Biomarker-based treatment selection in early-stage rectal cancer to promote organ preservation

Background Total mesorectal excision (TME) remains commonplace for T1–2 rectal cancer owing to fear of undertreating a small proportion of patients with node‐positive disease. Molecular stratification may predict cancer progression. It could be used to select patients for organ‐preserving surgery if specific biomarkers were validated. Methods Gene methylation was quantified using bisulphite pyrosequencing in 133 unirradiated rectal cancer TME specimens. KRAS mutation and microsatellite instability status were also defined. Molecular parameters were correlated with histopathological indices of disease progression. Predictive models for nodal metastasis, lymphovascular invasion (LVI) and distant metastasis were constructed using a multilevel reverse logistic regression model. Results Methylation of the retinoic acid receptor β gene, RARB, and that of the checkpoint with forkhead and ring finger gene, CHFR, was associated with tumour stage (RARB: 51·9 per cent for T1–2 versus 33·9 per cent for T3–4, P