Preoperative anemia in colorectal cancer: relationships with tumor characteristics, systemic inflammation, and survival

Abstract

Anemia is common in colorectal cancer (CRC) but its relationships with tumor characteristics, systemic inflammation, and survival have not been well characterized. In this study, blood hemoglobin levels and erythrocyte mean corpuscular volume (MCV) levels were measured in two independent cohorts of 148 CRC patients and 208 CRC patients, and their correlation with patient and tumor characteristics, systemic inflammatory markers (modified Glasgow Prognostic Score: mGPS; serum levels of thirteen cytokines, C-reactive protein, albumin), and survival were analyzed. We found that anemia, most frequently normocytic, followed by microcytic, was present in 43% of the patients. Microcytic anemia was most commonly associated with proximal colon tumor location. Average MCV and blood hemoglobin levels were lower in tumors with high T-class. Low blood hemoglobin associated with systemic inflammation, including high mGPS and high serum levels of C-reactive protein and IL-8. Particularly, normocytic anemia associated with higher mGPS. Normocytic anemia associated with a tendency towards worse overall survival (multivariate hazard ratio 1.61, 95% confidence interval 1.07–2.42, p = 0.023; borderline statistical significance considering multiple hypothesis testing). In conclusion, anemia in CRC patients is most frequently normocytic. Proximal tumor location is associated with predominantly microcytic anemia and systemic inflammation is associated with normocytic anemia.

The impact of preoperative anaemia and anaemic subtype on patient outcome in colorectal cancer

“…Since these serum marker combinations may explain why anaemia is associated with poor patient outcomes, we evaluated the association between anaemia and PNI (calculated from serum total lymphocyte count and albumin) and mGPS (scored from serum albumin and CRP), which reportedly predict cancer patient outcomes. A few studies have reported that anaemia is more common in CRC patients with increased mGPS . However, to our knowledge, this is the first report of PNI as an anaemia‐related prognostic marker for CRC.…”

“…Väyrynen et al . also showed that BRAF mutation and high microsatellite instability status, key right‐sided CRC features, had no significant association with anaemia. However, the fact that anaemia is strongly associated with right‐sided CRC highlights the utility of an immunological viewpoint when considering CRC patients with anaemia.…”

“…Furthermore, anaemia-induced preoperative immunodeficiency might play a key role in promoting the activity of residual cancer cells after surgery, leading to tumour recurrence. V€ ayrynen et al [9] also showed that BRAF mutation and high microsatellite instability status, key right-sided CRC features, had no significant association with anaemia. However, the fact that anaemia is strongly associated with right-sided CRC highlights the utility of an immunological viewpoint when considering CRC patients with anaemia.…”

“…Our current study also showed that patients with microcytic anaemia had higher systemic inflammation and poorer clinical outcomes. V€ ayrynen et al [9], on the other hand, showed that patients with an elevated inflammatory response tended to have normocytic anaemia. This difference may be due to differences in the number of cases, the analysis (only univariate analysis was performed in V€ ayrynen's paper) and the racial diversity [31].…”

“…Studies have assessed the prognostic or predictive value of anaemia in CRC, and have reported an association between anaemia and adverse outcomes after resection [9,10], chemotherapy [11] or radiotherapy [12]. Interestingly, anaemia has been correlated with the systemic inflammatory response [9] and serum total lymphocyte count [13], supporting the pathogenic and immunogenic influence of anaemia on cancer status. However, there are few studies that have comprehensively assessed the clinical characteristics and the prognostic value of anaemic subtypes in CRC.…”