Predictive clinicopathologic factors for limited response of T3 rectal cancer to combined modality therapy

Purpose The response of T3 rectal cancer to combined modality therapy (CMT) is highly predictive of long-term outcome following surgery. The aim of this study was to identify pretreatment factors associated with poor tumor response to neoadjuvant chemoradiation. Methods A prospective institutional database at Memorial Sloan-Kettering Cancer Center was queried for endorectal ultrasound (ERUS) stage T3N0-2 rectal cancer patients, treated with CMT followed by surgical resection, between 1998 and 2003. Preoperative clinicopathologic factors determined by biopsy, ERUS, proctoscopy, and digital rectal examination were correlated with the degree of downstaging of the primary mural lesion (tumor downstaging) in response to neoadjuvant therapy. Associations were analyzed by chi-square, Kaplan-Meier, and logistic regression. Results Of 274 patients, 51% obtained tumor downstaging in response to preoperative treatment, i.e., lower pathologic T-stage compared with pretreatment ERUS. Five-year recurrence-free survival was 89% in the cohort that obtained tumor downstaging compared with only 45% in the cohort that obtained no tumor downstaging. Factors significantly associated with limited or lack of tumor downstaging after CMT included: fixed tumor on digital rectal examination (p<0.021), near- circumferential tumor (p < 0.011), tumor stenosis (p < 0.025), metastatic disease (p < 0.012), biopsy-proven poorly differentiated pathology (p < 0.002), and radial extension >2.5 mm on ERUS (p < 0.031). On multivariate analysis, deep radial extension on ERUS, metastatic disease, and poorly differentiated pathology were in each, independently associated with limited or lack of tumor downstaging. Conclusions Pretreatment evaluation with biopsy, proctoscopy, and ERUS can identify T3 rectal cancer patients unlikely to respond well to CMT. These patients may be considered for alternative protocols and their tumors studied to ascertain the molecular events responsible for resistance to chemoradiation.