Treatment of colon cancer consists of surgical resection and chemotherapy. Stage II colon cancer is categorized into a high-risk group and low-risk group for recurrence, and chemotherapy is recommended for the high-risk group [1]. High-risk factors are perineural invasion, lymphovascular emboli, lymph node harvest less than 12, T4 stage, positive resection margin, obstruction, and perforation [2–4].

There is no doubt over treatment with chemotherapy for stage II colon cancer patients having high-risk factors. However, chemotherapy could cause side effects that makes patients’ compliance lower. Physicians face this dilemma, especially with patients who are old or have severe comorbidities. Therefore, this study was designed to determine the effectiveness of chemotherapy for patients with stage II colon cancer according to the number of high-risk factors.

From January 2007 to December 2012, 364 patients with stage II colon cancer who underwent curative resection were enrolled. Poor differentiation, lymphovascular emboli, perineural invasion, less than 12 harvested lymph nodes, T4 stage, malignancy-positive surgical margin, and cancer obstruction or perforation are considered high-risk factors. After surgery, postoperative 5-fluorouracil (5-FU)-based chemotherapy is administered orally.

Patients with stage II colon cancer were categorized into two groups depending on the performance of adjuvant chemotherapy and according to the numbers of positive high-risk factors. Age, sex, and tumor location were also compared as variables. Postoperative 5-year survival rates were investigated. Disease-free survival was not analyzed due to the small population of subgroups.

All of the patients underwent follow-up observation every 3 to 6 months for 2 years, and then every 6 months for 3 years. Follow-up examinations included a clinical history, physical examination, serum carcinoembryonic antigen assay, chest X-ray, abdominopelvic computed tomography or magnetic resonance imaging, colonoscopy, and positron emission tomography scanning if available.

Statistical analysis was performed by MedCalc (Ostend, Belgium). Analysis of differences between the two groups was by t-test or Fisher exact test. Analysis of overall survival (OS) and disease-free survival was performed by the Kaplan-Meier method and log-rank test. A P-value < 0.05 was set to indicate statistical significance. This study was approved by the Institutinal Review Board of Pusan National University Hospital (IRB No. H-1708-0003-057) and performed in accordance with the principles of the Declaration of Helsinki. The written informed consent was obtained.

Clinicopathological characteristics of patients with stage II colon cancer in this study was shown in Table 1. In terms of high-risk factors, 194 patients had none of the risk factors. Exclusively single high-risk factors, meaning patients having any kind of single high-risk factor were observed in 115 patients. One patient had four of high-risk factor. Adjuvant chemotherapy was given to 262 patients regardless of high-risk factors. Forty-five patients underwent no chemotherapy even with more than one high-risk factor (Table 2).

The 5-year OS rate of all patients was 84.6%, respectively. According to the presence of chemotherapy, 5-year OS was 86.6% and 79.4% for patients with chemotherapy and without chemotherapy. The 5-year OS rate according to number of high-risk factors in this study was summarized in Table 3. Comparing two groups of no high-risk factor and exclusively single high-risk factor, the 5-year OS rate was 87.1% and 87.0%, respectively. The 5-year OS rate was 85.1% and 87.8% in patients having none or exclusively single high-risk factors who underwent adjuvant chemotherapy and no chemotherapy, respectively (P= 0.505).

In the univariate analysis for OS, T4 stage and over 65 years old were significantly influenced having a worse OS rate (P= 0.003 and P=0.015). Including two more factors as adjuvant chemotherapy and number of high-risk factors, multivariate analysis showed that single factors of over 65 years old was significantly associated with a worse OS rate.

Although the incidence of colon cancer is gradually decreasing, it is still the second most common cancer. The standard treatment for colon cancer involves a combination of surgical resection, chemotherapy, and sometimes radiotherapy, and the need for treatment is almost always obvious except for stage IV colon cancer, which requires palliative care [1]. The recommended treatment for stage II colon cancer is ether follow-up observation or chemotherapy depending on the presence of risk factors and the pathology report [5–7]. For these patients, a 5-FU based oral anticancer drug is generally prescribed. Oral anticancer drugs have fewer side effects than oxaliplatin-based intravenous anticancer drugs, but severe side effects such as hand-foot syndrome sometimes occur. Therefore, it is hard to make a proper decision to prescribe anticancer drugs for stage II colon cancer patients who have underlying disease or are of old age.

Oncologic outcome of stage II colon cancer is reported as 70% to 85% in 5-year OS rate [8,9]. The effect of adjuvant chemotherapy has been well documented in patients with high-risk factors. Casadaban et al. [9] showed the improvement of OS in 15% to 20%. However, different aspects of effect over adjuvant chemotherapy in stage II colon cancer was reported in studies. Verhoeff et al. [10] concluded that only pT4 factor could influence OS rate with chemotherapy, and Babcock et al. [11] also reported similar result. In our study, pT4 factor showed a strong but insignificant influence on survival outcome. Over 65 years of age only affected OS rate significantly in multivariate analysis.

Patients with stage II colorectal cancer are often recommended to undergo adjuvant chemotherapy if they have just one high-risk factor, including perineural invasion, after surgery. Nevertheless, side effects such as hand-foot syndrome, diarrhea, and mucositis following oral chemotherapy can occur and chemotherapy is terminated early in up to 50% of cases [12]. The proportion of patients treated with oral chemotherapy who reported that the treatment was “very convenient” or that they were “very satisfied” was 60% to 70% [13]. Early termination of chemotherapy was reported in 13.8%, and 55.2% of patients experienced dose reduction [14,15]. In our study, early termination of chemotherapy was reported in 42 patients (11.5%) with unreported cause and dose reduction not assessed.

The present study has the inherent limitations of a retrospective study and small sample size of relevant patients. Therefore further investigation is required to reach a concrete conclusion. The criteria of old age could differ between study groups (e.g., over 70 years old). However, this study highlights the lack of a significant survival benefit of adjuvant chemotherapy in patients having none or exclusively single high-risk factors of stage II colon cancer. It will be necessary to evaluate a larger sample size to draw a firm conclusion.