Immune checkpoint inhibitors in advanced upper and lower tract urothelial carcinoma: a comparison of outcomes

Stepan M Esagian; Ali Raza Khaki; Leonidas N Diamantopoulos; Lucia Carril-Ajuria; Daniel Castellano; Ivan De Kouchkovsky; 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; Ariel Nelson; Christopher J Hoimes; Evan Shreck; Benjamin A Gartrell; Alex Sankin; Abhishek Tripathi; Roubini Zakopoulou; Aristotelis Bamias; Alejo Rodriguez-Vida; Alexandra Drakaki; Sandy Liu; Vivek Kumar; Mark P Lythgoe; David J Pinato; Jure Murgic; Ana Fröbe; Monika Joshi; Pedro Isaacsson Velho; Noah Hahn; Lucia Alonso Buznego; Ignacio Duran; Marcus Moses; Pedro Barata; Matthew D Galsky; Guru Sonpavde; Evan Y Yu; Pavlos Msaouel; Vadim S Koshkin; Petros Grivas

doi:10.1111/bju.15324

Immune checkpoint inhibitors in advanced upper and lower tract urothelial carcinoma: a comparison of outcomes

BJU Int. 2021 Aug;128(2):196-205. doi: 10.1111/bju.15324. Epub 2021 Feb 8.

Authors

Stepan M Esagian¹, Ali Raza Khaki^{2

3}, Leonidas N Diamantopoulos⁴, Lucia Carril-Ajuria⁵, Daniel Castellano⁵, Ivan De Kouchkovsky⁶, Joseph J Park⁷, Ajjai Alva⁷, Mehmet A Bilen⁸, Tyler F Stewart⁹, Rana R McKay⁹, Victor S Santos¹⁰, Neeraj Agarwal¹⁰, Jayanshu Jain¹¹, Yousef Zakharia¹², Rafael Morales-Barrera¹³, Michael E Devitt¹⁴, Ariel Nelson^{15

16}, Christopher J Hoimes^{15

17}, Evan Shreck¹⁸, Benjamin A Gartrell¹⁸, Alex Sankin¹⁸, Abhishek Tripathi¹⁹, Roubini Zakopoulou²⁰, Aristotelis Bamias²¹, Alejo Rodriguez-Vida²², Alexandra Drakaki²³, Sandy Liu²³, Vivek Kumar²⁴, Mark P Lythgoe²⁵, David J Pinato²⁵, Jure Murgic²⁶, Ana Fröbe^{26

27}, Monika Joshi²⁸, Pedro Isaacsson Velho²⁹, Noah Hahn²⁹, Lucia Alonso Buznego³⁰, Ignacio Duran³⁰, Marcus Moses³¹, Pedro Barata³¹, Matthew D Galsky³², Guru Sonpavde³³, Evan Y Yu^{2

3}, Pavlos Msaouel^{34

35}, Vadim S Koshkin⁶, Petros Grivas^{2

3}

Affiliations

¹ Faculty of Medicine, School of Health Sciences, Democritus University of Thrace, Alexandroupolis, Greece.
² Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
³ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁴ Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
⁶ Division of Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
⁷ Division of Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI, USA.
⁸ Winship Cancer Institute of Emory University, Atlanta, GA, USA.
⁹ Division of Hematology/Oncology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
¹⁰ Division of Oncology, Department of Medicine, University of Utah, Salt Lake City, UT, USA.
¹¹ Department of Medicine, University of Iowa, Iowa City, IA, USA.
¹² Division of Oncology, Department of Medicine, University of Iowa, Iowa City, IA, USA.
¹³ Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
¹⁴ Division of Hematology/Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA.
¹⁵ Division of Medical Oncology, Seidman Cancer Center at Case Comprehensive Cancer Center, Cleveland, OH, USA.
¹⁶ Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
¹⁷ Division of Medical Oncology, Duke University, Durham, NC, USA.
¹⁸ Department of Medical Oncology and Urology, Montefiore Medical Center, Bronx, NY, USA.
¹⁹ Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
²⁰ Department of Clinical Therapeutics, School of Medicine, Alexandra General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
²¹ 2nd Propaedeutic Dept of Internal Medicine, School of Medicine, ATTIKON University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
²² Medical Oncology Department, Hospital del Mar Research Institute, Barcelona, Spain.
²³ Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
²⁴ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²⁵ Department of Surgery and Cancer, Imperial College London, London, UK.
²⁶ Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia.
²⁷ School of Dental Medicine, Zagreb, Croatia.
²⁸ Division of Hematology/Oncology, Department of Medicine, Penn State Cancer Institute, Hershey, PA, USA.
²⁹ Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
³⁰ Hospital Universitario Marques de Valdecilla, IDIVAL, Santander, Spain.
³¹ Deming Department of Medicine, Section of Hematology/Oncology, Tulane University, New Orleans, LA, USA.
³² Division of Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³³ Genitourinary Oncology Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
³⁴ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³⁵ Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

PMID: 33556233
DOI: 10.1111/bju.15324

Abstract

Objectives: To compare clinical outcomes between patients with locally advanced (unresectable) or metastatic urothelial carcinoma (aUC) in the upper and lower urinary tract receiving immune checkpoint inhibitors (ICIs).

Patients and methods: We performed a retrospective cohort study collecting clinicopathological, treatment, and outcome data for patients with aUC receiving ICIs from 2013 to 2020 across 24 institutions. We compared the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between patients with upper and lower tract UC (UTUC, LTUC). Uni- and multivariable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Subgroup analyses were performed stratified based on histology (pure, mixed) and line of treatment (first line, subsequent line).

Results: Out of a total of 746 eligible patients, 707, 717, and 738 were included in the ORR, OS, and PFS analyses, respectively. Our results did not contradict the hypothesis that patients with UTUC and LTUC had similar ORRs (24% vs 28%; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.43-1.24), OS (median 9.8 vs 9.6 months; adjusted hazard ratio [aHR] 0.93, 95% CI 0.73-1.19), and PFS (median 4.3 vs 4.1 months; aHR 1.01, 95% CI 0.81-1.27). Patients with mixed-histology UTUC had a significantly lower ORR and shorter PFS vs mixed-histology LTUC (aOR 0.20, 95% CI 0.05-0.91 and aHR 1.66, 95% CI 1.06-2.59), respectively).

Conclusion: Overall, patients with UTUC and LTUC receiving ICIs have comparable treatment response and outcomes. Subgroup analyses based on histology showed that those with mixed-histology UTUC had a lower ORR and shorter PFS compared to mixed-histology LTUC. Further studies and evaluation of molecular biomarkers can help refine patient selection for immunotherapy.

Keywords: #uroonc; #utuc; bladder cancer; checkpoint inhibitor; immunotherapy; upper tract urothelial cancer; variant histology.

Publication types

Comparative Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Carcinoma, Transitional Cell / drug therapy*
Carcinoma, Transitional Cell / pathology
Cohort Studies
Female
Humans
Immune Checkpoint Inhibitors / therapeutic use*
Male
Middle Aged
Neoplasm Staging
Retrospective Studies
Treatment Outcome
Urologic Neoplasms / drug therapy*
Urologic Neoplasms / pathology

Substances

Immune Checkpoint Inhibitors

Grants and funding

T32 CA009515/CA/NCI NIH HHS/United States