Alterations in fibroblast growth factor receptor 3 (FGFR3) occur in ∼15% of muscle-invasive bladder cancers (MIBCs) and metastatic urothelial carcinomas (mUCs).
To determine the association between FGFR3 status and response to platinum-based chemotherapy in patients with MIBC or mUC.
The authors conducted a retrospective review and comparison of patients having (1) MIBC treated with neoadjuvant chemotherapy (NAC), (2) mUC treated with first-line platinum-based chemotherapy (M1 cohort), and (3) MIBC who were from The Cancer Genome Atlas (TCGA).
Platinum-based chemotherapy.
Pathologic response, recurrence-free (RFS) or progression-free (PFS) survival, and overall survival (OS) were compared between patients with FGFR3 alteration (FGFR3alt) and those without it (FGFR3wild type [FGFR3wt]) in the three cohorts.
Nine of 72 NAC patients (13%) had FGFR3alt, of whom none had pathologic complete response and three had residual non-MIBC (carcinoma in situ, n = 1; pT1, n = 2). FGFR3alt was associated with shorter RFS (hazard ratio, 2.74; p = 0.044) but not OS. Among TCGA patients who underwent adjuvant chemotherapy (n = 74), FGFR3alt patients had shorter RFS as well. Conversely, among chemotherapy-naive TCGA patients, FGFR3alt was associated with longer RFS and OS. In the M1 cohort (FGFR3alt, n = 27; FGFR3wt, n = 81), FGFR3alt was associated with higher rates of pulmonary metastases and nonregional lymphadenopathy. Despite lower response rates among FGFR3alt patients (37% vs 49%; p = 0.056), PFS and OS were not significantly different from FGFR3wt patients.
FGFR3 status is associated with lower responses to platinum-based chemotherapy, which may prompt exploration of nonchemotherapeutic approaches for perioperative management of FGFR3alt urothelial cancers.
Approximately 15% of bladder cancers harbor mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Our findings suggest that FGFR3 mutations might be associated with lower responses and shorter time to recurrence among patients with muscle-invasive bladder cancer who received perioperative platinum-based chemotherapy. FGFR3 status does not significantly impact response to chemotherapy among those with metastatic urothelial cancers.
European urology. 2020 Aug 01 [Epub ahead of print]
Min Yuen Teo, Jose Mauricio Mota, Karissa A Whiting, Han A Li, Samuel A Funt, Chung-Han Lee, David B Solit, Hikmat Al-Ahmadie, Matthew I Milowsky, Arjun V Balar, Eugene Pietzak, Guido Dalbagni, Bernard H Bochner, Irina Ostrovnaya, Dean F Bajorin, Jonathan E Rosenberg, Gopa Iyer
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Division of Hematology/Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Department of Medical Oncology, NYU Langone Health, New York, NY, USA., Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA. Electronic address: .