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Why test

Biomarker testing is used to drive treatment decisions in an approach known as personalised medicine to ensure each patient receives the most appropriate treatment for their cancer

The goal of biomarker testing is to inform treatment decisions for optimal outcomes

  • The spectrum of bladder cancer is diverse1
    • Urothelial bladder cancer can present with divergent differentiation patterns that include squamous, glandular, micropapillary, nested, lymphoepithelioma-like, plasmacytoid and sarcomatoid variants1 differentiated by pathological and biomarker analysis2
    • Advanced bladder cancer occurs when the cancer has spread to 1 or more lymph node within the pelvis or has metastasised to the lungs, bones or liver3
  • While the list of biomarkers for prognosis and treatment selection for advanced bladder cancer is growing, their clinical relevance remains unclear due to lack of external validation in external datasets4

PD-L1, an immune checkpoint ligand, is a potential biomarker expressed in many immunogenic cancers, including bladder cancer

  • The potential for immune responses are increased in tumours with high rates of somatic mutations5
  • Tumours can evade detection by the immune system by co-opting inhibitory checkpoint pathways that suppress antitumour immune responses, such as PD-1, PD-L1 and CTLA-46
  • Many tumours achieve this through overexpression of PD-L17

PD-L1 expression is measured across a continuum from no/low expression through moderate and high expression

  • Unlike some other diagnostic biomarkers used in the oncology setting, PD-L1 expression does not provide a binary result such as positive/negative or mutated/wild type7,8
  • Determining tumour PD-L1 expression status may help identify patients more likely to respond to immunotherapy-based treatment regimens5

There is emerging evidence to suggest that PD-L1 can inform clinical decision-making7

PD-L1 expression status with bladder cancer

CTLA-4, cytotoxic T-lymphocyte-associated antigen-4; PD-1, programmed cell death-1; PD-L1, programmed cell death ligand-1; QoL, quality of life

REFERENCES

  1. Chalasani V, et al. Can Urol Assoc J 2009;3(6 Suppl. 4):S193–8
  2. Diamandis EP. Clin Chem 2004;50:793–5
  3. Cancer Research UK. Last accessed March 2017
    http://www.cancerresearchuk.org/about-cancer/type/bladder-cancer/treatment/bladder-cancer-stage-and-grade
  4. Ru Y, et al. Curr Opin Urol 2011:21:420–7
  5. Powles T, et al. Nature 2014;515:558–62
  6. Patel SP, Kurzrock R. Mol Cancer Ther 2015;14:847–56
  7. Ilie M, et al. Virchows Arch 2016;468:511–25
  8. Kerr KM, Hirsch FR. Arch Pathol Lab Med 2016;140:326–31
  9. Kerr KM, et al. J Thorac Oncol 2015;10:985–9
  10. Dizon DS, et al. J Clin Oncol 2016;34:987–1011
  11. Mahoney KM, Atkins MB. Oncology 2014;28:39–48
  12. Kelly CM, Shahrokni A. J Oncol 2016;2016:6186543
  13. Kiebert GM, et al. Qual Life Res 1994;3:175–82
  14. Maione P, et al. Rev Recent Clin Trials 2011;6:44–51

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