New prognostic model in patients with advanced urothelial carcinoma treated with second-line immune checkpoint inhibitors.

Bellmunt Risk Score, based on Eastern Cooperative Oncology Group (ECOG) performance status (PS), hemoglobin levels and presence of liver metastases, is the most established prognostic algorithm for patients with advanced urothelial cancer (aUC) progressing after platinum-based chemotherapy. Nevertheless, existing algorithms may not be sufficient following the introduction of immunotherapy. Our aim was to develop an improved prognostic model in patients receiving second-line atezolizumab for aUC.

Patients with aUC progressing after cisplatin/carboplatin-based chemotherapy and enrolled in the prospective, single-arm, phase IIIb SAUL study were included in this analysis. Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The development and internal validation of a prognostic model for overall survival (OS) was performed using Cox regression analyses, bootstrapping methods and calibration.

In 936 patients, ECOG PS, alkaline phosphatase, hemoglobin, neutrophil-to-lymphocyte ratio, liver metastases, bone metastases and time from last chemotherapy were identified as independent prognostic factors. In a 4-tier model, median OS for patients with 0-1, 2, 3-4 and 5-7 risk factors was 18.6, 10.4, 4.8 and 2.1 months, respectively. Compared with Bellmunt Risk Score, this model provided enhanced prognostic separation, with a c-index of 0.725 vs 0.685 and increment in c-statistic of 0.04 (p<0.001). Inclusion of PD-L1 expression did not improve the model.

We developed and internally validated a prognostic model for patients with aUC receiving postplatinum immunotherapy. This model represents an improvement over the Bellmunt algorithm and could aid selection of patients with aUC for second-line immunotherapy.


Journal for immunotherapy of cancer. 2023 Jan [Epub]

Aristotelis Bamias, Axel Merseburger, Yohann Loriot, Nicholas James, Ernest Choy, Daniel Castellano, F Lopez-Rios, Fabio Calabrò, Mario Kramer, Guillermo de Velasco, Roubini Zakopoulou, Kimon Tzannis, Cora N Sternberg

Second Propaedeutic Department of Internal Medicine, National and Kapodistrian University of Athens, Chaidari, Greece ., University Clinic Schleswig-Holstein-Lubeck, Lübeck, Germany., Institut Gustave-Roussy, Villejuif, France., Royal Marsden Hospital NHS Trust, London, UK., Cardiff University, Cardiff, UK., Hospital Universitario 12 de Octubre, Madrid, Spain., Hospital Universitario HM Sanchinarro, Madrid, Spain., GU Oncology Unit, San Camillo Forlanini Hospital, Roma, Italy., University of Athens, Athens, Greece., National and Kapodistrian University of Athens, Athens, Greece., Hematology and Oncology Englander Institute for Precision Medicine Weill Cornell Medicine, New York, New York, USA.