The prognostic and predictive factors for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy

Background Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is the standard treatment for locally advanced rectal cancer (LARC). Despite of improvements of neoadjuvant treatments, local recurrence is still problematic. Besides well-known clinical prognostic factors, more reliable predictive factors must be identified for predicting treatment response and prognosis of LARC. We aimed to investigate the clinical, laboratory, radiological, and histopathological parameters that predict response to neoadjuvant therapy. Methods A total of 51 patients with LARC who received neoadjuvant CRT between 2015-2018 in Antalya Training and Research Hospital were included in the study. Demographic characteristics of patients, pre-treatment laboratory parameters (CEA, CA 19-9, albumin, LDH, hemoglobin, lymphocyte count, thrombocyte count), grade, ulcer and necrosis in endoscopic biopsy materials, lymphovascular invasion (LVI) in resection materials after treatment, perineural invasion (PNI) presence, and degree of intratumoral lymphocytic response were examined. Post-operative tumor response rating was grouped according to the Modified Ryan Regression System. According to the pathological response status, numerical variables were compared with one-way analysis of variance. Frequency differences between pathological response grading were investigated by Chi-square test. Multivariate regression analyses were performed to reveal the factors predicting pathological responses. Survival analyses were performed using the Kaplan-Meier method. Results LARC pts who were treated with neoadjuvant CRT were included in the study. Median age was 64 ±12.4 (range 27-87) years. Clinical stage were T2 (21%), T3 (53%) and T4 (26%) and nod positivity rate was 77%. Pathologic grade was mostly grade 2. According to RECIST, ORR was 45.4%. According to Modified Ryan criteria; regression grade 0 and 1 (group 1: complete and near complete response) rate was 17.6 and 5.9%, grade 2 (group 2: partial response) was 51% and grade 3 (group 3: poor/no response) was 3.9%. Clinical characteristics, CT regimens and radiological response rates were similar between regression groups. 27.6% pts with radiological responders had no pathologic response. pN+ rate was 17% in the pts with good pathologic response. LVI rate was higher in the pts with group 3. NLR were similar between the 3 groups but TLR was different between groups 1 and 3 (p=0.015). TLR was higher than 135 in the pts with regression grade 2 and 3. According to regression analyses, PNI, NLR ≥2.8 and TLR ≥135 were independent predictive factors for regression grades. Median follow-up was 26 (range 3-97.2) months, median DFS was 19.58±4.6(95%CI:10.5-28.67) months. Median OS was not reached. Median DFS were similar between regression grades. However, regression grades, NLR and CEA were predictive factors for median DFS. Conclusions In concordance with the literature, we concluded that neoadjuvant CRT enhances the tumor immunologic response. Initially high NLR and TLR were predictive factors for neoadjuvant treatment response in the pts with LARC. Initially high CEA levels, LVI and PNI were poor prognostic factors. Radiological responses cannot always be correlated with pathological responses. Not only the primary tumor, but also lymph nodes must be evaluated carefully. Legal entity responsible for the study The author. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.