Journals / Akdeniz Tıp Dergisi / 2026 / Cilt: 12 Sayı: 1

The Benefit of Upfront Cytoreductive Surgery on the Effect of Immunotherapy After Tyrosine Kinase Inhibitor Therapies in Clear Cell Renal Cell Carcinomas

Berrak Hücreli Böbrek Hücreli Karsinomlarda Tirozin Kinaz İnhibitörleri Sonrası İmmünoterapide Ön Sitoredüktif Cerrahinin Etkisi

Esin Avşar Küçükkurt(AKDENIZ UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE)0000-0002-7584-2232
Derya Kıvrak Salim(UNIVERSITY OF HEALTH SCIENCES, ANTALYA HEALTH RESEARCH CENTER, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, ONCOLOGY)0000-0003-4107-3460
Pages
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Publication Date
2026-09-21
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Progression-free survival (PFS1, PFS2) and overall survival (OS) were assessed by Kaplan-Meier analysis.

📌 3 Key Takeaways

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Objective & Hypothesis:Aim: This study aimed to evaluate the effect of upfront cytoreductive nephrectomy on survival outcomes in patients with metastatic clear cell renal cell carcinoma (RCC) who received tyrosine kinase inhibitor (TKI) therapy followed by immunotherapy (nivolumab).
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Key Findings & Data:Materials and Methods: This retrospective, single-center study included 38 patients treated between 2010 and 2023.
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Conclusion & Impact:Progression-free survival (PFS1, PFS2) and overall survival (OS) were assessed by Kaplan-Meier analysis.
🔬Design:Araştırma Makalesi
📍Scope:2010 Verileri
⚙️Variables:renal hücreli karsinom · sitoredüktif nefrektomi · immünoterapi

Abstract

Aim: This study aimed to evaluate the effect of upfront cytoreductive nephrectomy on survival outcomes in patients with metastatic clear cell renal cell carcinoma (RCC) who received tyrosine kinase inhibitor (TKI) therapy followed by immunotherapy (nivolumab). Materials and Methods: This retrospective, single-center study included 38 patients treated between 2010 and 2023. All patients received sunitinib as first-line and nivolumab as second-line therapy. The patients were divided into two groups based on whether they underwent primary tumor resection (PTR group) or not (non-PTR group). Progression-free survival (PFS1, PFS2) and overall survival (OS) were assessed by Kaplan-Meier analysis. Results: The objective response rate was 79% in the PTR group and 22% in the non-PTR group (p=0.003). The median PFS1 was 16.7 months in the PTR group and 7.1 months in the non-PTR group (p=0.006). Median PFS2 was not reached in the PTR group, whereas it was 54.1 months in the non-PTR group (p=0.290). Although the OS was longer in the PTR group, the difference was not statistically significant (p=0.108). Conclusion: Upfront cytoreductive nephrectomy appears to improve response rates and progression-free survival in patients with metastatic RCC receiving sequential TKI and nivolumab therapy. However, this effect on overall survival was not statistically significant. These findings warrant validation through prospective, large-scale studies.

Özet

Amaç: Bu çalışmanın amacı, metastatik berrak hücreli renal karsinom (mRHK) tanısı almış ve birinci basamakta tirozin kinaz inhibitörü (TKİ), ikinci basamakta immünoterapi (nivolumab) ile tedavi edilen hastalarda ilk basamakta yapılan sitoredüktif nefrektominin sağkalım sonuçla- rı üzerindeki etkisini araştırmaktır. Gereç ve Yöntemler: Bu retrospektif, tek merkezli çalışmada 2010–2023 yılları arasında tedavi edilen 38 hasta incelendi. Tüm hastalara birinci basamakta sunitinib, ikinci basamakta nivolumab uygulandı. Hastalar ilk basamakta tümör rezeksiyonu yapılanlar (PTR grubu) ve yapılmayanlar (non-PTR grubu) olarak ikiye ayrıldı. Progresyonsuz sağkalım (PFS1, PFS2) ve genel sağkalım (OS) analizleri Kaplan-Meier yöntemiyle değerlendirildi. Bulgular: PTR grubunda objektif yanıt oranı %79 iken no-PTR grubunda %22 idi (p=0,003). Medyan PFS1 PTR grubunda 16,7 ay, no-PTR grubunda 7,1 ay olarak saptandı (p=0,006). Medyan PFS2 PTR grubunda henüz ulaşılmamışken, non-PTR grubunda 54,1 ay idi (p=0,290). PTR grubunda OS daha uzun olmakla birlikte istatistiksel anlamlılık göstermedi (p=0,108). Sonuç: TKİ sonrası nivolumab alan mHRK hastalarında ilk basamakta sitoredüktif nefrektomi, yanıt oranını artırmakta ve progresyonsuz sağkalımı uzatmaktadır. Ancak genel sağkalım üzerindeki etkisi istatistiksel olarak anlamlı bulunmamıştır. Prospektif ve geniş ölçekli çalışmalarla bu sonuçların doğrulanması gereklidir.

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Cite This Article

Küçükkurt, E. A., Salim, D. K. (2026). The Benefit of Upfront Cytoreductive Surgery on the Effect of Immunotherapy After Tyrosine Kinase Inhibitor Therapies in Clear Cell Renal Cell Carcinomas. Akdeniz Tıp Dergisi, Cilt: 12 Sayı: 1. https://doi.org/10.53394/akd.1864045

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References (23)

  1. Znaor A, Lortet-Tieulent J, Laversanne M, Jemal A, Bray F. International variations and trends in renal cell carcinoma incidence and mortality. Eur Urol 2015; 67(3):519–30.
  2. Thompson RH, Ordonez MA, Iasonos A, Secin FP, Guillonneau B, Russo P, Touijer K. Renal cell carcinoma in young and old patients-Is there a difference? J Urol 2008; 180(4):1262–6.
  3. Ljungberg B, Campbell SC, Choi HY, Jacqmin D, Lee JE, Weikert S, Kiemeney LA. The epidemiology of renal cell carcinoma. Eur Urol 2011; 60(4):615–21.
  4. Warren AY, Harrison D. WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: Standards and controversies. World J Urol 2018; 36(12):1913–26.
  5. Barney DJ, Churchill EJ. Adenocarcinoma of the kidney with metastasis to the lung: Cured by nephrectomy and lobectomy. J Urol 1939; 42:269–76.
  6. Naito S, Kinoshita H, Kondo T, Shinohara N, Kasahara T, Saito K, Takayama T, Masumori N, Takahashi W, Takahashi M, Terachi T, Ozono S, Naito S, Tomita Y. Prognostic factors of patients with metastatic renal cell carcinoma with removed metastases: A multicenter study of 556 patients. Urology 2013; 82(4):846–51.
  7. Kim SH, Park WS, Park B, Pak S, Chung J. A retrospective analysis of the impact of metastasectomy on prognostic survival according to metastatic organs in patients with metastatic renal cell carcinoma. Front Oncol 2019; 9:413.
  8. Dragomir A, Nazha S, Wood LA, Rendon RA, Finelli A, Hansen A, So AI, Kollmannsberger C, Basappa NS, Pouliot F, Soulières D, Heng DYC, Kapoor A, Tanguay S. Outcomes of complete metastasectomy in metastatic renal cell carcinoma patients: The Canadian Kidney Cancer information system experience. Urol Oncol 2020; 38(10):799.e1–799.e10.
  9. Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED. Cytoreductive nephrectomy in patients with metastatic renal cancer: A combined analysis. J Urol 2004; 171(3):1071–6.
  10. Mejean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, Geoffrois L, Thiery-Vuillemin A, Cormier L, Lang H, Guy L, Gravis G, Rolland F, Linassier C, Lechevallier E, Beisland C, Aitchison M, Oudard S, Patard JJ, Theodore C, Chevreau C, Laguerre B, Hubert J, Gross-Goupil M, Bernhard JC, Albiges L, Timsit MO, Lebret T, Escudier B. Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med 2018; 379(5):417–27.
  11. Bex A, Mulders P, Jewett M, Wagstaff J, van Thienen JV, Blank CU, van Velthoven R, Del Pilar Laguna M, Wood L, van Melick HHE, Aarts MJ, Lattouf JB, Powles T, de Jong Md PhD IJ, Rottey S, Tombal B, Marreaud S, Collette S, Collette L, Haanen J. Comparison of immediate vs deferred cytoreductive nephrectomy in patients with synchronous metastatic renal cell carcinoma receiving sunitinib: The SURTIME randomized clinical trial. JAMA Oncol 2019; 5(2):164–70.
  12. Powles T, Plimack ER, Soulieres D, Waddell T, Stus V, Gafanov R, Nosov D, Pouliot F, Melichar B, Vynnychenko I, Azevedo SJ, Borchiellini D, McDermott RS, Bedke J, Tamada S, Yin L, Chen M, Molife LR, Atkins MB, Rini BI. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): Extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol 2020;21(12):1563–73.
  13. Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, Oyervides Juárez VM, Hsieh JJ, Basso U, Shah AY, Suárez C, Hamzaj A, Goh JC, Barrios C, Richardet M, Porta C, Kowalyszyn R, Feregrino JP, Żołnierek J, Pook D, Kessler ER, Tomita Y, Mizuno R, Bedke J, Zhang J, Maurer MA, Şimşek B, Ejzykowicz F, Schwab GM, Apolo AB, Motzer RJ. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2021; 384(9):829–41.
  14. Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 2018; 378(14):1277–90.
  15. Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Kopyltsov E, Méndez-Vidal MJ, Kozlov V, Alyasova A, Hong SH, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med 2021; 384(14):1289–1300.
  16. Bell H, Cotta BH, Salami SS, Kim H, Vaishampayan U. 'PROBE'ing the role of cytoreductive nephrectomy in advanced renal cancer. Kidney Cancer J 2022; 6(1):3–9.
  17. Flanigan RC, Yonover PM. The role of radical nephrectomy in metastatic renal cell carcinoma. Semin Urol Oncol 2001; 19(2):98–102.
  18. Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R. Radical nephrectomy plus interferon-alfa based immunotherapy compared with interferon-alfa alone in metastatic renal-cell carcinoma: A randomised trial. Lancet 2001; 358(9286):966–70.
  19. Bakouny Z, El Zarif T, Dudani S, Connor Wells J, Gan CL, Donskov F, Shapiro J, Davis ID, Parnis F, Ravi P, Steinharter JA, Agarwal N, Alva A, Wood L, Kapoor A, Ruiz Morales JM, Kollmannsberger C, Beuselinck B, Xie W, Heng DYC, Choueiri TK. Upfront cytoreductive nephrectomy for metastatic renal cell carcinoma treated with immune checkpoint inhibitors or targeted therapy: An observational study from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol 2023; 83(2):145–51.
  20. Hutterer GC, Stoeckigt C, Stojakovic T, Jesche J, Eberhard K, Pummer K, Zigeuner R, Pichler M Low preoperative lymphocyte-monocyte ratio (LMR) represents a potentially poor prognostic factor in nonmetastatic clear cell renal cell carcinoma. Urol Oncol 2014; 32(7):1041-8.
  21. Xia WK, Wu X, Yu TH, Wu Y, Yao XJ, Hu H. Prognostic significance of lymphocyte-to-monocyte ratio (LMR) and C-reactive protein (CRP) in nonmetastatic clear cell renal cell carcinoma. Int J Urol Oncol. 2016;ePub.
  22. Naito S, Kinoshita H, Kondo T, Shinohara N, Kasahara T, Saito K, Takayama T, Masumori N, Takahashi W, Takahashi M, Terachi T, Ozono S, Naito S, Tomita Y. Prognostic factors of patients with metastatic renal cell carcinoma with removed metastases: A multicenter study of 556 patients. Urology 2013; 82(4):846–51.
  23. Powles T, Plimack ER, Soulieres D, Waddell T, Stus V, Gafanov R, Nosov D, Pouliot F, Melichar B, Vynnychenko I, Azevedo SJ, Borchiellini D, McDermott RS, Bedke J, Tamada S, Yin L, Chen M, Molife LR, Atkins MB, Rini BI. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): Extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol 2020;21(12):1563–73.