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The tumour–stroma ratio as predictive aid towards a biopsy‐based treatment strategy in rectal carcinoma
Author(s) -
Polack Meaghan,
Pelt Gabi W,
Heuvel Davita H,
KleinKranenbarg Elma Meershoek,
Roodvoets Annet G H,
Putter Hein,
Crobach Augustinus S L P,
Nagtegaal Iris D,
Peeters Koen C M J,
Tollenaar Rob A E M,
Krieken J Han J M,
Mesker Wilma E
Publication year - 2025
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.15423
Subject(s) - hazard ratio , biopsy , medicine , stroma , proportional hazards model , confidence interval , oncology , carcinoma , cohort , retrospective cohort study , pathology , immunohistochemistry
Aims Tumour–stroma ratio (TSR) scores of biopsy material in rectal carcinoma (RC) could aid a biomarker‐based, upfront and personalised treatment strategy selection for RC patients. In a large retrospective, multicentre cohort, we aimed to validate the predictive value of biopsy‐scored TSR on neoadjuvant therapy response, and secondarily, disease‐free and overall survival (DFS, OS). Methods and results Scanned haematoxylin and eosin‐stained RC biopsy slides were collected from Leiden University Medical Center ( N = 116) and from the clinical PROCTOR‐SCRIPT ( N = 142) and RAPIDO ( N = 271) trials. TSR was scored per protocol and categorised as stroma‐low (≤ 50%) or stroma‐high (> 50%). Major response was defined as tumour regression grade (TRG) 1 + 2 by Mandard, including pathological complete response. Ultimately, a large and varied cohort with 373 RC patients was established. Locally advanced RC was more often stroma‐high ( P < 0.001). We subsequently observed significantly lower major response rates in the stroma‐high RC after a neoadjuvant treatment approach (hazard ratio = 0.63, 95% confidence interval = 0.41–0.99; P = 0.044). Despite correction for well‐known risk factors in Cox hazard regression analysis, such as (y)pTNM substages or residual tumour status, the TSR had no singular significant influence on DFS nor OS in multivariate analysis ( P = 0.438; P = 0.934, respectively). Conclusions Biopsy‐scored TSR can predict neoadjuvant therapy efficacy, as RC patients with stroma‐high biopsies show less major response. However, patient survival is multifactorial, although response is an important predictor, influenced by TSR. Scoring TSR on RC biopsy material is a reliable histological parameter, implementation of which in treatment guidelines could improve upfront selection for a watch‐and‐wait strategy.