant patients to undergo chemoradiotherapy unnecessarily.In our study we determined that the CEA levels measured before therapy (cut off 5ng/ml) were effective in predicting the regression in T-sage of tumor in patients with advanced local rectum cancer.Wheeler regression scoring is not considered as an influential factor in evaluation of therapy-response. Distinct regression scorings may be more helpful.Consequently, pretreatment CEA value of ?5 ng/ml may provide insight into the increased possibility to respond to neoadjuvant therapy.