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`Continue
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`
`Trials should be designed to maximize inclusiveness and broad representative enrollment.
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`NCCN.org
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`Version 5.2024 — November 27, 2024
`
`Biliary Tract Cancers
`
`NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
`
`1
`
`JHU 2258
`Merck Sharp v. Johns Hopkins
`IPR2024-00623
`
`

`

`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
`¥ Patient advocacy
`† Medical oncology
`Þ Internal medicine
`oncology
`‡ Hematology/Hematology
`¤ Gastroenterology
`radiology
`ф Diagnostic/Interventional
`Comprehensive Cancer Center
`UT Southwestern Simmons
`Adam Yopp, MD ¶
`Mayo Clinic Comprehensive Cancer Center
`Motoyo Yano, MD, PhD ф
`Comprehensive Cancer Center
`UCSF Helen Diller Family
`Alan P. Venook, MD † ‡ Þ
`The University of Texas MD Anderson Cancer Center
`Jean-Nicolas Vauthey, MD ¶
`Comprehensive Cancer Center
`Indiana University Melvin and Bren Simon
`Anita Turk, MD †
`Clinic Taussig Cancer Institute
`Hospitals Seidman Cancer Center and Cleveland
`Case Comprehensive Cancer Center/University
`Kevin Stephans, MD §
`Yale Cancer Center/Smilow Cancer Hospital
`Stacey Stein, MD †
`City of Hope National Medical Center
`Gagandeep Singh, MD ¶
`University of Michigan Rogel Cancer Center
`Vaibhav Sahai, MBBS, MS †
`University of Wisconsin Carbone Cancer Center
`Sean Ronnekleiv-Kelly, MD ¶
`UCLA Jonsson Comprehensive Cancer Center
`Steven Raman, MD ф
`Fred Hutchinson Cancer Center
`James O. Park, MD ¶
`Duke Cancer Institute
`Manisha Palta, MD §
`City of Hope National Medical Center
`Laleh Melstrom, MD, MS ¶
`
`committee
` * Discussion section writing
`ξ Transplantation
`¶ Surgery/Surgical oncology
`oncology
`§ Radiotherapy/Radiation
`≠ Pathology
`
`NCCN Guidelines Panel Disclosures
`
`Continue
`at the University of Pennsylvania
`Abramson Cancer Center
`Matthew Levine, MD, PhD ξ
`Hospital
`Yale Cancer Center/Smilow Cancer
`Sajid Khan MD ¶
`Comprehensive Cancer Center
`UCSF Helen Diller Family
`R. Kate Kelley, MD † ‡
`Center of Northwestern University
`Robert H. Lurie Comprehensive Cancer
`Lawrence Jennings, MD, PhD ≠
`O'Neal Comprehensive Cancer Center at UAB
`Rojymon Jacob, MD §
`Roswell Park Comprehensive Cancer Center
`Renuka Iyer, MD Þ †
`University School of Medicine
`Jewish Hospital and Washington
`Siteman Cancer Center at Barnes-
`William G. Hawkins, MD ¶
`Fred Hutchinson Cancer Center
`William Harris, MD †
`University of Tennessee Health Science Center
`St. Jude Children's Research Hospital/The
`Evan S. Glazer, MD, PhD ¶
`Cancer Center
`The UChicago Medicine Comprehensive
`Joseph Franses, MD, PhD Þ † ‡
`Medicine
`Hospital and Washington University School of
`Siteman Cancer Center at Barnes-Jewish
`Darren Cullinan, MD, MSCI ¶
`Memorial Sloan Kettering Cancer Center
`Anne M. Covey, MD ф
`and Solove Research Institute
`Cancer Center - James Cancer Hospital
`The Ohio State University Comprehensive
`Jordan Cloyd, MD ¶
`
`
`
`Ryan Schonfeld, BA
`Cindy Hochstetler, PhD
`NCCN
`and Cleveland Clinic Taussig Cancer Institute
`University Hospitals Seidman Cancer Center
`Case Comprehensive Cancer Center/
`Prabhleen Chahal, MD ¤
`Fox Chase Cancer Center
`Jason Castellanos, MD, MS ¶
`UC San Diego Moores Cancer Center
`Adam Burgoyne, MD, PhD †
`Vanderbilt-Ingram Cancer Center
`Daniel Brown, MD † ф
`University of Colorado Cancer Center
`David Binder, MD §
`at the University of Utah
`Huntsman Cancer Institute
`Marshall Baker, MD, MBA ¶
`Cholangiocarcinoma Foundation
`Melinda Bachini ¥
`UC Davis Comprehensive Cancer Center
`Lydia Aye, DO ¤ ξ
`Fred & Pamela Buffett Cancer Center
`Chandrakanth Are, MBBS, MBA ¶
`Johns Hopkins Kimmel Cancer Center
`Robert Anders, MD, PhD ¤ ≠
`Moffitt Cancer Center
`Daniel A. Anaya, MD ¶
`UAB
`O'Neal Comprehensive Cancer Center at
`Mehmet Akce, MD † ‡
`Stanford Cancer Institute
`Aijaz Ahmed, MD ¤
`Center | Mass General Cancer Center
`Dana-Farber/Brigham and Women's Cancer
`Thomas Abrams, MD †
`Memorial Sloan Kettering Cancer Center
`*Michael I. D’Angelica, MD/Vice-Chair ¶
`Center of Northwestern University
`Robert H. Lurie Comprehensive Cancer
`*Al B. Benson, III, MD/Chair †
`
`Discussion
`Table of Contents
`NCCN Guidelines Index
`
`Biliary Tract Cancers
`NCCN Guidelines Version 5.2024
`
`Printed by Jill Strand on 1/2/2025 5:29:51 PM. For personal use only. Not approved for distribution. Copyright © 2025 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`2
`
`

`

`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
`be reproduced in any form without the express written permission of NCCN. ©2024.
`Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not
`or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN
`clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations
`treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual
`The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to
`
`See NCCN Categories of Preference.
`considered appropriate.
`recommendations are
`NCCN Categories of Preference: All
`and Consensus.
`See NCCN Categories of Evidence
`unless otherwise indicated.
`recommendations are category 2A
`Evidence and Consensus: All
`NCCN Categories of
`member-institutions.
`https://www.nccn.org/home/
`Find an NCCN Member Institution:
`
`Abbreviations (ABBR-1)
`
`AJCC Staging (ST-1)
`Biliary Tract Cancer Staging
`
`•Principles of Radiation Therapy (BIL-D)
`•Principles of Systemic Therapy (BIL-C)
`•Principles of Molecular Testing (BIL-B)
`•Principles of Imaging (BIL-A)
`
`•Principles of Pathology (EXTRA-B)
`•Principles of Surgery (EXTRA-A)
`•Post-Surgical Treatment, Surveillance (EXTRA-2)
`•Presentation, Workup, Primary Treatment (EXTRA-1)
`Extrahepatic Cholangiocarcinoma
`
`•Principles of Arterial/Locoregional Therapy for Intrahepatic Cholangiocarcinoma (INTRA-D)
`•Principles of Pathology (INTRA-C)
`•Principles of Mixed HCC-CCA (INTRA-B)
`•Principles of Surgery (INTRA-A)
`•Post-Surgical Treatment, Surveillance (INTRA-2)
`•Presentation, Workup, Primary Treatment (INTRA-1)
`Intrahepatic Cholangiocarcinoma
`
`•Principles of Pathology (GALL-B)
`•Principles of Surgery (GALL-A)
`•Post-Surgical Treatment, Surveillance (GALL-6)
`•Jaundice and Metastatic Disease (GALL-5)
`•Mass on Imaging (GALL-4)
`•Incidental Finding on Pathologic Review (GALL-3)
`•Hepatobiliary Surgery Expertise Unavailable (GALL-2)
`Surgery (GALL-1)
`•Incidental Finding of Suspicious Mass During
`Gallbladder Cancer
`
`Summary of the Guidelines Updates
`NCCN Biliary Tract Cancers Panel Members
`
`Discussion
`Table of Contents
`NCCN Guidelines Index
`
`Biliary Tract Cancers
`NCCN Guidelines Version 5.2024
`
`Printed by Jill Strand on 1/2/2025 5:29:51 PM. For personal use only. Not approved for distribution. Copyright © 2025 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`3
`
`

`

`Middle pathway, Options
`Top pathway, Options
`• Post-Surgical Treatment
`GALL-6
`GALL-3 through GALL-5)
`surgery. There are limited clinical trial data to define a standard regimen or definitive benefit. See Principles of Systemic Therapy (BIL-C). (Also for
`• Footnote k revised: For locoregionally advanced disease, consider neoadjuvant systemic chemotherapy to rule out rapid progression and avoid futile
`GALL-2
`• Footnote removed: The optimal diagnostic method is core needle biopsy. (Also for GALL-2, GALL-4, GALL-5)
`• Footnote d added: Principles of Pathology (GALL-B). (Also for GALL-2 through GALL-5)
`GALL-1
`Gallbladder Cancer
`Updates in Version 1.2024 of the NCCN Guidelines for Biliary Tract Cancers from Version 3.2023 include:
`solid tumors: Primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol 2024;42:47-58.
`• Reference 29 added: Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing
`BIL-C (5 of 5)
`For HER-2 positive tumors:
`• Subsequent-Line Therapy for Biliary Tract Cancers if Disease Progression
`BIL-C (3 of 5)
`Updates in Version 2.2024 of the NCCN Guidelines for Biliary Tract Cancers from Version 1.2024 include:
`including NSCLC: Update from the phase I/II TRIDENT-1 trial [abstract]. Ann Oncol 2023;34:Abstract 1372P.
`• Reference 15 added: Solomon BJ, Drilon A, Lin JJ, et al. Repotrectinib in patients (pts) with NTRK fusion-positive (NTRK+) advanced solid tumors,
`BIL-C (4 of 5)
`For NTRK gene fusion-positive tumors:
`• Primary Treatment for Unresectable and Metastatic Disease
`BIL-C (3 of 5)
`Updates in Version 3.2024 of the NCCN Guidelines for Biliary Tract Cancers from Version 2.2024 include:
`• The discussion was updated to reflect the changes in the algorithm.
`MS-1
`Updates in Version 4.2024 of the NCCN Guidelines for Biliary Tract Cancers from Version 3.2024 include:
`• The discussion was updated to reflect the changes in the algorithm.
`MS-1
`(HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncol 2023;24:772-782.
`• Reference 33 added: Harding JJ, Fan J, Oh DY, et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer
`BIL-C (5 of 5)
`For HER2-positive tumors:
`• Subsequent-Line Therapy for Biliary Tract Cancers if Disease Progression
`BIL-C (3 of 5)
`Updates in Version 5.2024 of the NCCN Guidelines for Biliary Tract Cancers from Version 4.2024 include:
`Terminologies in all NCCN Guidelines are being actively modified to advance the goals of equity, inclusion, and representation.
`
` ◊Zanidatamab-hrii (IHC3+) was added as a category 2A, useful in certain circumstances recommendation.
`
`Discussion
`Table of Contents
`NCCN Guidelines Index
`
`Biliary Tract Cancers
`NCCN Guidelines Version 5.2024
`
`Printed by Jill Strand on 1/2/2025 5:29:51 PM. For personal use only. Not approved for distribution. Copyright © 2025 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`UPDATES
`Continued
`
`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
` ◊Removed: Fluoropyrimidine-based chemoradiation followed by fluoropyrimidine- or gemcitabine-based chemotherapy.
` ◊Removed: Fluoropyrimidine- or gemcitabine-based chemotherapy followed by fluoropyrimidine-based chemoradiation.
` ◊Bullet 3: Added: Combination of chemotherapy and chemoradiation.
` ◊Fluoropyrimidine-based chemoradiation reworded as "chemoradiation". (Also for middle pathway)
`
` ◊Bullet 1: Fam-trastuzumab deruxtecan-nxki (IHC3+) was added as a category 2A recommendation.
`
` ◊Repotrectinib was added as a category 2A recommendation. (Also for Subsequent-Line Therapy for Biliary Tract Cancers if Disease Progression)
`
`4
`
`

`

` ◊Last bullet added: Consider neoadjuvant systemic therapy for locoregionally advanced disease to rule out rapid progression and avoid futile surgery
`
`Incidental Finding of Suspicious Mass During Surgery
`• Header revised: Principles of Surgery and Pathology
`GALL-A (1 of 2)
`Updates in Version 1.2024 of the NCCN Guidelines for Biliary Tract Cancers from Version 3.2023 include:
`
`(biopsy required). (Also for Mass on Imaging on GALL-A 2 of 2)
`
`Incidental Finding on Pathologic Review
`
` ◊Last bullet added: Consider neoadjuvant systemic therapy for locoregionally advanced disease to rule out rapid progression and avoid futile
`
`surgery. (Also for Gallbladder Cancer and Jaundice on GALL-A 2 of 2)
`
`Discussion
`Table of Contents
`NCCN Guidelines Index
`
`Biliary Tract Cancers
`NCCN Guidelines Version 5.2024
`
`Printed by Jill Strand on 1/2/2025 5:29:51 PM. For personal use only. Not approved for distribution. Copyright © 2025 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`Unresectable
`Resectable
`• Primary Treatment
`INTRA-1
`Intrahepatic Cholangiocarcinoma
`• New section: Principles of Pathology.
`GALL-B
`• Footnote removed: The optimal diagnostic method is core needle biopsy. (Also for GALL-A 2 of 2)
`• Footnote a added: Principles of Pathology (GALL-B). (Also for GALL-A 2 of 2)
`
` ◊Best supportive care bullet moved to a separate pathway. (Also for Metastatic disease pathway)
` ◊Bullet 4: Fluoropyrimidine-based chemoradiation reworded as "chemoradiation". (Also for R1 on INTRA-2)
` ◊Bullet 3: Added: Combination of chemotherapy and chemoradiation. (Also for EXTRA-1 and R1 on INTRA-2 and EXTRA-2)
` ◊Bullet 3 added: Consider ablation.
`
`UPDATES
`Continued
`
`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
`• New section added: Principles of Arterial/Locoregional Therapy for Intrahepatic Cholangiocarcinoma.
`INTRA-D
`• New section added: Principles of Pathology.
`INTRA-C
`• New section added: Principles of Mixed HCC-CCA.
`INTRA-B
`
`EXTRA-2)
`EXTRA-2)
`
` ◊Bullet removed: Fluoropyrimidine-based chemoradiation followed by fluoropyrimidine-based or gemcitabine-based chemotherapy. (Also for
` ◊Bullet removed: Fluoropyrimidine-based or gemcitabine-based chemotherapy followed by fluoropyrimidine-based chemoradiation. (Also for
`
`R1
`• Post-surgical Treatment
`INTRA-2
`• Footnote removed: The optimal diagnostic method is core needle biopsy.
`Adjuvant Chemotherapy (BIL-C, 1 of 5).
`• Footnote q added: For a list of gemcitabine-based regimens and fluoropyrimidine-based regimens to be used before or after chemoradiation, see
`• Footnote m added: For small single tumors <3 cm.
`• Footnote l: added: Principles of Principles of Arterial/Locoregional Therapy for Intrahepatic Cholangiocarcinoma (INTRA-D).
`• Footnote h added: Principles of Pathology (INTRA-C).
`• Footnote g added: Principles of Mixed HCC-CCA (INTRA-B).
`
` ◊Subsequent-line systemic therapy if progression on or after systemic therapy.
` ◊Reconsider resection or locoregional therapy or.
`
`Revised: Assess for response and.
`• Last column, middle and bottom pathways
`
`5
`
`

`

`UPDATES
`UPDATES
`Continued
`
`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
`• Footnote a added: Order does not indicate preference. (Also for BIL-C 2 of 5 and BIL-C 3 of 5)
`
` –Bullet removed: Capecitabine + cisplatin (category 3).
`
` ◊Other Recommended Regimens
`
`Adjuvant Therapy
`
` ▪Gemcitabine + cisplatin + albumin-bound paclitaxel (category 2B).
` ▪Durvalumab + gemcitabine + cisplatin.
` ▪Gemcitabine + cisplatin (Also for adjuvant therapy).
` ▪Gemcitabine + capecitabine.
` ▪Capecitabine + oxaliplatin (Also for adjuvant therapy).
` ▪FOLFOX (Also for adjuvant therapy).
`
`Other Recommended Regimens
`Header revised: Neoadjuvant Therapy (for gallbladder cancer only).
`• Principles of Systemic Therapy
`BIL-C (1 of 5)
`• References were updated.
`BIL-B (7 of 8 and 8 of 8)
`Bullet 3 added: Recommendation: Testing for KRAS G12C mutations is recommended for patients with unresectable or metastatic gallbladder cancer,
`• Other Biomarkers (RET/ROS1, KRAS G12C/Other KRAS, Other Tumor-Agnostic Markers)
`BIL-B (6 of 8)
`Last row added: KRAS G12C. (Also for Table 2 on BIL-B 3 of 8)
`• Table 1
`BIL-B (2 of 8)
`Bullet 2 revised: PET/CT has limited sensitivity but high specificity and may be considered when there is an equivocal finding or on a case-by-case
`• General Principles
`BIL-A
`Biliary Tract Cancers
`• New section added: Principles of Pathology.
`EXTRA-B
`Adjuvant Chemotherapy (BIL-C, 1 of 5).
`• Footnote o added: For a list of gemcitabine-based regimens and fluoropyrimidine-based regimens to be used before or after chemoradiation, see
`• Footnote removed: The optimal diagnostic method is core needle biopsy.
`• Footnote i added: Principles of Pathology (EXTRA-B).
`• Unresectable
`• Primary Treatment
`EXTRA-1
`Extrahepatic Cholangiocarcinoma
`Updates in Version 1.2024 of the NCCN Guidelines for Biliary Tract Cancers from Version 3.2023 include:
`
`intrahepatic CCA, or extrahepatic CCA.
`
`basis. The routine use of PET/CT in the preoperative setting has not been established in prospective trials.
`
` ◊Bullet 4: Fluoropyrimidine-based chemoradiation reworded as "chemoradiation". (Also for R1 on EXTRA-2)
`
` ◊Bullets removed:
` ◊Bullet 1 added: See Principles of Systemic Therapy, Primary Treatment for Unresectable and Metastatic Disease (BIL-C 2 of 5).
`
`Discussion
`Table of Contents
`NCCN Guidelines Index
`
`Biliary Tract Cancers
`NCCN Guidelines Version 5.2024
`
`Printed by Jill Strand on 1/2/2025 5:29:51 PM. For personal use only. Not approved for distribution. Copyright © 2025 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`6
`
`

`

`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
`Subsequent-Line Therapy for Biliary Tract Cancers if Disease Progression
`Other recommended regimens, recommendation removed: Gemcitabine + cisplatin + albumin-bound paclitaxel (category 2B).
`• Primary Treatment for Unresectable and Metastatic Disease
`BIL-C (2 of 5)
`Updates in Version 1.2024 of the NCCN Guidelines for Biliary Tract Cancers from Version 3.2023 include:
`
` ◊Useful in Certain Circumstances
` ◊Other Recommended Regimens
`
` –Recommendation removed: Lenvatinib + pembrolizumab (category 2B).
` –FOLFIRI changed from a category 2B to a category 2A recommendation.
`
` ◊Adagrasib was added as a category 2A recommendation.
` ◊Bullet 2: Tucatinib + trastuzumab was added as a category 2A recommendation.
`
` ◊Sub-bullet 2 revised: Selpercatinib for CCA (category 2B).
`
`Section significantly revised.
`• Principles of Radiation Therapy
`BIL-D
`• References were updated.
`BIL-C (4 of 5 and 5 of 5)
`Added For KRAS G12C mutation-positive tumors:
`For HER-2 positive tumors:
`• Subsequent-Line Therapy for Biliary Tract Cancers if Disease Progression
`For RET gene fusion-positive tumors:
`• Primary Treatment for Unresectable and Metastatic Disease
`BIL-C (3 of 5)
`
`Discussion
`Table of Contents
`NCCN Guidelines Index
`
`Biliary Tract Cancers
`NCCN Guidelines Version 5.2024
`
`Printed by Jill Strand on 1/2/2025 5:29:51 PM. For personal use only. Not approved for distribution. Copyright © 2025 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`7
`
`

`

`GALL-1
`and GALL-5
`GALL-3, GALL-4,
`Other Clinical Presentations
`
`j See NCCN Guidelines for Palliative Care.
`i Principles of Radiation Therapy (BIL-D).
`h Principles of Systemic Therapy (BIL-C).
`g Order does not indicate preference. The choice of treatment modality may depend on extent/location of disease and institutional capabilities.
`f Principles of Molecular Testing (BIL-B).
`germline testing and/or referral to a genetic counselor.
`e For patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) tumors or a family history suggestive of BRCA1/2 mutations, consider
`d Principles of Pathology (GALL-B).
`c Principles of Surgery (GALL-A).
`with staging.
`b If expertise unavailable or resectability unclear, visually inspect the abdomen, document all findings, and refer to surgeon with hepatobiliary expertise and/or proceed
`a Principles of Imaging (BIL-A).
`
`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
`PRIMARY TREATMENT
`
`PRESENTATION
`
`Discussion
`Table of Contents
`NCCN Guidelines Index
`
`Gallbladder Cancer
`NCCN Guidelines Version 5.2024
`
`Printed by Jill Strand on 1/2/2025 5:29:51 PM. For personal use only. Not approved for distribution. Copyright © 2025 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`therapyh
`systemic
`on or after
`Progression
`
`(GALL-6)
`Surveillance
`and
`Treatment
`Adjuvant
`
`CA 19-9
`antigen (CEA) and
`carcinoembryonic
`• Consider
`• Chest CT ± contrast
`MRI with IV contrast
`abdomen/pelvis CT/
`• Multiphasic
`WORKUPa
`POSTOPERATIVE
`
`carej
`• Best supportive
`(RT)i
`radiation therapy
`• Palliative
`(preferred)
`• Clinical trial
`(preferred)
`therapyh
`• Systemic
`Optionsg:
`
`malignant involvement
`± bile duct excision for
`+ lymphadenectomy
`bloc hepatic resectiond
`Cholecystectomyc + en
`
`GALL-2
`
`unavailableb
`expertise
`surgery
`Hepatobiliary
`
`(above)
`Workup
`Postoperative
`See
`
`testinge,f
`• Molecular
`performed
`previously
`Biopsy,d if not
`Unresectable
`
`surgery
`mass during
`suspicious
`finding of
`Incidental
`
`biopsyc,d
`staging ±
`Intraoperative
`
`availableb
`expertise
`surgery
`Hepatobiliary
`
`Resectabled
`
`Note: All recommendations are category 2A unless otherwise indicated.
`
`8
`
`

`

`GALL-2
`
`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
`to define a standard regimen or definitive benefit. See Principles of Systemic Therapy (BIL-C).
`k For locoregionally advanced disease, consider neoadjuvant systemic therapy to rule out rapid progression and avoid futile surgery. There are limited clinical trial data
`j See NCCN Guidelines for Palliative Care.
`i Principles of Radiation Therapy (BIL-D).
`h Principles of Systemic Therapy (BIL-C).
`g Order does not indicate preference. The choice of treatment modality may depend on extent/location of disease and institutional capabilities.
`f Principles of Molecular Testing (BIL-B).
`e For patients with dMMR/MSI-H tumors or a family history suggestive of BRCA1/2 mutations, consider germline testing and/or referral to a genetic counselor.
`d Principles of Pathology (GALL-B).
`c Principles of Surgery (GALL-A)
`with staging.
`b If expertise unavailable or resectability unclear, visually inspect the abdomen, document all findings, and refer to surgeon with hepatobiliary expertise and/or proceed
`a Principles of Imaging (BIL-A).
`
`therapyh
`systemic
`on or after
`Progression
`
`carej
`• Best supportive
`• Palliative RTi
`(preferred)
`• Clinical trial
`(preferred)
`• Systemic therapyh
`Options:g
`
`• Molecular testinge,f
`previously performed
`Biopsy,d if not
`Unresectable
`
`(GALL-6)
`Surveillance
`and
`Treatment
`Adjuvant
`
`malignant involvement
`± bile duct excision for
`+ lymphadenectomy
`bloc hepatic resectiond
`Cholecystectomyc + en
`
`Resectablec,k
`
`PRIMARY TREATMENT
`
`and CA 19-9
`• Consider CEA
`hepatic reserve
`• Assessment of
`consultation
`• Surgical
`tests (LFTs)
`• Liver function
`contrast
`• Chest CT ±
`contrasta
`CT/MRI with IV
`abdomen/pelvis
`• Multiphasic
`physical (H&P)
`• History and
`
`WORKUPa
`POSTOPERATIVE
`
`specialistc
`and refer to
`End surgery
`and
`biopsyd
`staging ±
`Intraoperative
`
`unavailableb
`expertise
`surgery
`Hepatobiliary
`
`PRESENTATION
`
`Discussion
`Table of Contents
`NCCN Guidelines Index
`
`Gallbladder Cancer
`NCCN Guidelines Version 5.2024
`
`Printed by Jill Strand on 1/2/2025 5:29:51 PM. For personal use only. Not approved for distribution. Copyright © 2025 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`Note: All recommendations are category 2A unless otherwise indicated.
`
`9
`
`

`

`GALL-3
`and GALL-5
`GALL-4
`Presentations
`Other Clinical
`
`m Butte JM, et al. HPB (Oxford) 2011;13:463-472.
`l Consider multidisciplinary review.
`to define a standard regimen or definitive benefit. See Principles of Systemic Therapy (BIL-C).
`k For locoregionally advanced disease, consider neoadjuvant systemic therapy to rule out rapid progression and avoid futile surgery. There are limited clinical trial data
`j See NCCN Guidelines for Palliative Care.
`i Principles of Radiation Therapy (BIL-D).
`h Principles of Systemic Therapy (BIL-C).
`g Order does not indicate preference. The choice of treatment modality may depend on extent/location of disease and institutional capabilities.
`f Principles of Molecular Testing (BIL-B).
`e For patients with dMMR/MSI-H tumors or a family history suggestive of BRCA1/2 mutations, consider germline testing and/or referral to a genetic counselor.
`d Principles of Pathology (GALL-B).
`c Principles of Surgery (GALL-A).
`a Principles of Imaging (BIL-A).
`
`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
`therapyh
`systemic
`on or after
`Progression
`
`• Best supportive carej
`• Palliative RTi
`• Clinical trial (preferred)
`(preferred)
`• Systemic therapyh
`Optionsg:
`
`testinge,f
`• Molecular
`Unresectable
`
`laparoscopym
`staging
`• Consider
`CT ± contrasta
`contrast, chest
`MRI with IV
`pelvis CT/
`abdomen/
`Multiphasic
`
`margins
`positive
`T1a with
`and/or
`greater
`T1b or
`
`(GALL-6)
`Surveillance
`Treatment and
`Adjuvant
`
`malignant involvement
`± bile duct excision for
`+ lymphadenectomy
`Hepatic resectionc,d
`
`Clinical trial
`or
`systemic therapyh,k
`Consider neoadjuvant
`
`Resectablec
`
`laparoscopym
`• Consider staging
`CT ± contrasta
`CT/MRI with IV contrast, chest
`Multiphasic abdomen/pelvis
`
`positive
`node
`duct
`Cystic
`
`reviewh
`pathologic
`finding on
`Incidental
`
`Observe
`
`margins)
`negative
`T1a (with
`
`PRIMARY TREATMENT
`
`WORKUPl
`POSTOPERATIVE
`
`PRESENTATION
`
`Discussion
`Table of Contents
`NCCN Guidelines Index
`
`Gallbladder Cancer
`NCCN Guidelines Version 5.2024
`
`Printed by Jill Strand on 1/2/2025 5:29:51 PM. For personal use only. Not approved for distribution. Copyright © 2025 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`Note: All recommendations are category 2A unless otherwise indicated.
`
`10
`
`

`

`GALL-4
`and GALL-5
`GALL-1, GALL-3,
`Other Clinical Presentations
`
`n CEA and CA 19-9 are baseline tests and should not be done to confirm diagnosis.
`to define a standard regimen or definitive benefit. See Principles of Systemic Therapy (BIL-C).
`k For locoregionally advanced disease, consider neoadjuvant systemic therapy to rule out rapid progression and avoid futile surgery. There are limited clinical trial data
`j See NCCN Guidelines for Palliative Care.
`i Principles of Radiation Therapy (BIL-D).
`h Principles of Systemic Therapy (BIL-C).
`g Order does not indicate preference. The choice of treatment modality may depend on extent/location of disease and institutional capabilities.
`f Principles of Molecular Testing (BIL-B).
`e For patients with dMMR/MSI-H tumors or a family history suggestive of BRCA1/2 mutations, consider germline testing and/or referral to a genetic counselor.
`d Principles of Pathology (GALL-B).
`c Principles of Surgery (GALL-A).
`a Principles of Imaging (BIL-A).
`
`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
`therapyh
`or after systemic
`Progression on
`
`• Best supportive carej
`• Palliative RTi
`• Clinical trial (preferred)
`• Systemic therapyh (preferred)
`Optionsg:
`
`• Molecular testinge,f
`Biopsyd
`
`Unresectable
`
`(GALL-6)
`Surveillance
`Treatment and
`Adjuvant
`
`malignant involvement
`± bile duct excision for
`+ lymphadenectomy
`+ en bloc hepatic resectiond
`Cholecystectomyc
`PRIMARY TREATMENT
`
`Resectablec,k
`
`laparoscopy
`• Consider staging
`• Consider CA 19-9n
`• Consider CEAn
`reserve
`• Assessment of hepatic
`• Surgical consultation
`• LFTs
`• Chest CT + contrasta
`CT/MRI with IV contrasta
`abdomen/pelvis
`• Multiphasic
`• H&P
`
`imaging
`Mass on
`
`PRESENTATION AND WORKUP
`
`Discussion
`Table of Contents
`NCCN Guidelines Index
`
`Gallbladder Cancer
`NCCN Guidelines Version 5.2024
`
`Printed by Jill Strand on 1/2/2025 5:29:51 PM. For personal use only. Not approved for distribution. Copyright © 2025 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`Note: All recommendations are category 2A unless otherwise indicated.
`
`11
`
`

`

`GALL-5
`GALL-4
`GALL-3 and
`Presentations
`Other Clinical
`
`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
`q Consider biliary drainage for patients with jaundice prior to resection and systemic therapy. Consider baseline CA 19-9 after biliary decompression.
`p Consult with a multidisciplinary team.
`(ERCP/PTC) are used more for therapeutic intervention.
`o Magnetic resonance cholangiopancreatography (MRCP) is preferred. Endoscopic retrograde cholangiopancreatography/percutaneous transhepatic cholangiography
`n CEA and CA 19-9 are baseline tests and should not be done to confirm diagnosis.
`to define a standard regimen or definitive benefit. See Principles of Systemic Therapy (BIL-C).
`k For locoregionally advanced disease, consider neoadjuvant systemic therapy to rule out rapid progression and avoid futile surgery. There are limited clinical trial data
`j See NCCN Guidelines for Palliative Care.
`i Principles of Radiation Therapy (BIL-D).
`h Principles of Systemic Therapy (BIL-C).
`g Order does not indicate preference. The choice of treatment modality may depend on extent/location of disease and institutional capabilities.
`f Principles of Molecular Testing (BIL-B).
`e For patients with dMMR/MSI-H tumors or a family history suggestive of BRCA1/2 mutations, consider germline testing and/or referral to a genetic counselor.
`d Principles of Pathology (GALL-B).
`c Principles of Surgery (GALL-A).
`a Principles of Imaging (BIL-A).
`
`therapyh
`or after systemic
`Progression on
`
`• Best supportive carej
`• Clinical trial (preferred)
`• Systemic therapyh (preferred)
`Optionsg:
`
`therapyh
`or after systemic
`Progression on
`
`• Best supportive carej
`• Palliative RTi
`• Clinical trial (preferred)
`• Systemic therapyh (preferred)
`Options:g
`
`(GALL-6)
`Surveillance
`Treatment and
`Adjuvant
`
`+ bile duct excision
`+ lymphadenectomy
` resectiond
`+ en bloc hepatic
`Cholecystectomyc
`
`
`
`
`PRIMARY TREATMENT
`
`• Molecular testinge,f
`Biopsyd
`
`Metastatic disease
`
`• Molecular testinge,f
`Biopsyd
`
`Unresectable
`
`• Clinical trial
`(category 2B)h,k
`systemic therapy
`• Consider neoadjuvant
`
`Resectablec
`
`• Biliary drainageq
`laparoscopy
`• Consider staging
`• Consider CA 19-9n
`• Consider CEAn
`• Surgical consultationp
`• Cholangiographyo
`contrasta
`pelvis CT/MRI with IV
`• Multiphasic abdomen/
`• Chest CT ± contrasta
`• LFTs
`• H&P
`
`Jaundice
`
`PRESENTATION AND WORKUP
`
`Discussion
`Table of Contents
`NCCN Guidelines Index
`
`Gallbladder Cancer
`NCCN Guidelines Version 5.2024
`
`Printed by Jill Strand on 1/2/2025 5:29:51 PM. For personal use only. Not approved for distribution. Copyright © 2025 National Comprehensive Cancer Network, Inc., All Rights Reserved.
`
`Note: All recommendations are category 2A unless otherwise indicated.
`
`12
`
`

`

`GALL-6
`
`Version 5.2024, 11/27/24 © 2024 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN.
`
`w Based on surveillance schedule used in the phase III BILCAP trial. Primrose JN, et al. Lancet Oncol 2019;20:663-673.
`v There are no data to support a specific surveillance schedule or tests for monitoring. Physicians should discuss appropriate follow-up schedules/imaging with patients.
`u For a list of gemcitabine-based regimens and fluoropyrimidine-based regimens to be used before or after chemoradiation, see Adjuvant Chemotherapy (BIL-C, 1 of 5).
`Am 2002;11:941-954).
`t There are limited clinical trial data to define a standard regimen or definitive benefit. Clinical trial participation is encouraged. (Macdonald OK, et al. Surg Oncol Clin N
`positive disease (Horgan AM, et al. J Clin Oncol 2012;30:1934-1940).
`s Adjuvant chemotherapy or chemoradiation has been associated with survival benefit in patients with biliary tract cancer (BTC), especially in patie