Hypoalbuminemia in colorectal cancer prognosis: Nutritional marker or inflammatory surrogate?

Table 1 Pretreatment serum albumin and colorectal cancer

Ref.	Design	Objective	Sample size	Findings	Comments
Heys et al[7]	Retrospective cohort study	ALB's prognostic value in localized and metastatic CRC	431 patients	On multivariate analysis, reduced OS with lower ALB	First report of ALB's prognostic value in CRC
Boonpipattanapong et al[26]	Retrospective cohort study	Preoperative CEA and ALB's prognostic value in CRC following curative surgery	384 patients	Combination of CEA ≥ 5 ng/dL and ALB ≤ 3.5 g/dL predicts lower 5-yr OS. No statistically significant association of either alone with survival	Linking a tumor marker (CEA) to a host marker (ALB) can have a prognostic significance
Lai et al[35]	Retrospective cohort study	Preoperative ALB's value in predicting postoperative outcomes in CRC	3849 patients	Short-term: More complications related to wounds, anastomosis, lungs and urinary system in low ALB group	No difference in short-term postoperative GI and cardiovascular complications
				Long-term: Lower 5-yr OS (60% vs 78%) and 5-yr RFS (73.5% vs 78.9%) in low compared to normal ALB group
Cengiz et al[36]	Retrospective cohort study	Pretreatment ALB and cholesterol's prognostic value in CRC following curative surgery	99 patients	2.8 RR of death in low compared to normal ALB group. No survival effect for cholesterol on multivariate analysis	No difference in CRC recurrence between low and normal ALB groups
Chandrasinghe et al[37]	Retrospective cohort study	Pretreatment ALB's prognostic value in rectal cancer following curative surgery	226 patients	Lower 5-yr OS (47% vs 69%) and RFS (69.7% vs 83%) in low compared to normal ALB group. No differences in 30-d postoperative mortality/complications	First report on ALB's long-term prognostic value in rectal cancer
Gupta et al[38]	Systematic review	Relationship between pretreatment ALB and cancer survival	59 studies in total; 29 on GI cancers including 12 on CRC	26 of 29 studies on GI cancers had higher OS with higher ALB on multivariate analysis	Inter-study differences in definition of low ALB (continuous variable vs cut-off points)

ALB: Serum albumin; CRC: Colorectal cancer; OS: Overall survival; RR: Relative risk; CEA: Serum carcinoembryonic antigen; RFS: Recurrence-free survival; GI: Gastrointestinal.

Table 2 Pretreatment albumin-to-globulin ratio and colorectal cancer

Ref.	Design	Objective	Sample size	Findings	Comments
Azab et al[43]	Retrospective cohort study	AGR's prognostic value in CRC-related mortality	534 patients	75% lower 4-yr mortality in high AGR (> 1.32) compared to low AGR tertile (< 1.03), independent of ALB	Study excluded patients who received preoperative chemotherapy
Shibutani et al[44]	Retrospective cohort study	AGR's prognostic value in unresectable metastatic CRC treated with palliative chemotherapy	66 patients	High AGR group had higher OS (HR = 2.25, P = 0.03) and PFS (HR = 2.66, P = 0.03) than low AGR group on multivariate analysis	No statistically significant difference in ORR between high and low AGR groups
Suh et al[45]	Retrospective cohort study	Relationship between AGR and cancer incidence among healthy adults	26974 adults (30 ≤ age ≤ 80)	Low AGR (< 1.1) had higher cancer incidence, an OR = 3.28 for CRC development and higher cancer mortality compared to AGR > 1.1	First report on association of low AGR with the risk of cancer incidence and mortality in healthy adults

AGR: Serum albumin-to-globulin ratio; ALB: Serum albumin; CRC: Colorectal cancer; OS: Overall survival; PFS: Progression-free survival; OR: Odds ratio; ORR: Overall response rate.

Table 3 Glasgow prognostic score and colorectal cancer

Ref.	Design	Objective	Sample size	Findings	Comments
Petrelli et al[50]	Systematic review and meta-analysis	Quantification of impact of mGPS on OS in CRC	2227 patients from 9 studies	High mGPS was associated with worse OS (HR = 1.69) and CSS (HR = 1.84)	Studies in meta-analysis did not control for concurrent conditions that may affect mGPS, such as sepsis or medications
McMillan et al[51]	Systematic review	Relationship between mGPS and cancer outcome	60 studies with 18 on CRC	Higher mGPS in CRC predicted numerous worse outcomes (e.g., postoperative infections, toxicity, survival, etc.)	Study looked at all cancer patients. CRC studies were geographically restricted to the United Kingdom and Japan
Richards et al[52]	Prospective cohort study	Correlation between parameters of body composition and systemic inflammatory response in operable CRC	174 patients	Elevated mGPS was associated with low skeletal muscle index (P = 0.001)	No association seen between skeletal mass index and tumor-related variables such as tumor stage
Read et al[55]	Prospective cohort study	Relationship between inflammatory/nutritional prognostic factors and outcomes in advanced CRC	51 patients	High GPS was associated with worse OS (HR = 2.27), while the nutritional status as measured by validated scores was not on multivariate analysis	Small and heterogeneous study population

GPS: Glasgow prognostic score; mGPS: Modified glasgow prognostic score; CRC: Colorectal cancer; OS: Overall survival; CSS: Cancer-specific survival.