In the present study, we focused on stage IV CRC including curative resected stage IV CRC and unresectable metastatic CRC, and demonstrated that CONUT score, PNI, and mGPS are independent prognostic factors for OS in patients with stage IV CRC regardless of curative potential. Our results are compatible with previous reports that PNI, mGPS, and CONUT score were prognostic factors in CRC patients undergoing curative resection (5, 7, 8, 14, 17), and that CONUT score was a prognostic factor in metastatic CRC patients undergoing chemotherapy (16). To our knowledge, this is the largest study to date that comprehensively assessed the prognostic significance of nutritional and inflammatory measures in patients with stage IV CRC. Given that nutritional and/or inflammatory status has been recognized as a host-related prognostic factor in pancreatic cancer and esophageal cancer (1), nutritional and inflammatory measures may also be useful for stage IV CRC in daily clinical practice.
We demonstrated that three nutritional and inflammatory measures tended to stratify OS in subgroup analysis according to the treatment strategy. Furthermore, multivariate analyses adjusted for known factors including surgical treatment revealed that the three nutritional and inflammatory measures were all independent prognostic factors for OS in patients with stage IV CRC. These results suggest that nutritional and inflammatory status may be a useful prognostic indicator regardless of treatment strategies. It is acceptable because nutritional status affects tolerability not only surgery but also chemotherapy(2, 22–27). Patients with advanced cancer are prone to malnutrition, which in turn can lead to postoperative complications and worse postoperative survival(22, 25, 27). Malnutrition is also associated with severe chemotherapy-related toxicity and reduced survival (2, 24). Although treatment strategies for stage IV CRC vary depending on guidelines (20, 28, 29), nutritional scores can be applied to the entire population of stage IV CRC patients.
In the present study, all nutritional and inflammatory measures were evaluated based on pretreatment data and adjusted for known factors. CONUT scores range from 0–12 points, and patients are typically allocated into two to four groups based on score (14, 30). Cut-off values differ by study, with no consensus. We divided our patients into three groups (low (0/1), intermediate (2/3), and high (≥ 4), determined using pretreatment data), and found that pretreatment CONUT score was an independent prognostic factor for OS in patients with stage IV CRC. However, it remains unclear whether CONUT scores change during clinical progression of the disease. Moreover, the impact of nutritional intervention on CONUT score is unclear. A number of studies have shown that nutritional intervention improves clinical outcomes of surgery and chemotherapy (31–35), suggesting that nutritional intervention should be considered for malnourished patients. CONUT score, which comprehensively evaluates prognosis and nutritional status, can be used as a tool to screen for patients who require nutritional intervention. Further prospective studies to assess how nutritional intervention improves CONUT scores and prognosis are warranted.
Many nutritional and inflammatory measures have been reported to be associated with cancer prognosis. However, it remains controversial as to which one of those measures is the most useful. Several studies have compared CONUT score with other measures. For instance, Toyokawa et al. (11) reported that CONUT score was an independent predictor of OS and relapse-free survival among thoracic esophageal squamous cell carcinoma patients and was superior to platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, and GPS. Liu et al. (12) reported that CONUT score was an independent prognostic factor in patients with stage II-III gastric cancer receiving curative resection and adjuvant chemotherapy. In the low PNI group, CONUT score effectively stratified cancer-specific survival, suggesting it is potentially a better predictor for evaluating nutritional risk than PNI. In the present study, CONUT score, PNI, and mGPS were adjusted for known factors (i.e., age, gender, ECOG performance status, location of primary tumor, CEA levels, histological type, M category, and surgical treatment), and all three measures were independent prognostic factors in patients with stage IV CRC. Among them, however, CONUT score was significantly associated with OS. In contrast, there was no significant difference in OS between consecutive mGPS scores, suggesting that the distribution of CONUT scores was more balanced than that of mGPS scores. Unlike CONUT score and mGPS, there were only two groups by PNI; thus, CONUT scores may be more useful in stratifying patients with stage IV CRC compared to PNI and mGPS.
This study has some limitations. First, given the retrospective design and collection of data from one institution, there may have been selection bias. Second, although consecutive patients were enrolled, there have been significant changes during the long study period (2001 to 2015) in treatment strategies, such as chemotherapy. Thus, our study may not be fully reflective of current medical practice. The correlation between nutritional and inflammatory status and prognosis in stage IV CRC warrants further consideration and validation in prospective studies.