A model combining clinical and genomic factors to predict response to PD-1/PD-L1 blockade in advanced urothelial carcinoma

Br J Cancer. 2020 Feb;122(4):555-563. doi: 10.1038/s41416-019-0686-0. Epub 2019 Dec 20.


Background: In metastatic urothelial carcinoma (mUC), predictive biomarkers that correlate with response to immune checkpoint inhibitors (ICIs) are lacking. Here, we interrogated genomic and clinical features associated with response to ICIs in mUC.

Methods: Sixty two mUC patients treated with ICI who had targeted tumour sequencing were studied. We examined associations between candidate biomarkers and clinical benefit (CB, any objective reduction in tumour size) versus no clinical benefit (NCB, no change or objective increase in tumour size). Both univariable and multivariable analyses for associations were conducted. A comparator cohort of 39 mUC patients treated with taxanes was analysed by using the same methodology.

Results: Nine clinical and seven genomic factors correlated with clinical outcomes in univariable analysis in the ICI cohort. Among the 16 factors, neutrophil-to-lymphocyte ratio (NLR) ≥5 (OR = 0.12, 95% CI, 0.01-1.15), visceral metastasis (OR = 0.05, 95% CI, 0.01-0.43) and single-nucleotide variant (SNV) count < 10 (OR = 0.04, 95% CI, 0.006-0.27) were identified as independent predictors of NCB to ICI in multivariable analysis (c-statistic = 0.90). None of the 16 variables were associated with clinical benefit in the taxane cohort.

Conclusions: This three-factor model includes genomic (SNV count >9) and clinical (NLR <5, lack of visceral metastasis) variables predictive for benefit to ICI but not taxane therapy for mUC. External validation of these hypothesis-generating results is warranted to enable use in routine clinical care.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / immunology*
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / immunology
  • Female
  • Humans
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Neutrophils / immunology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Urologic Neoplasms / drug therapy*
  • Urologic Neoplasms / genetics
  • Urologic Neoplasms / immunology


  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor