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

NCT07474025 | Not Yet Recruiting

• 1 other identifier: JulesBordetI
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Peritoneal (Metastatic) Cancer; Colorectal Cancer; Colorectal (Colon or Rectal) Cancer; Histopathological Growth Patterns (HGPs)

Keywords

Peritoneal cancer; Colorectal cancer; Histopathological Growth Patterns

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Association between histological growth patterns and peritoneal disease burden

  At time of surgery or staging laparoscopy.

• Association between histological growth patterns and histopathological tumor characteristics

  At time of histopathological analysis.

• Association between histological growth patterns and survival outcomes

  Up to 2 years after surgery or diagnosis of peritoneal metastases.

Study Arms (1)

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.

Eligibility Criteria

• Age: Up to 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jules Bordet Institute: lead

Study Sites (1)

Hub Bordet

Brussels, Brussels Capital, 1070, Belgium

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Residual tumor tissue samples from colorectal peritoneal metastases will be retained. These consist of peritoneal excisional biopsies obtained during staging laparoscopy (1 to 3 biopsies from accessible disease sites, preferentially the omentum and/or parietal peritoneum) and, when cytoreductive surgery is performed, up to 3 representative peritoneal metastasis samples collected from the surgical resection specimen (preferably omentum and/or parietal peritoneum). Samples are formalin-fixed and processed for routine histopathological assessment, including H\&E-stained slides for histological growth pattern evaluation.

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms; Colorectal Neoplasms; Colonic Neoplasms

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Gabriele Professor Liberale, MD, pHD

CONTACT

+32 2 541 31 11; gabriele.liberale@hubruxelles.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: March 16, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)