Sarcopenia was negatively associated with a long-term oncological prognosis. Sarcopenia patients showed significantly lower OS and DFS. However, there were no significant differences in short-term postoperative outcomes. Body composition factors other than sarcopenia did not significantly impact the patient’s survival. Sarcopenia was negatively associated with a long-term oncological prognosis. Sarcopenia patients showed significantly lower OS and DFS. However, there were no significant differences in short-term postoperative outcomes. Body composition factors other than sarcopenia did not significantly impact the patient’s survival.
Sarcopenia comprises both muscle loss and its dysfunction, which induce contractile impairment and metabolic and endocrine abnormalities. It affects whole-body metabolism and the immune or inflammatory response [34, 35]. The loss of muscle and the accumulation of intramuscular fat might be associated with metabolic syndrome via a complex interplay of factors including oxidative stress, proinflammatory cytokines, insulin resistance, hormonal changes, and mitochondrial dysfunction [36]. These factors may have contributed to long term survival.
The results of our study suggest that sarcopenia is a negative prognostic factor for both OS and DFS in patients with obstructive colorectal cancer. To our knowledge, this is the first report to describe the prognostic impact of sarcopenia specifically in patients with obstructive colorectal cancer. Other studies reported sarcopenia to have a negative effect on OS in patients undergoing resection for locally advanced rectal cancer after neoadjuvant chemoradiation therapy [14] and as an independent predictor of worse OS and DFS in stage I to III colorectal cancer [37].
Early studies of sarcopenia were often based on the work by Prado et. al [38]. In their study, they included sarcopenia data based on solid tumors of the lung or gastrointestinal tract from patients referred to a regional medical oncology service in Canada. However, because there are significant differences in body composition between different ethnicities, more data are needed from the Asian populations [39]. Moreover, more data are needed to assess the optimal cutoff value for sarcopenia for each ethnicity [12]. The Asian cut-off value for sarcopenia should be different from the one used in Western countries.
Sarcopenia was associated with a significantly increased risk of developing major complications [40]. However, one study reported that sarcopenia was not a predictor of postoperative complications [8]. In the present study, no significant differences in minor (11.8% vs. 12.5%) or major postoperative complications (5.6% vs. 6.9%) were observed between non-sarcopenia and sarcopenia patients (Table 3). All surgeries were performed at the three tertiary-referral hospitals where more than 100 colorectal cancer patients are treated annually by seven independent surgeons. These surgeons were qualified through live demonstrations held by the Korean Laparoscopic Colorectal Surgery Study Group and each submitted a videotape of their laparoscopic rectal surgery, which was subsequently reviewed by a trial steering committee to assess the surgeon's oncological technique [41].
Visceral obesity was reported to be a significant prognostic factor in predicting DFS in patients with resectable colorectal cancer [42]. Similarly, viscerally obese patients with rectal cancer have poorer DFS [43]. In contrast, BMI measurements were not correlated with any survival outcomes [42, 43]. Our data demonstrated that sarcopenia was negative associated with visceral obesity (Table 2) but there were no other significant differences in predicting DFS and OS in patients with obstructive colorectal cancer. A lower BMI was correlated with sarcopenia but not with prognosis. SMI was the most meaningful prognostic value among body composition factors.
According to a recent meta-analysis study [12], most studies (11/22, 50%) used SMI when applying muscle mass criteria in CT scan-based assessments of skeletal muscle index (SMI). Their defined cutoff values varied between 53.5 and 40.8 cm2 / m2 for men and 46.4 and 34.9 cm2 / m2 for women. To define a sarcopenia cutoff value for this study, we analyzed the association between body composition factors and sarcopenia in four different studies that included an Asian study population (46.4, 43.75, 43.2 and 40.8 cm2 / m2 for men and 37.5, 41.10, 35.3, 34.9 cm2/m2 for women for each study, respectively) [31, 44-46]. Among these, the cutoff value proposed by Takagi was applied differently to men and women and the inclusion criteria selected in their study was similar to ours. Additionally, their selected cutoff value did not differ significantly from the cutoff value of other Asian references. Thus, we used the same cutoff value proposed by Takagi [31], which was ideal for our study in Asian patients.
There are some limitations to this study. One possible limitation of the study is the definition of sarcopenia. It is based on the definition by the European Working Group on Sarcopenia in Older People (EWGSOP) and the Asian Working Group for Sarcopenia (AWGS), that relies on the presence of low muscle mass and low muscle function (muscle strength and physical performance) [47]. However, there is still no uniform standard to measure and define sarcopenia, including the protocol of grip strength measures till date [48], [49]. Sarcopenia can be measured by CT scan by assessing the muscle area in the L3 region [10]. This method is commonly used both to measure SMI and to define sarcopenia.
Another limitation of the study is bias of SMI results for the measurement of sarcopenia. There were no association between sarcopenia and nutrition status in this study (Supplementary Table 1&2). That is, clinicians were not blinded to the SMI results. Since this is a retrospective study, surgeons may have been more careful to perioperative management such as nutrition support to those with sarcopenia during and after surgery. It is apparent that patients who had sarcopenia were well managed in this study, as reflected by the complication rate with no significant difference shown between sarcopenia and non-sarcopenia patients. Owing to these limitations, the conclusion of our study may not be definite, and hence, the differences in postoperative outcome between sarcopenia and long-term outcomes in obstructive colon cancer must be probed further with prospective randomized studies. Despite these limitations, the results of our study emphasized that the sarcopenia diagnosed by L3SMI showed oncologic significance in obstructive colorectal cancer.
Treatment of obstructive colorectal cancer may occasionally require colonic stent implantation to improve the patient’s condition along with adjuvant chemotherapy that is often administered to these patients. Patients with obstructive colon cancer generally have poor prognosis and suffer large clinical burdens, including sarcopenia.
The CONUT score was originally developed as a tool for nutritional assessment, and is reported to be significantly associated with the prognosis of colorectal cancer [50]. Additionally, the preoperative CONUT score was an independent prognostic factor for cancer specific and disease free survival in obstructive colorectal cancer patients [21]. Results of this study suggest that sarcopenia is still considered to be an important factor in obstructive colorectal cancer, regardless of the patient's nutritional status or inflammatory condition.
In conclusion, a careful consideration and analysis of the patient's body composition status should be performed to overcome the large clinical burden in patients with obstructive colon cancer. In particular, sarcopenia should be considered in the patients’ risk assessments and stratification of oncologic prognosis. The sarcopenia, diagnosed by L3SMI, may be beneficial as a convenient, objective, and noninvasive marker, to guide individualized treatment decisions and improve follow-up outcomes in patients with colorectal cancer.