Clinicopathologic determinants of pathologic treatment response in neoadjuvant treated rectal adenocarcinoma

Neoadjuvant treatment (NAT) followed by total mesorectal excision is currently considered the standard of treatment for rectal adenocarcinoma. The degree of pathologic treatment response (pTR) correlates significantly with the recurrence free survival and overall survival (OS). However, it remains unclear which clinical and pathologic factors are associated with a more robust response to NAT, including showing pathologic complete response (pCR). Chemokine receptor 4 (CXCR4) overexpression has been associated with unfavorable OS in some studies. In this study, we sought to evaluate the clinicopathologic determinants of pTR in neoadjuvant treated rectal adenocarcinoma (NAT-RA). We retrospectively identified 91 patients who underwent pre-treatment diagnostic biopsy, NAT, and surgical resection at our institution. The archival slides were reviewed for pathologic features in the pre-treatment biopsies and for assessment of pTR in the resection specimens according to the current College of American Pathologist (CAP)'s guidelines. pCR was obtained in 16.5% of the cases, whereas 20.9% had near pCR, 30.8% had partial response, and 31.9% had a poor/no response. CXCR4 immunohistochemical analysis was also performed on the pre-treatment biopsies. Lower pre-treatment cT-stage (p = 0.019) and pre-treatment AJCC cTNM stage groups (p = 0.004), longer time interval between completion of NAT and resection (p = 0.022), and presence of tumor-infiltrating lymphocytes in the pre-treatment biopsies (p = 0.019) were significantly associated with a better pTR. CXCR4 nuclear expression was associated with a lower percentage of residual tumor (p = 0.036). Pre-treatment CEA levels, tumor differentiation, CAP treatment response groups and lower percentage of residual tumor were associated with a better OS.