Hypoalbuminemia and colorectal cancer patients: Any correlation?: A systematic review and meta-analysis

**Background:** Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. While surgery remains the best curative option, over 45% of CRC patients die from the tumor. Serum albumin is a simple, affordable, and reliable biomarker used to assess nutritional status and has been linked to prognosis in various diseases. Hypoalbuminemia is common in malnourished CRC patients, but its predictive value for postoperative outcomes had not been systematically evaluated prior to this study.

**Methods:** The authors conducted a systematic literature search across PubMed, Europe PMC, and Cochrane databases using terms including serum albumin, hypoalbuminemia, prognosis, outcome, colorectal cancer, and neoplasm. The search was completed on December 20, 2022. Inclusion criteria were English-language studies on adults undergoing colectomy, laparotomy, laparoscopy, or abdominoperineal resection for CRC. Exclusion criteria included abstract-only publications and studies not reporting key exposures or outcomes. Hypoalbuminemia was defined as plasma albumin < 3.5 mg/dL. The primary outcome was 30-day mortality; secondary outcomes were hospitalization time, thrombosis, surgical site infection, sepsis, and wound events. Two authors independently extracted data. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) and GRADE. Meta-analysis was performed using Review Manager 5.4 with a random-effects model, calculating risk ratios (RRs) via the Mantel-Haenszel algorithm with 95% confidence intervals. Statistical significance was set at P < .05.

**Key Results:** From 20,626 initial records, 19,152 remained after deduplication. After title/abstract screening, 48 full-text articles were assessed, and 7 observational studies (236,480 patients) were included. NOS scores ranged from 7 to 8, indicating moderate to sound quality. The meta-analysis found that preoperative hypoalbuminemia was not significantly associated with 30-day mortality (RR 2.05 [0.72, 5.86], P = .18, I² = 99%). However, hypoalbuminemia was significantly associated with morbidity (RR 2.28 [1.78, 2.93], P < .00001, I² = 87.5%), surgical complications (RR 1.69 [1.34, 2.13], P < .00001, I² = 98%), and prolonged hospitalization (RR 2.21 [1.93, 2.52], P < .00001, I² = 0%). The funnel plot showed qualitative asymmetry for mortality and surgical complications, suggesting potential publication bias. Subgroup analysis indicated hypoalbuminemia was associated with thromboembolic events, consistent with prior literature reporting adjusted hazard ratios of 1.28 to 1.8 for venous thromboembolism with low albumin.

**Clinical Implications:** Preoperative hypoalbuminemia is a significant predictor of postoperative morbidity, surgical complications, and extended hospital stay in CRC patients, though not of 30-day mortality. Given that serum albumin measurement is simple, affordable, and widely available, it can serve as a practical screening tool for preoperative risk stratification. Early identification of hypoalbuminemia may allow for nutritional optimization and enhanced perioperative care to reduce complications. The authors note that hypoalbuminemia reflects both malnutrition and an inflammatory state, as albumin is a negative acute-phase protein. Limitations include potential publication bias, the observational and retrospective nature of included studies, and the small number of studies (7) precluding meta-regression to adjust for confounders. Further research is needed to clarify confounding variables and the relationship between hypoalbuminemia and long-term outcomes such as metastasis.