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Metastatic Organotropism Differential Treatment Response in Urothelial Carcinoma: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials Publisher Pubmed



Kardoust Parizi M1, 3, 5, 7, 9, 10, 12, 14, 16, 18 ; Matsukawa A1, 3, 5, 7, 9, 10, 12, 14, 16, 18 ; Bekku K1, 3, 5, 7, 9, 10, 12, 14, 16, 18 ; Klemm J1, 3, 5, 7, 9, 10, 12, 14, 16, 18 ; Alimohammadi A1, 3, 5, 7, 9, 10, 12, 14, 16, 18 ; Laukhtina E1, 3, 5, 7, 9, 10, 12, 14, 16, 18 ; Karakiewicz P1, 3, 5, 7, 9, 10, 12, 14, 16, 18 ; Chiujdea S1, 3, 5, 7, 9, 10, 12, 14, 16, 18 ; Abufaraj M1, 3, 5, 7, 9, 10, 12, 14, 16, 18 ; Krauter J1, 3, 5, 7, 9, 10, 12, 14, 16, 18 ; Shariat SF1, 3, 5, 7, 9, 10, 12, 14, 16, 18
Authors
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Authors Affiliations
  1. 1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  2. 2. Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  4. 4. Department of Urology, Jikei University School of Medicine, Tokyo, Japan
  5. 5. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  6. 6. Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
  7. 7. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  8. 8. Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  9. 9. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  10. 10. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  11. 11. Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
  12. 12. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  13. 13. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada
  14. 14. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  15. 15. Spitalul Clinic Judetean Mures, Universitatea de Medicina si Farmacie, Stiinte si Tehnologie, Targu Mures, Romania
  16. 16. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  17. 17. Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan
  18. 18. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
  19. 19. Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan
  20. 20. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic
  21. 21. Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
  22. 22. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA
  23. 23. Department of Urology, Weill Cornell Medical College, New York, NY, USA

Source: European urology oncology Published:2024


Abstract

CONTEXT: The optimal therapeutic agent with respect to metastatic sites is unclear in advanced urothelial carcinoma (UC). OBJECTIVE: To investigate the metastatic organotropism differential treatment response in patients with advanced or metastatic UC. EVIDENCE ACQUISITION: A systematic search and network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The primary endpoints of interest were the objective response rate, overall survival (OS), and progression-free survival with respect to different metastatic sites. EVIDENCE SYNTHESIS: Twenty-six trials comprising 9082 patients met our eligibility criteria, and a formal NMA was conducted. Durvalumab plus tremelimumab as first-line systemic therapy was significantly associated with better OS than chemotherapy in visceral metastasis (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.67-0.98). Pembrolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with visceral metastasis (HR 0.75, 95% CI 0.60-0.95). Atezolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with liver metastasis (in the population of >5% of tumor-infiltrating immune cells) and lymph node metastasis (HR 0.51, 95% CI 0.28-0.96, and HR 0.59, 95% CI 0.37-0.96, respectively). CONCLUSIONS: Administration of immune-oncology treatments with respect to metastatic sites in patients with advanced or metastatic UC might have a positive impact on survival outcomes in both the first- and the second-line setting. Nevertheless, further investigations focusing on metastatic organotropism differential response with reliable oncological outcomes are needed to identify the optimal management strategy for these patients. PATIENT SUMMARY: Although the supporting evidence for oncological benefits of therapeutic systemic agents with respect to metastatic sites is not yet strong enough to provide a recommendation in advanced or metastatic urothelial carcinoma, clinicians may take into account tumor organotropism only in discussion with the patient fully informed on the optimal treatment decision to be taken. Copyright © 2023. Published by Elsevier B.V.