To compare clinical outcomes with anti-PD(L)1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation (RT) prior to developing metastatic disease.
We performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first [1st ] & second or greater [2nd+ ]). Logistic regression was used to compare ORR; Kaplan-Meier analysis and Cox regression for PFS and OS. Multivariable models were adjusted for known prognostic factors.
We included 562 patients (1st line: 342 and 2nd+ : 220). There was no difference in outcomes based on prior locoregional treatment among those treated with 1st line ICI. In the 2nd+ line, prior RS was associated with higher ORR (adjusted odds ratio [aOR] 2.61 [95% CI 1.19-5.74]), longer OS (adjusted hazard ratio [aHR] 0.61 [95% CI 0.42-0.88]) and PFS (aHR 0.63 [95% CI 0.45-0.89]) vs no prior RS. This association remained significant when the type of prior locoregional treatment (RS and RT) was modeled separately.
Prior RS prior to developing advanced disease was associated with better outcomes in patients with aUC treated with ICI in the 2nd+ , but not in the 1st line setting. While further validation is needed, our findings can have implications on prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include retrospective nature, lack of randomization, possible selection and confounding biases.
BJU international. 2021 Oct 01 [Epub ahead of print]
Dimitrios Makrakis, Rafee Talukder, Leonidas N Diamantopoulos, 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, Victor S Santos, Neeraj Agarwal, Jayanshu Jain, Yousef Zakharia, Rafael Morales-Barrera, Michael E Devitt, Michael Grant, Mark P Lythgoe, David J Pinato, Ariel Nelson, Christopher J Hoimes, Evan Shreck, Benjamin A Gartrell, Alex Sankin, Abhishek Tripathi, Roubini Zakopoulou, Aristotelis Bamias, Jure Murgic, Ana Fröbe, Alejo Rodriguez-Vida, Alexandra Drakaki, Sandy Liu, Vivek Kumar, Giuseppe Di Lorenzo, Monika Joshi, Pedro Isaacsson-Velho, Lucia Alonso Buznego, Ignacio Duran, Marcus Moses, Pedro Barata, Guru Sonpavde, Evan Y Yu, Jonathan L Wright, Petros Grivas, Ali Raza Khaki
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA., Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., 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, USA., Division of Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI, USA., Winship Cancer Institute of Emory University, Atlanta, GA, USA., Division of Hematology/Oncology, Department of Medicine, University of California San Diego, La Jolla, CA, USA., Division of Oncology, Department of Medicine, University of Utah, Salt Lake City, UT, USA., Department of Medicine, University of Iowa, Iowa City, IA, USA., Division of Oncology, Department of Medicine, University of Iowa, Iowa City, IA, USA., 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, USA., Department of Surgery and Cancer, Imperial College London, London, UK., Division of Medical Oncology, Seidman Cancer Center at Case Comprehensive Cancer Center, Cleveland, OH, USA., Departments of Medical Oncology and Urology, Montefiore Medical Center, Bronx, NY, USA., Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Department of Clinical Therapeutics, Alexandra General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece., 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., Medical Oncology Department, Hospital del Mar Research Institute, Barcelona, Spain., Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Oncology University of Molise and ASL, Salerno, Italy., Division of Hematology/Oncology, Department of Medicine, Penn State Cancer Institute, Hershey, PA, USA., Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA., Hospital Universitario Marques de Valdecilla. IDIVAL. Santander, Spain., Deming Department of Medicine, Section of Hematology/Oncology, Tulane University, New Orleans, LA, USA., Genitourinary Oncology Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Department of Urology, University of Washington, Seattle, WA, USA.