Liver-First, Bowel-First, or Simultaneous Resection for Synchronous Colorectal Liver Metastases: Outcomes, Quality of Life, and Cost-Effectiveness (OPTIMAL)

Optimizing Treatment of Synchronous Colorectal Liver Metastases - Creation of a Treatment Algorithm

The goal of this observational study is to learn about treatment outcomes, quality of life, and healthcare costs in patients with colorectal cancer who have liver metastases detected at the same time as their primary tumor (synchronous colorectal liver metastases, CRLM). The main questions it aims to answer are:

Do patients who undergo simultaneous removal of both the bowel tumor and liver metastases in one operation differ in their ability to complete the intended treatment compared to patients who undergo staged operations (bowel first or liver first)? Does the choice of surgical strategy affect quality of life and healthcare costs?

Patients with synchronous CRLM discussed at a multidisciplinary team meeting at participating Swedish university hospitals will be followed prospectively for up to 5 years. Treatment is not influenced by the study - all surgical decisions are made as part of routine clinical care. Patients in the quality-of-life sub-study will complete validated questionnaires (EORTC QLQ-C30, QLQ-LM21, and QLQ-CR29) at multiple time points from diagnosis through 36 months. Healthcare costs and health literacy will also be assessed in parallel sub-studies.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Metastases From Colorectal Cancer

Detailed Description

Background Patients with colorectal cancer who have liver metastases detected at the time of diagnosis (synchronous colorectal liver metastases, CRLM) require removal of both the bowel tumor and the liver metastases to achieve cure. Three surgical strategies are available: removing the bowel tumor first (bowel-first), removing the liver metastases first (liver-first), or removing both in a single operation (simultaneous resection). There is currently no consensus on which strategy is best, and practice varies considerably between hospitals and surgeons.

Study 1: Treatment Completion and Survival (Primary Study)

This prospective observational study enrolls all patients with synchronous CRLM discussed at a multidisciplinary team (MDT) meeting at participating Swedish university hospitals, where curative treatment of both the primary tumor and liver metastases is considered possible. Enrollment runs from May 2025 to May 2027, with follow-up continuing for up to 5 years.

Participation does not influence treatment in any way - all surgical and oncological decisions are made entirely according to routine clinical practice. Because the study is observational and involves no change to clinical care, an opt-out consent procedure is applied: patients are informed about the study and data collection, and are given four weeks to decline participation. If no objection is received, prospective data collection begins. Patients may withdraw at any time, and all their data will be deleted upon withdrawal.

The primary outcome is failure to Return to Intended Oncological Treatment (RIOT) - that is, the proportion of patients who do not complete their planned surgical treatment and the reasons for this. In a staged approach, this most commonly occurs when disease progression during the interval between the first and second operation renders the second operation unfeasible. Secondary outcomes include 3- and 5-year overall survival, recurrence-free survival, 90-day mortality, 30-day readmission, and complication severity assessed by the Comprehensive Complication Index and Clavien-Dindo classification.

Study 2: Health-Related Quality of Life Nested within the Study 1 cohort, this sub-study examines how the three surgical strategies affect patients' health-related quality of life (HRQoL) over time. Patients provide active informed consent to participate. Quality of life is measured using three validated questionnaires - the EORTC QLQ-C30 (general cancer), QLQ-LM21 (liver metastases-specific), and QLQ-CR29 (colorectal cancer-specific) - at multiple time points from diagnosis through 36 months after completion of surgical treatment. The time points vary according to whether the patient undergoes simultaneous or staged resection, and whether chemotherapy is administered before or after surgery. A total of 200 patients (100 undergoing simultaneous resection, 100 undergoing staged resection) are needed to detect a clinically meaningful difference in quality of life between groups.

Study 3: Healthcare Costs and Cost-Effectiveness All patients consenting to Study 2 are also included in this health economic sub-study. Direct and indirect healthcare costs are collected over the 12 months following diagnosis, covering hospital admissions, chemotherapy, radiotherapy, imaging, and multidisciplinary team meetings. Costs are obtained using Diagnosis-Related Group (DRG) and Cost Per Patient (CPP) measures and will be presented in multiple currencies. The primary endpoint is the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) gained, comparing the three surgical strategies.

Study 4: Health Literacy Also nested within the Study 2 consent framework, this sub-study assesses patients' ability to access, understand, and apply health information - referred to as health literacy - using the validated Swedish version of the European Health Literacy Survey Questionnaire (HLS-EU-Q16). Questionnaires are administered at three time points: at inclusion before any treatment, at 6 months, and at 12 months. The study examines whether health literacy levels are associated with treatment outcomes and quality of life, which may inform how clinical teams communicate with and support patients through complex treatment decisions.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Jennie Engstrand, Md, PhD; Phone Number: +46 8 123 800 00; Email: jennie.engstrand@ki.se

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with synchronous colorectal liver metastases (CRLM) discussed at a hepatobiliary and/or colorectal multidisciplinary team (MDT) meeting at participating Swedish university hospitals. The population includes all patients in whom curative treatment of both the primary colorectal tumor and liver metastases is considered feasible by the MDT, irrespective of WHO performance status, suitability for chemotherapy, prior history of malignancy, or the presence of treatable extrahepatic disease. Patients are identified consecutively at MDT meetings.

Description

Inclusion Criteria:

• Age over 18 years
• Histologically proven colorectal cancer
• Radiological evidence of liver metastases (contrast-enhanced CT or MRI), detected prior to resection of the primary colorectal tumor
• Primary colorectal tumor (colon or rectum) in situ at time of inclusion
• Discussed at a hepatobiliary and/or colorectal multidisciplinary team (MDT) meeting
• Planned curative treatment of both the primary colorectal tumor AND the liver metastases (by resection, ablation, or transplantation)
• Planned curative treatment of any extrahepatic disease, if present

Exclusion Criteria:

• Unable to give informed consent (Studies 4-6 only; opt-out applies to Study 3)
• Untreatable extrahepatic metastases at the discretion of the MDT
• Not scheduled for curative resection of both the primary tumor and liver metastases
• Emergency resection of the primary tumor performed prior to MDT referral

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Synchronous colorectal liver metastases; Simultaneous Resection, Bowel-First Staged Resection, Liver-First Staged Resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure to Return to Intended Oncological Treatment (RIOT)	The proportion of patients who do not complete their planned surgical treatment pathway, and the reasons for failure. In staged resections, this most commonly occurs when disease progression during the interval between operations renders the second operation unfeasible.	From date of MDT discussion to completion of intended treatment, assessed up to 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Survival assessed from the date of diagnosis of the primary colorectal tumor	Time frame: 3 and 5 years from diagnosis
Recurrence-Free Survival	Defined as the absence of tumor or metastases on a CT scan undertaken after completion of all intended treatment (both liver and primary tumor resection).	3 and 5 years from completion of treatment.
90-Day Mortality	Death from any cause within 90 days of the first surgical procedure.	90 days from first surgery.
30-Day Readmission	Unplanned hospital readmission within 30 days of any surgical procedure.	30 days from each surgical procedure.
Major complications	Severity of postoperative complications assessed using the Clavien-Dindo classification (grade ≥3 defined as major) and the Comprehensive Complication Index (CCI).	30 and 90 days from each surgical procedure
Full Treatment Completion	The proportion of patients who complete all intended oncological and surgical treatment as planned at the initial MDT meeting	From MDT discussion to completion of intended treatment, assessed up to 24 months.
Health-Related Quality of Life (Study 2)	Measured using three validated EORTC questionnaires - the QLQ-C30 (general cancer), QLQ-LM21 (liver metastases-specific), and QLQ-CR29 (colorectal cancer-specific). A mean difference of more than 10 points between groups on a 0-100 scale is considered clinically meaningful	At inclusion, then at multiple time points through 36 months after completion of surgical treatment, varying by treatment scenario.
Incremental Cost-Effectiveness Ratio (Study 3)	Cost per quality-adjusted life year (QALY) gained, comparing the three surgical strategies. Direct and indirect healthcare costs collected over 12 months from diagnosis including hospital admissions, chemotherapy, radiotherapy, imaging, and MDT meetings.	Time frame: 12 months from diagnosis.
Health Literacy (Study 4)	Level of health literacy assessed using the validated Swedish version of the European Health Literacy Survey Questionnaire (HLS-EU-Q16), and its correlation with treatment outcomes, quality of life and education level.	At inclusion before any treatment, at 6 months, and at 12 months from inclusion.

Collaborators and Investigators

• Sponsor: Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: April 27, 2026
• First Submitted That Met QC Criteria: April 27, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Survival; Colorectal cancer; Quality of life; Health Literacy; Liver metastases; Cost-Effectiveness; Healthcare Costs; Multidisciplinary management; Surgical strategy; Simultaneous resection; Liver first; Bowel first; Staged resections
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 2025-00266-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data will not be openly shared due to Swedish data protection legislation and GDPR restrictions. Aggregated, anonymized data may be shared with researchers following appropriate ethical approval and execution of data and research collaboration agreements. Requests for data access can be directed to the principal investigator.

Drug and device information, study documents

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