Advances in Diagnosis,Prognosis,and Treatment of Renal Cell Carcinoma

Abstract

Renal cell carcinoma (RCC) remains a biologically heterogeneous malignancy with evolving therapeutic paradigms. Over the past two decades, advances in systemic therapies, surgical techniques, and local treatments have improved outcomes, yet challenges remain in predicting outcomes, tailoring treatment to risk, and treatment integration. This Special Collection, Renal Cell Carcinoma—From Genetics to Oncological and Surgical Treatments: New Insights, highlights recent innovations across these domains. Contributions include validation of prognostic tools such as the G8 geriatric screening and GRANT scores, exploration of stereotactic body radiotherapy for oligometastatic disease, and the emerging role of exosomes as biomarkers and therapeutic vehicles. Together, these findings underscore the importance of integrating molecular profiling, real-world data, and technological advances to guide personalized RCC management, with the ultimate aim of improving survival while preserving quality of life.

Renal cell carcinoma (RCC) remains a complex malignancy, marked by biological heterogeneity and evolving treatment paradigms. Its clinical presentation is highly variable, sometimes mimicking other conditions and earning the epithet of “the great pretender”. ¹ Over the last two decades, the shift from cytokine-based therapies to targeted agents and, more recently, immune checkpoint inhibitors has dramatically improved patient outcomes. ² Meanwhile, advances in surgical techniques and local therapies continue to redefine standards of care.^3,4,5 Despite this progress, clinicians face persistent challenges: improving ways to predict outcomes, adjusting treatment based on risk, and integrating systemic and loco-regional strategies.

The purpose of this Special Collection, Renal Cell Carcinoma—From Genetics to Oncological and Surgical Treatments: New Insights, is to highlight recent innovations in the diagnostic and therapeutic management of RCC, and to explore how current research is shaping future practice. The contributions in this issue illustrate complementary aspects of this evolving landscape.

Nagpal et al ⁶ investigated the prognostic role of the G8 geriatric screening tool in metastatic RCC patients treated with first-line ipilimumab–nivolumab. Their findings confirm that a low G8 score (≤14) correlates with worse overall survival, but loses significance in patients over 70 years. In contrast, the Meet-URO score, incorporating the neutrophil-to-lymphocyte ratio and bone metastases, remains a strong predictor of both progression-free and overall survival across all age groups. This underscores the need for multifactorial prognostic models that integrate clinical, biological, and inflammatory markers, particularly in the immunotherapy era.

In a different disease setting, Maffezzoli et al ⁷ provide an external validation of the GRANT score in papillary RCC patients undergoing surgery. By analyzing nearly 2000 cases, the authors demonstrate that this simple model (based on tumor grade, age, nodal status, and T stage) effectively stratifies patients into distinct risk groups with clear prognostic implications. The GRANT score's reproducibility and ease of use make it an attractive tool for clinical practice, particularly in histologies where dedicated prognostic models remain scarce and therapeutic options limited. Its use could also be considered in rare subtypes, such as collecting duct carcinoma, where real-world data remain limited. ⁸

Vandaele et al ⁴ review the role of stereotactic body radiotherapy (SBRT) for extracranial oligometastatic RCC. Traditionally considered radioresistant, RCC has shown encouraging responses to SBRT, with local control rates often exceeding 80%–90% and minimal toxicity. Beyond palliation, SBRT may delay systemic therapy initiation, synergize with immunotherapy, and expand the therapeutic arsenal for carefully selected patients. The integration of SBRT into multidisciplinary care exemplifies how local approaches can complement systemic innovation.

In parallel, Boussios and Ovsepian ⁹ explore the emerging role of exosomes as diagnostic and therapeutic nanovehicles in RCC. These extracellular vesicles are not only key mediators of tumor progression, metastasis, and drug resistance, but also promising candidates for liquid biopsy–based biomarkers. Specific exosomal miRNAs and proteins have been shown to distinguish RCC patients from healthy individuals, track disease recurrence, and predict treatment response. Moreover, experimental studies suggest that engineered exosomes may serve as innovative drug delivery systems or even immunotherapy platforms, such as dendritic cell vaccines loaded with tumor-derived exosomes. While their dual role, as drivers of resistance and potential therapeutic allies, poses challenges, exosome research opens new perspectives for precision oncology in RCC.

Together, these studies highlight interconnected priorities in RCC: the refinement of prognostic tools for both localized and advanced disease, the validation of models in non–clear cell subtypes, the expansion of therapeutic strategies beyond conventional surgery and systemic drugs, and the exploration of exosome-based biomarkers.

This Special Collection provides a timely overview of the progress made and the challenges ahead. By bridging genetics, prognostic modeling, systemic therapy, local innovation, and nanotechnology, it emphasizes a central message: the future of RCC management lies in precision and integration, with the ultimate goal of improving survival while preserving quality of life.