# Outcomes and management of primary tumors in metastatic MSI/dMMR colorectal cancer patients treated with immune checkpoint inhibitors: a cohort study

## TL;DR

This study examines how to manage the primary tumor in colorectal cancer patients treated with immune checkpoint inhibitors, finding that some tumors shrink significantly and resection may be needed for symptoms.

## Contribution

The study provides new insights into the management of primary tumors in metastatic colorectal cancer patients undergoing immunotherapy.

## Key findings

- 40% of patients with unresected primary tumors achieved pathological complete response.
- PT resection was performed in 15 patients due to clinical events or non-symptomatic reasons.
- Close monitoring is recommended for patients with unresected primary tumors during immunotherapy.

## Abstract

The optimal management of primary tumor (PT) in microsatellite instability-high metastatic colorectal cancer patients treated with immune checkpoint inhibitors (ICIs) remains unclear.

We retrospectively analyzed a prospective, single-center cohort to assess PT outcomes in this setting.

Among 210 patients, 21% received first-line ICI; we focused on 33 patients (16%) without prior PT resection at ICI initiation. Early progressive disease (<6 months) occurred in 10 patients (5%), with eight deaths (<1 year); two underwent surgery for symptomatic PT. Among the remaining 23 patients (11%) with disease control (≥6 months), 15 had PT resection due to clinical events (n = 5) or for non-symptomatic reasons (n = 10), including seven with pathological complete response and eight with residual tumor. Eight patients had no PT resection, including two with metastatic and/or local progressive diseases. After a median 75-month follow-up, only six patients (3%) remained progression-free with PT in place and no residual endoscopic tumor.

If PT is left in place at ICI initiation, close monitoring is required due to its specific evolution. Resection may be indicated for symptomatic stenosis. Prospective trials are needed to define the role of endoscopic monitoring and indication of PT resection in first-line ICI.

•Some 16% of dMMR/MSI-H mCRC patients had unresected primary tumor (PT) at ICI initiation.•Some 40% of patients with unresected PT achieved pathological complete response.•Median time to PT resection after ICI was 15 months.•PT surgery may be needed for obstruction, perforation, or symptomatic stenosis.•Close PT monitoring is recommended; prospective trials are needed to guide resection.

Some 16% of dMMR/MSI-H mCRC patients had unresected primary tumor (PT) at ICI initiation.

Some 40% of patients with unresected PT achieved pathological complete response.

Median time to PT resection after ICI was 15 months.

PT surgery may be needed for obstruction, perforation, or symptomatic stenosis.

Close PT monitoring is recommended; prospective trials are needed to guide resection.