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Colorectal cancer with synchronous unresectable liver metastases: resecting the primary tumor improves survival

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Abstract

Purpose

The optimal treatment strategy of patients affected by colorectal cancer (CRC) with synchronous unresectable liver metastases (SULM) is at present undefined. It is not known if a palliative primary tumor resection followed by chemotherapy could have a survival benefit compared to upfront chemotherapy (CT). The aim of the study is to analyze the safety and effectiveness of both therapeutic strategies in a group of patients treated at one institution.

Methods

A prospectively collected database was queried for patients affected by colorectal cancer with synchronous unresectable liver metastases between January 2004 and December 2018, defining and comparing 2 groups: patients treated by chemotherapy alone (group 1) vs patients who underwent primary tumor resection with or without a first line chemotherapy (group 2). The primary end point was Overall Survival (OS), estimated by the Kaplan–Meier method.

Results

One hundred sixty-seven patients were included: 52 in group 1 and 115 in group 2, median follow-up 48 months (range 25–126). A difference of 14 months in overall survival was observed between group 2 compared to group 1 (28 vs 14 months respectively; p < 0.001). Furthermore, overall survival increased in patients who underwent liver metastases resection (p < 0.001) or percutaneous radiofrequency ablation after surgery (p < 0.001).

Conclusion

With the limits of a retrospective analysis, the study shows that surgical resection of the primary tumor has a significant impact on survival compared to chemotherapy alone. Randomized controlled trials are needed to confirm these data.

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References

  1. The Global Cancer Observatory - All Rights Reserved - March 2021

  2. Mantke R, Schmidt U, Wolff S, Kube R, Lippert H (2012) Incidence of synchronous liver metastases in patients with colorectal cancer in relationship to clinico-pathologic characteristics. Results of a German prospective multicentre observational study. Eur J Surg Oncol

  3. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29. Epub 2012

  4. Clavien PA, Petrowsky H, DeOliveira ML, Graf R (2007) Strategies for safer liver surgery and partial liver transplantation. N Engl J Med

  5. Scheithauer W, Rosen H, Kornek GV, Sebesta C, Depisch D (1993) Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. BMJ

  6. Lucas AS, O’Neil BH, Goldberg RM (2011) A decade of advances in cytotoxic chemotherapy for metastatic colorectal cancer. Clin Colorectal Cancer

  7. Aslam MI, Kelkar A, Sharpe D, Jameson JS (2010) Ten years experience of managing the primary tumors in patients with stage IV colorectal cancer. Int J Surg

  8. Cirocchi R, Trastulli S, Abraha I, Vettoretto N, Boselli C, Montedori A, Parisi A, Noya G, Platell C (2012) Non-resection versus resection for an asymptomatic primary tumour in patients with unresectable stage IV colorectal cancer. Cochrane Database Syst Rev

  9. Clancy C, Burke JP, Barry M, Kalady MF, Coffey JC (2014) A meta-analysis to determine the effect of primary tumor resection for stage IV colorectal cancer with unresectable metastases on patient survival Ann Surg Oncol

  10. Tarantino I, Warschkow R, Worni M, Cerny T, Ulrich A, Schmied B, Guller U (2014) Prognostic relevance of palliative primary tumor removal in 37,793 metastatic colorectal cancer patients A population-based, propensity score–adjusted trend analysis. Ann Surg

  11. Slesser AAP, Khan F, Chau I, Khan AZ, Mudan S, Tekkis PP, Brown G, Rao S (2015) The effect of a primary tumor resection on the progression of synchronous colorectal liver metastases: an exploratory study. EJSO

  12. Rahbari NN, Lordick F, Fink C, Bork U, Stange A, Jäger D, Luntz SP, Englert S, Rossion I, Koch M, Büchler MW, Kieser M, Weitz J, SYNCHRONOUS trial group (2012) Resection of the primary tumor versus no resection prior to systemic therapy in patients with colon cancer and synchronous unresectable metastases (UICC stage IV): Anche SYNCHRONOUS-a randomised controlled multicentre trial (ISRCTN30964555). BMC Cancer

  13. Cotte E, Villeneuve L, Passot G, Boschetti G, Bin-Dorel S, Francois Y, Glehen O, French Research Group of Rectal Cancer Surgery (GRECCAR) (2015) GRECCAR 8: impact on survival of the primary tumor resection in rectal cancer with unresectable synchronous metastasis: a randomized multicentre study. BMC Cancer

  14. Vaqué J, García Armengol J, Mora L et al  Resection vs no Resection of the primary in colorectal cancer with unresectable metastases. A ClinicalTrials.gov Identifier: NCT02015923

  15. Ojima H, Ike H, Shiomi A, Watanabe J, Takii Y, Yamaguchi T, Katsumata K, Ito M, Okuda J, Hyakudomi R, Shimada Y, Katayama H, Fukuda H, JCOG Colorectal Cancer Study Group (2021) Dave E W van der Kruijssen 1, Sjoerd G Elias 2, Geraldine R Vink 1 3, Karlijn L van Rooijen 1, Jorine ’t Lam-Boer 4, Linda Mol 5, Cornelis J A Punt 2, Johannes H W de Wilt 4, Miriam Koopman 1; CAIRO4 working group sixty-day mortality of patients with metastatic colorectal cancer randomized to systemic treatment vs primary tumor resection followed by systemic treatment: The CAIRO4 Phase 3 randomized clinical trial. JAMA Surg 156(12):1093–1101

  16. Jegatheeswaran S, Mason JM, Hancock HC et al (2013) The liver‐ first approach to the management of colorectal cancer with synchronous hepatic metastases. JAMA Surg

  17. Qureshi MS, Goldsmith PJ, Maslekar S et al (2012) Synchronous resection of colorectal cancer and liver metastases: comparative views of colorectal and liver surgeons. Colorectal Dis

  18. Kelly ME, Spolverato G, Lê GN, Mavros MN, Doyle F, Pawlik TM, Winter DC (2015) Synchronous colorectal liver metastasis: a network meta-analysis review comparing classical, combined, and liver-first surgical strategies. J Surg Oncol

  19. Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Köhne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Österlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taïeb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D (2016) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol

  20. Ruers T, Punt C, Van Coevorden F et al (2015) Radiofrequency ablation (RFA) combined with chemotherapy for unresectable colorectal liver metastases (CRC LM): long-term survival results of a randomized phase II study of the EORTC-NCRI CCSG-ALM Intergroup 40004 (CLOCC). J Clin Oncol

  21. Essner R, Lee JH, Wanek LA, Itakura H, Morton DL (2004) Contemporary surgical treatment of advanced-stage melanoma. Arch Surg

  22. Flanigan RC, Salmon SE, Blumenstein BA et al (2001) Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med

  23. Mickisch GH, Garin A, van PH, de PL, Sylvester R (2001) Radical nephrectomy plus interferonalfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet

  24. Harris E, Barry M, Kell MR (2013) Meta-analysis to determine if surgical resection of the primary tumor in the setting of stage IV breast cancer impacts survival. Ann Surg Oncol

  25. Danna EA, Sinha P, Gilbert M et al (2004) Surgical removal of primary tumor reverses tumor induced immunosuppression despite the presence of metastatic disease. Cancer Res

  26. Norton L, Massague J (2006) Is cancer a disease of self-seeding? Nat Med

  27. Paget S (1989) The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev

  28. Lim C, Eveno C, Pocard M (2013) Microenvironment and colorectal liver metastases angiogenesis: surgical implications. Bull Cancer

  29. Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature

  30. van der Wal GE, Gouw AS, Kamps JA, Moorlag HE, Bulthuis ML, Molema G, de Jong KP (2012) Angiogenesis in synchronous and metachronous colorectal liver metastases: the liver as a permissive soil. Ann Surg

  31. Karoui M, Roudot-Thoraval F, Mesli F, Mitry E, Aparicio T, Des Guetz G, Louvet C, Landi B, Tiret E (2011) Primary colectomy in patients with stage IV colon cancer and unresectable distant metastases improves overall survival: results of a multicentric study

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Authors and Affiliations

  1. Department of Surgical Sciences, University of Torino, C.so Dogliotti 14, 10126, Torino, Italy

    Nicola Leone, Simone Arolfo & Mario Morino

  2. Department of Onco-hematology, Medical Oncology, Città della Salute, e della Scienza Molinette University Hospital, Torino, Italy

    Rosella Spadi

  3. General Surgery, Department of Surgical Sciences, University of Torino, Torino, Italy

    Maria Roberta Fortunato

  4. Department of Medical Sciences, University of Torino, Torino, Italy

    Roberto Passera

Authors
  1. Nicola Leone
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  2. Simone Arolfo
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  3. Rosella Spadi
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  4. Maria Roberta Fortunato
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  5. Roberto Passera
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  6. Mario Morino
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Contributions

Nicola Leone designed the study, acquired data and analyzed data, drafted the article and approved its final version. Simone Arolfo designed the study, acquired data and analyzed data, drafted the article and approved its final version. Rosella Spadi acquired data, revised the article and approved its final version. Maria Roberta Fortunato acquired data, revised the article and approved its final version. Roberto Passera analyzed data, drafted and revised the article and approved its final version. Mario Morino designed the study, analyzed and interpreted data, revised the article and approved its final version.

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Correspondence to Nicola Leone.

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Leone, N., Arolfo, S., Spadi, R. et al. Colorectal cancer with synchronous unresectable liver metastases: resecting the primary tumor improves survival. Int J Colorectal Dis 38, 169 (2023). https://doi.org/10.1007/s00384-023-04469-8

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  • DOI: https://doi.org/10.1007/s00384-023-04469-8

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