Integrating Peritoneal Histological Growth Patterns Into Preoperative Decision-Making for Colorectal Peritoneal Metastses

Integrating Peritoneal Histological Growth Patterns Into Preoperative Decision-Making for Colorectal Peritoneal Metastses: A Prospective Study

Colorectal cancer (CRC) remains the third most commonly diagnosed malignancy worldwide and the second leading cause of cancer-related death, with approximately 15% of patients presenting with synchronous liver metastases (LM) and 7% with peritoneal metastases (PM) at diagnosis. Despite curative-intent resection of the primary tumor, 16-20% of patients subsequently develop metachronous LM and up to 19% develop PM within three years [1-5].

Surgery remains the only potentially curative treatment for patients with colorectal peritoneal metastases (CRPM), offering long-term (>10years) disease-free survival (DFS) in a subset of highly selected patients [6,7]. However, selecting candidates for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) remains challenging and requires balancing the potential oncologic benefit of complete cytoreduction against perioperative risks and postoperative morbidity [6-8].

Consequently, strong prognostic markers-clinical, biological, or genetic-are crucial to refine surgical decision-making. Currently, the two most consistent clinical determinants of outcome are the extent of disease (Peritoneal Cancer Index, PCI) and the completeness of cytoreduction (CC-score) [6-8]. Over the last decade, surgical selection has become more restrictive (e.g., PCI threshold moving from 25 to 17), and molecular profiles such as BRAF mutations have been associated with poor outcomes, potentially guiding against aggressive surgery in selected cases [8,9]. Yet, these markers are insufficient to fully capture inter-patient heterogeneity and do not reliably individualize surgical benefit [8,9].

In colorectal liver metastases (CRLM), the histological growth pattern (HGP) at the tumor-liver interface has emerged as a robust prognostic biomarker, with the desmoplastic HGP (d-HGP) associated with superior survival compared with replacement or pushing patterns [10,11]. International consensus guidelines have standardized HGP scoring for CRLM, enabling reproducible assessment and cross-study comparison [12]. Large multicentric cohorts also suggest possible modulation of HGP by systemic chemotherapy, supporting its value as a marker of intrinsic tumor biology and treatment response [13,14].

Transposing this concept to the peritoneum, our group identified two reproducible peritoneal HGP in colorectal peritoneal metastases: the pushing pattern (P-HGP) and the infiltrating pattern (I-HGP). Across two monocentric studies, a dominant P-HGP (>50-60% of the tumor-peritoneum interface) was strongly associated with prolonged disease-free and overall survival (OS) [15,16].

Taken together, these findings support HGP of PM as a potential histological biomarker to refine patient selection for CRS ± HIPEC beyond current clinical and molecular criteria.

However, existing data derive exclusively from retrospective single-center cohorts, underscoring the need for prospective validation to:

Confirm the independent prognostic value of HGP of PM (for overall and disease-free survival) in contemporary clinical practice; Standardize sampling and pathological assessment (standard operating procedures, central review, and interobserver reproducibility studies); Develop and validate a histo-prognostic scoring system integrating PM HGP with relevant clinicopathological variables, aimed at predicting patient outcomes and supporting preoperative decision-making for CRS ± HIPEC candidacy.

This prospective cohort study is designed to address these objectives without modifying standard care. By collecting clinicopathological and survival data prospectively, it will provide robust evidence for the integration of HGP into a multivariable prognostic model capable of stratifying surgical candidates and guiding individualized treatment strategies.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer; Colorectal (Colon or Rectal) Cancer; Histopathological Growth Patterns (HGPs); Peritoneal (Metastatic) Cancer

Detailed Description

Colorectal cancer (CRC) remains the third most commonly diagnosed malignancy worldwide and the second leading cause of cancer-related death, with approximately 15% of patients presenting with synchronous liver metastases (LM) and 7% with peritoneal metastases (PM) at diagnosis. Despite curative-intent resection of the primary tumor, 16-20% of patients subsequently develop metachronous LM and up to 19% develop PM within three years [1-5].

Surgery remains the only potentially curative treatment for patients with colorectal peritoneal metastases (CRPM), offering long-term (>10years) disease-free survival (DFS) in a subset of highly selected patients [6,7]. However, selecting candidates for cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) remains challenging and requires balancing the potential oncologic benefit of complete cytoreduction against perioperative risks and postoperative morbidity [6-8].

Consequently, strong prognostic markers-clinical, biological, or genetic-are crucial to refine surgical decision-making. Currently, the two most consistent clinical determinants of outcome are the extent of disease (Peritoneal Cancer Index, PCI) and the completeness of cytoreduction (CC-score) [6-8]. Over the last decade, surgical selection has become more restrictive (e.g., PCI threshold moving from 25 to 17), and molecular profiles such as BRAF mutations have been associated with poor outcomes, potentially guiding against aggressive surgery in selected cases [8,9]. Yet, these markers are insufficient to fully capture inter-patient heterogeneity and do not reliably individualize surgical benefit [8,9].

In colorectal liver metastases (CRLM), the histological growth pattern (HGP) at the tumor-liver interface has emerged as a robust prognostic biomarker, with the desmoplastic HGP (d-HGP) associated with superior survival compared with replacement or pushing patterns [10,11]. International consensus guidelines have standardized HGP scoring for CRLM, enabling reproducible assessment and cross-study comparison [12]. Large multicentric cohorts also suggest possible modulation of HGP by systemic chemotherapy, supporting its value as a marker of intrinsic tumor biology and treatment response [13,14].

Transposing this concept to the peritoneum, our group identified two reproducible peritoneal HGP in colorectal peritoneal metastases: the pushing pattern (P-HGP) and the infiltrating pattern (I-HGP). Across two monocentric studies, a dominant P-HGP (>50-60% of the tumor-peritoneum interface) was strongly associated with prolonged disease-free and overall survival (OS) [15,16].

Taken together, these findings support HGP of PM as a potential histological biomarker to refine patient selection for CRS ± HIPEC beyond current clinical and molecular criteria.

However, existing data derive exclusively from retrospective single-center cohorts, underscoring the need for prospective validation to:

Confirm the independent prognostic value of HGP of PM (for overall and disease-free survival) in contemporary clinical practice; Standardize sampling and pathological assessment (standard operating procedures, central review, and interobserver reproducibility studies); Develop and validate a histo-prognostic scoring system integrating PM HGP with relevant clinicopathological variables, aimed at predicting patient outcomes and supporting preoperative decision-making for CRS ± HIPEC candidacy.

This prospective cohort study is designed to address these objectives without modifying standard care. By collecting clinicopathological and survival data prospectively, it will provide robust evidence for the integration of HGP into a multivariable prognostic model capable of stratifying surgical candidates and guiding individualized treatment strategies.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Gabriele Professor Liberale, MD, pHD; Phone Number: +32 2 541 31 11; Email: gabriele.liberale@hubruxelles.be

Study Locations

• Belgium
  • Brussels Capital
    • Brussels, Brussels Capital, Belgium, 1070
      • Hub Bordet
      • Contact: Ali CHANNAWI, MD; Phone Number: +32494817818; Email: ali.channawi@ulb.be
      • Contact: Email: ali.channawi@ulb.be
      • Sub-Investigator: Ali Channawi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult patients with histologically confirmed colorectal cancer and suspected or confirmed peritoneal metastases who undergo surgical evaluation or treatment (staging laparoscopy and/or cytoreductive surgery ± HIPEC) as part of routine clinical care at participating centers. Peritoneal metastasis tissue samples obtained during these procedures are used for histopathological analysis to evaluate histological growth patterns and their association with clinicopathological characteristics and clinical outcomes.

Description

Inclusion Criteria:

• Age ≥ 18 years
• Histologically confirmed colorectal adenocarcinoma
• Suspected or confirmed peritoneal metastases from colorectal cancer based on imaging or prior clinical evaluation
• Patients undergoing staging laparoscopy and/or cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) as part of standard clinical care
• Availability of peritoneal metastasis tissue samples suitable for histopathological analysis
• Written informed consent provided for participation in the study

Exclusion Criteria:

• Age < 18 years
• Peritoneal metastases originating from non-colorectal primary tumors
• Absence of available or adequate peritoneal metastasis tissue samples for histological growth pattern analysis
• Patients who decline or withdraw informed consent
• Patients unable to provide informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Patients with colorectal peritoneal metastases; Adult patients with histologically confirmed colorectal cancer and suspected or confirmed peritoneal metastases undergoing standard-of-care surgical evaluation or treatment (staging laparoscopy and/or cytoreductive surgery ± HIPEC). Peritoneal metastasis tissue samples obtained during routine clinical care are analyzed histologically to assess histological growth patterns and their association with clinical and pathological outcomes. No experimental intervention is performed as part of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distribution of histological growth patterns (HGP) in colorectal peritoneal metastases	Histological characterization of colorectal peritoneal metastases according to predefined histological growth pattern criteria (e.g., pushing, infiltrative/replacement, or mixed patterns) on hematoxylin and eosin (H&E)-stained tissue sections obtained from peritoneal biopsies or surgical specimens. The proportion of each HGP type will be determined.	At time of histopathological analysis of surgical or laparoscopic biopsy specimens (baseline, during initial surgical evaluation).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between histological growth patterns and peritoneal disease burden	Assessment of the relationship between histological growth pattern and extent of peritoneal disease as measured by the Peritoneal Cancer Index (PCI).	At time of surgery or staging laparoscopy.
Association between histological growth patterns and histopathological tumor characteristics	Evaluation of associations between HGP and tumor-related characteristics including differentiation grade, molecular markers, and other pathological features of colorectal cancer.	At time of histopathological analysis.
Association between histological growth patterns and survival outcomes	Evaluation of the relationship between HGP and clinical outcomes including overall survival and progression-free survival.	Up to 2 years after surgery or diagnosis of peritoneal metastases.

Collaborators and Investigators

• Sponsor: Jules Bordet Institute

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal cancer; Peritoneal cancer; Histopathological Growth Patterns
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: JulesBordetI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared publicly due to patient confidentiality considerations and institutional data protection policies in accordance with applicable regulations (including GDPR).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No