Predictive Factors for a Pathologic Complete Response in Patients Receiving Preoperative Chemoradiation for Locally Advanced Rectal Cancer

Abstract

Preoperative chemoradiation (CRT) is the standard of care for patients with locally advanced rectal cancer. The factors that predict for a pathologic complete response (pCR), however, have yet to be fully defined. The purpose of this study, therefore, is to identify patient, tumor, and treatment factors that predict for a pCR in these patients. We retrospectively analyzed the treatment outcome for 53 adult patients with T3 and/or N+ rectal cancer who underwent preoperative CRT at our institution. Three patients (6%) had T2 N+ disease, 24 patients (45%) had T3 N0 disease, and 26 patients (49%) had T3 N+ disease. Radiation therapy consisted of 4,500 cGy delivered to the whole pelvis followed by a 540 cGy boost to the primary tumor and/or involved lymph nodes. Chemotherapy consisted of a fluoropyrimidine alone in 26 patients or a fluoropyrimidine with oxaliplatin in 27 patients. Serum carcinoembryonic antigen (CEA) was recorded at the time of diagnosis for 43 patients. The interval from the last day of CRT to the day of surgery was recorded for all patients. The pCR rate was 23% for our cohort of patients. On univariate analysis, 100% (3/3) of patients with T2 tumors had a CR compared with 18% (9/50) of patients with T3 tumors (p = 0.009 by Fisher's exact test). The interval between the end of CRT and surgery was of predictive significance (p = 0.02 by t test), in that patients who achieved a pCR had a mean interval of 72 days between the end of CRT and surgery and patients not achieving a pCR had a mean interval of 51 days. There was a trend (p = 0.17 by t test) for lower serum CEA at diagnosis to be associated with a pCR. Lymph node status, location of tumor within the rectum, patient age, patient gender, and the type of chemotherapy did not have an effect on pCR. On multivariate analysis, a longer time interval between CRT and surgery was associated with a 1.04-fold greater likelihood of a pCR (p = 0.02) and an increasing CEA at the time of diagnosis, when measured as a continuous variable, was associated with a 0.83-fold reduction in the likelihood of a pCR (p = 0.09). Our study suggests that a longer time interval between the end of CRT and surgery as well as a lower serum CEA at diagnosis are associated with higher pCR rates. Given the small number of patients in our study with T2 tumors, we can only infer that a lower T stage may also be associated with a higher pCR rate. Consequently, the optimal interval between CRT and surgery may be longer than the currently recommended 4 to 6 weeks and more aggressive preoperative therapy may be appropriate for patients with significantly elevated serum CEA levels at diagnosis. We believe that additional studies with larger sample sizes are warranted to confirm these findings.