Towards implementation of the tumour-stroma ratio in colorectal cancer

Abstract

Colorectal cancer is the third most prevalent tumour type with high morbidity and mortality rates. To improve patient-related outcomes, implementation of additional biomarkers in international guidelines is pivotal. The dynamic tumour microenvironment, influences tumour behaviour and harbours a myriad of targets, specifically, the tumour-stroma ratio (TSR). The TSR is validated here as a pathological prognosticator in colorectal cancer scored on haematoxylin-and-eosin-stained slides. Stroma-high tumours (>50% intratumoural stroma percentage) are more aggressive and less likely to respond to treatment compared to stroma-low counterparts (≤50%), based on biopsy data, the primary tumour itself, and lymph nodes. The TSR can support patient selection for specific treatment strategies. For example, frail and/or older patients with stroma-high tumours may be offered less or no (neo-)adjuvant therapy, while fitter and/or younger patients may be offered more intensive or experimental treatments. New techniques, e.g. the fibroblast activation protein inhibitor (FAPI) tracer for PET-CT scanning, and artificial intelligence, may help map the TSR and other tumour characteristics more quickly and accurately in the future. Moreover, the TSR qualifies as a 'robust pathological parameter’ with highest levels of evidence. In conclusion, the TSR as prognostic biomarker should urgently be implemented in (inter)national guidelines, e.g. the TNM classification.