5 days ago
Rapid Review Quiz: Advanced and Metastatic Renal Cell Carcinoma
Advanced and metastatic renal cell carcinoma (RCC) remains a complex and clinically significant disease that often presents diagnostic and therapeutic challenges. Whereas early-stage RCC can be curable with surgery, advanced RCC frequently carries a poor prognosis and demands nuanced, multidisciplinary management. Rapid advancements in systemic therapies, particularly immunotherapy and targeted agents, have transformed the treatment landscape, making ongoing clinical familiarity essential. Understanding current approaches to diagnosis, prognostication, and treatment selection is critical for optimizing outcomes in this evolving field.
Patients with metastatic RCC have a 5-year survival rate of 17.4%. This contrasts greatly with the 5-year survival rate of 92.9% among patients with localized RCC. The overall 5-year survival rate in RCC is 78.6%, highlighting the dramatic impact of disease stage on long-term outcomes.
Learn more about prognosis of RCC.
The most common type of bone metastasis in RCC is osteolytic, resulting from bone resorption due to osteoclast activity. These lesions lead to bone destruction and are frequently associated with complications such as fractures. Osteoblastic lesions, characterized by excessive bone deposition, are associated with other types of cancer but are not commonly seen in RCC. Osteoblastic lesions are a type of sclerotic lesion.
Learn more about imaging in RCC.
A robust T-cell-mediated antitumor response requires activation of the local interferon gamma signaling pathway within the tumor microenvironment. Adaptive resistance to ICI therapy in RCC is largely attributed to an impaired response to interferon gamma, a key cytokine in anti-tumor immunity. The release of immunosuppressive cytokines can also contribute to resistance by dampening T-cell activity.
However, resistance is not caused by a lack of immunosuppressive cells in the tumor microenvironment. On the contrary, regulatory T cells and myeloid-derived suppressor cells often accumulate in the tumor microenvironment and inhibit effective immune responses.
Learn more about PD-1/PD-L1 inhibitors for RCC.
CAR-T therapy has reshaped therapeutic approaches in several hematologic cancers, but its effectiveness in solid tumors such as RCC remains limited. This relatively reduced effectiveness is largely due to poor CAR T-cell infiltration into solid tumors and an immunosuppressive tumor microenvironment that impairs CAR-T activity.
CAR-T therapies are still investigational in RCC, with no FDA-approved treatments currently available.
Cytokine release syndrome (CRS) is one of the most common and clinically significant toxicities associated with CAR-T therapy. It is caused by elevated levels of inflammatory cytokines and may present with fever, myalgia, and arthralgia. In severe cases, CRS can lead to endothelial activation and disruption of the blood-brain barrier.
Learn more about experimental therapeutic approaches for RCC.
NCCN guidelines recommend initiating systemic therapy in patients with either extensive distant metastases or tumors containing a substantial sarcomatoid component before considering cytoreductive nephrectomy. Thermal ablation is typically reserved for select patients with stage T1 disease. Stereotactic body radiation therapy, another form of ablative therapy, may be appropriate for localized (stage I, II, or III) renal cancer in patients who are not ideal candidates for surgery.
Current guidelines from the American Society of Clinical Oncology are aligned with these NCCN recommendations, stating that first-line treatment for patients with metastatic RCC exhibiting sarcomatoid features should be systemic therapy, specifically an ICI-based combination. This therapy may consist of ipilimumab plus nivolumab, or alternatively, an ICI paired with a tyrosine kinase inhibitor.
Learn more about radiation therapy for RCC.
