Review article

https://doi.org/10.21860/medflum2025_336639

Combined Immunotherapy and Personalized Approach in Renal Cell Carcinoma Treatment – Challenges and Perspectives

Ivona Antončić ; Klinički bolnički centar Rijeka, Klinika za tumore, Rijeka, Hrvatska; Sveučilište u Rijeci, Medicinski fakultet, Rijeka, Hrvatska *
Ivona Mićović ; Sveučilište u Rijeci, Medicinski fakultet, Rijeka, Hrvatska; Klinički bolnički centar Rijeka, Klinički zavod za patologiju i citologiju, Rijeka, Hrvatska
Christophe Štemberger ; Sveučilište u Rijeci, Medicinski fakultet, Rijeka, Hrvatska; Klinički bolnički centar Rijeka, Klinički zavod za patologiju i citologiju, Rijeka, Hrvatska
Dag Zahirović ; Klinički bolnički centar Rijeka, Klinika za tumore, Rijeka, Hrvatska
Dean Markić ; Sveučilište u Rijeci, Medicinski fakultet, Rijeka, Hrvatska; Klinički bolnički centar Rijeka, Klinika za urologiju, Rijeka, Hrvatska

* Corresponding author.

Abstract

The treatment of kidney cancer presents a significant challenge for clinicians dueto its biological heterogeneity and often late diagnosis, with metastatic forms having a fiveyearsurvival rate of only 12%. The introduction of immune checkpoint inhibitors (PD-1, PDL1,CTLA-4) in combination with tyrosine kinase inhibitors has significantly improvedtreatment outcomes, with a median overall survival of 46 to 53 months. Adjuvant use ofpembrolizumab after nephrectomy has shown a 32% reduction in the risk of recurrence ordeath, establishing it as the new standard of care for high-risk patients. Biomarkers such asPD-L1 expression and the systemic immune-inflammation index enable risk stratification,while personalized ctDNA tests can detect disease progression up to 13.6 weeks beforeradiological changes. Major challenges include a high rate of immune-mediated side effects,atypical responses such as pseudoprogression and hyperprogression and economicconstraints due to the high cost of therapies. Tumor heterogeneity m mechanisms ofresistance further complicate the prediction of therapeutic response. Future treatmentpossibilities lie in triplet combinations, radiotherapy in synergy with immunotherapy andthe development of AI-based predictive models for more precise personalization oftreatment. Integrating various biomarkers and machine learning promises to improveclinical decision-making and reduce toxicity, thus achieving a more sustainable and effectivecare model for patients with advanced kidney cancer.

Keywords

biomarkers; immunotherapy; kidney cancer

Hrčak ID:

336639

URI

https://hrcak.srce.hr/336639

Publication date:

1.12.2025.

Article data in other languages: croatian

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