Tumour-stroma ratio has poor prognostic value in nonpedunculated T1 colorectal cancer: A multicentre case-cohort study

Hao Dang; Gabi W van Pelt; Krijn J C Haasnoot; Yara Backes; Sjoerd G Elias; Tom C J Seerden; Matthijs P Schwartz; Bernhard W M Spanier; Wouter H de Vos Tot Nederveen Cappel; Jeroen D van Bergeijk; Koen Kessels; Joost M J Geesing; John N Groen; Frank Ter Borg; Frank H J Wolfhagen; Cornelis A Seldenrijk; Mihaela G Raicu; Anya N Milne; Anja U G van Lent; Lodewijk A A Brosens; G Johan A Offerhaus; Peter D Siersema; Rob A E M Tollenaar; James C H Hardwick; Lukas J A C Hawinkels; Leon M G Moons; Miangela M Lacle; Wilma E Mesker; Jurjen J Boonstra; Dutch T1 CRC Working Group

doi:10.1177/2050640620975324

Tumour-stroma ratio has poor prognostic value in nonpedunculated T1 colorectal cancer: A multicentre case-cohort study

United European Gastroenterol J. 2021 Feb 10. doi: 10.1177/2050640620975324. Online ahead of print.

Authors

Hao Dang¹, Gabi W van Pelt², Krijn J C Haasnoot³, Yara Backes³, Sjoerd G Elias⁴, Tom C J Seerden⁵, Matthijs P Schwartz⁶, Bernhard W M Spanier⁷, Wouter H de Vos Tot Nederveen Cappel⁸, Jeroen D van Bergeijk⁹, Koen Kessels¹⁰, Joost M J Geesing¹¹, John N Groen¹², Frank Ter Borg¹³, Frank H J Wolfhagen¹⁴, Cornelis A Seldenrijk¹⁵, Mihaela G Raicu¹⁵, Anya N Milne¹⁵, Anja U G van Lent¹⁶, Lodewijk A A Brosens¹⁷, G Johan A Offerhaus¹⁷, Peter D Siersema¹⁸, Rob A E M Tollenaar², James C H Hardwick¹, Lukas J A C Hawinkels¹, Leon M G Moons³, Miangela M Lacle¹⁷, Wilma E Mesker², Jurjen J Boonstra¹; Dutch T1 CRC Working Group

Affiliations

¹ Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands.
² Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
³ Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
⁴ Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
⁵ Department of Gastroenterology and Hepatology, Amphia Hospital, Breda, The Netherlands.
⁶ Department of Gastroenterology and Hepatology, Meander Medical Centre, Amersfoort, The Netherlands.
⁷ Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The Netherlands.
⁸ Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, The Netherlands.
⁹ Department of Gastroenterology and Hepatology, Gelderse Vallei, Ede, The Netherlands.
¹⁰ Department of Gastroenterology and Hepatology, Sint Antonius Hospital, Nieuwegein, The Netherlands.
¹¹ Department of Gastroenterology and Hepatology, Diakonessenhuis, Utrecht, The Netherlands.
¹² Department of Gastroenterology and Hepatology, Sint Jansdal, Harderwijk, The Netherlands.
¹³ Department of Gastroenterology and Hepatology, Deventer Hospital, Deventer, The Netherlands.
¹⁴ Department of Gastroenterology and Hepatology, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
¹⁵ Pathology DNA, Sint Antonius Hospital, Nieuwegein, The Netherlands.
¹⁶ Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
¹⁷ Department of Pathology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
¹⁸ Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands.

PMID: 33566452
DOI: 10.1177/2050640620975324

Abstract

Background: Current risk stratification models for early invasive (T1) colorectal cancer are not able to discriminate accurately between prognostic favourable and unfavourable tumours, resulting in over-treatment of a large (>80%) proportion of T1 colorectal cancer patients. The tumour-stroma ratio (TSR), which is a measure for the relative amount of desmoplastic tumour stroma, is reported to be a strong independent prognostic factor in advanced-stage colorectal cancer, with a high stromal content being associated with worse prognosis and survival. We aimed to investigate whether the TSR predicts clinical outcome in patients with non-pedunculated T1 colorectal cancer.

Methods: Haematoxylin and eosin (H&E)-stained tumour tissue slides from a retrospective multicentre case cohort of patients with nonpedunculated surgically treated T1 colorectal cancer were assessed for TSR by two independent observers who were blinded for clinical outcomes. The primary end point was adverse outcome, which was defined as the presence of lymph node metastasis in the resection specimen or colorectal cancer recurrence during follow-up.

Results: All 261 patients in the case cohort had H&E slides available for TSR scoring. Of these, 183 were scored as stroma-low, and 78 were scored as stroma-high. There was moderate inter-observer agreement κ = 0.42). In total, 41 patients had lymph node metastasis, 17 patients had recurrent cancer and five had both. Stroma-high tumours were not associated with an increased risk for an adverse outcome (adjusted hazard ratio = 0.66, 95% confidence interval 0.37-1.18; p = 0.163).

Conclusions: Our study emphasises that existing prognosticators may not be simply extrapolated to T1 colorectal cancers, even though their prognostic value has been widely validated in more advanced-stage tumours.

Keywords: T1 colorectal cancer; desmoplasia; prognosis; tumour microenvironment; tumour-stroma ratio.