EP426 - Efficacy of Immune Checkpoint inhibitors in microsatellite instable colorectal cancers metastatic to the peritoneum: An institutional experience and systematic review.

Image or Table (Do Not add text here):

Purpose/Background: Metastatic colorectal cancer (mCRC) with deficient mismatch repair (dMMR) is characterized by frequent and durable responses to programmed cell death 1 (PD-1) blockade. However, a major clinical challenge for patients treated with immune checkpoint inhibitors (ICIs) is the management of residual peritoneal disease (PD). Current imaging modalities and response criteria, such as iRECIST, perform poorly in predicting pathological response, leading to a high rate of discordance between radiological and pathological findings. Additionally, this has not been well studied in patients with PD. In this study, we sought to determine the clinical and pathological response rates in patients undergoing surgery for residual PD after ICI treatment utilizing a systematic review and single institutional experience.

Methods/Interventions: A systematic literature search was performed using Medline, EMBASE, Cochrane, and Web of Science. A total of 1696 studies were screened, and twelve studies met inclusion criteria, including three retrospective observational studies and case reports/series adhering to CARE guidelines. Retrospective observational studies were assessed for quality using the Newcastle-Ottawa Scale. These studies reported outcomes of ICI-treated peritoneal carcinomatosis secondary to dMMR colorectal cancer, specifically clinical responses using iRECIST criteria, pathological responses, overall response rate (ORR), and postoperative complications. Data extracted included study characteristics, tumor characteristics (such as metastatic sites), and treatment-related factors. Additionally, we analyzed our institutional experience of treating seven patients with peritoneal metastases secondary to dMMR colorectal cancer using ICI.

Results/Outcomes: The overall cohort included 82 patients (75 from the literature and 7 from our institution). The median age was 65 years (range 55-73). Forty-one tumors were right-sided, and 18 were left-sided. Seventy patients had isolated peritoneal metastases, while 12 had ≥2 metastatic sites. Forty-eight patients received PD-1 inhibitor monotherapy, and 14 received dual checkpoint inhibitor therapy (PD-1 and CTLA-4). Using iRECIST criteria, 37 patients had partial response, 13 complete response, 16 stable disease, and 12 progressive disease, yielding a cumulative ORR of 87% based on imaging. Thirty-two patients underwent surgery: 27 for residual disease, 4 for symptomatic disease, and 1 for progressive disease at a sanctuary site. Complete pathological response was observed in 25 out of 32 patients (78%) who underwent surgery. Postoperative complications (Clavien-Dindo grade ≥3) were reported in 8 patients (25%).

Conclusion/Discussion: In this study, we found that there is a significant discrepancy between imaging and pathologic response in patients with peritoneal metastasis undergoing surgery after treatment with ICI therapy. Additionally, 25% of patients experienced significant complications in the setting of a nearly 80% complete pathologic response rate. This response rate is consistent with research in recent clinical trials involving neoadjuvant ICI therapy in resectable colon cancer, suggesting excellent responses in this challenging patient group. Future studies focused on improving detection of residual disease in patients after ICI treatment are important to identify which patients are most likely to benefit from surgical intervention.