This study showed that sarcopenia, which was defined by TPI, was significantly associated with a longer postoperative hospital stay in patients with stage Ⅲ colon cancer who underwent laparoscopic radical resection, and patients with sarcopenia had a poorer completion rate of adequate AC. Sarcopenia was also a significant prognostic predictor for 3-year DFS.
Nowadays, there are two main methods to quantify sarcopenia, including measuring cross-sectional skeletal muscle area or cross-sectional area of psoas muscles at the level of the L3. In this study, we defined sarcopenia by measuring a sectional area of psoas muscles due to its operability and clinical practicality.
Sarcopenia was diagnosed in 19.6% to 32.9% of colorectal cancer patients in early studies.[8, 11] There were 45.9% of patients being classified as sarcopenia in our study. This may because we only included patients with stage Ⅲ colon cancer, which was more likely to cause frailty. We found patients with sarcopenia had longer postoperative hospital stay than those without sarcopenia, though the overall rate of postoperative morbidity was not significantly different between the two groups. A longer postoperative hospital stay may be due to the frailty caused by sarcopenia, which made the patients need more time to recover from the surgical trauma.
In the past 30 years, AC has been the standard treatment for patients with stage Ⅲ colon cancer since the previous studies have shown the benefits in relapse-free survival and overall survival by using AC.[21, 22] Consistent with early studies, our study showed AC significantly improved 3-year OS and DFS. However, due to economic, physical, or psychological factors, not all patients with stage Ⅲ colon cancer can finish the formal AC in clinical practice. Roger H et al found that up to 40% of patients with stage Ⅲ or high-risk stage Ⅱ colon cancer did not receive recommended AC in their study.
According to the final results of a prospective, pooled analysis of six randomized, phase 3 trials (IDEA collaboration), the 5-year overall survival between 3 months and 6months of AC was similar (82.1% versus 81.2%, HR 0.96 [0.85-1.08]), which supported the use of 3 months of adjuvant CAPOX for most patients with stage III colon cancer. In our study, we define that receiving AC more than 3 months of CAPOX as an adequate AC. For the first time, we found sarcopenia was a significant factor to influence the compliance of receiving both AC and adequate AC for patients with stage Ⅲ colon cancer. Patients with sarcopenia had significantly lower compliance than those without sarcopenia. In addition, among patients who received AC, the rate of receiving adequate AC in the non-sarcopenia group was higher than in the sarcopenia group.
The reason for a lower rate of adequate AC in the sarcopenia group may be that the surgery trauma aggravated the frailty of patients who had sarcopenia, which makes them unable to withstand the toxicity and complications of AC. Nowadays, some studies explored the feasibility and efficacy of neoadjuvant chemotherapy for locally advanced colon cancer and demonstrated the potential benefit when compared to AC[25-27]. Considering the low compliance of AC in patients with sarcopenia, neoadjuvant chemotherapy may be an option, and better nutrition support for the malnourished sarcopenia patients before the operation may benefit the short-term and long-term outcome, which need further study to confirm.
The prognostic significance of sarcopenia in patients with colorectal cancer (CRC) is controversial. A retrospective study of 220 stage Ⅰ-Ⅲ CRC found that sarcopenia was an independent risk factor for both recurrence-free survival (RFS) and OS. However, another study including 494 patients with CRC showed sarcopenia did not significantly correlate with OS or RFS. The reason for the different results between the two studies may be that they used different diagnostic criteria. In this study, when using the TPI as the diagnostic criteria for sarcopenia, we found sarcopenia was a significantly negative prognosis factor of 3-year DFS in patients with stage Ⅲ colon cancer. There was a tendency that patients with sarcopenia had poorer 3-year OS than those without sarcopenia (79.6% vs 90.0%, P=0.092), though the P-value did not reach the significance, the possible reason for these results is the relatively small sample size and inadequate follow up.
There were some limitations of this study that should be addressed. First, this was a single-institution, retrospective study with relatively small sample size. Second, we used the predefined cutoff for sarcopenia in the previous study, which may be not appropriated for the population included in this study. The optimal cut-off values for TPI that define sarcopenia in Asian patients with colon cancer, still require further investigation. Third, limited by data, the dose intensity of chemotherapy drugs was not analyzed in this study, and whether the dose intensity influenced the completion rate of AC was not discussed.