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Multidisciplinary Treatment with Surgery and Chemotherapy of Liver Metastases from Colorectal Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 March 2026) | Viewed by 16078

Special Issue Editors

Prof. Dr. Luca Viganò

E-Mail Website
Guest Editor
1. Hepatobiliary Unit, Department of Minimally Invasive General and Oncologic Surgery, Humanitas Gavazzeni University Hospital, Bergamo, Italy
2. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy
Interests: liver surgery; colorectal liver metastases; hepatocellular carcinoma; cholangiocarcinoma; multidisciplinary approach; prognosis and recurrence; postoperative outcome; artificial intelligence and radiomics; precision medicine; genetics
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Pietro Majno

E-Mail Website
Guest Editor
Ente Ospedaliero Cantonale, Bellinzona, Switzerland
Interests: liver surgery; colorectal liver metastases; hepatocellular carcinoma; cholangiocarcinoma; multidisciplinary approach; prognosis and recurrence; postoperative outcome; artificial intelligence and radiomics; precision medicine; genetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A multidisciplinary collaboration is the cornerstone of success in managing patients with colorectal liver metastases. Hepatobiliary surgeons have achieved remarkable outcomes, but only thanks to increasing collaboration with all other disciplines involved in the field.

New horizons are emerging for all specialists, including innovative targeted therapies and immunotherapies, more precise ablation techniques, and internal and external radiation techniques. Even standard resection is no longer the same, with an increasing place taken by the robotic approach. Liver transplantation is gaining increasing prominence. It has the potential to bridge the gap for patients with unresectable disease and it could even replace resective surgery for those with a high tumor burden.

Addressing the challenges of the future requires a multidisciplinary team with continuously updated expertise, open dialog, and innovative, personalized treatment strategies.

In this Special Issue, we aim to highlight cutting-edge advances and explore emerging solutions in the multidisciplinary management of colorectal liver metastases. We invite research papers by surgeons, medical oncologists, radiation oncologists, interventional and diagnostic radiologists and all other specialists across the multiple phases of care for these complex patients.

We look forward to receiving your contributions.

Prof. Dr. Luca Viganò
Prof. Dr. Pietro Majno
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • colorectal liver metastases
  • liver surgery
  • oncology
  • multidisciplinary approach
  • prognosis
  • recurrence
  • precision medicine
  • genetics
  • tumor biology
  • liver transplantation
  • perioperative therapy and conversion therapy

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Published Papers (5 papers)

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Research

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18 pages, 1616 KB  
Article
Oncologic and Surgical Outcomes After Short-Course Neoadjuvant CAPOX Plus Bevacizumab in High-Risk Colorectal Liver Metastases
by Yawen Dong, Madita Tschoegl, Florian Lehner, Jonas Santol, Francesca Notte, Mariel Gramberger, Mohammed Salem, Edanur Cenan, Rebecca Thonhauser, Thomas Hoblaj, Rosemarie Valenta, Birgit Gruenberger and Thomas Gruenberger
Cancers 2026, 18(3), 521; https://doi.org/10.3390/cancers18030521 - 5 Feb 2026
Viewed by 722
Abstract
Background: The optimal duration of neoadjuvant therapy for high-risk colorectal liver metastases (CRLM) remains debated. While prolonged chemotherapy may enhance response, it also increases toxicity and risks delaying potentially curative resection. These considerations have raised the question whether a short-course neoadjuvant strategy might [...] Read more.
Background: The optimal duration of neoadjuvant therapy for high-risk colorectal liver metastases (CRLM) remains debated. While prolonged chemotherapy may enhance response, it also increases toxicity and risks delaying potentially curative resection. These considerations have raised the question whether a short-course neoadjuvant strategy might achieve sufficient oncologic selection and response while minimizing treatment-related morbidity. Methods: Patients with synchronous or metachronous CRLM who received two cycles of neoadjuvant CAPOX plus bevacizumab followed by curative-intent liver resection treated between 2014 and 2024 at Health Network Vienna, Austria, were included. Clinicopathologic characteristics, treatment tolerability, response assessments (biochemical, radiologic, and pathologic), and survival outcomes were collected and analyzed. Results: A total of 57 patients were included (65% synchronous, 35% metachronous), with the rectum being the most frequent primary tumor site (45.6%). Most liver lesions were <5 cm (84.2%), and 47% had bilobar disease. Minor hepatectomy was performed in 65% of cases, predominantly via open surgery (72%). Grade ≥3 treatment-related adverse events occurred in 6 patients (10.6%), mainly neutropenia and diarrhea. Biochemically, 53.7% achieved >50% tumor marker reduction. Radiologic assessment showed partial response in 31.6% and complete response in 1.7%. Pathologic evaluation revealed TRG 3 as the most common finding (57.1%), followed by TRG 2 in 22.5%. Subgroup analyses demonstrated significantly improved OS and RFS in patients receiving adjuvant therapy and in those with tumors < 5 cm. Conclusion: A two-cycle, short-course regimen of CAPOX plus bevacizumab proved both effective and safe in high-risk CRLM, achieving meaningful biochemical, radiologic, and pathologic responses with acceptable toxicity. This abbreviated approach allowed delivery of neoadjuvant therapy while limiting cumulative treatment-related toxicity, supporting its feasibility as a neoadjuvant strategy in selected high-risk CRLM patients. Full article
(This article belongs to the Special Issue Multidisciplinary Treatment with Surgery and Chemotherapy of Liver Metastases from Colorectal Cancer)
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Review

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19 pages, 2240 KB  
Review
Critical Evaluation of Treatment Response, Driver Mutations, and Circulating Tumor DNA as Markers of Tumor Biology in Colorectal Liver Metastasis
by Mikel Madi, Antony Haddad, Kyoji Ito, Neal Bhutiani and Jean-Nicolas Vauthey
Cancers 2026, 18(7), 1111; https://doi.org/10.3390/cancers18071111 - 30 Mar 2026
Viewed by 766
Abstract
Background: Improved assessment of tumor biology has contributed to better outcomes in colorectal liver metastasis (CLM). Previously, tumor biology was assessed based on clinical factors such as number and size of metastases, primary tumor characteristics, and extent of extrahepatic disease. Currently, tumor biology [...] Read more.
Background: Improved assessment of tumor biology has contributed to better outcomes in colorectal liver metastasis (CLM). Previously, tumor biology was assessed based on clinical factors such as number and size of metastases, primary tumor characteristics, and extent of extrahepatic disease. Currently, tumor biology assessment includes response to chemotherapy, genetic mutations, and circulating tumor DNA (ctDNA). Methods: A review of the literature in Medline/Pubmed, Embase, and Cochrane Library was conducted using keywords and MeSH terms. Results: Tumor response to chemotherapy can be assessed using pathologic and radiologic criteria. Radiologic morphologic response has been associated with more accurate determination of outcomes compared with size-based criteria. Pathologic tumor response can be assessed by the percentage of cancer cells remaining within each tumor, the ratio of cancer cells to fibrosis, and the thickness of the tumor–normal liver interface. Six driver mutations are consistently associated with outcomes in CLM: RAS/BRAF, TP53, SMAD4, FBXW7, and APC. All are associated with decreased overall survival (OS) and recurrence-free survival (RFS) except for APC, which is associated with better survival. More than 50% of patients have co-mutations, and a three-tier pathway-centric risk score integrating these mutations offers a more comprehensive approach. While mutations should be considered when evaluating for locoregional therapy, it should not influence ablation margins, surgical margins, or parenchymal sparing approach. Preoperative ctDNA is associated with worse survival, but clearance after hepatectomy is associated with improved survival. Postoperative ctDNA status is associated with recurrence and has the potential to guide the choice of adjuvant chemotherapy. Conclusion: Tumor biology enables informed, precise, and personalized decision-making. Integration of response to chemotherapy, driver mutations, and ctDNA into routine practice is critical to improve CLM management. Full article
(This article belongs to the Special Issue Multidisciplinary Treatment with Surgery and Chemotherapy of Liver Metastases from Colorectal Cancer)
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26 pages, 1050 KB  
Review
How to Integrate Surgery into the Multidisciplinary Treatment of Liver-Only Metastatic Colorectal Cancer
by Leticia Pérez-Santiago, Dixie Huntley Pascual, José Saúl Sánchez Lara, Marisol Huerta and Dimitri Dorcaratto
Cancers 2026, 18(3), 489; https://doi.org/10.3390/cancers18030489 - 2 Feb 2026
Viewed by 818
Abstract
Background: Colorectal liver metastases (CRLM) represent a major determinant of prognosis in patients with metastatic colorectal cancer and account for a substantial proportion of cancer-related mortality worldwide. Over the last decades, survival outcomes have improved significantly as a result of advances in systemic [...] Read more.
Background: Colorectal liver metastases (CRLM) represent a major determinant of prognosis in patients with metastatic colorectal cancer and account for a substantial proportion of cancer-related mortality worldwide. Over the last decades, survival outcomes have improved significantly as a result of advances in systemic therapies, refinement of surgical techniques, and, most importantly, the widespread implementation of multidisciplinary management strategies. Within this evolving landscape, surgery remains the cornerstone of potentially curative treatment, although its optimal integration with systemic and locoregional therapies requires careful patient selection and individualized treatment planning. Methods: This narrative review explores the contemporary role of surgery within the multidisciplinary management of CRLM, emphasizing how surgical decision-making is integrated with medical oncology, radiology, interventional procedures, and emerging technologies. Results: The pivotal role of multidisciplinary team meetings in defining resectability, treatment sequencing, and therapeutic intent is highlighted. Key technical and oncological criteria guiding upfront resection, neoadjuvant or conversion strategies, and staged approaches are reviewed, including assessment of future liver remnant, optimization of liver volume and function, tumor burden, molecular profile, and dynamic prognostic models. In addition, the review summarizes current evidence supporting parenchyma-sparing liver surgery and the integration of local therapies such as thermal ablation, irreversible electroporation, stereotactic body radiotherapy, selective internal radiation therapy, and hepatic artery infusion chemotherapy within multimodal treatment algorithms. Complex clinical scenarios, including synchronous disease, extensive bilobar metastases, chemotherapy-associated liver injury, and the emerging role of liver transplantation in highly selected patients with liver-only disease, are also addressed. Conclusions: Modern CRLM management has evolved toward a highly individualized, biology-driven approach in which surgery is optimally integrated within a multidisciplinary framework to maximize curative potential and long-term survival. Full article
(This article belongs to the Special Issue Multidisciplinary Treatment with Surgery and Chemotherapy of Liver Metastases from Colorectal Cancer)
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35 pages, 887 KB  
Review
Prognostic Factors in Colorectal Liver Metastases: An Exhaustive Review of the Literature and Future Prospectives
by Maria Conticchio, Emilie Uldry, Martin Hübner, Antonia Digklia, Montserrat Fraga, Christine Sempoux, Jean Louis Raisaro and David Fuks
Cancers 2025, 17(15), 2539; https://doi.org/10.3390/cancers17152539 - 31 Jul 2025
Cited by 10 | Viewed by 11957
Abstract
Background: Colorectal liver metastasis (CRLM) represents a major clinical challenge in oncology, affecting 25–50% of colorectal cancer patients and significantly impacting survival. While multimodal therapies—including surgical resection, systemic chemotherapy, and local ablative techniques—have improved outcomes, prognosis remains heterogeneous due to variations in [...] Read more.
Background: Colorectal liver metastasis (CRLM) represents a major clinical challenge in oncology, affecting 25–50% of colorectal cancer patients and significantly impacting survival. While multimodal therapies—including surgical resection, systemic chemotherapy, and local ablative techniques—have improved outcomes, prognosis remains heterogeneous due to variations in tumor biology, patient factors, and institutional practices. Methods: This review synthesizes current evidence on prognostic factors influencing CRLM management, encompassing clinical (e.g., tumor burden, anatomic distribution, timing of metastases), biological (e.g., CEA levels, inflammatory markers), and molecular (e.g., RAS/BRAF mutations, MSI status, HER2 alterations) determinants. Results: Key findings highlight the critical role of molecular profiling in guiding therapeutic decisions, with RAS/BRAF mutations predicting resistance to anti-EGFR therapies and MSI-H status indicating potential responsiveness to immunotherapy. Emerging tools like circulating tumor DNA (ctDNA) and radiomics offer promise for dynamic risk stratification and early recurrence detection, while the gut microbiome is increasingly recognized as a modulator of treatment response. Conclusions: Despite advancements, challenges persist in standardizing resectability criteria and integrating multidisciplinary approaches. Current guidelines (NCCN, ESMO, ASCO) emphasize personalized strategies but lack granularity in terms of incorporating novel biomarkers. This exhaustive review underscores the imperative for the development of a unified, biomarker-integrated framework to refine CRLM management and improve long-term outcomes. Full article
(This article belongs to the Special Issue Multidisciplinary Treatment with Surgery and Chemotherapy of Liver Metastases from Colorectal Cancer)
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Other

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19 pages, 1577 KB  
Systematic Review
Prognostic Scores for Liver Resection in Colorectal Metastases: Performance, Limitations, and Methodological Pitfalls—A Systematic Review and Meta-Analysis
by Luca Viganò, Luca Risi, Elisa Ragaini, Francesca Ieva and Elena Desiato
Cancers 2026, 18(4), 625; https://doi.org/10.3390/cancers18040625 - 14 Feb 2026
Viewed by 953
Abstract
Background/Objectives: The prediction of survival after resection of colorectal liver metastases is crucial for planning treatment strategies. Several prognostic scores have been proposed, but their reliability is debated. The present study aims to review available prognostic scores, focusing on their performance and the [...] Read more.
Background/Objectives: The prediction of survival after resection of colorectal liver metastases is crucial for planning treatment strategies. Several prognostic scores have been proposed, but their reliability is debated. The present study aims to review available prognostic scores, focusing on their performance and the methodological approaches adopted for their evaluation. Methods: A systematic literature review was conducted using PubMed, Embase, and the Cochrane Database, including studies published between January 2015 and June 2024. Only English-language studies reporting the external validation of prognostic models were included. A random-effects meta-analysis was performed. Results: Overall, 48 prognostic scores were externally validated across 48 studies (n = 33,602 patients). A total of 286 performance measurements were reported, utilizing 17 different metrics and considering four outcomes: overall survival (OS), cancer-specific survival, recurrence-free survival (RFS), and recurrence rate. For OS, the pooled C-index values for the Fong, GAME, and RAS mutation Clinical Risk scores were 0.578 (0.570–0.587), 0.609 (0.592–0.625), and 0.579 (0.471–0.688), respectively. For RFS, the pooled C-index for the Fong score was 0.616 (0.578–0.653). Scores incorporating genetic, immunological and radiomic data performed better than purely clinical ones (C-index = 0.610, 0.657 and 0.635, respectively, vs. 0.585, p < 0.05). Analogously, the scores including perioperative data outperformed preoperative ones (C-index = 0.671 vs. 0.600, p = 0.007). Conclusions: The current survival prediction relies on scores with low reliability (C-index ≤ 0.65). Despite the abundance of available data, their heterogeneity and variable quality have limited their usability. Future research should prioritize the development of new prognostic tools and the standardization of prognostic modeling and reporting. Full article
(This article belongs to the Special Issue Multidisciplinary Treatment with Surgery and Chemotherapy of Liver Metastases from Colorectal Cancer)
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