Intra-tumoural stromal morphometry predicts disease recurrence but not response to 5-fluorouracil – results from the QUASAR trial of colorectal cancer

Introduction: The biological importance of tumour-associated stroma is increasingly apparent, yet clinical utility remains ill-defined. In stage-II / Dukes B colorectal cancer (CRC), clinical biomarkers are urgently required to direct therapeutic options. We report here prognostic/predictive analyses, and molecular associations, of stromal morphometric quantification in the Quick and Simple and Reliable (QUASAR) trial of CRC. Materials and methods: Relative proportions of tumour epithelium (PoT) or stroma (PoS) were morphometrically quantified using digitised haematoxylin and eosin sections derived from 1,800 patients enrolled in QUASAR which randomised 3,239 (91% stage II) CRC patients between adjuvant fluorouracil/folinic acid (FUFA) chemotherapy and observation. The prognostic/predictive value of PoT/PoS measures were determined by stratified log-rank analyses. Results: High tumour stroma (≥50%) was associated with increased recurrence risk: 31.3% (143/457) recurrence for ≥50% versus 21.9% (294/1,343) if <50% [Rate ratio (RR)=1.62; 95%CI 1.30-2.02, p