This study investigated the prognosis of high-risk stage II (T4N0) and low-risk stage III (T1-2N1, T1-2N2, T3N1) colorectal cancers, including the effects of postoperative chemotherapy. The number of patients who received AC was less in the T4N0 group. Survival analysis showed that T4N0 patients had a worse prognosis than the other groups. Multivariate analysis of RFS and OS showed that T4N0 was an independent predictor of a poor prognosis. The efficacy of AC for OS was demonstrated in T1-2N1 patients, but not in T4N0 patients.
In the present study, there was a difference in prognosis for each group. Moreover, high-risk II appeared to have a worse prognosis than low-risk Stage III. Previous reports suggested that the reason for the poor prognosis of T4N0 is the infrequent use of systemic chemotherapy in stage II patients and stage migration due to inadequate lymph node retrieval [3].
In the present study, AC was one of the prognostic factors for both OS and RFS in the overall cohort, but the efficacy of AC for T4N0 patients was not demonstrated. On the other hand, AC was associated with a better prognosis in Stage III. A previous retrospective study showed a benefit of chemotherapy in T4N0 patients, which differed from the present results [2]. There are several possible reasons why AC was not shown to be effective for T4N0 patients in the present study. One possible reason may be that only 28% of the patients in the present study received AC, whereas 86% of the patients in the previous study received AC, and the sample number may have been small [4]. Another possibility is that, of the patients who received AC, the number of patients who received doublet therapy was small. Furthermore, it has been reported that MSI-high tumors account for 6–10% of Stage II colorectal cancers, suggesting that fluoropyrimidine monotherapy may be ineffective in MSI-high tumors [5]. However, T4N0 tends to have a higher incidence of complications, and in cases where complications arise, many patients experience a decline in ADL or a delay in the initiation of adjuvant therapy, making it difficult to administer postoperative adjuvant therapy. Therefore, we believe that preoperative treatment should be considered for both rectal and colon cancer in T4N0 cases. Preoperative chemotherapy for T4N0 colon cancer has shown an effective downstaging effect to pT2 or less in about 8% of cases, with minimal risk of upstaging [6]. In the present study, T4N0 had a higher tendency for peritoneal dissemination recurrence compared to other groups. If downstaging of the T factor can be achieved through preoperative treatment, it may prevent the occurrence of peritoneal dissemination metastasis due to surgical manipulation and reduce the incidence of postoperative peritoneal dissemination recurrence.
The multivariable analysis for OS and RFS in all patients identified PS > 3, AC, and Group D (T4N0) as independent factors associated with prognosis. Patients with poor PS may not be able to receive AC, or it may be difficult for them to receive systemic chemotherapy after relapse. In the present study, even though the percentage of patients with good PS was higher in Group D than in other groups, the rate of AC was lower. Considering the low rate of AC administration likely due to Stage II, it is important to note that T4N0 has a poor prognosis. Therefore, as previously mentioned, preoperative chemotherapy might be recommended.
In the present study, the factor associated with poor RFS in Group D (T4N0) was rectal location, and the factors associated with poor OS were male and poor PS. There have been many studies showing that T4N0 has a poor prognosis, but few studies have identified which of these cases have a poor prognosis [1, 2]. The reason why the factor associated with poor RFS is the rectum may be that, in surgery for T4 rectal cancer, it is more difficult to ensure a circumferential resection margin, and local recurrence is more common than for colon cancer [7]. Therefore, it is better to perform intensive AC for T4 rectal cancer. The reason why the rectum was not a prognostic factor for OS may be that local control of rectal recurrence may be possible with radiation therapy or metastasectomy.
The present study has several limitations. First, this was a retrospective study of a relatively small cohort. Second, the chemotherapy regimen and duration depended on the surgeon’s choice and the patient’s wishes. Third, in this study, the number of T4N0 cases was small, the rate of chemotherapy administration was low, and the chemotherapy regimens varied, which may have impacted the survival analysis.
In conclusion, the results suggest that high-risk Stage II colorectal cancer may have a worse prognosis than low-risk Stage III colorectal cancer. In addition, AC was effective in improving the prognosis of low-risk Stage III patients. For T4N0 cases, further large-scale studies are needed to evaluate the appropriate use of adjuvant chemotherapy.