Evaluating MRI response criteria in microsatellite instability-high rectal cancer treated with immune checkpoint inhibitors

TL;DR

MRI response criteria for rectal cancer may not work well with immunotherapy, as they were designed for traditional treatments.

Contribution

The study shows that MRI patterns after immunotherapy differ from those after radiochemotherapy in MSI-H rectal cancer.

Findings

MRI complete remission was 36% (5/14), rising to 50% when mucinous tumors were excluded.

All mucinous tumors retained T2-hyperintense signals despite no viable tumor cells.

Delayed fibrotic response was observed in some cases for over 3 months.

Abstract

Immune checkpoint inhibitors (ICIs), particularly anti-programmed cell death protein 1 (PD-1) agents, have enabled consideration of non-operative management in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) rectal cancer. Standard magnetic resonance imaging (MRI) response criteria—developed for chemoradiotherapy—may not accurately reflect treatment effects with ICIs, however.

We retrospectively analyzed 14 patients with locally advanced MSI-H/dMMR rectal adenocarcinoma treated with neoadjuvant anti-PD-1 monotherapy. All patients achieved a complete pathological response. MRI assessment included T2-weighted, diffusion-weighted, and contrast-enhanced sequences. Treatment response was defined as complete pathological response by surgical pathology (proctectomy), or by endoscopic and biopsy-confirmed complete remission (watch-and-wait strategy).

MRI showed distinct post-treatment patterns: split scar sign (n = 2), fibrotic response (n = 5), lesion disappearance (n = 1), and residual intermediate T2 signal (n = 6). All mucinous tumors retained T2-hyperintense residues. In select cases, fibrotic response was beyond 3 months. In two surgical cases, histological analysis revealed residual mucinous material without viable tumor cells.

MRI response patterns after anti-PD-1 monotherapy in MSI-H/dMMR rectal cancer differ from those observed after radiochemotherapy, suggesting the need to adapt current imaging criteria for accurate response assessment and informed surgical decision making. Persistent MRI abnormalities are frequent despite complete pathological response, and warrant cautious interpretation in the ICI setting.

•MRI complete remission was 36% (5/14), rising to 50% (5/10) when mucinous tumors were excluded.•All mucinous tumors (4/4) retained T2-hyperintense signals despite the absence of viable tumor cells.•In select cases, a delayed fibrotic response was observed for >3 months.•MRI response patterns in MSI-H/dMMR rectal cancer differ between anti-PD-1 monothearpy and radiochemotherapy.

MRI complete remission was 36% (5/14), rising to 50% (5/10) when mucinous tumors were excluded.

All mucinous tumors (4/4) retained T2-hyperintense signals despite the absence of viable tumor cells.

In select cases, a delayed fibrotic response was observed for >3 months.

MRI response patterns in MSI-H/dMMR rectal cancer differ between anti-PD-1 monothearpy and radiochemotherapy.

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