Keiichiro Mori1, Fahad Quhal2, Takafumi Yanagisawa3, Satoshi Katayama4, Benjamin Pradere5, Ekaterina Laukhtina6, Pawel Rajwa7, Hadi Mostafaei8, Reza Sari Motlagh9, Takahiro Kimura10, Shin Egawa10, Karim Bensalah11, Pierre I Karakiewicz12, Manuela Schmidinger5, Shahrokh F Shariat13. 1. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: morikeiichiro29@gmail.com. 2. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia. 3. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. 4. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. 5. Department of Urology, Medical University of Vienna, Vienna, Austria. 6. Department of Urology, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. 7. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Medical University of Silesia, Zabrze, Poland. 8. Department of Urology, Medical University of Vienna, Vienna, Austria; Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 9. Department of Urology, Medical University of Vienna, Vienna, Austria; Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 10. Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. 11. Department of Urology, University of Rennes, Rennes, France. 12. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada. 13. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Medical University of Silesia, Zabrze, Poland; Research Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Urology, Weill Cornell Medical College, New York, New York, USA; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.
Abstract
BACKGROUND: Recently, immune checkpoint inhibitor (ICI)-combination therapies have radically altered the treatment landscape in metastatic renal cell carcinoma (mRCC). No phase 3 trials have assessed the impact of cytoreductive nephrectomy (CN) for efficacy in mRCC patients treated with ICI-combination therapy. We aimed to assess the role of ICI-combination therapy based on CN status. METHODS: Multiple databases were searched for articles published until June 2021. Studies comparing overall and/or progression-free survival (OS/PFS) in mRCC patients treated with ICI combination-therapy were deemed eligible. RESULTS: Six studies met the eligibility criteria. ICI-combination therapy was associated with significantly better OS/PFS than sunitinib in patients who had undergone CN (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.59-0.77/HR, 0.57; 95% CI, 0.44-0.74, respectively; both P < 0.001), and in those who had not (HR, 0.69; 95% CI, 0.57-0.85/HR, 0.63; 95% CI, 0.52-0.77, respectively; both P < 0.001). Although the OS and PFS benefits of ICI-combination therapy were larger in those undergoing CN, the HR for OS and PFS indicated that ICI-combination therapy's treatment effect did not differ substantially with or without CN. In network meta-analyses, nivolumab plus cabozantinib was the most effective regimen in those undergoing CN, and pembrolizumab plus lenvatinib for those not undergoing CN. CONCLUSION: The effect of ICI combination therapy did not differ between mRCC patients undergoing and not undergoing CN. As each ICI combination regimen varied widely in its effect in patients undergoing and not undergoing CN, CN may contribute to better treatment decision-making for ICI-combination therapy recipients.
BACKGROUND: Recently, immune checkpoint inhibitor (ICI)-combination therapies have radically altered the treatment landscape in metastatic renal cell carcinoma (mRCC). No phase 3 trials have assessed the impact of cytoreductive nephrectomy (CN) for efficacy in mRCC patients treated with ICI-combination therapy. We aimed to assess the role of ICI-combination therapy based on CN status. METHODS: Multiple databases were searched for articles published until June 2021. Studies comparing overall and/or progression-free survival (OS/PFS) in mRCC patients treated with ICI combination-therapy were deemed eligible. RESULTS: Six studies met the eligibility criteria. ICI-combination therapy was associated with significantly better OS/PFS than sunitinib in patients who had undergone CN (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.59-0.77/HR, 0.57; 95% CI, 0.44-0.74, respectively; both P < 0.001), and in those who had not (HR, 0.69; 95% CI, 0.57-0.85/HR, 0.63; 95% CI, 0.52-0.77, respectively; both P < 0.001). Although the OS and PFS benefits of ICI-combination therapy were larger in those undergoing CN, the HR for OS and PFS indicated that ICI-combination therapy's treatment effect did not differ substantially with or without CN. In network meta-analyses, nivolumab plus cabozantinib was the most effective regimen in those undergoing CN, and pembrolizumab plus lenvatinib for those not undergoing CN. CONCLUSION: The effect of ICI combination therapy did not differ between mRCC patients undergoing and not undergoing CN. As each ICI combination regimen varied widely in its effect in patients undergoing and not undergoing CN, CN may contribute to better treatment decision-making for ICI-combination therapy recipients.