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DOI: 10.1055/a-2442-4797
Das muskelinvasive und metastasierte Urothelkarzinom aus Sicht der Pathologie
Muscle-invasive and metastatic urothelial carcinoma from a pathological point of viewZusammenfassung
Das muskelinvasive und metastasierte Urothelkarzinom ist eine heterogene Erkrankung mit breitem morphologischem und molekularem Spektrum. Mit der Novelle der WHO-Klassifikation haben sich einige Veränderungen in der Nomenklatur und Einteilung muskelinvasiver und metastasierter Urothelkarzinome ergeben. Aufgrund zunehmender Individualisierung therapeutischer Optionen gewinnt die korrekte Diagnose morphologischer Varianten des Urothelkarzinoms, die mit spezifischen molekularen Alterationen assoziiert sind, zunehmend an Bedeutung. Die morphologischen Varianten korrelieren zudem mit molekularen Subtypen des Urothelkarzinoms. Darüber hinaus sind sowohl morphologische als auch molekulare Subtypen mit immunologischen und anderen molekularen Eigenschaften assoziiert, die z.B. in Form des PD-L1- und des NECTIN-4-Status relevant für moderne Immuntherapien oder Antikörper-Drugkonjugate sein könnten. Mit der anstehenden Zulassung von Erdafitinib (FGFR3-Inhibitor) werden in Zukunft auch molekulare Tumorboards für Patienten mit metastasiertem Urothelkarzinom an Bedeutung gewinnen.
Abstract
Muscle-invasive and metastatic urothelial carcinoma is a heterogeneous disease with a broad morphological and molecular spectrum. The amendment of the WHO classification has resulted in some changes in the nomenclature and classification of muscle-invasive and metastatic urothelial carcinomas. Due to the increasing individualisation of therapeutic options, the correct diagnosis of morphological variants of urothelial carcinoma, which are associated with specific molecular alterations, is becoming more and more important. The morphological variants also correlate with molecular subtypes of urothelial carcinoma. In addition, both morphological and molecular subtypes are associated with immunological and other molecular characteristics that could be relevant for modern immunotherapies or antibody-drug conjugates, e.g. in the form of PD-L1 and NECTIN-4 status. With the pending approval of erdafitinib (FGFR3 inhibitor), molecular tumour boards for patients with metastatic urothelial carcinoma will also become more important in the future.
Schlüsselwörter
Urothelkarzinom - Molekularpathologie - histopathologische Risikofaktoren - immunologische Risikofaktoren - molekulare SubtypenKeywords
Urothelial carcinoma - molecular pathology - histopathological risk factors - immunological risk factors - molecular subtypesPublication History
Received: 26 March 2024
Accepted after revision: 08 October 2024
Article published online:
27 November 2024
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Literatur
- 1 WHO Classification of Tumours Editorial Board. Urinary and male genital tumours. Vol. WHO classification of tumours series, 5th ed.; vol. 8. 2022. International Agency for Research on Cancer;
- 2 Alfred Witjes J. et al. European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2023 Guidelines. Eur Urol 2024; 85: 17-31
- 3 Kamoun A. et al. A Consensus Molecular Classification of Muscle-invasive Bladder Cancer. Eur Urol 2020; 77: 420-433
- 4 Zinnall U. et al. Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype. Hum Pathol 2018; 80: 55-64
- 5 Weyerer V. et al. Pure Large Nested Variant of Urothelial Carcinoma (LNUC) Is the Prototype of an FGFR3 Mutated Aggressive Urothelial Carcinoma with Luminal-Papillary Phenotype. Cancers (Basel) 2020; 12: 763
- 6 Siefker-Radtke AO. et al. Phase II clinical trial of neoadjuvant alternating doublet chemotherapy with ifosfamide/doxorubicin and etoposide/cisplatin in small-cell urothelial cancer. J Clin Oncol 2009; 27: 2592-2597
- 7 Kaushik D. et al. Long-term results of radical cystectomy and role of adjuvant chemotherapy for small cell carcinoma of the bladder. Int J Urol 2015; 22: 549-554
- 8 Eckstein M. et al. Proposal for a Novel Histological Scoring System as a Potential Grading Approach for Muscle-invasive Urothelial Bladder Cancer Correlating with Disease Aggressiveness and Patient Outcomes. Eur Urol Oncol 2024; 7: 128-138
- 9 Sjödahl G. et al. Molecular Subtypes as a Basis for Stratified Use of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer A Narrative Review. Cancers (Basel) 2022; 14: 1692
- 10 Powles T. et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med 2024; 390: 875-888
- 11 Bajorin DF. et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. New England Journal of Medicine 2021; 384: 2102-2114
- 12 Diamantis N, Banerji U. Antibody-drug conjugates – an emerging class of cancer treatment. Br J Cancer 2016; 114: 362-367
- 13 Challita-Eid PM. et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016; 76: 3003-3013
- 14 Birrer MJ. et al. Antibody-Drug Conjugate-Based Therapeutics: State of the Science. J Natl Cancer Inst 2019; 111: 538-549
- 15 Powles T. et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med 2021; 384: 1125-1135
- 16 Chu CE. et al. Heterogeneity in NECTIN4 Expression Across Molecular Subtypes of Urothelial Cancer Mediates Sensitivity to Enfortumab Vedotin. Clin Cancer Res 2021; 27: 5123-5130
- 17 Rosenberg J. et al. EV-101: A Phase I Study of Single-Agent Enfortumab Vedotin in Patients With Nectin-4-Positive Solid Tumors, Including Metastatic Urothelial Carcinoma. J Clin Oncol 2020; 38: 1041-1049
- 18 Bahlinger V. et al. Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts. Histopathology 2024; 84: 863-876
- 19 Klumper N. et al. Membranous NECTIN-4 Expression Frequently Decreases during Metastatic Spread of Urothelial Carcinoma and Is Associated with Enfortumab Vedotin Resistance. Clin Cancer Res 2023; 29: 1496-1505
- 20 Mosele F. et al. Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial. Nat Med 2023; 29: 2110-2120
- 21 Aggen DH, Chu CE, Rosenberg JE. Scratching the Surface: NECTIN-4 as a Surrogate for Enfortumab Vedotin Resistance. Clin Cancer Res 2023; 29: 1377-1380
- 22 Meric-Bernstam F. et al. Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial. J Clin Oncol 2024; 42: 47-58
- 23 Klumper N. et al. NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer. J Clin Oncol 2024; 42: 2446-2455
- 24 Mitra AP. Molecular substratification of bladder cancer: moving towards individualized patient management. Ther Adv Urol 2016; 8: 215-233
- 25 Knepper TC. et al. Key Lessons Learned from Moffitt’s Molecular Tumor Board: The Clinical Genomics Action Committee Experience. Oncologist 2017; 22: 144-151
- 26 Bryce AH. et al. Experience with precision genomics and tumor board, indicates frequent target identification, but barriers to delivery. Oncotarget 2017; 8: 27145-27154
- 27 Harada S. et al. Implementation and utilization of the molecular tumor board to guide precision medicine. Oncotarget 2017; 8: 57845-57854
- 28 Loriot Y. et al. Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. N Engl J Med 2023; 389: 1961-1971