Dr Alan Tan Provides Overview of RCC Prevalence, Presentation, Diagnosis

Alan Tan, MD, is an assistant professor in the Division of Hematology, Oncology and Cell Therapy at Rush Medical College and is also the director of GU Medical Oncology. He specializes in kidney cancer, bladder cancer, prostate cancer, and melanoma. Here, in this interview with The American Journal of Managed Care® (AJMC®), he describes how renal cell cancer is typically discovered and how it is treated, depending on the stage.

AJMC®: What is renal cell carcinoma, and can you describe its pathophysiology and clinical presentation?

Tan: Renal cell carcinoma— it's also called kidney cancer, and there's different types of kidney cancer—but renal cell carcinoma, when we're talking about that, about 80%, 80% to 85% of it is a pathology called clear cell kidney cancer. And then the other 15%, we call it non-clear cell kidney cancer. And it's basically a cancer that starts in the actual kidney organ, and it can metastasize to different sites, most commonly the lungs, the lymph nodes, and then also the bones, the liver, the brain, etc. But the more common sites are the lungs and the lymph nodes.

Most of it comes from some risk factors like smoking, environmental exposures, sometimes finding kidney stones. And the minority comes as a hereditary factor. Usually, if it's a hereditary kidney cancer, we're talking about usually non-clear cell kidney cancer, and they usually have some kind of family history. They're usually diagnosed younger, usually anywhere from age 30s to 40s, but even sometimes in their late teens, too. As far as the pathophysiology, you know, I think in in general, we think the pathogenesis of kidney cancer, it follows something in the VHL gene, the von Hippel-Lindau gene. It can get very complex but in general, there's usually some alteration in the VHL pathway inside of a cancer cell. For clinical presentation, actually a lot of these present with hematuria, so bleeding in the urine, and flank pain.

But oftentimes, these are diagnosed incidentally. Maybe a patient had a car accident or a skiing accident, and they had to have an abdominal scan. And then incidentally, there is a kidney mass that's maybe 2 centimeters, or 3 centimeters, but sometimes it's like a 15-centimeter tumor and they never knew about it. And it was found incidentally. So that's the kind of stage where if it hasn't spread yet, you can still cure it with surgery. Surgery is still the mainstay of curing a kidney cancer. But if it's metastasized, we can talk about more things. Hopefully, that's a good introduction.

AJMC®: What does the typical patient look like who has RCC? Is this someone who's young, someone who's old, a particular demographic, for who is at risk for developing?

Tan: The average would be probably in the mid-to-late 60s for diagnosis of kidney cancer. And it could be earlier stage or late stage, but usually it's not young. But like I was mentioning, the ones that are non-clear cell and hereditary are the ones that present young.

AJMC®: How common is renal cell carcinoma—what is the incidence or prevalence of this disease in the United States?

Tan: I think currently, it's about half a million patients living with kidney cancer in the United States. It's not very common, but it's common enough to really be disruptive and be recognized that patients need treatment options, because when it becomes metastasized, a lot of patients are dying still.

AJMC®: How is RCC typically diagnosed? And what are those diagnostic tools or imaging modalities that are used to catch RCC?

Tan: It's found by a CT scan, or any type of abdominal imaging. A radiologist could already say this is highly suspicious for kidney cancer. There's not too many kidney tumors that look differently. Usually a radiologist is able to have enough training to say this is very likely RCC or kidney cancer. But to really clinch the diagnosis, you still need tissue. If it's metastatic kidney cancer, you often like to see if there's a chance to biopsy the metastatic site. Maybe like there's a 1-centimeter or 2-centimeter lung lesion, then you can do like a CT guided lung biopsy, and get your answer there. But oftentimes, if it's compelling enough, then you know the treatment is going to be a nephrectomy. If it's compelling enough, the urologist goes in there and does maybe a robotic nephrectomy, left or right nephrectomy. That's how you get your diagnosis.

AJMC®: What are some of the potential complications associated with renal cell carcinoma? What are some of the outcomes really that someone might experience with renal cell carcinoma?

Tan: The ultimate would be death, because of metastasis to the brain, the liver and to other organs, so that's the worst thing. The metastatic cancer in general can put a person at risk for complications such as blood clots, so DVT, pulmonary embolism. And then the treatment associated with it also can cause that too. Today we're using immunotherapy alone or immunotherapy with these pills that are called TKIs, or tyrosine kinase inhibitors. And those increase the risk of both bleeding and clotting disorders. So those are some things, but the range of presentations in this cancer can vary, like weight loss, poor appetite, pain of course, especially if it's pushing on an organ or metastasized to bone pain, poor quality of life, shortness of breath if you have a lot of pulmonary involvement, you could have pleural effusions causing respiratory symptoms as well, too. So those are some of the significant ones. Ongoing hematuria can be an issue as well.

AJMC®: What does advanced mean in renal cell carcinoma? And how does advanced disease differ from an early-stage renal cell carcinoma?

Tan: Advanced can mean stage III or IV. In the past we usually weren't really treating stage III with immunotherapies. But now, we actually have an immunotherapy FDA approved for the high risk for advanced kidney cancer and that's with something called adjuvant Keytruda, or pembrolizumab. But the more common setting is stage IV kidney cancer. This is metastatic RCC, and like I mentioned, 80% to 85% is clear cell and now, in the last 5 years, we just have a luxury of options. You know, we have immunotherapy combinations; that started in 2018. But you're asking how do symptoms present. Oftentimes they might be actually asymptomatic, like I mentioned. It's found by accident and then they get a kidney mass. And then you do full staging workup, and then you will often see tiny lung nodules there. And then you eventually prove that this is stage IV.

So that's probably like the good risk—patients that have this is found incidentally. And then they usually, we have this criteria called the IMDC criteria. And you can risk this based on 6 different factors. But sometimes people that are asymptomatic might not even require treatment right away. But it can vary to that versus, oh, stroke symptoms, if they have brain metastases, or 20-, 30-pound weight loss, pain in the back, or core compression, if it's metastasized to the spine. I would say that's like the extreme scenario. And then they can have something called paraneoplastic syndrome where their calcium levels are really high. And then that makes them really confused and really looking very sick and needing to be hospitalized.