Optimizing the Use of Next-Generation Sequencing Assays in Patients With Urothelial Carcinoma: Recommendations by the 2023 San Raffaele Retreat Panel.

BACKGROUND

The application of precision medicine in clinical practice implies a thorough evaluation of actionable genomic alterations to streamline therapeutic decision making. Comprehensive genomic profiling of tumor via next-generation sequencing (NGS) represents a great opportunity but also several challenges. During the 2023 San Raffaele Retreat, we aimed to provide expert recommendations for the optimal use of NGS in urothelial carcinoma (UC).

MATERIALS AND METHODS

A modified Delphi method was utilized, involving a panel of 12 experts in UC from European and United States centers, including oncologists, urologists, pathologists, and translational scientists. An initial survey, conducted before the meeting, delivered 15 statements to the panel. A consensus was defined when ≥70% agreement was reached for each statement. Statements not meeting the consensus threshold were discussed during the meeting.

RESULTS

Nine of the 15 statements covering patient selection, cancer characteristics, and type of NGS assay, achieved a consensus during the survey. The remaining six statements addressing the optimal timing of NGS use, the ideal source of tumor biospecimen for NGS testing, and the subsequent need to evaluate the germline nature of certain genomic findings were discussed during the meeting, leading to unanimous agreement at the end of the conference.

CONCLUSION

This consensus-building effort addressed multiple unanswered questions regarding the use of NGS in UC. The opinion of experts was in favor of broader use of NGS. In a setting where recommendations/guidelines may be limited, these insights may aid clinicians to provide informed counselling and raise the bar of precision and personalized therapy.

Informations de copyright

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Déclaration de conflit d'intérêts

Disclosure Andrea Necchi: Honoraria: Roche, MSD, AstraZeneca, Janssen, Foundation Medicine, BMS, Astellas. Consulting or Advisory role: MSD, Roche, Bayer, AstraZeneca, Clovis Oncology, Janssen, Incyte, Seattle Genetics/Astellas, Bristol-Myers Squibb, Rainier Therapeutics, Bycicle Therapeutics, GlaxoSmithKline, Basilea Pharmaceutica, Catalym. Research Funding (Institution): MSD, AstraZeneca, Ipsen, Gilead. Travel, Accommodations, Expenses: Roche, MSD, AstraZeneca, Janssen, Rainer Therapeutics, Pfizer. Employment and Stock Ownership (spouse): Bayer. Jeffrey S. Ross: employee of Foundation Medicine; equity owner of Roche Holdings, Celsius therapeutics and Tango Therapeutics. Petros Grivas: consulting for MSD, BMS, AstraZeneca, EMD Serono, SeaGen, Pfizer, Janssen, Roche, Astellas, Gilead, Fresenius Kabi, Strata Oncology, Abbvie; research funding: Acrivon Therapeutics, ALX Oncology, BMS, Genentech, Gilead, EMD Serono, MSD, QED Therapeutics. Philippe E. Spiess: no financial disclosures to report, only leadership positions: president of the Global Society of Rare Genitourinary Tumors, vice-chair of the NCCN bladder and penile cancer panel, member of the ASCO/EAU panel on penile cancer. Ewan A. Gibb: employee of Veracyte Inc. Ashish M. Kamat: Grants or Contracts: FKD Therapies (now Ferring), Patient Centered Outcomes, Research Institute (PCORI), Photocure, Seagen, EnGene, Arquer Diagnostics, SWOG. Advisory Board/Consulting Fees: Astellas Pharma, Biological Dynamics, Bristol-Myers Squibb, CG Oncology, Cystotech, Eisai, EnGene, Ferring, Imagin Medical, Imvax, Incyte, Janssen, Medac, Merck, Nonagen Bioscience, Pfizer, Photocure, Protara Therapeutics, Roche, Seagen, Sessen Bio, Theralase, Urogen Pharma, US Biotest, Vivet Therapeutics. Patents: CyPRIT (Cytokine Predictors of Response to Intravesical Therapy), Joint patent with MD Anderson Cancer Center. Leadership or fiduciary role in other board, society, committee or advocacy group: European Urology Oncology, International Bladder Cancer Group (IBCG), International Bladder Cancer Network (IBCN), Journal of Urology, UroToday. Shilpa Gupta: consulting for for Bristol Myers Squibb, Merck, Bayer, Pfizer, EMD Sorono, Seattle Genetics, Gilead Sciences, Foundation Medicine, Guardant, and Astellas; Speaker bureau for Seattle Genetics, Bristol Myers Squibb and Gilead Sciences; and is a shareholder of Moderna, Nektar Therapeutics and BioNTech. Lars Dyrskjøt: sponsored research agreements with C2i Genomics, Natera, AstraZeneca, Photocure, and Ferring; advisory/consulting role at Ferring, MSD and UroGen; received speaker honoraria from AstraZeneca, Pfizer and Roche and received travel support from MSD. Board member at BioXpedia. Neeraj Agarwal: No personal COIs since April 15, 2021. Consultancy to Astellas, Astra Zeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics. Research funding to Neeraj Agarwal's institution: Arnivas, Astellas, Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, Telix, and Tracon.