Direct tumour-adipocyte contact / Stroma AReactive Invasion Front Area (TAC/SARIFA) predicts adverse outcome in colorectal cancer: a focused evidence synthesis and meta-analysis.

AIMS: Direct tumour-adipocyte interaction at the invasion front, termed Stroma AReactive Invasion Front Areas (SARIFA), has recently emerged as a novel H&E-based biomarker in colorectal cancer (CRC). SARIFA positivity is defined by a direct tumour-adipocyte contact (TAC) without intervening stroma or inflammatory infiltrate. We performed a focused evidence synthesis of all published studies and a meta-analysis to summarize the evidence on the prognostic value of TAC/SARIFA in CRC.

METHODS AND RESULTS: Eligible studies, identified via PubMed (7 May 2026), were observational cohorts reporting multivariable-adjusted hazard ratios (HRs) for TAC/SARIFA positivity vs negativity, with cancer-specific survival (CSS) and overall survival (OS) as endpoints. All included studies were retrospective in design. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Adjusted HRs were pooled using random-effects meta-analysis with restricted maximum-likelihood estimation and Hartung-Knapp confidence intervals. Of 17 records identified, 12 CRC-focused original publications were included in the qualitative synthesis. Seven cohorts (5,932 patients) contributed CSS and five cohorts (4,545 patients) OS data, drawn from eight independent cohorts across six studies. All studies were rated good quality (NOS 7-9/9). TAC/SARIFA positivity was associated with inferior CSS (pooled HR 1.77, 95% confidence interval [CI] 1.55-2.01) and OS (pooled HR 1.53, 95% CI 1.39-1.68), with no relevant heterogeneity detected.

CONCLUSION: TAC/SARIFA positivity is independently associated with inferior CSS and OS in CRC, warranting prospective validation. We propose TAC as a more descriptive terminology.