Predicting pCR in Colorectal Cancer Immunotherapy

Predicting pCR in Colorectal Cancer Immunotherapy

Evaluating neoadjuvant immunotherapy response accurately remains a significant challenge for oncologists managing dMMR/MSI-H colorectal cancer. While immunotherapy often yields exceptional results, traditional radiological assessments frequently fail to reflect the true pathological state. Specifically, imaging often shows residual masses even when viable cancer cells are no longer present. Consequently, physicians need more reliable methods to determine if a patient has achieved a pathological complete response (pCR) before surgery. Researchers recently investigated new qualitative morphological changes to bridge this diagnostic gap.

Improving Neoadjuvant Immunotherapy Response Assessment

A recent study investigated how specific morphological changes on scans could predict successful treatment outcomes. Researchers analyzed data from 43 patients with locally advanced colorectal cancer harboring dMMR or POLE mutations. Interestingly, they found that 25 of these patients achieved a pathological complete response after their treatment. However, 84% of these successful responders showed \”pseudoresidual disease\” on standard imaging. Furthermore, a new combined model integrating morphological changes and endoscopy performed significantly better than conventional radiology alone. This model achieved a higher area under the curve, offering a more precise tool for clinical evaluation.

Recognizing Atypical Patterns and Adverse Events

Clinicians must also identify atypical response patterns like dissociated responses and immune-related adverse events. For instance, about 7% of patients in the study exhibited dissociated responses where different lesions reacted differently to the therapy. Additionally, the researchers identified rare cases of immunotherapy-induced Trousseau’s syndrome during the observation period. Notably, recognizing these specific imaging features is essential to prevent clinicians from misinterpreting them as metastatic disease progression. Therefore, adopting a comprehensive diagnostic approach ensures better personalized treatment for every patient.

Frequently Asked Questions

Q1: What is pseudoresidual disease in neoadjuvant immunotherapy?

Pseudoresidual disease occurs when imaging suggests lingering tumor tissue despite the patient achieving a pathological complete response. This pattern is very common in dMMR colorectal cancer patients treated with immunotherapy, occurring in up to 84% of responders.

Q2: How does the combined model improve diagnostic accuracy?

The combined model integrates qualitative morphological changes seen on scans with endoscopic findings. This approach provides a more comprehensive view of the tumor’s status than radiological criteria alone, leading to a higher predictive value for a complete response.

References

1. Luo Y et al. Endoscopic and imaging evaluations of neoadjuvant immunotherapy in patients with locally advanced colorectal cancer with dMMR/MSI-H or POLE/POLD1 mutation. Eur Radiol. 2026 May 13. doi: 10.1007/s00330-026-12602-8. PMID: 42128946.
2. Cercek A et al. PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022;386(25):2363-2376.
3. Zhang X et al. Neoadjuvant Immunotherapy for dMMR/MSI-H Colorectal Cancer: Mechanisms and Future Directions. Frontiers in Immunology. 2023;14:1145630.