CT staging performance in an international trial of neoadjuvant chemotherapy for locally advanced colon cancer

Objectives: In the Fluorouracil, Oxaliplatin and Targeted Receptor pre-Operative Therapy (FOxTROT) trial, neoadjuvant chemotherapy (NAC) significantly reduced recurrence risk, compared to upfront surgery, in locally advanced colon cancer. This analysis evaluates the correlation between radiological and pathological staging within the trial to support the adoption of CT-based patient selection.

Methods: In this preplanned analysis of prospectively collected data, local radiological and pathological staging were compared in upfront surgery participants. T stage, N stage, and extramural venous invasion (EMVI) status were evaluated using overall agreement, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Subgroup analyses explored the impact of mismatch repair status and tumour side.

Results: A total of 354 participants were included. T stage agreement was 63.0%; T3 and T4 tumours were correctly identified in 78.9% and 41.1% of participants, respectively. The PPV for T3-4 status was 94.5%. N stage agreement was 39.8%; for N status (positive vs. negative), overall agreement, sensitivity, specificity, PPV, and NPV were 54.1%, 81.1%, 26.0%, 53.2%, and 57.1%, respectively. For EMVI, these values were 54.9%, 71.0%, 41.2%, 50.7%, and 62.5%, respectively. Accuracy metrics did not differ significantly by tumour side or mismatch repair status.

Conclusions: CT effectively predicted T3-4 status with minimal overstaging, but performed poorly for individual T stage, N stage, and EMVI. We propose radiological T3-4 status should be adopted as the primary biomarker for neoadjuvant patient selection, with molecular biomarkers to guide treatment choice.

Advances in knowledge: In this multicentre trial, local radiologists accurately identified T3-4 status to select participants for NAC, indicating utility for future neoadjuvant trials and clinical practice.