Colorectal cancer (CRC) of the clinical tumor stage T4b (cT4b) refers to advanced tumors with direct invasion of adjacent structures and the tumors are considered unresectable. Despite advancements in aggressive surgery and combination chemotherapy, the prognosis of cT4b CRC remains poor. Optimizing the therapeutic sequence administered to patients with cT4b CRC to improve clinical outcomes is crucial. In the present study, patients with unresectable cT4b and nodal stage N1-2 CRC were investigated at a single institution. A total of 20 consecutive patients were treated with pre-operative concurrent chemoradiation by using 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) since February 2015 and were regularly followed up until March 2020. Due to their poor response to concurrent chemoradiation (CCRT) with FOLFOX, the chemotherapy regimen was changed to irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) as the second-line neoadjuvant treatment. Genetic alterations, such as microsatellite instability (MSI), were documented, and the expression levels of excision repair cross-complementing group 1 (ERCC1) and ERCC2 were examined. Of the 20 patients, the tumors of 14 patients (70%) became resectable after FOLFIRI administration. The median duration between the last date of radiotherapy and surgery was 32.7 weeks (range, 10.1-59.3 weeks). Of note, 4 of the 14 patients with resectable tumors (28.6%) achieved a pathologic complete response. The median overall survival and progression-free survival were 27.5 months (range, 12-39 months) and 27.5 months (range, 8-39 months), respectively. The cancerous specimens of all of the patients (100%) exhibited ERCC2 overexpression and 18 specimens (90%) had ERCC1 overexpression. Only one tumor (5%) exhibited high MSI. The present study indicated that ERCC overexpression associated with the poor response of FOLFOX-based CCRT and FOLFIRI after FOLFOX-based CCRT failure may have a potential role in conversion to resectable tumors by neoadjuvant treatment in cT4b CRC. However, a further prospective study with more patients is required to improve the precision of the conclusions.

It has been reported that 20-25% of patients with colorectal cancer (CRC) have metastases at the time of diagnosis. Liver and lung are the most common metastatic sites. The aim of the present study was to investigate the association of KRAS and NRAS mutations with clinicopathological features and prognosis of patients with initial liver-metastasis only (LiM-only) or lung-metastasis only (LuM-only) metastatic CRC (mCRC). Overall, 166 patients with CRC with initial LiM-only (n=124) and LuM-only (n=42) were retrospectively analyzed from January 2014 to December 2017. The median follow-up time was 19.2 months (1.0-57.1 months). Patient characteristics at diagnosis were collected. Genomic DNA was isolated from frozen primary CRC tissues for targeting KRAS and NRAS. Patients with LuM-only were significantly older compared with those with LiM-only (65.5 vs. 61.5 years; P=0.05). There was no significant differences between the LiM-only and LuM-only groups in terms of sex, location of the primary tumor, serum carcinoembryonic antigen level, histological grade and RAS mutation status. KRAS mutations were detected in 43 (41.0%) patients with LiM-only and 13 (35.1%) patients with LuM-only. The overall survival time (OS) of LuM-only was more favorable compared with that of patients with LiM-only (44.5 vs. 24.7 months); however, there was no significant difference (P=0.095). The progression-free survival (PFS) and OS in the RAS wild-type group were significantly improved compared with the RAS mutant cohorts (P=0.004 and P=0.031, respectively) in the LiM-only group. In patients with stage IV CRC, those with synchronous LiM-only mCRC had a higher incidence of metastasis but a less favorable PFS and OS compared with patients with LuM-only. RAS mutation status exhibited a significant association with the survival outcome in patients with LiM-only mCRC.