Impact of Tumor–Stroma Ratio on the Prognosis of Colorectal Cancer: A Systematic Review

Abstract

BackgroundIt is critical to develop a reliable and cost-effective prognostic tool for colorectal cancer (CRC) stratification and treatment optimization. Tumor–stroma ratio (TSR) may be a promising indicator of poor prognosis in CRC patients. As a result, we conducted a systematic review on the predictive value of TSR in CRC.MethodsThis study was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline. An electronic search was completed using commonly used databases PubMed, CENTRAL, Cochrane Central Register of Controlled Trials, and Google scholar till the last search up to May 30, 2021. STATA version 13 was used to analyze the data.ResultsA total of 13 studies [(12 for disease-free survival (DFS) and nine studies for overall survival (OS)] involving 4,857 patients met the inclusion criteria for the systematic review in the present study. In individuals with stage II CRC, stage III CRC, or mixed stage CRC, we observed a significantly higher pooled hazard ratio (HR) in those with a low TSR/greater stromal content (HR, 1.54; 95% CI: 1.20 to 1.88), (HR, 1.90; 95% CI: 1.35 to 2.45), and (HR, 1.70; 95% CI: 1.45 to 1.95), respectively, for predicting DFS. We found that a low TSR ratio had a statistically significant predictive relevance for stage II (HR, 1.43; 95% CI: 1.09 to 1.77) and mixed stages of CRC (HR, 1.65; 95% CI: 1.31 to 2.0) for outcome OS.ConclusionIn patients with CRC, low TSR was found to be a prognostic factor for a worse prognosis (DFS and OS).

Investigating the role of core needle biopsy in evaluating tumor-stroma ratio (TSR) of invasive breast cancer: a retrospective study

“…By examining TSR of colon carcinoma, the authors divided these tumors into "stroma-rich" and "stroma-poor" groups by a cutoff TSR value of 50% and illustrated a profound prognostic signi cance between the two groups. Since its rst appearance, the use of TSR has gained popularity with many subsequent illustrating its effect on survival outcomes [13,14]. The application of TSR concept in tumor prognostication has spread to other solid tumors such as ovarian carcinoma, cervical squamous cell carcinoma, hepatocellular carcinoma, non-small cell lung cancer, nasopharyngeal squamous cell carcinoma, pancreatic ductal adenocarcinoma, and invasive bladder cancer [15][16][17].…”

Stroma AReactive Invasion Front Areas (SARIFA): a novel histopathologic biomarker in colorectal cancer patients and its association with the luminal tumour proportion

“…SARIFA-status is assessed using routine Haematoxylin & Eosin (H&E) stained tissue sections from CRC resection specimens. Another known H&E based prognostic biomarker in CRC [9] , [10] , [11] , [12] , [13] , [14] is the intratumoural stroma content. Whilst SARIFA-status can only be assessed in tissue regions where tumour cells have the opportunity to get into contact with fat cells (especially in the submucosa and subserosa/adventitia), the intratumoural stroma content can be measured in all regions of the tumour including in material from the luminal tumour surface e.g.…”

“…There have been several studies highlighting the relevance of tumour-stroma ratio/tumour cell proportion/tumour cell density/proportion of tumour (PoT) for prognosis prediction in CRC patients: High intra-tumour stroma content measured using different methods has been shown to predict poor prognosis in several different CRC patient cohorts [9] , [10] , [11] , [12] , [13] , [14] , [15] and other tumour types. Moreover, it has been suggested that tumour stroma is actively involved in CRC development and progression, and that disruption of the tumour-stroma interaction may inhibit tumour progression and metastasis formation [16] .…”

Unselective Measurement of Tumor‐to‐Stroma Proportion in Colon Cancer at the Invasion Front– an Elusive Prognostic Factor. Original Patient Data and Review of the Literature

“…In general a stromal content of more than around 50% is assessed by the different authors, although different cut-off values are also used for very-high stroma tumors. Both optical and automated reading of stroma is used [3] TSR is not yet adopted in clinical guidelines, and we consider its adoption early. In our study we tried to confirm or dismiss the hypothesis that a simple, unselective optical measurement of stroma quantity at the invasion front is an easy-to-use and strong prognostic tool.…”