On March 5, 2021, The National Comprehensive Cancer Network (NCCN) released an update to its guideline for hepatobiliary cancers. The version 1.2021 update features guideline updates in hepatocellular carcinoma (HCC), gallbladder cancer, intrahepatic cholangiocarcinoma, and biliary tract cancer.
Hepatocellular Carcinoma
For HCC, screening was modified from “ultrasound ± alpha fetoprotein” to “ultrasound + alpha fetoprotein.”
In the workup section, under multidisciplinary evaluation for confirmed HCC, a bullet was revised to “abdominal/pelvic CT or MRI with contrast, if not previously done or needs updating.” Additionally, a new bullet was added, “consider referral to a hepatologist.” In the last column, there was a revision to “liver-confirmed disease, inoperable by performance status, comorbidity, or with minimal or unknown extrahepatic disease.
For potentially resectable or transplantable HCC, under surgical assessment, a bullet was added, “extended criteria.” Under the surveillance column, a bullet was revised to “refer to a hepatologist for a discussion of antiviral therapy for carriers of hepatitis if not previously done.”
For unresectable HCC not eligible for transplant, treatment options were divided into 2 separate pathways: upper pathway and lower pathway. The upper pathway lists locoregional therapy as the preferred option. The lower pathway includes the options of clinical trial, systemic therapy, and best supportive care. “Consider early imaging per local protocol,” was added under surveillance.
For metastatic disease or extensive liver tumor burden pathways, the recommendation was revised to “biopsy for histologic confirmation if not previously done.”
In the section for principles of imaging, screening and surveillance was revised. In the section for principles of biopsy, initial biopsy was revised and “histologic grading or molecular characterization is desired,” was removed.
Principles of radiation therapy was separated from the principles of locoregional therapy.
In the section for principles of locoregional therapy, arterially directed therapies were revised extensively. A new sub-bullet was added under the 3rd bullet, “With RE, delivery of ≥205 Gy to the tumor may be associated with increased overall survival.” Another sub-bullet was added under the 4th bullet, “randomized controlled trials have shown that Y-90 is not superior to sorafenib for treating advanced HCC. RE may be appropriate in some patients with advanced HCC, specifically patients with segmental or local portal vein, rather than main portal vein thrombosis.” Additionally, “the angiographic endpoint of embolization may be chosen by the treating physician” was removed. The last bullet was revised to “benefit in three randomized trials; other randomized phase III trials are ongoing to investigate other systemic therapies including immunotherapy in combination with arterial therapies.
In the section for principles of radiation therapy, the heading was modified to “External Beam Radiation Therapy.” Under treatment modalities, “SBRT (1-5 fractions)” was revised to “typically 3-5 fractions.” Under RT dosing, the doses of EBRT were modified to “initial volumes to 45 Gy in 1.8 Gy per fraction” and “boost to 50 to 60 Gy in 1.8-2 Gy per fraction.” The doses of SBRT were modified to 30-50 Gy (typically in 3-5 fractions) …”
For first-line therapy, the preferred regimens, sorafenib and Lenvatinib were moved under “other recommended regimens.” Under “useful in certain circumstances,” the recommendation for nivolumab was modified to include Child-Pugh Class A or B.
For subsequent-line therapy, nivolumab (Child-Pugh Class A or B), nivolumab + ipilimumab (Child-Pugh Class A only), and pembrolizumab (Child-Pugh Class A only) were moved to “other recommended regimens.”
Gallbladder Cancer
In the postoperative workup section, under unresectable gallbladder cancer, tumor mutational burden testing was added under additional molecular testing.
In the section for principles of surgery and pathology, under mass on imaging: patients presenting with gallbladder mass/disease suspicious of gallbladder cancer, a bullet was revised to “staging should be carried out with multiphasic cross-sectional imaging of the chest, abdomen, and pelvis.”
Intrahepatic Cholangiocarcinoma
For resectable isolate intrahepatic mass, under primary treatment, a bullet was revised to “resection and regional lymphadenectomy.” Additionally, “consider lymphadenectomy for accurate staging” was removed.
Biliary Tract Cancers
In the section for principles of radiation therapy, there were revisions noted for unresectable disease: “all tumors irrespective of the location may be amendable to EBRT.” Under RT dosing, EBRT and SBRT were added as sub-bullets. Under EBRT, doses were modified to “initial volumes to 45 Gy in 1.8 Gy per fraction” and “boost to 50 to 60 Gy in 1.8-2 Gy per fraction.” Under SBRT, the doses were modified to 30-50 Gy (typically in 3-5 fractions) depending…” and “for intrahepatic tumors, SBRT (typically 3-5 fractions) …”
In the section for principles of systemic therapy, under neoadjuvant therapy, 5-fluorouracil + cisplatin (category 2B) and capecitabine + cisplatin (category 2B) were removed from other recommended regimens. Under adjuvant therapy, 5-fluorouracil + cisplatin (category 3) was removed from other recommended regimens.
Under other recommended regimens for primary treatment of unresectable and metastatic disease, 5-fluorouracil + cisplatin and capecitabine + cisplatin changed from category 2A to category 2B recommendations. Under useful in certain circumstances for subsequent-line therapy in biliary tract cancers, a bullet was revised to “For MSI-H/dMMR tumors/TMB-H tumors.” Additionally, bullets were added, “For BRAF-V600E mutated tumors: Dabrafenib + trametinib,” “nivolumab (category 2B),” and “Lenvatinib + pembrolizumab (category 2B).”—Janelle Bradley
