Prognostic factors and preoperative therapy in resectable intrahepatic cholangiocarcinoma

Close metadata

OBJECTIVE

To identify prognostic factors and role of preoperative therapy for resectable intrahepatic cholangiocarcinoma (IHCC).

MATERIAL AND METHODS

We analyzed the results of surgical and combined treatment of IHCC between 1999 and 2023. Immediate and long-term outcomes were evaluated depending on negative prognostic factors and additional therapy.

RESULTS

The study included 195 patients. Postoperative complications grade ≥III were observed in 35 (17.9%) case. Mortality rate was 3.1% (n=6). Thirty-eight patients (19.5%) underwent treatment before surgery, 109 (55.9%) ones — after surgery. The median overall survival was 31 months, 5-year overall survival — 32.0%. The following factors worsened overall survival: node size ≥8 cm (HR 1.45; 95% CI 0.97—2.17), invasion (HR 1.63; 95% CI 1.07—2.47), multiple lesion (HR 1.51; 95% CI 1.00—2.28). R1 resection worsened disease-free survival (HR 1.88; 95% CI 1.14—3.10). Lymph node metastases decreased overall (HR 1.96; 95% CI 1.27- 3.04) and disease-free survival (HR 2.37; 95% CI 1.63—3.44). Two and more negative factors worsened overall (p=0.0013) and disease-free survival (p=0.0005). Absence of adjuvant therapy worsened overall (HR 2.12; 95% CI 1.41—3.20) and disease-free survival (HR 1.42; 95% CI 0.99—2.04). There was a trend towards higher overall (p=0.088) and progression-free survival (p=0.029) in case of preoperative therapy (n=195). In unfavorable prognosis group, preoperative therapy (n=33) was superior to standard treatment (resection+capecitabine after surgery, n=26). There was a trend towards higher overall survival (p=0.066) and significantly better progression-free survival (17 vs 13 months, p=0.018).

CONCLUSION

Negative prognostic factors for resectable IHCC are lesion size ≥8 cm, intrahepatic and regional metastases, invasion into neighboring structures, R1 resection. Combination of negative factors worsened prognosis. Adjuvant therapy improved postoperative outcomes. Preoperative therapy may be advisable in case of negative factors and high risk of R1 resection.

Keywords:

biliary cancer

liver resection

combined treatment

neoadjuvant therapy

adjuvant therapy

Authors:

Polyakov A.N.

Blokhin National Cancer Research Center

SPIN RSCI: 9924-0256
Scopus AuthorID: 57190413973
ORCID: 0000-0001-5348-5011

Patyutko Yu.I.

Blokhin National Medical Research Center of Oncology

RSCI AuthorID: 137980
Scopus AuthorID: 55666204300
ORCID: 0000-0001-9254-1346

Granov D.A.

Blokhin National Cancer Research Center

ORCID: 0000-0002-8746-8452

Bazin I.S.

Blokhin National Cancer Research Center

ORCID: 0000-0003-2624-9341

Rutkin I.O.

Blokhin National Cancer Research Center

ORCID: 0000-0002-9018-0433

Korshak A.V.

Blokhin National Medical Cancer Research Center

ORCID: 0009-0002-8236-2808

Turlak A.S.

Granov Russian Research Center of Radiology and Surgical Technologies

ORCID: 0000-0002-2207-767X

Podluzhnyi D.V.

Blokhin National Medical Cancer Research Center

ORCID: 0000-0001-7375-3378

Received:

09.04.2024

Accepted:

23.04.2024

List of references:

Mauro E, Ferrer-Fàbrega J, Sauri T, Soler A, Cobo A, Burrel M, Iserte G, Forner A. New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy. Cancers. 2023;15(4):1244. https://doi.org/10.3390/cancers15041244
Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D, Anthony A, Corrie P, Falk S, Finch-Jones M, Wasan H, Ross P, Wall L, Wadsley J, Evans JTR, Stocken D, Praseedom R, Ma YT, Davidson B, Neoptolemos JP, Iveson T, Raftery J, Zhu S, Cunningham D, Garden OJ, Stubbs C, Valle JW, Bridgewater J; BILCAP study group. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncology. 2019;20(5):663-673. https://doi.org/10.1016/S1470-2045(18)30915-X
Kobayashi S, Ikeda M, Nakachi K, Ueno M, Okusaka T, Todaka A, Satoi S, Tomokuni A, Konishi M, Furuse J. A Multicenter Survey on Eligibility for a Randomized Phase III Trial of Adjuvant Chemotherapy for Resected Biliary Tract Cancer (JCOG1202, ASCOT). Annals of Surgical Oncology. 2023;30(12):7331-7337. https://doi.org/10.1245/s10434-023-13913-6
Kupietzky A, Ariche A. Surgical Aspects of Intrahepatic Cholangiocarcinoma. Cancers. 2022;14(24):6265. https://doi.org/10.3390/cancers14246265
Zhang XF, Xue F, Dong DH, Weiss M, Popescu I, Marques HP, Aldrighetti L, Maithel SK, Pulitano C, Bauer TW, Shen F, Poultsides GA, Soubrane O, Martel G, Koerkamp BG, Itaru E, Lv Y, Pawlik TM. Number and Station of Lymph Node Metastasis After Curative-intent Resection of Intrahepatic Cholangiocarcinoma Impact Prognosis. Annals of Surgery. 2021;274(6):e1187-e1195. https://doi.org/10.1097/SLA.0000000000003788
Tsilimigras DI, Sahara K, Wu L, Moris D, Bagante F, Guglielmi A, Aldrighetti L, Weiss M, Bauer TW, Alexandrescu S, Poultsides GA, Maithel SK, Marques HP, Martel G, Pulitano C, Shen F, Soubrane O, Koerkamp BG, Moro A, Sasaki K, Aucejo F, Zhang XF, Matsuyama R, Endo I, Pawlik TM. Very Early Recurrence After Liver Resection for Intrahepatic Cholangiocarcinoma: Considering Alternative Treatment Approaches. JAMA Surgery. 2020;155(9):823-831. https://doi.org/10.1001/jamasurg.2020.1973
Nevermann N, Bode J, Vischer M, Feldbrügge L, Knitter S, Krenzien F, Pelzer U, Fehrenbach U, Auer TA, Lurje G, Schmelzle M, Pratschke J, Schöning W. A surgical strategy for intrahepatic cholangiocarcinoma — the hilar first concept. Langenbeck’s Archives Surgery. 2023;408(1):296. https://doi.org/10.1007/s00423-023-03023-y
Conci S, Viganò L, Ercolani G, Gonzalez E, Ruzzenente A, Isa G, Salaris C, Fontana A, Bagante F, Pedrazzani C, Campagnaro T, Iacono C, De Santibanes E, Pinna DA, Torzilli G, Guglielmi A. Outcomes of vascular resection associated with curative intent hepatectomy for intrahepatic cholangiocarcinoma. European Journal of Surgical Oncology. 2020;46(9):1727-1733. https://doi.org/10.1016/j.ejso.2020.04.007
Franssen S, Soares KC, Jolissaint JS, Tsilimigras DI, Buettner S, Alexandrescu S, Marques H, Lamelas J, Aldrighetti L, Gamblin TC, Maithel SK, Pulitano C, Margonis GA, Weiss MJ, Bauer TW, Shen F, Poultsides GA, Marsh JW, Cercek A, Kemeny N, Kingham TP, D’Angelica M, Pawlik TM, Jarnagin WR, Koerkamp BG. Comparison of Hepatic Arterial Infusion Pump Chemotherapy vs Resection for Patients With Multifocal Intrahepatic Cholangiocarcinoma. JAMA Surgery. 2022;157(7):590-596. https://doi.org/10.1001/jamasurg.2022.1298
Jansson H, Villard C, Nooijen LE, Ghorbani P, Erdmann JI, Sparrelid E. Prognostic influence of multiple hepatic lesions in resectable intrahepatic cholangiocarcinoma: A systematic review and meta-analysis. European Journal of Surgical Oncology. 2023;49(4):688-699. https://doi.org/10.1016/j.ejso.2023.01.006
Yamada T, Nakanishi Y, Okamura K, Tsuchikawa T, Nakamura T, Noji T, Asano T, Tanaka K, Kurashima Y, Ebihara Y, Murakami S, Shichinohe T, Mitsuhashi T, Hirano S. Impact of serum carbohydrate antigen 19-9 level on prognosis and prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma. Journal of Gastroenterology and Hepatology. 2018. https://doi.org/10.1111/jgh.14124
Wei F, Lu C, Cai L, Yu H, Liang X, Cai X. Can laparoscopic liver resection provide a favorable option for patients with large or multiple intrahepatic cholangiocarcinomas? Surgical Endoscopy. 2017;31(9):3646-3655. https://doi.org/10.1007/s00464-016-5399-3
Kojima T, Umeda Y, Fuji T, Niguma T, Sato D, Endo Y, Sui K, Inagaki M, Oishi M, Ota T, Hioki K, Matsuda T, Aoki H, Hirai R, Kimura M, Yagi T, Fujiwara T. Efficacy of surgical management for recurrent intrahepatic cholangiocarcinoma: A multi-institutional study by the Okayama Study Group of HBP surgery. PLoS One. 2020;15(9):e0238392. https://doi.org/10.1371/journal.pone.0238392
Murakami Y, Uemura K, Sudo T, Hashimoto Y, Nakashima A, Kondo N, Sakabe R, Kobayashi H, Sueda T. Is para-aortic lymph node metastasis a contraindication for radical resection in biliary carcinoma? World Journal of Surgery. 2011;35(5):1085-1093. https://doi.org/10.1007/s00268-011-1036-4
Gu J, Xia L, Xu B, Lu T, Halmurat O, Wang J, Zhang J, Ding Y, Xia Q. Clinical prognostic significance of regional and extended lymphadenectomy for biliary cancer with para-aortic lymph node metastasis: A systematic review and meta-analysis. Digestive and Liver Disease. 2016;48(7):717-725. https://doi.org/10.1016/j.dld.2016.03.019
Rizzo A, Brandi G. Neoadjuvant therapy for cholangiocarcinoma: A comprehensive literature review. Cancer Treatment and Research Communications. 2021;27:100354. https://doi.org/10.1016/j.ctarc.2021.100354
Scott A, Wong P, Melstrom LG. Surgery and hepatic artery infusion therapy for intrahepatic cholangiocarcinoma. Surgery. 2023;S0039-6060(23)00045-4. https://doi.org/10.1016/j.surg.2023.01.019
Yadav S, Xie H, Bin-Riaz I, Sharma P, Durani U, Goyal G, Borah B, Borad MJ, Smoot RL, Roberts LR, Go RS, McWilliams RR, Mahipal A. Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: A propensity score matched analysis. European Journal of Surgical Oncology. 2019;45(8):1432-1438. https://doi.org/10.1016/j.ejso.2019.03.023
Kamarajah S, Giovinazzo F, Roberts KJ, Punia P, Sutcliffe RP, Marudanayagam R, Chatzizacharias N, Isaac J, Mirza DF, Muiesan P, Dasari BV. The role of down staging treatment in the management of locally advanced intrahepatic cholangiocarcinoma: Review of literature and pooled analysis. Annals of Hepato-Biliary-Pancreatic Surgery. 2020;24(1):6-16. https://doi.org/10.14701/ahbps.2020.24.1.6
Endo Y, Moazzam Z, Woldesenbet S, Araujo Lima H, Alaimo L, Munir MM, Shaikh CF, Guglielmi A, Aldrighetti L, Weiss M, Bauer TW, Alexandrescu S, Poultsides GA, Kitago M, Maithel SK, Marques HP, Martel G, Pulitano C, Shen F, Cauchy F, Koerkamp BG, Endo I, Pawlik TM. Predictors and Prognostic Significance of Postoperative Complications for Patients with Intrahepatic Cholangiocarcinoma. World Journal of Surgery. 2023;47(7):1792-1800. https://doi.org/10.1007/s00268-023-06974-x
Kang SH, Choi Y, Lee W, Ahn S, Cho JY, Yoon YS, Han HS. Laparoscopic liver resection versus open liver resection for intrahepatic cholangiocarcinoma: 3-year outcomes of a cohort study with propensity score matching. Surgical Oncology. 2020;33:63-69. https://doi.org/10.1016/j.suronc.2020.01.001
Cercek A, Boerner T, Tan BR, Chou JF, Gönen M, Boucher TM, Hauser HF, Do RKG, Lowery MA, Harding JJ, Varghese AM, Reidy-Lagunes D, Saltz L, Schultz N, Kingham TP, D’Angelica MI, DeMatteo RP, Drebin JA, Allen PJ, Balachandran VP, Lim KH, Sanchez-Vega F, Vachharajani N, Majella Doyle MB, Fields RC, Hawkins WG, Strasberg SM, Chapman WC, Diaz LA Jr, Kemeny NE, Jarnagin WR. Assessment of Hepatic Arterial Infusion of Floxuridine in Combination With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial. JAMA Oncology. 2020;6(1):60-67. https://doi.org/10.1001/jamaoncol.2019.3718
Conci S, Ruzzenente A, Viganò L, Ercolani G, Fontana A, Bagante F, Bertuzzo F, Dore A, Pinna AD, Torzilli G, Iacono C, Guglielmi A. Patterns of Distribution of Hepatic Nodules (Single, Satellites or Multifocal) in Intrahepatic Cholangiocarcinoma: Prognostic Impact After Surgery. Annals of Surgical Oncology. 2018;25(12):3719-3727. https://doi.org/10.1245/s10434-018-6669-1
Spolverato G, Yakoob MY, Kim Y, Alexandrescu S, Marques HP, Lamelas J, Aldrighetti L, Gamblin TC, Maithel SK, Pulitano C, Bauer TW, Shen F, Poultsides GA, Marsh JW, Pawlik TM. The Impact of Surgical Margin Status on Long-Term Outcome After Resection for Intrahepatic Cholangiocarcinoma. Annals of Surgical Oncology. 2015;22(12):4020-4028. https://doi.org/10.1245/s10434-015-4472-9
Reames BN, Ejaz A, Koerkamp BG, Alexandrescu S, Marques HP, Aldrighetti L, Maithel SK, Pulitano C, Bauer TW, Shen F, Poultsides GA, Martel G, Marsh JW, Pawlik TM. Impact of major vascular resection on outcomes and survival in patients with intrahepatic cholangiocarcinoma: A multi-institutional analysis. Journal of Surgical Oncology. 2017;116(2):133-139. https://doi.org/10.1002/jso.24633
Alaimo L, Moazzam Z, Brown ZJ, Endo Y, Ruzzenente A, Guglielmi A, Aldrighetti L, Weiss M, Bauer TW, Alexandrescu S, Poultsides GA, Maithel SK, Marques HP, Martel G, Pulitano C, Shen F, Soubrane O, Koerkamp BG, Endo I, Pawlik TM. Application of Hazard Function to Investigate Recurrence of Intrahepatic Cholangiocarcinoma After Curative-Intent Liver Resection: A Novel Approach to Characterize Recurrence. Annals of Surgical Oncology. 2023;30(3):1340-1349. https://doi.org/10.1245/s10434-022-12463-7
Edeline J, Hirano S, Bertaut A, Konishi M, Benabdelghani M, Uesaka K, Watelet J, Ohtsuka M, Hammel P, Kaneoka Y, Joly JP, Yamamoto M, Monard L, Ambo Y, Louvet C, Ando M, Malka D, Nagino M, Phelip JM, Ebata T. Individual patient data meta-analysis of adjuvant gemcitabine-based chemotherapy for biliary tract cancer: combined analysis of the BCAT and PRODIGE-12 studies. European Journal of Cancer. 2022;164:80-87. https://doi.org/10.1016/j.ejca.2022.01.009
Maithel SK, Keilson JM, Cao HST, Rupji M, Mahipal A, Lin BS, Javle MM, Cleary SP, Akce M, Switchenko JM, Rocha FG. NEO GAP: A Single-Arm, Phase II Feasibility Trial of Neoadjuvant Gemcitabine, Cisplatin, and Nab-Paclitaxel for Resectable, High-Risk Intrahepatic Cholangiocarcinoma. Annals of Surgical Oncology. 2023;30(11):6558-6566. https://doi.org/10.1245/s10434-023-13809-5

Close metadata