Jennie Engstrand

Introduction: Treatment strategies for colorectal cancer liver metastases (CRLM) are increasingly complex, driving interest in advanced prognostic tools. Externally validated benchmarks based on established clinical risk scores are needed to contextualise emerging models. However, existing scores remain difficult to apply and compare, because they provide categorical risk strata rather than individualised probabilities, and because model parameters are rarely published. Here, we validate and recalibrate seven established risk scores to derive individualised recurrence probabilities for future score benchmarking. Method: Patients undergoing index CRLM resection from two tertiary centres were included: Karolinska University Hospital (retrospective KaroLiver cohort [2013–2021, follow-up to 2025, n=709]) and Oslo University Hospital (OSLO-COMET trial cohort [2012–2016, follow-up to 2022, n=198]). Performance of the GAME, m-CS, Fong, Nordlinger, Nagashima, Konopke and Helsinki scores was assessed using recurrence-free survival as the primary outcome. Results: Among 709 patients in KaroLiver (median age 67 years [IQR 59–74]; 434 men [61%]), 422 (60%) had synchronous metastases and 444 (63%) received neoadjuvant chemotherapy. All scores significantly stratified recurrence risk (log-rank P<0.001; time-dependent AUC 0.63–0.74 at 3 years), albeit with performance differences across time points. Recalibrated models showed good agreement between predicted and observed recurrence and were externally validated in OSLO-COMET with broadly comparable net benefit. Models were implemented in the online tool PLATO (Personalised Liver metastases risk AssessmenT in Oncology). Conclusion: Established CRLM risk scores can be translated into individualised probabilistic recurrence estimates at clinically relevant time points, supporting patient communication, risk-adapted surveillance and transparent benchmarking of next-generation prognostic models.

Purpose: The Karolinska Liver Metastases (KaroLiver) cohort was established to investigate associations between clinical characteristics and histopathological features in patients treated with curative intent for colorectal cancer liver metastases (CRLM). The cohort combines whole-slide digital histopathology images with detailed oncological, surgical, radiological and survival data, enabling comprehensive analyses of treatment trajectories, clinical outcomes and metastatic tumour biology. Participants: KaroLiver is a retrospective observational cohort comprising all consecutive patients who received curative-intent, liver-directed treatment for CRLM at Karolinska University Hospital in Stockholm, Sweden. The hospital is the primary regional referral centre for HPB surgery, serving the population of approximately 2.5 million people in the Stockholm-Gotland healthcare region. Patient enrolment is continuously updated in accordance with amended ethical approvals and evolving scientific questions. The cohort currently comprises 811 patients who underwent 1204 liver interventions between February 2012 and January 2022. Detailed clinical, oncological, surgical, pathological, molecular, recurrence and survival data are collected. Findings to date: Median overall survival (OS) in the current cohort is 51.0 months (95% CI 46.2–57.1 months), and median recurrence-free survival (RFS) is 10.4 months (95% CI 9.2–11.9 months). The five-year OS rate is 44.9% (95% CI 41.2–48.8%). Studies using the cohort have so far identified a liver injury-derived stromal capsule in a subset of metastases, associated with improved survival. The cohort has also enabled the identification of histopathological markers of tumour biology, sex-based differences in treatment and survival, and associations between post-hepatectomy liver failure and oncological outcomes. Future plans: Current research priorities include advanced histology-based prognostic scoring, sex differences in recurrence and retreatment, tumour biology and outcomes in early-onset versus average-onset CRLM, as well as CT- and MRI-based radiomics, all integrated within KaroLiver’s histopathological framework. Data sharing is supported, given that regulatory requirements are met. Retrospective accrual and outcome updates will continue for current and future studies, subject to the required approvals. Strengths and limitations of this study: □ Selection bias in KaroLiver is minimised through consecutive, population-based accrual of all patients receiving curative-intent liver-directed treatment for CRLM at a high-volume Swedish tertiary centre. □ Granular data on recurrence, including site, timing, and intent of retreatment, enable detailed analyses of disease trajectories beyond the index hepatectomy. □ KaroLiver is linked to CT and MRI examinations from diagnosis through recurrence; combined with detailed histopathological and molecular pathology data, this provides a platform for translational research, based on specific, defined research questions. □ The observational design limits causal inference, and changes in treatment strategies and follow-up protocols over the study period may introduce temporal confounding that must be accounted for in analyses. □ Molecular data, including RAS / RAF mutation status and mismatch repair status, are incomplete, reflecting real-world clinical practice and the gradual adoption of tumour profiling over the study period.

Background and purpose: Real-world data on management and outcomes of patients with simultaneously diagnosed synchronous colorectal liver and lung metastases are limited. This national study evaluated referral patterns, treatment strategies, and survival in a population-based cohort.Patient/material and methods: This retrospective cohort study used Swedish national registries to identify patients with synchronous liver and lung metastatic colorectal cancer (CRC), defined as metastases detected within 6 months of CRC diagnosis between 2008 and 2016. Medical record review provided additional information on diagnosis confirmation, multidisciplinary team (MDT) referral, metastatic burden, and treatment. Logistic regression identified factors associated with MDT referral and curative treatment, and Cox regression with a time-varying covariate assessed survival.Results: Among 2703 registry-identified patients, medical records were accessible for 855. After exclusion of extrahepatic, non-pulmonary metastases, 556 remained for analysis. A total of 189 patients (34%) were discussed at a liver MDT conference. Referred patients were younger, had lower metastatic burden, and better performance status than non-referred. Median survival was 24 months (95% CI [confidence interval] 21–28) for referred versus 10 months (95% CI 7–12) for non-referred patients. Curative local treatment of liver and/or lung metastases was performed in 101 patients (18%), and complete metastasectomy in 34 (6%), conferring superior survival compared with liver-only intervention (hazard ratio 0.34, 95% CI 0.18–0.61). The main reason for non-referral was presumed non-resectability.Interpretation: Referral to an MDT and subsequent local treatment were associated with improved survival, although this may partly reflect favorable patient and tumor characteristics influencing referral and treatment decisions. Patients with adequate physiological reserve should routinely be evaluated in an organ-specific MDT for potential curative treatment.

Background: Sex-related differences in colorectal cancer biology and care are increasingly recognized, but their impact on colorectal liver metastases (CRLM) management remains unclear. Previous Swedish registry studies suggested that women undergo CRLM surgery less often than men. This study aimed to further explore sex-associated patterns of referral rates, resectability assessment, and survival in a contemporary, multidisciplinary team (MDT)-reviewed cohort of patients with CRLM. Methods: The study enrolled all patients with CRLM referred to the Stockholm regional liver MDT between 2013 and 2021. Tumor characteristics, treatment allocation, and survival were compared by sex. Multivariable logistic and Cox regression models were used to assess predictors of resection and survival. Results: Of 1207 MDT-referred patients, 467 (39%) were women and 740 (61%) were men. The women were younger at diagnosis and had a higher prevalence of KRAS mutations, whereas metastatic burden and extrahepatic spread were comparable between the sexes. Curative interventions were performed for 59% of the women and 62% of the men ( p = 0.219), with no differences in surgical extent, complications, or postoperative outcomes. Among palliatively treated patients, survival was similar, and multivariable Cox models identified no independent association between sex and survival in any subgroup. Conclusions: In this large, population-based MDT cohort, sex was not associated with differences in resectability, treatment, or survival. The study underscored the importance of centralized and mandatory MDT referral pathways to ensure equitable access to curative-intent treatment and standardized management for all patients with metastatic colorectal cancer.