Predictors and Risk Factors of Pathologic Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer: A Population-Based Analysis

Abstract

Background: Patients with rectal cancer who achieve pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) may have a better prognosis and may be eligible for non-operative management. The aim of this research was to identify variables for predicting pCR in rectal cancer patients after nCRT and to define clinical risk factors for poor outcome after pCR to nCRT and radical resection in rectal cancer patients. Methods: A retrospective review was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2013. Non-metastatic rectal cancer patients who received radical resection after neoadjuvant chemoradiotherapy were included in this study. Multivariate analysis of the association between clinicopathological characteristics and pCR was performed, and a logistic regression model was used to identify independent predictors for pCR. A nomogram based on the multivariate logistics regression was built with decision curve analyses to evaluate the clinical usefulness. Results: A total of 6,555 patients were included in this study. The proportion of patients with pCR was 20.5% ( n = 1,342). The nomogram based on multivariate logistic regression analysis showed that clinical T4 and N2 stages were the most significant independent clinical predictors for not achieving pCR, followed by mucinous adenocarcinoma and positive pre-treatment serum CEA results. The 3-year overall survival rate was 92.4% for those with pCR and 88.2% for those without pCR. Among all the pCR patients, mucinous adenocarcinoma patients had the worst survival, with a 3-year overall survival rate of 67.5%, whereas patients with common adenocarcinoma had an overall survival rate of 93.8% ( P < 0.001). Univariate and multivariate analyses showed that histology and clinical N2 stage were independent risk factors. Conclusion: Mucinous adenocarcinoma, positive pre-treatment serum CEA results, and clinical T4 and N2 stages may impart difficulty for patients to achieve pCR. Mucinous adenocarcinoma and clinical N2 stage might be indicative of a prognostically unfavorable biological tumor profile with a greater propensity for local or distant recurrence and decreased survival.

A Comprehensive Evaluation of Associations Between Routinely Collected Staging Information and The Response to (Chemo)Radiotherapy in Rectal Cancer

“…The material is not large enough to draw firm conclusions from, and it is also retrospectively collected. Nonetheless, similar results were seen in other studies investigating factors associated with pCR after preoperative CRT [13,19,21] or scRT [36]. Tumors in stage cT2 also constitute most patients with CR after CRT [37].…”

“…However, in the groups receiving scRT+CT as many as 26% of the mucinous tumors had a CR (13 of 50 patients). This was not expected, as previous studies have indicated that rectal tumors with mucus production have poor response to CRT [20,21,35,48]. Too few patients are included in our study to be able to make firm conclusions, but if true, mucinous tumors could also reach pCR and should thus not be excluded from organ preservation, unless RT is given alone.…”

“…In a meta-analysis including 23 studies with almost 8500 patients, a low CEA level with cut-offs between 3.0 and 5.0 µg/L meant a doubling of the chance of reaching pCR than elevated levels [44], i.e., similar to our finding. Other studies have also found a correlation between elevated pre-treatment CEA level and pCR after CRT [19,21]. CEA is likely one of the most powerful predictors of response to preoperative RT/CRT and may be clinically relevant.…”

“…Numerous studies have explored what predicts a good response, or a pCR at surgery [4,[12][13][14][15][16][17][18][19][20][21]. However, these studies have thus far been unsuccessful in detecting any clinically useful marker for response prediction.…”

Serum Apolipoprotein A-I Predicts Response of Rectal Cancer to Neoadjuvant Chemoradiotherapy

“…A series of studies has confirmed the predictive ability of serum carcinoembryonic antigen (CEA) in pathological complete response (pCR). [8][9][10] In a study by Song et al, carbohydrate antigen 19-9 (CA19-9) appeared to predict downstaging to stage 0-I. 11 Even indices from the complete blood count, such as the platelet-lymphocyte ratio, have been shown to predict pCR.…”