An Overview of Systemic Targeted Therapy in Renal Cell Carcinoma, with a Focus on Metastatic Renal Cell Carcinoma and Brain Metastases

Abstract

The most commonly diagnosed malignancy of the urinary system is represented by renal cell carcinoma. Various subvariants of RCC were described, with a clear-cell type prevailing in about 85% of all RCC tumors. Patients with metastases from renal cell carcinoma did not have many effective therapies until the end of the 1980s, as long as hormonal therapy and chemotherapy were the only options available. The outcomes were unsatisfactory due to the poor effectiveness of the available therapeutic options, but then interferon-alpha and interleukin-2 showed treatment effectiveness, providing benefits but only for less than half of the patients. However, it was not until 2004 that targeted therapies emerged, prolonging the survival rate. Currently, new technologies and strategies are being developed to improve the actual efficacy of available treatments and their prognostic aspects. This article summarizes the mechanisms of action, importance, benefits, adverse events of special interest, and efficacy of immunotherapy in metastatic renal cell carcinoma, with a focus on brain metastases.

Adverse renal outcomes following targeted therapies in renal cell carcinoma: a systematic review and meta-analysis

“…Although kidney related adverse events are not the leading adverse events in studies on targeted therapy in RCC ( Di Lorenzo et al, 2011 ), the findings of this study and previous studies consistently suggest these events are not uncommon ( Ruiz et al, 2014 ; Krawczyk et al, 2023 ; Semenescu et al, 2023 ). The reported rate of proteinuria is higher than renal function impairment.…”

Fatal tumoral hemorrhage from brain metastases of renal cell carcinoma after stereotactic radiotherapy and immune checkpoint inhibitor and vascular endothelial growth factor‐targeted therapy combinations

“…2 In the current era, new therapeutic options for RCC are emerging, counting TKIs, mostly VEGF receptor inhibitors, and ICIs. 3 The KEYNOTE-581/CLEAR study highlighted the efficacy of pembrolizumab and lenvatinib, positioning it as a primary treatment for advanced clear cell RCC. 4 These new therapeutic approaches have extended the median survival of BM patients to approximately 14 months, although this is still less than those without BM.…”

“…According to the latest evidence, BM RCC is primarily managed with neurosurgery and/or radiotherapy, with additive therapeutic benefits from systemic therapy, such as ICIs or TKIs. 3 , 8 While RCC has traditionally been considered radioresistant, recent findings suggest fractionated high‐dose radiotherapy could be beneficial. SRT has been recognized as a safe and effective treatment for small, solitary, and multiple metastatic brain tumors, offering high local control.…”