Colorectal liver metastases: global trends in epidemiology, modern opportunities for treatment

Aliev S.A.; Aliev E.S.

doi:https://doi.org/10.17116/onkolog20211003160

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Abstract:

According to the literature, the review presents global trends in the epidemiology of colorectal cancer and the state-of-the-art in the treatment of patients with colorectal liver metastases. It describes conventional and current treatments, including cytoreductive (resection) surgery, minimally invasive procedures for local destruction (radiofrequency thermal ablation, microwave ablation, cryoablation), stereotactic radiotherapy, radiosurgery, targeted therapy, and X-ray endovascular methods (chemoinfusion, chemoembolization, and radioembolization). It is postulated that the search for new chemotherapeutic and targeted drugs can contribute to the improvement of treatment results in patients with potentially resectable colorectal liver metastases. The possibilities and prospects of liver transplantation as an absolute alternative to the existing methods of treatment for patients with unresectable multiple bilobar colorectal metastases are highlighted. The data available in the lit erature on the use of liver transplantation in this category of patients indicate the undeniable advantages of the method. The prospects for the treatment of patients with unresectable multiple bilobar colorectal liver metastases are clearly planned multicenter randomized trials of liver transplantation. There is reason to believe that the results of the ongoing studies and their meta-analysis will be able to develop an international consensus on this issue and a unified global strategy for the treatment of this severe category of patients in the foreseeable future.

Keywords:

colorectal cancer

liver metastases

unresectable multiple bilobar metastases

minimally invasive methods of local treatment

liver transplantation

Authors:

Aliev S.A.

Azerbaijan Medical University

Aliev E.S.

Azerbaijan Medical University

Received:

10.03.2021

Accepted:

18.03.2021

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References:

Aliev FSh, Desyatov EN, Krytskikh AG, Aliev VF, Leimanchenko PI. The epidemiology of colorectal cancer: world and regional tendencies. Meditsinskaya nauka i obrazovanie Urala. 2016;(4):126-128. (In Russ).
Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683-691. https://doi.org/10.1136/gutjnl-2015-310912
Rex DK, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, Kaltenbax T, Levin ThR, Liebarman D, Robertson DJ. Colorectal cancer screening: Recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc. 2017;86(1):18-33. https://doi.org/10.1016/j.gie.2017.04.003
Rawla P, Sunkara T, Barsouk A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors. Prz Gastroenterol. 2019;14(2):89-103. https://doi.org/10.5114/pg.2018.81072
Siegel RL, Miller KD, Goding SA, Fedewa SA, Butterly LF, Anderson CJ, Cercek A. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020;70(3):145-164. https://doi.org/10.3322/caac.21601
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69-90. https://doi.org/10.3322/caac.20107
American Cancer Society. Cancer facts and figures 2014. Atlanta: American Cancer Society; 2014.
Shelygin YuA. Colon cancer. In: Shelygin YuA, Blagorodnyi LA, eds. Handbook of coloproctology. M.: Litterra; 2014. (In Russ).
Kaprin AD, Starinskii VV, Petrova GV, eds. The state of cancer care for the population of Russia in 2014. M.: MNIOI im. P.A. Gertsena — filial FGBU «NMIRTs»; 2015. (In Russ.).
Yang XF, Pan K. Diagnosis and management of acute complications in patients with colon cancer: bleeding, obstruction, and perforation. Chin J Cancer Res. 2014;26(3):331-340. https://doi.org/10.3978/j.issn.1000-9604.2014.06.11
Pak H, Maghsoud LH, Soltanian A, Gholami F. Surgical complications in colorectal cancer patients. Ann Med Surg. 2020;55:13-18. https://doi.org/10.1016/j.amsu.2020.04.024
Aliev VA, Barsukov YuA, Nikolaev AV. Colorectal cancer with synchronous metastases: rationale for cytoreductive surgers and outlooks — surgeon’s view. Oncological Proctology=Onkologicheskaya proktologiya. 2012;(4):15-21. (In Russ).
Mahnken AH, Pereira PL, de Baere T. Interventional Oncologic Approaches to liver metastases. Radiology. 2013;266(2):407-430. https://doi.org/10.1148/radiol.12112544
Ejaz A, Semenov E, Spolverato G, Kim Y, Tanner D, Hundt J, Rawlik TM. Synchronous primary colorectal and liver metastasis: impact of operative approach on clinical outcomes and hospital charges. HPB (Oxford). 2014;16(12):1117-1126. https://doi.org/10.1111/hpb.12302
Kelly ME, Spolverato G, Le GN, Mavros MN, Doyle F, Pawlik TM, Winter DS. Synchronous colorectal liver metastasis: a network meta-analysis review comparing classical, combined, and liver-first surgical strategies. J Surg Oncol. 2015;111(3):341-351. https://doi.org/10.1002/jso.23819
Maistrenko NA, Khvatov AA, Sazonov AA. Postoperative complications of combined surgeries in patients with disseminated forms of colon cancer. Grekov’s Bulletin of Surgery=Vestnik khirurgii imeni I.I. Grekova. 2017;176(2):86-94. (In Russ.). https://doi.org/10.24884/0042-4625-2017-176-2-86-94
Zarour LR, Anand S, Billingsley KG, Bisson WH, Cercek A, Clarke MF, Coussens LM, Gast CE, Geltzeiler CB, Hansen L, Kelley KA, Lopez CD, Rana SR, Ruhl R, Tsikitis VL, Vaccaro GM, Wong MH, Mayo SC. Colorectal liver metastases: evoling paradigms and future directions. Cell Mol Gastroenterol. Hepatol. 2017;3(2):163-173.
de Long MC, Beckers RCJ, van Woerden V, Sijmons JML, Bemelmans MHA, van Dam RM, Dejong CHC. The liver-first approach in patients with colorectal cancer and synchronous colorectal liver metastases HPB (Oxford). 2018;20(7):631-640. https://doi.org/10.1016/j.hpb.2018.01.005
Engstrand J, Nilson H, Stromberg C, Jonas E, Freedman J. Colorectal cancer liver metastases — a population-based study on incidence, management and survival. BMC Cancer. 2018;18(1):78. https://doi.org/10.1186/s12885-017-3925-x
Venkat ShR, Mohan PP, Gandhi RT. Colorectal liver metastasis: overview of treatment paradigm highlighting the role ablation. AJR Am J Roentgenol. 2018;210(4):883-890. https://doi.org/10.2214/AJR.17.18574
Chow FC-L, Chok KS-H. Colorectal liver metastases: An update on multidisciplinary approach. World J Hepatol. 2019;11(2):150-172. https://doi.org/10.4254/wjh.v11.i2.150
Ferrand F, Malka D, Bourredjem A, Allonier C, Bouché O, Louafi S, Boige V, Mousseau M, Raoul JL, Bedenne L, Leduc B, Deguiral P, Faron M, Pignon JP, Ducreux M. Impact of primary tumor resection on survival of patients with colorectal cancer and synchronous metastases treated by chemotherapy. Eur J Cancer. 2013;49(1):90-97. https://doi.org/10.1016/j.ejca.2012.07.006
Kurpeshev OK, Osinskii SP, Florovskaya NYu, Silant’eva IK, Lebedeva TV. Lifespan of patients with metastatic colorectal cancer in the liver after incomplete courses of chemotherapy or symptomatic treatment. Oncology = Onkologiya. 2013;15(4):301-306. (In Ukraine).
Folprecht G, Gruenberger T, Bechstein W, Suedhoff T, Rentsch A, Köhne CH. Survival of patients colorectal liver metastases treated with FOLFOX/cetuximab or multidisciplinary concept (CELM study)+. Ann Oncol. 2014;25(5):1018-1025. https://doi.org/10.1093/annonc/mdu088
Imai K, Adam R, Biaba H. How to increase the resectability of initially uncresectable colorectal liver metastases: a surgical perspective. Ann Gastroenterol Surg. 2019;3(5):476-486. https://doi.org/10.1002/ags3.12276
Lemke J, Cammerer G, Ganser J, Scheele J, Xu P, sander S, Henne-Bruns D, Kornmann M. Survival and prognostic factors of colorectal liver metastases after surgical and nonsurgical treatment. Clin Colorectal Cancer. 2016;15(4):183-192. https://doi.org/10.1016/j.clcc.2016.04.007
Adam R, de Gramont A, Figueras J, Kukodo N, Kinstlinger F, Loyer E, Poston G, Roigier Ph, Rubbia-Brand L, Sobrero A, et al. Managing synchronous liver metastases form colorectal cancer: a multidisciplinary international consensus. Cancer Treat Rev. 2015;41(9):729-741. https://doi.org/10.1016/j.ctrv.2015.06.006
Kemeny NE, Chou JF, Boucher TM, Capanu M, DeMatteo RP, Jarnagin WR, Allen PJ, Fong YC, Cercek A, D’Angelica MI. Updated long-term survival for patient with metastatic colorectal cancer treated with liver resection followed by hepatic arterial infusion an systemic chemotherapy. J Surg Oncol. 2016;113(5):477-484. https://doi.org/10.1002/jso.24189
Wanis KN, Pineda-Solis K, Tun-Abraham ME, Yeoman J, Welch S, Vogt K, Van Koughnett JAM, Ott M, Hernandez-Alejandro R. Management of colorectal cancer with synchronous liver metastases: impact of multidisciplinary case conference review. Hepatobiliary Surg Nutr. 2017;6(3):162-169. https://doi.org/10.21037/hbsn.2017.01.01
Qadan M, D’Angelica MI. Extending the limits of resection for colorectal liver metastases: positive resection margin and outcome after resection of colorectal cancer liver metastases. J Gastrointest Surg. 2017;21(1):196-198. https://doi.org/10.1007/s11605-016-3253-5
Vallance AE, van der Meulen J, Kuryba A, Charman SC, Botterill ID, Prasad KR, Hill J, Jayne DG, Walker K. The liming of liver resection in patients with colorectal cancer and synchronous liver metastases: a population-based study of current practice and survival. Colorectal Dis. 2018;20(16):486-495. https://doi.org/10.1111/codi.14019
Cetin B, Bilgetekin I, Cengiz M, Oset A. Managing synchronous liver metastases in colorectal cancer. Indian J Surg Oncol. 2018;9(14):461-471. https://doi.org/10.1007/s13193-018-0765-3
Muangkaew P, Cho JY, Han HS, Yoon YS, Choi Y, Jang JY, Cho H, Jang JS, Kwon SU. Outcomes of simultaneous major liver resection and colorectal surgery for colorectal liver metastases. J Gastrointest Surg. 2016;20(3):554-563.
Silberhumer GR, Paty PB, Denton B, Guillem J, Gonen M, Araujo RLC, Nash GM, Temple LK, Allen PJ, DeMatteo RP, Weiser MR, Wong WD, Jarnagin WR, D’Angelica MI, Fong Y. Long-term oncologic outcomes for simultaneous resection of synchronous metastatic liver and primary colorectal cancer. Surgery. 2016;160(1):67-73. https://doi.org/10.1016/j.surg.2016.02.029
Fukami Y, Kaneoka Y, Maeda A, Takayama Y, Onoe Sh, Isogai M. Simultaneous resection for colorectal cancer and synchronous liver metastases. Surg Today. 2016;46(2):176-182. https://doi.org/10.1007/s00595-015-1188-1
Ponomarenko AA, Achkasov SI, Panina MV, Rybakov EG. Simultaneous resections for synchronous colorectal cancer liver metastases. Koloproktologiya. 2017;4:45-53. (In Russ.).
Gavrilidis P, Sutcliffe RP, Hodson J, Marudanayagam R, Isaac J, Azonlay D, Roberts KJ. Simultaneous versus delayed hepatectomy for synchronous colorectal liver metastases: a systemic review and meta-analysis. HPB (Oxford). 2018;20(1):11-19. https://doi.org/10.1016/j.hpb.2017.08.008
Zhang XL, Liu RF, Zhang D, Zhang YS, Wang T. laparoscopic versus open liver resection for colorectal liver metastases: a systematic review and meta-analysis of studies with propensity score-based analysis. Int J Surg. 2017;44:191-203. https://doi.org/10.1016/j.ijsu.2017.05.073
Fretland ÅA, Dagenborg VJ, Bjørnelv GMW, Kazaryan AM, Kristiansen R, Fagerland MW, Hausken J, Tønnessen TI, Abildgaard A, Barkhatov L, Yaqub S, Røsok BI, Bjørnbeth BA, Andersen MH, Flatmark K, Aas E, Edwin B. Laparoscopic versus open resection for colorectal liver metastases: The OSLO-COMET randomized controlled trial. Ann Surg. 2018;267(2):199-207. https://doi.org/10.1097/SLA.0000000000002353
Torchua NR, Ponomarenko AA, Rybakov EG, Achkasov SI. Laparoscopic liver resection in surgery for colorectal cancer metastases. Koloproktologiya. 2019;18(1):58-65. (In Russ.). https://doi.org/10.33878/2073-7556-2019-18-1-58-65
Stilwell AP, Buettner PG, Ho YH. Meta-analysis of survival of patients with stage IV colorectal cancer managed with surgical resection versus chemotherapy alone. World J Surg. 2010;34(4):794-807. https://doi.org/10.1007/s00268-009-0366-y
Abdulaev MA, Napol’skaya EV, Tsikoridze MYu. Minimally invasive methods of local treatment of colorectal cancer liver metastases: state of the art (a review of literature). Pelvic Surgery and Oncology=Tazovaya khirurgiya i onkologiya. 2016;6(1):43-7. (In Russ.). https://doi.org/10.17650/2220-3478-2016-6-1-43-47
Kozlov SV, Kaganov OI, Tkachev MV, Kozlov AM, Shvets DS. Radiofrequency thermal ablation of the combined treatment of patients with liver bilobar metastases. P.A. Herzen Journal of Oncology= Zhurnal imeni P.A.Gertsena. 2014;3(3):11-7. (In Russ.).
Ko S, Jo H, Park E, Kim S, Seo HI. Comparative analysis of radiofregnency ablation and resection for resectable colorectal liver metastases. World J. Gastroenterol. 2014;20(2):525-531. https://doi.org/10.3748/wjg.v20.i2.525
Shady W, Petre EN, Gonen M, Erinjeri JP, Brown KT, Covey AM, Alago W, Durack JC, Maybody M, Brody A, Stegelbaum RH, et al. Percitaneous radiofregency ablation of colorectal cancer liver metastases: factors affecting outcomes- A1-year experience at a single center. Radiology. 2016; 278(2):601-611. https://doi.org/10.1148/radiol.2015142489
Cherkasov MF, Dmitriev AV, Groshilin VS, Pomazkov AA, Startsev YuM, Melikova SG. Experience of surgical treatment of colorectal cancer with liver metastases. Koloproktologiya. 2017;(2):62-67. (In Russ.). https://doi.org/https://doi.org/10.33878/2073-7556-2017-0-2-62-67
van Amerongen MJ, Jenniskens SFM, van den Boezem PB, Fütterer JJ, de Wilt JHW. Radiofrequency ablation compared to surgical resection for curative treatment of patients with colorectal liver metastases — a meta-analysis. HPB (Oxford). 2017;19(9):749-756. https://doi.org/10.1016/j.hpb.2017.05.011
Ionkin DA, Zhavoronkova OI, Stepanova YuA, Gavrilov YaYa, Vishnevskii VA, Chzhao AV. Thermal methods of local destruction (RFA, cryodestruction, MVA) in metastatic colorectal liver cancer. Postgraduate Bulletin of the Volga Region=Acpiranskii vectnik Povolzh’ya. 2018;18(5-6):127-145. (In Russ.).
Song P, Sheng L, Sun Y, An Y, Guo Y, Zhang Y. The clinical utility and outcomes of microwave ablation for colorectal cancer liver metastases. Oncotarget. 2017;8(31):51792-51799. https://doi.org/10.18632/oncotarget.15244
Zhou F, Yu X, Liang P, Han Z, Cheng Z, Yu J, Liu F, Hu Y. Does primary tumor location impact the prognosis of colorectal liver metastases patients after microwavw ablation? — Lessons from 10 yearsexperience. Oncotarget. 2017;8(59):100791-100800. https://doi.org/10.18632/oncotarget.18764
Shady W, Petre EH, Do KG, Gonen M, Yarmohammadi H, Brown KT, Kemeny NE, D’Angelica M, Kihgham PT, Solomon SB, Sofocleous CT. Percutaneous microwave versus radiofrequency ablation of colorectal liver metastases: ablation with clear margins (Ao) provides the best local tumor control. J Vasc Interv Radiol. 2018;29(2):268-275. https://doi.org/10.1016/j.jvir.2017.08.021
Li Zh, Fu Y, Li Q, Yan F, Zhao J, Dong X, Zhang Y. Cryoablation plus chemotherapy in colorectal cancer patients with liver metastases. Tumour Biol. 2014;35(11):10841-10848. https://doi.org/10.1007/s13277-014-2374-2
Ihnat P, Skacelikova E, Penka I, Tesar M. Stereotactic body radiotherapy using the «Cyber Knife» system in the treatment of patients with liver metastases: state of the art. Onco Targets Ther. 2018;11:4685-4691. https://doi.org/10.2147/OTT.S165878
Mahadevan A, Blanck O, Lanciano R, Reddada A. Stereotactic body radiotherapy (SBPT) for liver metastases — clinical outcomes from the international multiinstitutional RSSearch patients registry. Radiat Oncol. 2018;13(1):2-11. https://doi.org/10.1186/s13014-018-0969-2
Mendez RA, Keskin-Cambay F, van Os RM, Nuyttens JJ, Heijmen BJM, Uzermans JNM, Verhoef C. Institutional experience in the treatment of colorectal liver metastases with stereotactic body radiation therapy. Rep Pract Oncol Radiother. 2017;22:126-131. https://doi.org/10.1016/j.rpor.2016.10.003
Yuan ZY, Meng MB, Liu CL, Wang HH, Jiang C, Song YC, Zhuang HQ, Yang D, Wang JS, Wei W, Li FT, Zhao LJ, Wang P. Stereotactic body radiation therapy using the Cyber Knife system for patients with liver metastases. Onco Targets Ther. 2014;7:915-923. https://doi.org/10.2147/OTT.S58409
Chapelli N, Matysiak-Budnik T, D onane F, Metaire S, Rougier P, Touchefeu Y. Hepatic arterial infusion in the management of colorectal cancer liver metastasis: current and future perspective. Dig Liver Dis. 2018;50(3):220-225. https://doi.org/10.1016/j.dld.2017.12.004
Vigano L, Darwich SS, Rimassa L, Cimino M, Carnaghi C, Donadon M, Procopio F, Personeni N, Del Fabbo D, Santoro A, Torzilli G. Progression of colorectal liver metastases from the end of chemotherapy to resection: a new contraindication to surgery? Ann Surg Oncol. 2018;25(6):1676-1685. https://doi.org/10.1245/s10434-018-6387-8
Al-Sharif E, Simoneau E, Hassanin M. Portal vein embolization effect on colorectal cancer liver metastasis progression: lessons learned. World J Clin Oncol. 2015;6(5):142-146. https://doi.org/10.5306/wjco.V6.i5.142
Massman A, Rodt T, Marquardt S, Seidel R, Thomas K, Wacker F, Richter GM, Kanczor HU, Bücker A, Pereira PL, Sommer CM. Transarterial chemoembolization (TACE) for colorectal liver metastases — current status and critical review. Langenbecks Arch Surg. 2015;400(6):641-659. https://doi.org/10.1007/s00423-015-1308-9
Shady W, Kishore S, Gavane S, Do RK, Osborne JR, Ulaner GA, Gonen M, Ziv E, Boas FE, Sofocleous CT. Metabolic tumor volume and total lesion glucolysis on FDG-PET?CT can predict overall survival after (90) Y radioembolization of colorectal liver metastases: a comparison with SUVmax, SUVpeak and RESIST 1.0. Eur J Radiol. 2016;85(6):1224-1231. https://doi.org/10.1016/j.ejrad.2016.03.029
Cui CH, Huang SX, Qi J, Zhu HJ, Huang ZH, Yu JL. Neoadjuvant chemotherapy (NCT) p;us targeted agents versus NCT alone in colorectal liver metastases patients: a systemic review and meta-analysis. Oncotarget. 2015;6(41):44005-44018. https://doi.org/10.18632/oncotarget.5875
Vladimirova LYu, Abramova NA, Storozhokova AE. Targeted therapy with anti-EGFR monoclonal antibodies in the treatment of colorectal cancer. Malignant Tumours=Zlokačestvennye opuholi. 2016;4(suppl 1):87-91. (In Russ.).
Sabanathan D, Eslick GD, Shannon J. Use of neoadjuvant chemotherapy plus molecular targeted therapy in colorectal liver metastases: a systematic review and meta-analysis. Clin Colorectal Cancer. 2016;15(4):141-147. https://doi.org/10.1016/j.clcc.2016.03.007
Starzl TE, Fung JJ. Themes of liver transplantation. Hepatology. 2010;51(6):1869-1884. https://doi.org/10.1002/hep.23595
Hagness M, Foss A, Line PD, Scholtz T, Jorgensen PF, Fosby B, Boberg KM, Mathisen O, Gladhaug IP, Egge TS, Solberg S, Hausken J, Dueland S. Liver transplantation for nonresectable liver metastases from colorectal cancer. Ann Surg. 2013;257(5):800-806. https://doi.org/SLA.0b013e3182823957
Caicedo LA, Buitrago D, Thomas LS, Villegas JI, Duque M, Serrano O, Arrunategui AM, Restrepo JG, Echeverri GJ. Liver transplantation for unresectable metastases from colon adenocarcinoma. Case Rep Gastroenterol. 2016;10(3):808-813. https://doi.org/10.1159/000454984
Toso C, Pinto MH, Abdres A, Castro-Sonsa F, Adam R, Kalil A, Clavien PA, Furtado E, Barroso E, Bismuth H. Compagnosis hepatobiliaires group. Liver transplantation for colorectal liver metastatic:survival without recurrence can be achieved. Liver Transpl. 2017;23(8):1073-1076. https://doi.org/10.1002/lt.24791
Smedman TM, Line PD, Hagness M, Syversveen T, Grut H, Dueland S. Liver transplantation for unresectable colorectal liver metastases in patients and donors with extended criteria (SECA‐II arm D study). BJS Open. 2020;4(3):467-477. https://doi.org/10.1002/bjs5.50278
Sapisochin G. University Health Network, Toronto. Assessment of a protocol using a combination of neo-adjuvant chemotherapy plus living donor liver transplantation for non-resectable liver metastases from colorectal cancer. https://clinicaltrials. gov/ct2/show/NCT 02864485
Porshennikov IA, Sokolov AV, Shchekina EE, Chubukov AYu, Tret’yakova TA, Ostanina AV, Kartashov AS, Korobeinikova MA, Yushina EG, Bykov AYu. Liver transplantation for metastatic colorectal cancer (case report). Annals of HPB Surgery=Annaly khirurgicheskoy gepatologii. 2018;23(4)54-67. (In Russ.). https://doi.org/10.16931/1995-5464.2018454-67