Metastatic renal cell carcinoma

Renal cell carcinoma is the most common form of kidney cancer and accounts for close to 74,000 new cases annually.

Most patients with localized disease, the disease amenable to surgical removal with definitive intent.

Approximately 1/3 of patients treated with curative surgery will develop metastatic disease recurrence.

30% of patients present with metastatic disease at diagnosis.

Historically treatment for metastatic renal cell carcinoma included high-dose interleukin-2 and interferon-alpha with subsequent therapies such as vascular endothelial growth factor receptor inhibitors, mammalian targeting rapamycin inhibitors and immunotherapy with checkpoint inhibitors.

Median survival has improved with modern treatments from less than one year in the 1990s over four years in recent trials.

Cytoreductive nephrectomy followed by systemic therapy can improve time to disease progression and overall survival.

Reductive nephrectomy is reserved for up front setting for those with more favorable features such as minimal extrarenal disease and few histologic risk factors.

Reductive nephrectomy can be considered in the deferred setting for patients who have excellent systemic disease responses following systemic therapy.

Upfront cytoreductive therapy is associated with a significant survival benefit regardless of the systemic therapy used, and this holds for immune checkpoint inhibitor therapy.

Asymptomatic patients can be followed for an indolent course, before the institution of systemic therapy.

Initial treatments for metastatic renal cell carcinoma include combination therapy with nivolumab/ipilimumab.

Other effective combinations include Pembrolizumab/axitinib, cabozantinib/nivolumab, levantinib/pembrolizumab: generally these combinations are more inspective than sutinib, which was formally the primary agent for metastatic disease.

Adjuvant immune checkpoint inhibitors following nephrectomy for localized renal cell carcinoma to prevent recurrence is not fully mature but suggests prolongation of disease-free interval.

Immune checkpoint inhibitors (ICIs) are the standard of care for first line treatment of metastatic renal cancer (Nivolumab/ipilimumab).

Combination therapy with ICIs and VEGF directed agents: axitinib/Pembrolizumab, axitinib/a Eli about,  cabozantinib/Nivolumab, levantinib/Pembrolizumab are efficacious.

Sutinib has  been the comparison agent in above studies.

Treatment options in the refractory setting generally do not produce long-term responses.

Options for treatment of patients whose cancer has progressed on front lineImmune checkpoint inhibitors largely focus on targeted therapies with VEGF-R TK I monotherapy: axitinib,cabozantinib, or the combination of levantinib and mTOR inhibitor everolimus.


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