Synchronous and metachronous colorectal liver metastases: impact of primary tumor location on patterns of recurrence and survival after hepatic resection Colorectal liver surgery and prognosis

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Ingrid Garajova
Rita Balsano
Chiara Tommasi
Raffaele Dalla Valle
Giuseppe Pedrazzi
Matteo Ravaioli
Andrea Spallanzani
Francesco Leonardi
Chiara Santini
Francesco Caputo
Mattia Riefolo
Mario Giuffrida
Fabio Gelsomino


colorectal cancer, liver metastases, hepatectomy, synchronous metastases, metachronous metastases, primary tumor, outcome


Background:Considerable differences in terms of prognosis exist between the right-sided (RCC) and the left-sided colon cancer (LCC). Aim of the work: In this study, we evaluated prognostic implications of primary tumor location (PTL) among patients who underwent curative-intent hepatectomy for synchronous (SM) and metachronous (MM) colorectal liver metastases (CRLM).Methods:The study population included all consecutive patients affected by CRLM scheduled for first liver resection at three Italian oncological centers. Results:A total of 204 patients who underwent CRLM resection were included, 50% with RCC. Synchronous lesions were prevalent (n=133, 65%). Median OS was respectively 40.3 months for SM-RCC, 53.5 months for SM-LCC, 64.5 months for MM-RCC and 81.6 months for MM-LCC. Patients with MM-LCC showed an OS better than patients with SM-RCC (p=0.008) and SM-LCC (p=0.002). PTL had no influence on RFS. RCC group had less recurrences (75% vs 86.5%), though further surgery with curative-intent was possible more in LCC group (29.3% vs 32.5%). Cox proportional hazards model analysis showed that age and the presence of SM vs MM was associated with a significantly higher hazard ratio (HR) for death (HR=1.024; 95%CI=1.005-1.043; p=0.011 and HR=2.010; 95%CI=1.328-3.043; p=0.001, respectively). Conclusions:We confirmed that patients with CRLM and right-sided primary colon cancer experience worse survival after hepatic resection. The timing of metastasis has been revealed as important prognostic factor.


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1. Ferlay J, Soerjomataram I. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136(5):E359-86.
2. Stintzing S, Tejpar S. Understanding the role of primary tumour localisation in colorectal cancer treatment and outcomes. Eur J Cancer 2017;84:69-80.
3. Mouradov D, Sloggett C, Jorissen RN,et al. Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer. Cancer Res 2014;74(12):3238-47
4. Rowan A, Halford S, Gaasenbeek M, et al. Refining molecular analysis in the pathways of colorectal carcinogenesis. Clin Gastroenterol Hepatol 2005;3(11):1115-23.
5. Lee MS, McGuffey EJ, Morris JS, et al. Association of CpG island methylator phenotype and EREG/AREG methylation and expression in colorectal cancer. Br J Cancer 2016;114(12):1352-61.
6. Baek SK. Laterality: Immunological Differences Between Right-Sided and Left-Sided Colon Cancer. Ann Coloproctol 2019;35(6):291-293.
7. Lee MS, Advani SM. Association of primary (1°) site and molecular features with progression free survival (PFS) and overall survival (OS) of metastatic colorectal cancer (mCRC) after anti-epidermal growth factor receptor (αEGFR) therapy. J Clin Oncol 2016; 34:15_suppl, 3506-3506
8. Kwak HD, Ju JK. Immunological Differences Between Right-Sided and Left-Sided Colorectal Cancers: A Comparison of Embryologic Midgut and Hindgut. Ann Coloproctol 2019;35(6):342-346.
9. Zabijak L, Attencourt C, Guignant C, et al. Increased tumor infiltration by mucosal-associated invariant T cells correlates with poor survival in colorectal cancer patients. Cancer Immunol Immunother 2015;64(12):1601-8.
10. Lee GH, Malietzis G, Askari A, et al. Is right-sided colon cancer different to left-sided colorectal cancer? - a systematic review. Eur J Surg Oncol 2015;41(3):300-8.

11. Creasy JM, Sadot E, Koerkamp BG, et al. The Impact of Primary Tumor Location on Long Term Survival in Patients Undergoing Hepatic Resection for Metastatic Colon Cancer. Ann Surg Oncol 2018;25(2):431-438.
12. Sasaki K, Andreatos N, Margonis GA, et al. The prognostic implications of primary colorectal tumor location on recurrence and overall survival in patients undergoing resection for colorectal liver metastasis. J Surg Oncol 2016;114(7):803-809.
13. Brandi G, Corbelli J, de Rosa F, et al. Second surgery or chemotherapy for relapse after radical resection of colorectal cancer metastases. Langenbecks Arch Surg 2012;397(7):1069-77.
14. Gelsomino F, Spallanzani A, Garajovà I. The treatment of rectal cancer with synchronous liver metastases: A matter of strategy. Crit Rev Oncol Hematol 2019;139:91-95.
15. Gavriilidis P, Sutcliffe RP, Hodson J, et al. Simultaneous versus delayed hepatectomy for synchronous colorectal liver metastases: a systematic review and meta-analysis. HPB (Oxford) 2018;20(1):11-19.
16. Petrelli F, Tomasello G, Borgonovo K, et al. Prognostic Survival Associated With Left-Sided vs Right-Sided Colon Cancer: A Systematic Review and Meta-analysis. JAMA Oncol 2017;3(2):211-219.
17. Zhang Y, Ma J, Zhang S, et al. A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites. Int J Colorectal Dis 2015;30(9):1173-83.
18. Nakamura Y, Hokuto D, Koyama F, et al. The prognosis and recurrence pattern of right- and left- sided colon cancer in Stage II, Stage III, and liver metastasis after curative resection. Ann Coloproctol 2020. Epub ahead of print.
19. Loupakis F, Yang D, Yau L, et al. Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst 2015;107(3):dju427.
20. Holch JW, Ricard I, Stintzing S, et al. The relevance of primary tumour location in patients with metastatic colorectal cancer: A meta-analysis of first-line clinical trials. Eur J Cancer 2017;70:87-98.
21. Tran B, Kopetz S, Tie J, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer 2011;117(20):4623-32.
22. Yamashita S, Brudvik KW, Kopetz SE, et al. Embryonic Origin of Primary Colon Cancer Predicts Pathologic Response and Survival in Patients Undergoing Resection for Colon Cancer Liver Metastases. Ann Surg 2018;267(3):514-520.
23. Gasser E, Braunwarth E, Riedmann M, et al. Primary tumour location affects survival after resection of colorectal liver metastases: A two-institutional cohort study with international validation, systematic meta-analysis and a clinical risk score. PLoS One 2019;14(5):e0217411.
24. Hackl C, Neumann P, Gerken M, et al. Treatment of colorectal liver metastases in Germany: a ten-year population-based analysis of 5772 cases of primary colorectal adenocarcinoma. BMC Cancer 2014;14:810.
25. Tomlinson JS, Jarnagin WR, DeMatteo RP, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol 2007;25(29):4575-80.
26. Jones RP, Jackson R, Dunne DF, et al. Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases. Br J Surg 2012;99(4):477-86.
27. Dupré A, Malik HZ, Jones RP, et al. Influence of the primary tumour location in patients undergoing surgery for colorectal liver metastases. Eur J Surg Oncol 2018;44(1):80–6.
28. Scherman P, Syk I, Holmberg E, et al. Influence of primary tumour and patient factors on survival in patients undergoing curative resection and treatment for liver metastases from colorectal cancer. BJS Open 2020;4(1):118-132.
29. Russolillo N, Sperti E, Langella S, et al. Impact of primary tumor location on patterns of recurrence and survival of patients undergoing resection of liver metastases from colon cancer. HPB (Oxford) 2020;22(1):116-123.
30. Liu W, Wang HW, Wang K, et al.The primary tumor location impacts survival outcome of colorectal liver metastases after hepatic resection: A systematic review and meta-analysis. Eur J Surg Oncol 2019;45(8):1349-1356.
31. Pantaleo MA, Astolfi A, Nannini M, et al. Gene expression profiling of liver metastases from colorectal cancer as potential basis for treatment choice. Br J Cancer 2008;99(10):1729-34.
32. van der Geest LG, Lam-Boer J, Koopman M, et al. Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases. Clin Exp Metastasis 2015;32(5):457-65.
33. Manfredi S, Lepage C, Hatem C, et al. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 2006;244(2):254-9.
34. Colloca GA, Venturino A, Guarneri D. Different variables predict the outcome of patients with synchronous versus metachronous metastases of colorectal cancer. Clin Transl Oncol 2020;22(8):1399-1406.
35. Ghiringhelli F, Hennequin A, Drouillard A, et al. Epidemiology and prognosis of synchronous and metachronous colon cancer metastases: a French population-based study. Dig Liver Dis 2014;46(9):854-8.
36. Mekenkamp LJ, Koopman M, Teerenstra S, et al. Clinicopathological features and outcome in advanced colorectal cancer patients with synchronous vs metachronous metastases. Br J Cancer 2010;103(2):159-64.