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- Title
Development and Validation of an Inflammatory Prognostic Index to Predict Outcomes in Advanced/Metastatic Urothelial Cancer Patients Receiving Immune Checkpoint Inhibitors.
- Authors
Mokbel, Sara; Baciarello, Giuilia; Lavaud, Pernelle; Omlin, Aurelius; Calabrò, Fabio; Cathomas, Richard; Aeppli, Stefanie; Parent, Pauline; Giannatempo, Patrizia; Koster, Kira-Lee; Appel, Naara; Gonnet, Philippe; Angius, Gesuino; Tsantoulis, Petros; Arkenau, Hendrick-Tobias; Cattrini, Carlo; Messina, Carlo; Zeghondy, Jean; Morelli, Cristina; Loriot, Yohann
- Abstract
Simple Summary: Immune checkpoint inhibitors (ICIs) are standard treatment for advanced/metastatic urothelial cancer (a/mUC) following progression on platinum agents. Traditionally, PDL-1 expression has been utilised to predict response to ICIs; however, this is not a robust selection marker. Therefore, alternative prognostic markers are needed to better select a subset of patients with a/mUC who are more likely to benefit. This study found that baseline systemic inflammatory profile and the absence of early serum inflammatory biomarker changes are associated with significantly better outcomes in patients. We developed and validated an immune prognostic index (U-IPI) specific to a/mUC patients on ICI treatment created using the five most statistically significant inflammatory markers. The U-IPI developed is an easily implementable prognostic tool to early predict benefit from ICIs. Background: Immune checkpoint inhibitors (ICIs) improve overall survival (OS) in advanced/metastatic urothelial cancer (a/mUC) patients. Preliminary evidence suggests a prognostic role of inflammatory biomarkers in this setting. We aimed to develop a disease-specific prognostic inflammatory index for a/mUC patients on ICIs. Methods: Fifteen variables were retrospectively correlated with OS and progression-free survival (PFS) in a development (D, n = 264) and a validation (V, n = 132) cohort of platinum-pretreated a/mUC pts receiving ICIs at L2 or further line. A nomogram and inflammatory prognostic index (U-IPI) were developed. The index was also tested in a control cohort of patients treated with chemotherapy only (C, n = 114). Results: The strongest predictors of OS were baseline platelet/lymphocyte (PLR) and neutrophil/lymphocyte (NLR) ratios, and lactate dehydrogenase (LDH), NLR, and albumin changes at 4 weeks. These were used to build the U-IPI, which can distinctly classify patients into good or poor response groups. The nomogram scoring is significant for PFS and OS (p < 0.001 in the D, V, and combined cohorts) for the immunotherapy (IO) cohort, but not for the control cohort. Conclusions: The lack of a baseline systemic inflammatory profile and the absence of early serum inflammatory biomarker changes are associated with significantly better outcomes on ICIs in a/mUC pts. The U-IPI is an easily applicable dynamic prognostic tool for PFS and OS, allowing for the early identification of a sub-group with dismal outcomes that would not benefit from ICIs, while distinguishing another that draws an important benefit.
- Subjects
BLADDER tumors; PREDICTIVE tests; NEUTROPHIL lymphocyte ratio; QUESTIONNAIRES; RESEARCH methodology evaluation; RETROSPECTIVE studies; LACTATE dehydrogenase; TUMOR markers; EXPERIMENTAL design; METASTASIS; IMMUNE checkpoint inhibitors; PLATELET lymphocyte ratio; RESEARCH methodology; PROGRESSION-free survival; OVERALL survival
- Publication
Cancers, 2024, Vol 16, Issue 8, p1465
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers16081465