Analysis of outcomes of the first line systemic therapy in patients with solitary, single and multiple metastases of renal cell carcinoma

Abstract

BACKGROUND: Currently there are practically no works in the literature to assess the outcomes of systemic therapy in patients with solitary, single and multiple metastases of renal cell carcinoma.

AIM: The aim of the study was to analyze the outcomes of systemic drug therapy of the first line in patients with solitary, single and multiple metastases of renal cell carcinoma.

MATERIALS AND METHODS: The data of 981 patients with metastatic renal cell carcinoma who underwent systemic therapy of the first line at the City Oncological Hospital No. 62 in Moscow and the City Oncological Dispensary in St. Petersburg from 2006 to 2022 were retrospectively analyzed. All patients underwent clinical, laboratory and pathomorphological examination. 90 (9.2%) patients had solitary metastases, 252 (25.7%) single metastases and 639 (65.1%) multiple metastases. An analysis was made of the outcomes of 1st line therapy, which were conditionally divided into favorable, including all cases of complete response, partial response and stabilization, and unfavorable — progression during treatment, death or deregistration. Subsequently patients who had previously received chemotherapy or cytokine treatment were excluded from the analysis.

RESULTS: Complete response (3.3%) and deregistration (5.56%) were more often observed in patients with solitary metastases, stabilization more often occurred in patients with single metastases (51.1%), partial response (9.4%) and death (6.2%) — in patients with multiple metastases. In patients with multiple metastases treated with immune checkpoint inhibitors a partial response was observed in almost half of the cases. Stabilization and progression were observed in almost the same percentage of cases (about a quarter of cases), and only two patients had a fatal outcome, which is slightly lower than in patients receiving tyrosine kinase inhibitors. Frequent outcomes when using tyrosine kinase inhibitors were stabilization of the process (40.72% of cases) or progression (38.72%), a complete and partial response was rarely recorded. Significant differences in the occurrence of favorable and unfavorable outcomes were revealed in patients with multiple metastases, depending on the number of affected organs and the prescribed drug. When comparing the results of systemic therapy of the first line, a higher efficiency of tyrosine kinase inhibitors was observed in solitary metastases of tumors with a high and moderate degree of differentiation. Systemic therapy of G3 tumors with solitary metastases had low efficacy in the appointment of tyrosine kinase inhibitors in 27.27% of patients. Higher efficiency was noted in single and multiple metastases. The effectiveness of immune checkpoint inhibitors was revealed in 70.6% of patients with single and multiple metastases.

CONCLUSIONS: When choosing systemic therapy for metastatic renal cell carcinoma in clinical practice, it is necessary to take into account such prognostic factors as histological variants, the degree of differentiation of the tumor and the number of affected organs.

Keywords

metastatic renal cell carcinoma / solitary metastases / single metastases / multiple metastases / tyrosine kinase inhibitors / immune checkpoint inhibitors

References

[1] Capitanio U, Bensalah K, Bex A, et al. Epidemiology of Renal Cell Carcinoma. Eur Urol. 2019;75(1):74–84. DOI: 10.1016/j.eururo.2018.08.036

[2] Capitanio U., Bensalah K., Bex A., et al. Epidemiology of Renal Cell Carcinoma // Eur Urol. 2019. Vol. 75, No. 1. P. 74–84. DOI: 10.1016/j.eururo.2018.08.036

[3] Padala SA, Barsouk A, Thandra KC, et al. Epidemiology of Renal Cell Carcinoma. World J Oncol. 2020;11(3):79–87. DOI: 10.14740/wjon1279

[4] Padala S.A., Barsouk A., Thandra K.C., et al. Epidemiology of Renal Cell Carcinoma // World J Oncol. 2020. Vol. 11, No. 3. P. 79–87. DOI: 10.14740/wjon1279

[5] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. DOI: 10.3322/caac.2149

[6] Bray F., Ferlay J., Soerjomataram I., et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries // CA Cancer J Clin. 2018. Vol. 68, No. 6. P. 394–424. DOI: 10.3322/caac.2149

[7] Massari F, Rizzo A, Mollica V, et al. Immune-based combinations for the treatment of metastatic renal cell carcinoma: a meta-analysis of randomised clinical trials. Eur J Cancer. 2021;154:120–127. DOI: 10.1016/j.ejca.2021.06.01

[8] Massari F., Rizzo A., Mollica V., et al. Immune-based combinations for the treatment of metastatic renal cell carcinoma: a meta-analysis of randomised clinical trials // Eur J Cancer. 2021. Vol. 154. P. 120–127. DOI: 10.1016/j.ejca.2021.06.01

[9] Tsimafeyeu I, Shatkovskaya O, Krasny S, et al. Overall survival in patients with metastatic renal cell carcinoma in Russia, Kazakhstan, and Belarus: a report from the RENSUR3 registry. Cancer Rep (Hoboken). 2021;4(3): e1331. DOI: 10.1002/cnr2.1331

[10] Tsimafeyeu I., Shatkovskaya O., Krasny S., et al. Overall survival in patients with metastatic renal cell carcinoma in Russia, Kazakhstan, and Belarus: a report from the RENSUR3 registry // Cancer Rep (Hoboken). 2021. Vol. 4, No. 3. P. e1331. DOI: 10.1002/cnr2.1331

[11] Abdou E, Pedapenki RM, Abouagour M, et al. Patient selection and risk factors in the changing treatment landscape of metastatic renal cell carcinoma. Expert Rev Anticancer Ther. 2020;20(10): 831–840. DOI: 10.1080/14737140.2020.1810572

[12] Abdou E., Pedapenki R.M., Abouagour M., et al. Patient selection and risk factors in the changing treatment landscape of metastatic renal cell carcinoma // Expert Rev Anticancer Ther. 2020. Vol. 20, No. 10. P. 831–840. DOI: 10.1080/14737140.2020.1810572

[13] Tran J, Ornstein MC. Clinical Review on the Management of Metastatic Renal Cell Carcinoma. JCO Oncol Pract. 2022;18(3):187–196. DOI: 10.1200/OP.21.00419

[14] Tran J., Ornstein M.C. Clinical Review on the Management of Metastatic Renal Cell Carcinoma // JCO Oncol Pract. 2022. Vol. 18, No. 3. P. 187–196. DOI: 10.1200/OP.21.00419

[15] Pecoraro A, Palumbo C, Knipper S, et al. Histologic Subtype, Tumor Grade, Tumor Size, and Race Can Accurately Predict the Probability of Synchronous Metastases in T2 Renal Cell Carcinoma. Clin Genitourin Cancer. 2020;18(5): e610–e618. DOI: 10.1016/j.clgc.2020.02.001

[16] Pecoraro A., Palumbo C., Knipper S., et al. Histologic Subtype, Tumor Grade, Tumor Size, and Race Can Accurately Predict the Probability of Synchronous Metastases in T2 Renal Cell Carcinoma // Clin Genitourin Cancer. 2020. Vol. 18, No. 5. P. e610–e618. DOI: 10.1016/j.clgc.2020.02.001

[17] Shi H, Cao C, Wen L, et al C. Prognostic value of the ratio of maximum to minimum diameter of primary tumor in metastatic clear cell renal cell carcinoma. BMC Urol. 2022;22(1):95. DOI: 10.1186/s12894-022-01047-y

[18] Shi H., Cao C., Wen L., et al. Prognostic value of the ratio of maximum to minimum diameter of primary tumor in metastatic clear cell renal cell carcinoma // BMC Urol. 2022. Vol. 22, No. 1. P. 95. DOI: 10.1186/s12894-022-01047-y

[19] Buonerba C, Dolce P, Iaccarino S, et al. Outcomes Associated with First-Line anti-PD-1/ PD-L1 agents vs. Sunitinib in Patients with Sarcomatoid Renal Cell Carcinoma: A Systematic Review and Meta-Analysis. Cancers (Basel). 2020;12(2):408. DOI: 10.3390/cancers12020408

[20] Buonerba C., Dolce P., Iaccarino S., et al. Outcomes Associated with First-Line anti-PD-1/PD-L1 agents vs. Sunitinib in Patients with Sarcomatoid Renal Cell Carcinoma: A Systematic Review and Meta-Analysis // Cancers (Basel). 2020. Vol. 12, No. 2. P. 408. DOI: 10.3390/cancers12020408

[21] Graham J, Wells JC, Dudani S, et al. Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy. Eur J Cancer. 2022;171: 124–132. DOI: 10.1016/j.ejca.2022.05.00

[22] Graham J., Wells J.C., Dudani S., et al. Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy // Eur J Cancer. 2022. Vol. 171. P. 124–132. DOI: 10.1016/j.ejca.2022.05.00

[23] Zhou L, Liu Y, Mo J, et al. Clinicopathological characteristics and prognosis of metastatic collecting duct carcinoma. Urol Oncol. 2022;40(8):385.e1–385.e8. DOI: 10.1016/j.urolonc.2022.05.01

[24] Zhou L., Liu Y., Mo J., et al. Clinicopathological characteristics and prognosis of metastatic collecting duct carcinoma // Urol Oncol. 2022. Vol. 40, No. 8. P. 385.e1–385.e8. DOI: 10.1016/j.urolonc.2022.05.01

[25] Gong J, Maia MC, Dizman N, et al. Metastasis in renal cell carcinoma: Biology and implications for therapy. Asian J Urol. 2016;3(4):286–292. DOI: 10.1016/j.ajur.2016.08.00

[26] Gong J., Maia M.C., Dizman N., et al. Metastasis in renal cell carcinoma: Biology and implications for therapy // Asian J Urol. 2016. Vol. 3, No. 4. P. 286–292. DOI: 10.1016/j.ajur.2016.08.00

[27] Flippot R, Dalban C, Laguerre B, et al. Safety and Efficacy of Nivolumab in Brain Metastases From Renal Cell Carcinoma: Results of the GETUG-AFU26 NIVOREN Multicenter Phase II Study. J Clin Oncol. 2019;37(23):2008–2016. DOI: 10.1200/JCO.18.02218

[28] Flippot R., Dalban C., Laguerre B., et al. Safety and Efficacy of Nivolumab in Brain Metastases From Renal Cell Carcinoma: Results of the GETUG-AFU26 NIVOREN Multicenter Phase II Study // J Clin Oncol. 2019. Vol. 37, No. 23. P. 2008–2016. DOI: 10.1200/JCO.18.02218

[29] Motzer RJ, Sharma P, McDermott DF, et al. CheckMate 025 phase III trial: outcomes by key baseline factors and prior therapy for nivolumab (NIVO) versus everolimus (EVE) in advanced renal cell carcinoma (RCC). J Clin Oncol. 2016;34(2S):498. DOI: 10.1200/jco.2016.34.2_suppl.498

[30] Motzer R.J., Sharma P., McDermott D.F., et al. CheckMate 025 phase III trial: outcomes by key baseline factors and prior therapy for nivolumab (NIVO) versus everolimus (EVE) in advanced renal cell carcinoma (RCC) // J Clin Oncol. 2016. Vol. 34, No. 2S. P. 498. DOI: 10.1200/jco.2016.34.2_suppl.498

RIGHTS & PERMISSIONS

Eco-Vector