Systemic inflammatory indices have been proposed as prognostic biomarkers in several malignancies; however, their role in patients receiving avelumab maintenance for advanced urothelial carcinoma (aUC) remains poorly defined. This study aimed to evaluate the prognostic impact of inflammatory markers in this context and to develop a composite score for outcome stratification. We retrospectively analyzed patients with aUC who were treated with avelumab maintenance therapy. Systemic inflammatory markers - including the neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-eosinophil ratio (NER), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) - were collected at baseline and after treatment initiation (cycle 3), and changes from baseline to cycle three were analyzed (increase versus stability/decrease). Overall survival (OS), the primary endpoint, was evaluated using Kaplan-Meier and Cox models. A prognostic score was created from the multivariable analysis. Time-dependent Receiver operating characteristics (ROC) analysis was employed to evaluate model discrimination at 6, 12, and 24 months. The prognostic impact on disease control rate (DCR - secondary endpoint) was assessed using logistic regression and ROC curves. A total of 358 patients were included in the study. In the multivariable analysis, high NLR, high NER, low LMR, increasing NLR trend, bone and liver metastases were independently associated with worse OS. These variables were incorporated into a 0-6 point prognostic score, which demonstrated good discrimination (C-index 0.76; AUC at 6, 12, and 24 months: 0.87, 0.75, and 0.73, respectively). The score remained prognostic across subgroups and following sensitivity analyses. High LMR, low NER, the absence of liver metastases, and the absence of bone metastases were independently associated with higher DCR. A response-associated score combining these variables showed a decreasing DCR from 69% (score 0) to 25% (score 4). Baseline and dynamic inflammatory markers may serve as prognostic factors for OS in patients with aUC undergoing avelumab maintenance therapy. A composite score that integrates laboratory and clinical features could allow for clinically meaningful stratification of survival and response outcomes, with potential applications in clinical practice. However, a prospective evaluation is necessary.
Scientific reports. 2026 Jun 17 [Epub ahead of print]
Brigida Anna Maiorano, Giandomenico Roviello, Alessandro Rizzo, Francesco Ciccimarra, Marco Maruzzo, Francesco Pierantoni, Carlo Messina, Marco Messina, Martina Fanelli, Antonello Veccia, Mimma Rizzo, Alessia Cavo, Vincenza Conteduca, Vincenzo Emanuele Chiuri, Linda Cerbone, Michela Roberto, Federico Paolieri, Daniele Galanti, Gian Paolo Spinelli, Alessia Mennitto, Marco Pisino, Roberto Filippi, Valentina Guadalupi, Maria Cossu Rocca, Pierangela Sepe, Palma Fedele, Michele Dionese, Simona Secondino, Sara Elena Rebuzzi, Francesca Vignani, Mariella Sorarù, Antonio Doronzo, Martina Catalano, Elisabetta Gambale, Daniele Santini, Matteo Santoni, Massimo Di Maio, Lorenzo Antonuzzo, Andrea Necchi
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