The impact of primary region resection on the therapeutic outcome of combination regimens for metastatic renal cell carcinoma

Teishima,Jun; Hara,Takuto; Tobe,Taisuke; Hirata,Junichiro; Ueki,Hideto; Wakita,Naoto; Shiraishi,Yusuke; Okamura,Yasuyoshi; Bando,Yukari; Terakawa,Tomoaki; Furukawa,Junya; Harada,Ken-Ιchi; Nakano,Yuzo; Fujisawa,Masato

doi:10.3892/ol.2023.14057

The impact of primary region resection on the therapeutic outcome of combination regimens for metastatic renal cell carcinoma

Authors:
- Jun Teishima
- Takuto Hara
- Taisuke Tobe
- Junichiro Hirata
- Hideto Ueki
- Naoto Wakita
- Yusuke Shiraishi
- Yasuyoshi Okamura
- Yukari Bando
- Tomoaki Terakawa
- Junya Furukawa
- Ken-Ιchi Harada
- Yuzo Nakano
- Masato Fujisawa
View Affiliations

Affiliations: Department of Surgery, Division of Urology, Kobe University, Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan, Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807‑8555, Japan
Published online on: September 20, 2023 https://doi.org/10.3892/ol.2023.14057
Article Number: 470

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to clarify the relationship between the therapeutic outcome of combination regimens, including immune checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs), and cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). The present study retrospectively assessed the association between treatment efficacy and prognosis with or without CN, and the timing of CN in 151 patients treated with combination regimens for mRCC who were categorized as intermediate/poor risk. The first‑line regimens included the ICI‑ICI and ICI‑TKI regimens in 98 and 53 cases, respectively. In patients with recurrence after radical surgery (n=66), the 50% PFS times of the ICI‑ICI and the ICI‑TKI groups were 33.6 months and not reached (NR) (P=0.4032), respectively, and the 50% OS times were 53.7 months and NR (P=0.6886), respectively. Among the 38 patients with metastasis from the initial diagnosis who underwent upfront CN, the 50% PFS times of the ICI‑ICI and the ICI‑TKI groups were 10.5 and 8.2 months (P=0.5806), respectively, and the 50% OS times were NR and 15.8 months (P=0.0587), respectively. Among the 51 patients who did not receive upfront CN, the 50% PFS time of the ICI‑TKI group was significantly higher than that in the ICI‑ICI group (4.1 months and NR, respectively; P=0.0210), and the 50% OS times were 29.8 months and NR (P=0.7343), respectively. In conclusion, according to the analysis of real‑world data, good therapeutic efficacy can be achieved with any regimen in patients with recurrence after radical surgery. In addition, improved results could be achieved through treatment with ICI‑TKI in patients without upfront CN.

View Figures

View References

1	Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer statistics, 2022. CA Cancer J Clin. 72:7–33. 2022. View Article : Google Scholar : PubMed/NCBI
2	Rini BI, Battle D, Figlin RA, George DJ, Hammers H, Hutson T, Jonasch E, Joseph RW, McDermott DF, Motzer RJ, et al: The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC). J Immunother Cancer. 7:3542019. View Article : Google Scholar : PubMed/NCBI
3	Pal SK, Ghate SR, Li N, Swallow E, Peeples M, Zichlin ML, Perez JR, Agarwal N and Vogelzang NJ: Real-world survival outcomes and prognostic factors among patients receiving first targeted therapy for advanced renal cell carcinoma: A SEER-medicare database analysis. Clin Genitourin Cancer. 15:e573–e582. 2017. View Article : Google Scholar : PubMed/NCBI
4	Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S, et al: Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 378:1277–1290. 2018. View Article : Google Scholar : PubMed/NCBI
5	Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, Venugopal B, Kollmannsberger C, Negrier S, Uemura M, et al: Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 380:1103–1115. 2019. View Article : Google Scholar : PubMed/NCBI
6	Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulières D, Melichar B, et al: Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 380:1116–1127. 2019. View Article : Google Scholar : PubMed/NCBI
7	Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, Oyervides Juárez VM, Hsieh JJ, Basso U, Shah AY, et al: Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 384:829–841. 2021. View Article : Google Scholar : PubMed/NCBI
8	Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Kopyltsov E, Méndez-Vidal MJ, et al: Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med. 384:1289–1300. 2021. View Article : Google Scholar : PubMed/NCBI
9	Choueiri TK, Xie W, Kollmannsberger C, North S, Knox JJ, Lampard JG, McDermott DF, Rini BI and Heng DY: The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. J Urol. 185:60–66. 2011. View Article : Google Scholar : PubMed/NCBI
10	Bhindi B, Abel EJ, Albiges L, Bensalah K, Boorjian SA, Daneshmand S, Karam JA, Mason RJ, Powles T and Bex A: Systematic review of the role of cytoreductive nephrectomy in the targeted therapy era and beyond: An individualized approach to metastatic renal cell carcinoma. Eur Urol. 75:111–128. 2019. View Article : Google Scholar : PubMed/NCBI
11	Singla N, Hutchinson RC, Ghandour RA, Freifeld Y, Fang D, Sagalowsky AI, Lotan Y, Bagrodia A, Margulis V, Hammers HJ and Woldu SL: Improved survival after cytoreductive nephrectomy for metastatic renal cell carcinoma in the contemporary immunotherapy era: An analysis of the national cancer database. Urol Oncol. 38:604.e9–604.e17. 2020. View Article : Google Scholar : PubMed/NCBI
12	Hall ME, Bhindi B, Luckenbaugh AN, Laviana AA, Moses KA, Satkunasivam R, Rini B, Klaassen Z and Wallis CJD: Association between cytoreductive nephrectomy and survival among patients with metastatic renal cell carcinoma receiving modern therapies: A systematic review and meta-analysis examining effect modification according to systemic therapy approach. Cancer Causes Control. 32:675–680. 2021. View Article : Google Scholar : PubMed/NCBI
13	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, et al: Comparison of immediate vs deferred cytoreductive nephrectomy in patients with synchronous metastatic renal cell carcinoma receiving sunitinib: The SURTIME randomized clinical trial. JAMA Oncol. 5:164–170. 2019. View Article : Google Scholar : PubMed/NCBI
14	Méjean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, Geoffrois L, Thiery-Vuillemin A, Cormier L, Lang H, et al: Sunitinib alone or after nephrectomy in metastatic renal-cell carcinoma. N Engl J Med. 379:417–427. 2018. View Article : Google Scholar : PubMed/NCBI
15	Heng DYC, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, Eigl BJ, Ruether JD, Cheng T, North S, et al: Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: Results from a large, multicenter study. J Clin Oncol. 27:5794–5799. 2009. View Article : Google Scholar : PubMed/NCBI
16	Yates JW, Chalmer B and McKegney FP: Evaluation of patients with advanced cancer using the Karnofsky performance status. Cancer. 45:2220–2224. 1980. View Article : Google Scholar : PubMed/NCBI
17	Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar : PubMed/NCBI
18	Stühler V, Herrmann L, Rausch S, Stenzl A and Bedke J: Real world data on IO-based therapy for metastatic renal cell carcinoma. J Cancer Res Clin Oncol. 149:3249–3258. 2023. View Article : Google Scholar : PubMed/NCBI
19	Iinuma K, Yamada T, Kameyama K, Taniguchi T, Kawada K, Ishida T, Nagai S, Enomoto T, Ueda S, Takagi K, et al: The efficacy and safety of immune checkpoint inhibitor and tyrosine kinase inhibitor combination therapy for advanced or metastatic renal cell carcinoma: A multicenter retrospective real-world cohort study. Cancers (Basel). 15:9472023. View Article : Google Scholar : PubMed/NCBI
20	Bosma NA, Warkentin MT, Gan CL, Karim S, Heng DYC, Brenner DR and Lee-Ying RM: Efficacy and safety of first-line systemic therapy for metastatic renal cell carcinoma: A systematic review and network meta-analysis. Eur Urol Open Sci. 37:14–26. 2022. View Article : Google Scholar : PubMed/NCBI
21	Ernst MS, Navani V, Wells JC, Donskov F, Basappa N, Labaki C, Pal SK, Meza L, Wood LA, Ernst DS, et al: Outcomes for international metastatic renal cell carcinoma database consortium prognostic groups in contemporary first-line combination therapies for metastatic renal cell carcinoma. Eur Urol. 84:109–116. 2023. View Article : Google Scholar : PubMed/NCBI
22	Hara T, Furukawa J, Shiraishi Y, Okamura Y, Bando Y, Terakawa T, Harada K, Nakano Y and Fujisawa M: Impact of cytoreductive nephrectomy prior to combination therapy of ipilimumab plus nivolumab in metastatic renal cell carcinoma. Int J Urol. May 2–2023.(Epub ahead of print). View Article : Google Scholar
23	Escudier B, Motzer RJ, Tannir NM, Porta C, Tomita Y, Maurer MA, McHenry MB and Rini BI: Efficacy of nivolumab plus ipilimumab according to number of IMDC risk factors in CheckMate 214. Eur Urol. 77:449–453. 2020. View Article : Google Scholar : PubMed/NCBI
24	Dudani S, Graham J, Wells JC, Bakouny Z, Pal SK, Dizman N, Donskov F, Porta C, de Velasco G, Hansen A, et al: First-line immuno-oncology combination therapies in metastatic renal-cell carcinoma: Results from the international metastatic renal-cell carcinoma database consortium. Eur Urol. 76:861–867. 2019. View Article : Google Scholar : PubMed/NCBI