[Predictive Biomarkers in Bladder Cancer]

Overview

Journal Pathologe

Specialty Pathology

Date 2019 Nov 10

PMID 31705236

Citations 3

Authors

H Reis

T Szarvas

Affiliations

Soon will be listed here.

Abstract

Background: In the last few years, significant progress has been achieved in the therapeutic options for advanced urothelial bladder cancer.

Objectives: The aim of this work was to give an overview of the status and future perspective of the therapeutic options in this setting. Its focus is on the discussion of tissue-based therapy-predictive markers, which are evaluated through (molecular) pathology and thereby strengthening the role of pathology itself.

Materials And Methods: Current (clinical study) data, the literature, and our own expertise were considered and summarized in the areas of therapy prediction of platinum-based chemotherapy, immunotherapy, and other therapeutic approaches.

Results And Conclusions: Molecular subtypes exhibit a predictive value both in platinum-based chemotherapy as well as in immunotherapy. However, further work is required to elucidate the predictive role of molecular subtypes in both settings. Changes in the DNA damage repair enzyme (DDR) genes, ERCC2, and ERBB2 as well as differences in the expression of EMMPRIN, survivin, and HMGA2 show promising results as further markers of chemotherapy efficacy. In the prediction of immunotherapy success, this mainly relates to the evaluation of the tumor mutation burden (TMB), tumor neoantigen burden (TNB), APOBEC signatures (MSig1; 3A/3B), and CD8-positive T‑effector cell signature. When using the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib, which has not yet been approved in Germany, the evaluation of specific FGFR mutations and/or gene fusions by a companion diagnostic test is mandatory in the USA.

Citing Articles

Proteasomal Processing Immune Escape Mechanisms in Platinum-Treated Advanced Bladder Cancer.

Wessolly M, Mairinger F, Herold T, Hadaschik B, Szarvas T, Reis H Genes (Basel). 2022; 13(3).

PMID: 35327977 PMC: 8948673. DOI: 10.3390/genes13030422.

[Molecular pathology of urogenital tumors : Recommendations from the 2019 International Society of Urological Pathology (ISUP) Consensus Conference].

Hommerding O, Allory Y, Argani P, Bismar T, Bubendorf L, Canete-Portillo S Pathologe. 2021; 42(3):310-318.

PMID: 33398501 PMC: 8084837. DOI: 10.1007/s00292-020-00888-4.

Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes.

Rybicka M, Woziwodzka A, Sznarkowska A, Romanowski T, Stalke P, Dreczewski M Cancers (Basel). 2020; 12(11).

PMID: 33171788 PMC: 7694950. DOI: 10.3390/cancers12113295.

References

Hedegaard J, Lamy P, Nordentoft I, Algaba F, Hoyer S, Ulhoi B . Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma. Cancer Cell. 2016; 30(1):27-42. DOI: 10.1016/j.ccell.2016.05.004. View

Mariathasan S, Turley S, Nickles D, Castiglioni A, Yuen K, Wang Y . TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018; 554(7693):544-548. PMC: 6028240. DOI: 10.1038/nature25501. View

Lawrence M, Stojanov P, Polak P, Kryukov G, Cibulskis K, Sivachenko A . Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013; 499(7457):214-218. PMC: 3919509. DOI: 10.1038/nature12213. View

Reis H, Szarvas T . [Urachal cancer - current concepts of a rare cancer (German version)]. Pathologe. 2018; 39(Suppl 2):291-300. DOI: 10.1007/s00292-018-0498-7. View

Groenendijk F, De Jong J, Fransen van de Putte E, Michaut M, Schlicker A, Peters D . ERBB2 Mutations Characterize a Subgroup of Muscle-invasive Bladder Cancers with Excellent Response to Neoadjuvant Chemotherapy. Eur Urol. 2015; 69(3):384-8. DOI: 10.1016/j.eururo.2015.01.014. View

Krafft U, Tschirdewahn S, Hess J, Harke N, Hadaschik B, Olah C . Validation of survivin and HMGA2 as biomarkers for cisplatin resistance in bladder cancer. Urol Oncol. 2019; 37(11):810.e7-810.e15. DOI: 10.1016/j.urolonc.2019.04.015. View

Choudhury A, Nelson L, Teo M, Chilka S, Bhattarai S, Johnston C . MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle-invasive bladder cancer. Cancer Res. 2010; 70(18):7017-26. PMC: 2941719. DOI: 10.1158/0008-5472.CAN-10-1202. View

Rosenberg J, Hoffman-Censits J, Powles T, van der Heijden M, Balar A, Necchi A . Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016; 387(10031):1909-20. PMC: 5480242. DOI: 10.1016/S0140-6736(16)00561-4. View

Bertz S, Hartmann A, Knuchel-Clarke R, Gaisa N . [Specific types of bladder cancer]. Pathologe. 2016; 37(1):40-51. DOI: 10.1007/s00292-015-0129-5. View

10.

Dyrskjot L, Thykjaer T, Kruhoffer M, Jensen J, Marcussen N, Hamilton-Dutoit S . Identifying distinct classes of bladder carcinoma using microarrays. Nat Genet. 2002; 33(1):90-6. DOI: 10.1038/ng1061. View

11.

Sjodahl G, Eriksson P, Liedberg F, Hoglund M . Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification. J Pathol. 2017; 242(1):113-125. PMC: 5413843. DOI: 10.1002/path.4886. View

12.

Su H, Jiang H, Tao T, Kang X, Zhang X, Kang D . Hope and challenge: Precision medicine in bladder cancer. Cancer Med. 2019; 8(4):1806-1816. PMC: 6488142. DOI: 10.1002/cam4.1979. View

13.

Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J . Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017; 18(3):312-322. DOI: 10.1016/S1470-2045(17)30065-7. View

14.

Hoffmann A, Wild P, Leicht C, Bertz S, Danenberg K, Danenberg P . MDR1 and ERCC1 expression predict outcome of patients with locally advanced bladder cancer receiving adjuvant chemotherapy. Neoplasia. 2010; 12(8):628-36. PMC: 2915407. DOI: 10.1593/neo.10402. View

15.

Linder B, Boorjian S, Cheville J, Sukov W, Thapa P, Tarrell R . The impact of histological reclassification during pathology re-review--evidence of a Will Rogers effect in bladder cancer?. J Urol. 2013; 190(5):1692-6. DOI: 10.1016/j.juro.2013.05.040. View

16.

Sjodahl G, Lauss M, Lovgren K, Chebil G, Gudjonsson S, Veerla S . A molecular taxonomy for urothelial carcinoma. Clin Cancer Res. 2012; 18(12):3377-86. DOI: 10.1158/1078-0432.CCR-12-0077-T. View

17.

McConkey D, Lee S, Choi W, Tran M, Majewski T, Lee S . Molecular genetics of bladder cancer: Emerging mechanisms of tumor initiation and progression. Urol Oncol. 2010; 28(4):429-40. PMC: 2901550. DOI: 10.1016/j.urolonc.2010.04.008. View

18.

Choi W, Porten S, Kim S, Willis D, Plimack E, Hoffman-Censits J . Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell. 2014; 25(2):152-65. PMC: 4011497. DOI: 10.1016/j.ccr.2014.01.009. View

19.

Lodewijk I, Duenas M, Rubio C, Munera-Maravilla E, Segovia C, Bernardini A . Liquid Biopsy Biomarkers in Bladder Cancer: A Current Need for Patient Diagnosis and Monitoring. Int J Mol Sci. 2018; 19(9). PMC: 6163729. DOI: 10.3390/ijms19092514. View

20.

Chalmers Z, Connelly C, Fabrizio D, Gay L, Ali S, Ennis R . Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017; 9(1):34. PMC: 5395719. DOI: 10.1186/s13073-017-0424-2. View