Diagnostic and Therapeutic Innovations in Renal Cell Carcinoma: A Urologic Oncology Review
DOI:
https://doi.org/10.65327/kidneys.v15i1.619Keywords:
Renal cell carcinoma, Precision medicine, Molecular diagnostics, Risk stratification, Nephron-sparing therapyAbstract
Renal cell carcinoma (RCC) is a biologically heterogeneous disease. In the recent past, the clinical management of RCC has been redefined by the new development of diagnostic imaging, molecular and genetic profiling. The following review attempts to provide the current events in diagnosing, risk stratification, and management of RCC through the lens of nephrology. A literature review was performed thoroughly with the emphasis on the developments in imaging modalities, molecular and genetic diagnostics, prognostic models, and novel therapeutic methods. Literary evidence of clinical trials, systematic reviews, and international guidelines was analyzed. The result showed that imaging and radiomics advances have enhanced the characterization of tumors and the assessment of risks associated with RCC, whereas molecular and genetic diagnostics have allowed a fine classification of the disease. The Therapeutic interventions, such as setting up targeted therapy, immunotherapy and minimally invasive surgery procedures, have taken a huge step forward in oncologic outcomes. The changes in the management of RCC over the years, the concept of advanced diagnostics, along with the modern modalities, have revolutionized the management process of this cancer. Oncologic efficacy should be offset with renal preservation by using multidisciplinary nephrology-centered approaches. Additional studies and fair practice of precision medicine is also essential to ensure better outcomes and life of patients with RCC.
Downloads
References
Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthélémy P, Porta C, George S, Powles T. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. New England Journal of Medicine. 2018 Apr 5;378(14):1277-90. DOI: 10.1056/NEJMoa1712126
Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, Pouliot F, Alekseev B, Soulières D, Melichar B, Vynnychenko I. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. New England Journal of Medicine. 2019 Mar 21;380(12):1116-27. DOI: 10.1056/NEJMoa1816714
Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, Venugopal B, Kollmannsberger C, Negrier S, Uemura M, Lee JL. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. New England Journal of Medicine. 2019 Mar 21;380(12):1103-15. DOI: 10.1056/NEJMoa1816047
Powles T, Plimack ER, Soulières D, Waddell T, Stus V, Gafanov R, Nosov D, Pouliot F, Melichar B, Vynnychenko I, Azevedo SJ. 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. The Lancet Oncology. 2020 Dec 1;21(12):1563-73. 10. DOI 1016/S1470-2045(20)30436-8
Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Kopyltsov E, Méndez-Vidal MJ, Kozlov V. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. New England Journal of Medicine. 2021 Apr 8;384(14):1289-300. DOI: 10.1056/NEJMoa203571
Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, Oyervides Juárez VM, Hsieh JJ, Basso U, Shah AY, Suárez C. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. New England journal of medicine. 2021 Mar 4;384(9):829-41. DOI: 10.1056/NEJMoa2026982
Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, Hajek J, Symeonides SN, Lee JL, Sarwar N, Thiery-Vuillemin A. Adjuvant pembrolizumab after nephrectomy in renal-cell carcinoma. New England Journal of Medicine. 2021 Aug 19;385(8):683-94. DOI: 10.1056/NEJMoa210639
Shuch B, Pantuck AJ, Bernhard JC, Morris MA, Master V, Scott AM, Van Praet C, Bailly C, Önal B, Aksoy T, Merkx R. [89Zr] Zr-girentuximab for PET–CT imaging of clear-cell renal cell carcinoma: a prospective, open-label, multicentre, phase 3 trial. The Lancet Oncology. 2024 Oct 1;25(10):1277-87. DOI: 10.1016/S1470-2045(24)00402-9
Powles T, Choueiri TK, Albiges L, Peltola K, de Velasco G, Burotto M, Suarez C, Ghatalia P, Iacovelli R, Lam ET, Verzoni E. Health-related quality of life with belzutifan versus everolimus for advanced renal cell carcinoma (LITESPARK-005): patient-reported outcomes from a randomised, open-label, phase 3 trial. The Lancet Oncology. 2025 Apr 1;26(4):491-502. DOI: 10.1016/S1470-2045(25)00032-4
Motzer RJ, Jonasch E, Agarwal N, Alva A, Bagshaw H, Baine M, Beckermann K, Carlo MI, Choueiri TK, Costello BA, Derweesh IH. NCCN Guidelines® insights: kidney cancer, version 2.2024: featured updates to the NCCN Guidelines. Journal of the National Comprehensive Cancer Network. 2024 Feb 1;22(1):4-16. DOI: 10.6004/jnccn.2024.0008.
Geertsen L, Koldby KM, Thomassen M, Kruse T, Lund L. Circulating tumor DNA in patients with renal cell carcinoma. A systematic review of the literature. European Urology Open Science. 2022 Mar 1;37:27-35. https://doi.org/10.1016/j.euros.2021.12.006
Tang C, Sherry AD, Seo A, Hara K, Choi H, Liu S, Sun X, Montoya A, Ludmir EB, Shah AY, Jonasch E. Metastasis-directed radiotherapy without systemic therapy for oligometastatic clear-cell renal-cell carcinoma: primary efficacy analysis of a single-arm, single-centre, phase 2 trial. The Lancet Oncology. 2025 Oct 1;26(10):1289-99. DOI : 10.1016/S1470-2045(25)00380-8
Correa AF, Kalashnikova E, Wu HT, Winters RM, Balcioglu M, Sudhaman S, Connolly DC, Gong Y, Uzzo RG, Sethi H, ElNaggar AC. Association of circulating tumor DNA with patient prognosis in surgically resected renal cell carcinoma. The Oncologist. 2024 Oct;29(10):887-93. https://doi.org/10.1093/oncolo/oyae180
Ursprung S, Beer L, Bruining A, Woitek R, Stewart GD, Gallagher FA, Sala E. Radiomics of computed tomography and magnetic resonance imaging in renal cell carcinoma a systematic review and meta-analysis. European radiology. 2020 Jun;30(6):3558-66. DOI https://doi.org/10.1007/s00330-020-06666-3
Mühlbauer J, Egen L, Kowalewski KF, Grilli M, Walach MT, Westhoff N, Nuhn P, Laqua FC, Baessler B, Kriegmair MC. Radiomics in renal cell carcinoma a systematic review and meta-analysis. Cancers. 2021 Mar 17;13(6):1348. https://doi.org/10.3390/cancers13061348
Rallis KS, Kleeman SO, Grant M, Ordidge KL, Sahdev A, Powles T. Radiomics for renal cell carcinoma: Predicting outcomes from immunotherapy and targeted therapies A narrative review. European Urology Focus. 2021 Jul 1;7(4):717-21. https://doi.org/10.1016/j.euf.2021.04.024
Ferro M, Crocetto F, Barone B, Del Giudice F, Maggi M, Lucarelli G, Busetto GM, Autorino R, Marchioni M, Cantiello F, Crocerossa F. Artificial intelligence and radiomics in evaluation of kidney lesions: a comprehensive literature review. Therapeutic Advances in Urology. 2023 Apr;15:17562872231164803. https://doi.org/10.1177/17562872231164803
Salu P, Reindl KM. Advancements in circulating tumor cell research: bridging biology and clinical applications. Cancers. 2024 Mar 20;16(6):1213. https://doi.org/10.3390/cancers16061213
Xing J, Liu Y, Wang Z, Xu A, Su S, Shen S, Wang Z. Incremental value of radiomics with machine learning to the existing prognostic models for predicting outcome in renal cell carcinoma. Frontiers in Oncology. 2023 Apr 28;13:1036734. doi: 10.3389/fonc.2023.1036734
Salimi M, Hajikarimloo B, Vadipour P, Abdolizadeh A, Fayedeh F, Seifi S. Non-invasive prediction of nuclear grade in renal cell carcinoma using CT-Based radiomics: a systematic review and meta-analysis. Abdominal Radiology. 2025 Jun 11:1-20. DOI https://doi.org/10.1007/s00261-025-05056-x
Oh CH, Kim HJ. Spontaneous Dramatic Regression of Clear Cell Renal Cell Carcinoma After Pazopanib-Induced Severe Systemic Inflammatory Syndrome: A Case Report and Literature Review. Current Oncology. 2025 Apr 30;32(5):260. https://doi.org/10.3390/curroncol32050260
Tabei A, Watanabe M, Ikeuchi H, Nakasatomi M, Sakairi T, Kaneko Y, Maeshima A, Kaira K, Hirato J, Nojima Y, Hiromura K. The analysis of renal infiltrating cells in acute tubulointerstitial nephritis induced by anti-PD-1 antibodies: a case report and review of the literature. Internal Medicine. 2018 Nov 1;57(21):3135-9. https://doi.org/10.2169/internalmedicine.0444-17
Cortazar FB, Kibbelaar ZA, Glezerman IG, Abudayyeh A, Mamlouk O, Motwani SS, Murakami N, Herrmann SM, Manohar S, Shirali AC, Kitchlu A. Clinical features and outcomes of immune checkpoint inhibitor–associated AKI: a multicenter study. Journal of the American Society of Nephrology. 2020 Feb 1;31(2):435-46. DOI: 10.1681/ASN.2019070676
Xu L, Wang D, Wu Y, Zhang C, Miao P. Immunotherapy combined with chemotherapy in neoadjuvant therapy for locally advanced renal pelvis carcinoma: A case report and literature review. IJS Oncology. 2022 Jan 1;7(1):68-74. DOI: 10.29337/ijsonco.141
Gowda S, Mathew P. Systemic Therapies for the Treatment of Renal Cell Carcinoma. InRenal Cancer: Contemporary Management 2025 Oct 1 (pp. 435-446). Cham: Springer Nature Switzerland. DOI https://doi.org/10.1007/978-3-031-97599-8_22
Takeda M, Akamatsu S, Kita Y, Goto T, Kobayashi T. The Roles of Extracellular Vesicles in the Progression of Renal Cell Carcinoma and Their Potential for Future Clinical Application. Nanomaterials. 2023 May 11;13(10):1611. https://doi.org/10.3390/nano13101611
Silverman SG, Pedrosa I, Ellis JH, Hindman NM, Schieda N, Smith AD, Remer EM, Shinagare AB, Curci NE, Raman SS, Wells SA. Bosniak classification of cystic renal masses, version 2019: an update proposal and needs assessment. Radiology. 2019 Aug;292(2):475-88. https://doi.org/10.1148/radiol.2019182646
Remer EM. Mimics and pitfalls in renal imaging. Radiologic Clinics. 2020 Sep 1;58(5):885-96. 10.1016/j.rcl.2020.05.001
Mayerhoefer ME, Materka A, Langs G, Häggström I, Szczypiński P, Gibbs P, Cook G. Introduction to radiomics. Journal of Nuclear Medicine. 2020 Apr 1;61(4):488-95. DOI: https://doi.org/10.2967/jnumed.118.222893
Zhu M, Gu Z, Chen F, Chen X, Wang Y, Zhao G. Application of artificial intelligence in the diagnosis and treatment of urinary tumors. Frontiers in Oncology. 2024 Aug 12;14:1440626. doi: 10.3389/fonc.2024.1440626
Urmantsev MF, Tavabilov RI, Bakeev MR. Genetic Variation and Metabolic Basis of Kidney Cancer: New Opportunities for Targeted Therapy. SURGERY and. 2024;14(3). DOI: 10.24060/2076-3093-2024-14-3-264-274
Choi JW, Hu R, Zhao Y, Purkayastha S, Wu J, McGirr AJ, Stavropoulos SW, Silva AC, Soulen MC, Palmer MB, Zhang PJ. Preoperative prediction of the stage, size, grade, and necrosis score in clear cell renal cell carcinoma using MRI-based radiomics. Abdominal Radiology. 2021 Jun;46(6):2656-64. DOIhttps://doi.org/10.1007/s00261-020-02876-x
Klatte T, Rossi SH, Stewart GD. Prognostic factors and prognostic models for renal cell carcinoma: a literature review. World journal of urology. 2018 Dec;36(12):1943-52. DOIhttps://doi.org/10.1007/s00345-018-2309-4
Pandolfo SD, Wu Z, Campi R, Bertolo R, Amparore D, Mari A, Verze P, Manfredi C, Franco A, Ditonno F, Cerrato C. Outcomes and techniques of robotic-assisted partial nephrectomy (RAPN) for renal hilar masses: a comprehensive systematic review. Cancers. 2024 Feb 6;16(4):693. https://doi.org/10.3390/cancers16040693
Khorasanchi A, Goodstein T, Dason S, Singer EA, Zimmerman D, Yang Y. Perioperative systemic therapy in high-risk renal cell carcinoma following nephrectomy: a narrative review. Translational Cancer Research. 2024 Jun 25;13(11):6511. doi: 10.21037/tcr-24-16
Ricketts CJ, De Cubas AA, Fan H, Smith CC, Lang M, Reznik E, Bowlby R, Gibb EA, Akbani R, Beroukhim R, Bottaro DP. The cancer genome atlas comprehensive molecular characterization of renal cell carcinoma. Cell reports. 2018 Apr 3;23(1):313-26. DOI: 10.1016/j.celrep.2018.03.075
Paner GP, Stadler WM, Hansel DE, Montironi R, Lin DW, Amin MB. Updates in the eighth edition of the tumor-node-metastasis staging classification for urologic cancers. European urology. 2018 Apr 1;73(4):560-9. https://doi.org/10.1016/j.eururo.2017.12.018
Takemura K, Navani V, Heng DY, Ernst MS. Prognostic factors in advanced renal cell carcinoma. InIntegrating Multidisciplinary Treatment for Advanced Renal Cell Carcinoma 2023 Nov 2 (pp. 233-250). Cham: Springer International Publishing. DOI https://doi.org/10.1007/978-3-031-40901-1_10
Alam R, Patel HD, Osumah T, Srivastava A, Gorin MA, Johnson MH, Trock BJ, Chang P, Wagner AA, McKiernan JM, Allaf ME. Comparative effectiveness of management options for patients with small renal masses: a prospective cohort study. BJU international. 2019 Jan;123(1):42-50. https://doi.org/10.1111/bju.14490
Chaudhary K, Pareek T, Devana SK, Sharma AP. Biomarkers in Renal Cell Carcinoma. InMolecular Biomarkers for Cancer Diagnosis and Therapy 2024 Jun 30 (pp. 483-492). Singapore: Springer Nature Singapore. DOI https://doi.org/10.1007/978-981-99-3746-2_23
Linehan WM, Schmidt LS, Crooks DR, Wei D, Srinivasan R, Lang M, Ricketts CJ. The metabolic basis of kidney cancer. Cancer discovery. 2019 Aug 1;9(8):1006-21. https://doi.org/10.1158/2159-8290.CD-18-1354
Chenam A, Lau C. Management of small renal masses. Genitourinary Cancers. 2018 Sep 1:105-26. DOIhttps://doi.org/10.1007/978-3-319-93339-9_5
Correa AF, Jegede OA, Haas NB, Flaherty KT, Pins MR, Adeniran A, Messing EM, Manola J, Wood CG, Kane CJ, Jewett MA. Predicting disease recurrence, early progression, and overall survival following surgical resection for high-risk localized and locally advanced renal cell carcinoma. European urology. 2021 Jul 1;80(1):20-31. https://doi.org/10.1016/j.eururo.2021.02.025
Mir MC, Capitanio U, Bertolo R, Ouzaid I, Salagierski M, Kriegmair M, Volpe A, Jewett MA, Kutikov A, Pierorazio PM. Role of active surveillance for localized small renal masses. European urology oncology. 2018 Aug 1;1(3):177-87.https://doi.org/10.1016/j.euo.2018.05.001
Ward RD, Tanaka H, Campbell SC, Remer EM. 2017 AUA renal mass and localized renal cancer guidelines: imaging implications. Radiographics. 2018 Nov;38(7):2021-33. https://doi.org/10.1148/rg.2018180127
ISSN 2307-1257
ISSN 2307-1265
