Practical guidelines for molecular testing of cholangiocarcinoma in clinical practice: Italian experts' position paper.

Biliary tract cancers (BTCs) represent a spectrum of malignancies associated with a dismal prognosis. Recent genomic profiling studies have provided a deeper understanding of the complex and heterogenous molecular landscape of BTCs, identifying several actionable genetic alterations, and expanding treatment options. Due to the high number and complexity of genetic alterations which require testing, next-generation sequencing (NGS) is currently the preferred approach over conventional methods (i.e., immunohistochemistry, fluorescence in-situ hybridization and PCR) for molecular profiling of BTCs and should be performed upfront in all BTC patients. However, BTC sampling often yields low tumor cellularity tissue, hampering NGS analysis. Future perspectives to overcome this obstacle include liquid biopsy and optimization of biopsy protocols. In this position paper, the authors discuss the current histopathologic, molecular, and therapeutic landscape of BTCs, provide a critical overview of the available testing methods for molecular diagnostics, and propose a practical diagnostic algorithm for molecular testing of BTC samples.
Competing Interests: Declaration of Competing Interest All other authors declare that they have no conflict of interest related to the present work. Conflict of interest statement MF has been involved in consulting/advisory roles in Astellas Pharma, Pierre Fabre, MSD, AstraZeneca, Janssen, GlaxoSmithKline, BMS, Incyte, Amgen, Novartis and Roche, and received research funding from Astellas Pharma, QED Therapeutics, Diaceutics and Macrophage Pharma. NN has been involved in consulting/advisory roles in MSD, Bayer, Biocartis, Illumina, Incyte, Roche, BMS, Merck, Thermofisher, AstraZeneca, Eli Lilly, Novartis; financial support to research projects (institutional grants) from Merck, Thermofisher, QIAGEN, Roche, AstraZeneca, Biocartis, Illumina, Sophia genetics; non-financial interests President of the International Quality Network for Pathology (IQN Path) and Past President of the Italian Cancer Society (SIC). GP has been involved in consulting/advisory roles in Roche, Illumina, Novartis, Lilly, AstraZeneca, Exact Sciences, ADS Biotech. GT has received honoraria from Molteni, Novartis and Pharmamar. AS has received consulting fees from Amgen, AstraZeneca, Basilea, Incyte, and Ipsen and lecture fees from Amgen, Incyte, Ipsen, Merck Serono, Roche, and Sanofi. LR has received consulting fees from AstraZeneca, Basilea, Bayer, BMS, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, and Zymeworks; lecture fees from AstraZeneca, Bayer, BMS, Eisai, Incyte, Ipsen, Merck Serono, Roche, and Servier; travel expenses from AstraZeneca; and institutional research funding from Agios, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, and Zymeworks. FG has been involved in consulting/advisory roles in MSD and GlaxoSmithKline; lecture fees from MSD, Incyte and GlaxoSmithKline.
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