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. 2025 May;32(5):3638-3647.
doi: 10.1245/s10434-024-16860-y. Epub 2025 Jan 22.

Patterns of Preoperative Tumor Markers Can Predict Resectability and Prognosis of Peritoneal Metastases: A Clustering Analysis

Malin Enblad  1 , Peter Cashin  2 , Lana Ghanipour  2 , Wilhelm Graf  2
Affiliations

Patterns of Preoperative Tumor Markers Can Predict Resectability and Prognosis of Peritoneal Metastases: A Clustering Analysis

Malin Enblad et al. Ann Surg Oncol. 2025 May.

Abstract

Background: Prediction of open-close and long-term outcome is challenging in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic scores often include factors not known at baseline. Therefore, we aimed to analyze whether patterns of preoperative tumor markers could aid in prediction of open-close surgery and outcome in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM).

Patients and methods: All patients accepted for CRS and HIPEC for PMP or colorectal PM at Uppsala University Hospital in 2013-2021 were included. The tumor markers CEA, CA19-9, CA125, CA72-4, and CA15-3 were clustered using the k-means algorithm; the average silhouette width determined the optimal numbers of clusters.

Results: Clustering of patients with PMP (n = 138) and colorectal PM (n = 213) resulted in two clusters each. PMPCluster-1 (n = 124) had a 5-year overall survival (OS) of 77% (95% CI 69-85%), 11 (9%) open-close surgeries, and a median peritoneal cancer index (PCI) of 17. PMPCluster-2 (n = 14) patients had poorer prognosis (36%, 95% CI 15-85%, p = 0.003), more often open-close (n = 6, 43%, p = 0.002), and higher PCI (median 36, p < 0.001). ColorectalCluster-1 (n = 191) had a 5-year OS of 28% (95% CI 21-37%), median PCI of 11, and 38 (20%) open-close surgeries. ColorectalCluster-2 (n = 22) had poorer prognosis (10%, 95% CI 3-36%, p = 0.02), higher PCI (median 26, p < 0.001), higher completeness of cytoreduction score (p = 0.005), but no difference in open-close surgery (n = 6, 27%, p = 0.411). PMPCluster-2 and ColorectalCluster-2 were characterized by markedly elevated tumor markers. Open-close surgery was unusual in cases of normal CA72-4.

Conclusions: Elevation of several preoperative tumor markers is associated with poor prognosis and increased risk of open-close. CA72-4 deserves increased attention.

Keywords: Clustering analysis; Cytoreductive surgery; HIPEC; Peritoneal metastases; Tumor markers.

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Conflict of interest statement

Disclosures: The authors declare no conflicts of interest. The study was funded by research grants from Uppsala University Hospital for M.E., the Bengt Ihre Research Fellowship, and the Lion’s Research Foundation in Uppsala.

Figures

Fig 1
Fig 1
a Scatterplot of patients with pseudomyxoma peritonei separated into two groups on the basis of clustering of tumor markers; b heatmaps of tumor marker levels for the two clusters, white indicates levels below the reference value and color intensity increases with each percentile of elevation from the reference value; c overall survival Kaplan–Meier curves and number at risk table for the two clusters; PC principal component, PMP pseudomyxoma peritonei
Fig. 2
Fig. 2
a Scatterplot of patients with colorectal peritoneal metastases separated into two groups on the basis of clustering of tumor markers; b heatmaps of tumor marker levels for the two clusters, white indicates levels below reference value and color intensity increases with each percentile of elevation from the reference value; c overall survival Kaplan–Meier curves and number at risk table for the two clusters; PC principal component
Fig. 3
Fig. 3
Distribution of preoperative CA72-4 values; values for patients with open–close laparotomy is indicated by red lines and reference value is indicated by black lines; a pseudomyxoma peritonei and b colorectal peritoneal metastases
See this image and copyright information in PMC

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