A novel predictive model effectively identifies patients likely to achieve a pathological complete response after total neoadjuvant therapy for locally advanced rectal cancer, aiding in selection for watch-and-wait strategies.

• In a study of 308 patients, the model predicted pCR with an area under the receiver operator curve (AUROC) of 0.71.
• External validation in 83 patients showed the model predicted persistent clinical complete response (pCCR) with an AUROC of 0.69.

This tool enhances surgical decision-making, improving patient management in rectal cancer.

• Model recalibration boosted predictive accuracy for pCCR to 0.17.