Prognostic and Predictive Biomarkers for Immunotherapy in Advanced Renal Cell Carcinoma

Overview

Journal Nat Rev Urol

Specialty Urology

Date 2022 Nov 22

PMID 36414800

Authors

Matteo Rosellini

Andrea Marchetti

Veronica Mollica

Alessandro Rizzo

Matteo Santoni

Francesco Massari

Affiliations

Soon will be listed here.

Abstract

The therapeutic algorithm of renal cell carcinoma has been revolutionized by the approval of immunotherapy agents by regulatory agencies. However, objective and durable responses are still not observed in a large number of patients, and prognostic and predictive biomarkers for immunotherapy response are urgently needed. Prognostic models used in clinical practice are based on clinical and laboratory factors (such as hypercalcaemia, neutrophil count or Karnofsky Performance Status), but, with progress in molecular biology and genome sequencing techniques, new renal cell carcinoma molecular features that might improve disease course and outcomes prediction have been highlighted. An implementation of current models is needed to improve the accuracy of prognosis in the immuno-oncology era. Moreover, several potential biomarkers are currently under evaluation, but effective markers to select patients who might benefit from immunotherapy and to guide therapeutic strategies are still far from validation.

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References

Siegel R, Miller K, Fuchs H, Jemal A . Cancer Statistics, 2021. CA Cancer J Clin. 2021; 71(1):7-33. DOI: 10.3322/caac.21654. View

Saad A, Gad M, Al-Husseini M, Ruhban I, Sonbol M, Ho T . Trends in Renal-Cell Carcinoma Incidence and Mortality in the United States in the Last 2 Decades: A SEER-Based Study. Clin Genitourin Cancer. 2018; 17(1):46-57.e5. PMC: 6348014. DOI: 10.1016/j.clgc.2018.10.002. View

Moch H, Cubilla A, Humphrey P, Reuter V, Ulbright T . The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol. 2016; 70(1):93-105. DOI: 10.1016/j.eururo.2016.02.029. View

Hsieh J, Purdue M, Signoretti S, Swanton C, Albiges L, Schmidinger M . Renal cell carcinoma. Nat Rev Dis Primers. 2017; 3:17009. PMC: 5936048. DOI: 10.1038/nrdp.2017.9. View

Marchetti A, Rosellini M, Mollica V, Rizzo A, Tassinari E, Nuvola G . The Molecular Characteristics of Non-Clear Cell Renal Cell Carcinoma: What's the Story Morning Glory?. Int J Mol Sci. 2021; 22(12). PMC: 8226484. DOI: 10.3390/ijms22126237. View

Cimadamore A, Massari F, Santoni M, Mollica V, Di Nunno V, Cheng L . Molecular characterization and diagnostic criteria of renal cell carcinoma with emphasis on liquid biopsies. Expert Rev Mol Diagn. 2019; 20(2):141-150. DOI: 10.1080/14737159.2019.1665510. View

Choueiri T, Motzer R . Systemic Therapy for Metastatic Renal-Cell Carcinoma. N Engl J Med. 2017; 376(4):354-366. DOI: 10.1056/NEJMra1601333. View

Bianchi M, Sun M, Jeldres C, Shariat S, Trinh Q, Briganti A . Distribution of metastatic sites in renal cell carcinoma: a population-based analysis. Ann Oncol. 2011; 23(4):973-80. DOI: 10.1093/annonc/mdr362. View

Rizzo A, Rosellini M, Marchetti A, Mollica V, Massari F . Determinants of treatment for first-line immune-based combinations in metastatic renal cell carcinoma: a critical overview of recent evidence. Immunotherapy. 2021; 13(8):685-692. DOI: 10.2217/imt-2020-0323. View

10.

Motzer R, Tannir N, Mcdermott D, Frontera O, Melichar B, Choueiri T . Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018; 378(14):1277-1290. PMC: 5972549. DOI: 10.1056/NEJMoa1712126. View

11.

Rini B, Plimack E, Stus V, Gafanov R, Hawkins R, Nosov D . Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019; 380(12):1116-1127. DOI: 10.1056/NEJMoa1816714. View

12.

Motzer R, Penkov K, Haanen J, Rini B, Albiges L, Campbell M . Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019; 380(12):1103-1115. PMC: 6716603. DOI: 10.1056/NEJMoa1816047. View

13.

Choueiri T, Powles T, Burotto M, Escudier B, Bourlon M, Zurawski B . Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021; 384(9):829-841. PMC: 8436591. DOI: 10.1056/NEJMoa2026982. View

14.

Motzer R, Alekseev B, Rha S, Porta C, Eto M, Powles T . Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021; 384(14):1289-1300. DOI: 10.1056/NEJMoa2035716. View

15.

Navani V, Heng D . Treatment Selection in First-line Metastatic Renal Cell Carcinoma-The Contemporary Treatment Paradigm in the Age of Combination Therapy: A Review. JAMA Oncol. 2021; 8(2):292-299. DOI: 10.1001/jamaoncol.2021.4337. View

16.

Massari F, Rizzo A, Mollica V, Rosellini M, Marchetti A, Ardizzoni A . 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.2021.06.015. View

17.

Ko J, Xie W, Kroeger N, Lee J, Rini B, Knox J . The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol. 2015; 16(3):293-300. DOI: 10.1016/S1470-2045(14)71222-7. View

18.

Dudani S, Savard M, Heng D . An Update on Predictive Biomarkers in Metastatic Renal Cell Carcinoma. Eur Urol Focus. 2019; 6(1):34-36. DOI: 10.1016/j.euf.2019.04.004. View

19.

Ghatalia P, Rathmell W . Systematic Review: ClearCode 34 - A Validated Prognostic Signature in Clear Cell Renal Cell Carcinoma (ccRCC). Kidney Cancer. 2018; 2(1):23-29. PMC: 6176730. DOI: 10.3233/KCA-170021. View

20.

Kapur P, Pena-Llopis S, Christie A, Zhrebker L, Pavia-Jimenez A, Rathmell W . Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation. Lancet Oncol. 2013; 14(2):159-167. PMC: 4674067. DOI: 10.1016/S1470-2045(12)70584-3. View