Kidney Cancer in a Nutshell

So let's start with kidney cancer.

When we say kidney cancer, usually we are talking about clear cell cancer renal cell carcinoma.

There are a couple other variants of kidney cancer.

There are some lower tract, or some urethral tract cancers that are in the kidney, like of the renal calyx.

That's not really what we're talking about.

There can be papillary cancer in the kidney that would fall under renal cell carcinoma.

There's some other ones.

There's sarcomatoid features as well, which is important.

Usually this is a disease of older patients, like many cancers are, with more of a prevalence towards men, and patients with a history of hypertension seem to have a higher risk of kidney cancer.

It's unclear if the hypertension leads to the kidney cancer as far as I know, or if there's something that leads to hypertension that also increases the risk of kidney cancer.

We know that many, many kidney cancers have alterations that lead to inactivation of the von Hippel-Lindau gene or its subsequent protein, which is a tumor suppressor gene that acts as a check to prevent the unmitigated release of vascular endothelial growth factor.

So you'll see that targeting VEGF is a huge part of this treatment paradigm.

The staging is kind of like most solid tumors, boringly simple.

Stage 1, small tumor, but in the kidney.

Stage 2, tumor, larger tumor, but still in the kidney.

Stage 3, and then stage 4, distant metastatic spread.

The cornerstone of treatment, as it is for most solid tumors with the curative intent, is surgery.

So nephrectomy or a partial nephrectomy for stage 1, 2, and 3.

There have been some attempts at adjuvant therapy with tyrosine kinase inhibitors that have shown no overall survival benefit.

There have been like five or six studies.

One showed disease-free survival benefit, but all the rest didn't.

Some had to be stopped early, largely ineffective.

We do have data supporting the use of adjuvant pembrolizumab, which has disease-free survival benefit and overall survival benefit.

in folks who have stage 3 disease or stage 2 with high-risk features like a grade 4 nuclear grade, or if they had sarcomatoid features, you could do adjuvant pembrolizumab for that same patient population.

Those high-risk folks that are stage 2 or stage 3, high-risk for occurrence, pembrolizumab and belzodifan, a hypoxia-inducible factor inhibitor, is approved, not yet having overall survival benefit for those patients.