Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI).
We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI.
We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd+ line.
We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant.
Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.
Clinical genitourinary cancer. 2022 Jun 05 [Epub ahead of print]
Dimitrios Makrakis, Rafee Talukder, Genevieve Ihsiu Lin, Leonidas N Diamantopoulos, Scott Dawsey, Shilpa Gupta, Lucia Carril-Ajuria, Daniel Castellano, Ivan de Kouchkovsky, Vadim S Koshkin, Joseph J Park, Ajjai Alva, Mehmet A Bilen, Tyler F Stewart, Rana R McKay, Nishita Tripathi, Neeraj Agarwal, Naomi Vather-Wu, Yousef Zakharia, Rafael Morales-Barrera, Michael E Devitt, Alessio Cortellini, Claudia Angela Maria Fulgenzi, David J Pinato, Ariel Nelson, Christopher J Hoimes, Kavita Gupta, Benjamin A Gartrell, Alex Sankin, Abhishek Tripathi, Roubini Zakopoulou, Aristotelis Bamias, Jure Murgic, Ana Fröbe, Alejo Rodriguez-Vida, Alexandra Drakaki, Sandy Liu, Eric Lu, Vivek Kumar, Giuseppe Di Lorenzo, Monika Joshi, Pedro Isaacsson-Velho, Lucia Alonso Buznego, Ignacio Duran, Marcus Moses, Albert Jang, Pedro Barata, Guru Sonpavde, Evan Y Yu, Robert Bruce Montgomery, Petros Grivas, Ali Raza Khaki
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA., Department of Epidemiology, University of Washington, Seattle, WA., Department of Medicine, University of Pittsburgh, Pittsburgh, PA., Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH., Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain., Division of Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA., Division of Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI., Winship Cancer Institute of Emory University, Atlanta, GA., Division of Hematology/Oncology, Department of Medicine, University of California San Diego, La Jolla, CA., Division of Oncology, Department of Medicine, University of Utah, Salt Lake City, UT., Department of Medicine, University of Iowa, Iowa City, IA., Division of Oncology, Department of Medicine, University of Iowa, Iowa City, IA., Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Division of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA., Department of Surgery and Cancer, Imperial College London, London, UK., Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI., Division of Medical Oncology, Seidman Cancer Center at Case Comprehensive Cancer Center, Cleveland, OH; Division of Medical Oncology, Duke University, Durham, NC., Departments of Medical Oncology and Urology, Montefiore Medical Center, Bronx, NY., Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Department of Clinical Therapeutics, Alexandra General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece., 2nd Propaedeutic Dept of Internal Medicine, ATTIKON University Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece., Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Zagreb., Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Zagreb; School of Dental Medicine, Zagreb, Croatia., Medical Oncology Department, Hospital del Mar Research Institute, Barcelona, Spain., Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA., Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Oncology University of Molise and Medical Oncology ASL, Salerno, Italy., Division of Hematology/Oncology, Department of Medicine, Penn State Cancer Institute, Hershey, PA., Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; Division of Oncology, Hospital Moinhos de Vento, Porto Alegre, Brazil., Hospital Universitario Marques de Valdecilla. IDIVAL. Santander, Spain., Deming Department of Medicine, Section of Hematology/Oncology, Tulane University, New Orleans, LA., Genitourinary Oncology Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA., Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA., Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA. Electronic address: ., Division of Oncology, Department of Medicine, Stanford University, Palo Alto, CA. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/35778337
Read an Expert Commentary by Bishoy Faltas, MD