ASCEND-BTC is a prospective, multi-center, observational study aimed at detecting early biliary tract cancer by combined assays of serum protein and cell-free DNA (cfDNA) methylation. The study will enroll approximately 492 participants diagnosed with biliary tract cancer and benign diseases.

Inclusion Criteria for Cancer Arm Participants:

• Age 40-75 years at the day of consenting to the study.
• Able to provide a written informed consent
• Pathologically confirmed biliary tract cancers.
• No prior or ongoing anti-cancer therapy (local or systematic) prior to study blood draw.

Exclusion Criteria for Cancer Arm Participants:

• Pregnancy or lactating women.
• Recipients of organ transplant or prior non-autologous (allogeneic) bone marrow transplant or stem cell transplant.
• Recipients of blood transfusion within 7 days prior to study blood draw.
• Recipients of any anti-cancer therapy within 30 days prior to study blood draw, due to diseases other than cancers.
• With other known malignant tumors or multiple primary tumors.

Inclusion Criteria for Benign Arm Participants:

• Age 40-75 years at the day of consenting to the study.
• Able to provide a written informed consent.
• Confirmed diagnosis of benign biliary tract diseases.
• No prior radical treatment of the benign diseases prior to study blood draw.

Exclusion Criteria for Benign Arm Participants:

• Pregnancy or lactating women.
• Recipients of organ transplant or prior non-autologous (allogeneic) bone marrow transplant or stem cell transplant.
• Recipients of blood transfusion within 7 days prior to study blood draw.
• Recipients of any anti-cancer therapy within 30 days prior to study blood draw, due to diseases other than cancers.
• Confirmed diagnosis of malignancies or precancerous lesion.
• A history of malignant tumors.

Eligible participants will be recruited from participating medical centers and assigned into two arms, including participants with new diagnosis of biliary tract cancer and benign biliary tract diseases.