Introduction Tumour budding is an increasingly important prognostic feature for pathologists to recognise. The phenomenon has been associated with a negative prognosis in rectal cancer when identified in surgical resection specimens.

Aims/Background The aim of this study was to correlate intra-tumoural budding (ITB) in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy (nCRT) and with long-term outcome.

Method Data from a prospectively maintained database was acquired for patients with locally advanced rectal cancer who underwent nCRT. Pre-treatment rectal biopsies were retrospectively reviewed for evidence of ITB. Multivariate logistic regression was used to identify factors contributing to cancer-specific death, expressed as hazard ratios (HRs) with 95 per cent confidence intervals (CIs).

Results Of 185 patients with locally advanced rectal cancer, 89 patients met the eligibility criteria, of whom 18 (20.2%) exhibited budding in a pre-treatment tumour biopsy. ITB predicted a poor pathological response to nCRT (higher ypT stage, p=0.032; lymph node involvement, p=0.018; lymphovascular invasion, p=0.004; and residual poorly differentiated tumours, p<0.001). No patients with ITB exhibited a TRG 1 or complete pathological response, providing 100% specificity and positive predictive value for non-response to nCRT. ITB was associated with a lower disease-free 5-year survival rate (33.3% vs. 77.5%, p<0.001), cancer-specific 5-year survival rate (61.1% vs. 87.3%, p=0.021) and predicted cancer-specific death (HR 3.51, 95% CI 1.03 - 11.93, p=0.040). Patients with tumor budding in initial biopsy have a significantly lower five-year disease-free survival rate (33.33% vs. 77.46%, p=<0.001) and lower cancer-specific survival rate (61.11% vs. 87.32%, p=0.021).⇓

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Figure 1

Kaplan-Meier survival curve relating to budding status in pre-treatment biopsy.

Conclusion ITB at diagnosis of rectal cancer identifies those who will poorly respond to nCRT and those with a poor prognosis.