Clinical trial NCT06200831: Simultaneous vs. Staged Resection of Colorectal Cancer With Synchronous Liver Metastases
Official title: Simultaneous vs. Staged Resection of Colorectal Cancer With Synchronous Liver Metastases - A Multicentre Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Cancer
Colorectal Neoplasms Malignant
Liver Metastasis Colon Cancer
Liver Metastases
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: University of Oslo
name: Haukeland University Hospital
name: St. Olavs Hospital
name: Helse Stavanger HF
name: University Hospital, Akershus
First posted: 2024-01-11
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The SYLMET Trial is a randomized trial to compare simultaneous and two-staged resection of primary colorectal and synchronous liver metastases. This is an investigator-initiated, multicentre, randomized controlled trial to assess complications (primary endpoint), survival, cost-effectiveness, and quality of life (secondary endpoints).This trial will include patients with resectable primary tumour in the colon or upper rectum with less than five liver metastases that is possible to treat with surgical resection and/or ablation (RFA/MWA) at time of evaluation.

Detailed description: Colorectal cancer (CRC) represents the second most common cause of cancer and cancer death in Norway, and the incidence is increasing (Cancer in Norway, 2021, Cancer Registry of Norway). The liver is the most common site of metastasis from CRC. More than 4500 individuals are diagnosed with CRC in Norway each year, and approximately 20% of patients present with liver metastases at time of diagnosis (synchronous metastases). Resection of both the primary tumor and liver metastases is considered the only curative treatment, and has been shown to improve long-term survival, and is considered standard of care. However, the optimal timing of surgical resection of synchronous liver metastases in relation to the primary tumor is not well defined. Traditionally, staged resection has been preferred (i.e., resection of the primary tumour and liver metastases on separate admissions with a period of recovery between the two operations), whereas simultaneous resection is appealing (i.e., resection of both primary and metastases in one operative session). Despite a lack of randomized controlled trials comparing these two surgical approaches, the number of simultaneous resections has increased at several institutions. The evolvement of both liver and colorectal surgery in the last decades has led to reduced complications, making simultaneous resections more feasible. Previous retrospective cohort studies and meta-analyses suggest that simultaneous and staged approach carry similar postoperative complication and perioperative mortality rates as well as long-term survival. A recently published prospective observational study on staged or simultaneous surgery, reported similar outcomes in selected patients. To date, there is only one published randomized controlled trial which was aborted after inclusion of half of the sample size, after an accrual time of 10 years18. Due to lack of evidence, the majority of surgical societies worldwide still treats this patient group with staged resections, resulting in two hospital admissions, two rounds of general anaesthesia and surgery, and finally two episodes of postoperative recovery and rehabilitation. If this trial demonstrates that simultaneous surgery is safe, feasible, and cost-effective, it will potentially have a practice-changing impact worldwide.

Eligibility criteria: Inclusion Criteria:

* Age 18-80 years old.
* Both CRC and liver metastases in situ at time of evaluation.
* Resectable primary tumor in the colon or upper rectum.
* Less than 5 liver metastases, evaluated by the multidisciplinary tumor board meeting as possible to treat with surgical resection and/or ablation (RFA/MWA).

Exclusion Criteria:

* Unresectable primary tumor.
* Locally advanced primary tumor (T4).
* Primary tumor in the lower rectum with indication for abdominoperineal resection.
* Acute or imminent bowel obstruction.
* Perforation or major bleeding from the primary tumor.
* Pre-treatment of the primary tumor with a colon stent.
* Liver resection requiring resection of more than 2 adjacent segments (Couinaud).
* Liver metastases planned treated with irreversible electroporation (IRE).
* Non-resectable lung metastases.
* Metastases outside of liver (besides resectable lung metastases).
* Eastern Cooperative Oncology Group (ECOG) Performance status ≥ 3.

Primary outcomes:
measure: Comprehensive Complication Index, CCI
timeFrame: 90 days
Secondary outcomes:
measure: Health Economics
timeFrame: 1 year
measure: Overall survival
timeFrame: 3 and 5 years
measure: Clavien Dindo Complications
timeFrame: 90 days
measure: Quality of Life: EQ-5D
timeFrame: Pre-operative, 30-days, 90-days, 6 months, 12 months
measure: Quality of Life: EORTC QLQ-30
timeFrame: Pre-operative, 30-days, 90-days, 6 months, 12 months
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Oslo University Hospital
name: Sheraz Yaqub, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kleive D, Aas E, Angelsen JH, Bringeland EA, Nesbakken A, Nymo LS, Schultz JK, Soreide K, Yaqub S. Simultaneous Resection of Primary Colorectal Cancer and Synchronous Liver Metastases: Contemporary Practice, Evidence and Knowledge Gaps. Oncol Ther. 2021 Jun;9(1):111-120. doi: 10.1007/s40487-021-00148-2. Epub 2021 Mar 23.
citation: Siriwardena AK, Serrablo A, Fretland AA, Wigmore SJ, Ramia-Angel JM, Malik HZ, Stattner S, Soreide K, Zmora O, Meijerink M, Kartalis N, Lesurtel M, Verhoef C, Balakrishnan A, Gruenberger T, Jonas E, Devar J, Jamdar S, Jones R, Hilal MA, Andersson B, Boudjema K, Mullamitha S, Stassen L, Dasari BVM, Frampton AE, Aldrighetti L, Pellino G, Buchwald P, Gurses B, Wasserberg N, Gruenberger B, Spiers HVM, Jarnagin W, Vauthey JN, Kokudo N, Tejpar S, Valdivieso A, Adam R; Joint E-AHPBA/ESSO/ESCP/ESGAR/CIRSE 2022 Consensus on colorectal cancer with synchronous liver metastases. The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE. HPB (Oxford). 2023 Sep;25(9):985-999. doi: 10.1016/j.hpb.2023.05.360. Epub 2023 Jul 13.
citation: Yaqub S, Margonis GA, Soreide K. Staged or Simultaneous Surgery for Colon or Rectal Cancer with Synchronous Liver Metastases: Implications for Study Design and Clinical Endpoints. Cancers (Basel). 2023 Apr 6;15(7):2177. doi: 10.3390/cancers15072177.