Kidney Cancer Awareness Month: Discovering Clinical Strategies to Improve Outcomes With Dr. Samuel Kareff, Dr. Waqas Haque, and Dr. Ulka Vaishampayan

In this edition of Oncology Data Advisor celebrating Kidney Cancer Awareness Month Dr. Samuel Kareff, Dr. Waqas Haque, and Dr. Ulka Vaishampayan discuss the rising incidence of kidney cancer, warning signs and symptoms to look out for, environmental risk factors such as tobacco use, emerging treatment strategies using immunotherapy and adjuvant therapy, considerations for genetic testing, and the importance of clinical trial participation for bringing these new advances to the forefront of care.

Samuel Kareff, MD, MPH: Good afternoon, everyone. Welcome to the Oncology Data Advisor Fellows Forum, where today we have a special edition celebrating Kidney Cancer Awareness Month and our fight towards genitourinary malignancies in general. I’m joined today by co-investigators from the University of Michigan and New York University (NYU). Thank you and welcome to you both.

Ulka Vaishampayan, MD: Thank you, pleasure to be here.

Waqas Haque, MD, MPH: Thanks so much.

Dr. Kareff: To start us off, why don’t we give the viewers a little bit of a clinical sense of what we’re discussing here. Dr. Haque, could you tell us a little bit about some of the warning signs or symptoms related to kidney cancer?

Dr. Haque: We see about 80,000 cases of kidney cancer per year. The majority of them are going to be in men, but about 30,000 of them happen in women as well. Typically, the most common sign you’re going to see is blood in the urine, like a rusty or dark color tinge of the urine. Sometimes it actually can be seen by the naked eye, but sometimes it can only be detected microscopically, so you might not know about it. Even beyond that, if you’re having back pain that’s not going away, if you’re having a chronic fever but it’s not from a urinary infection, or if you’re having some of the classic signs like weight loss, those are really some things that might make you a little more concerned.

Dr. Kareff: These are certainly important warning signs to look out for. Related to that, we should definitely not be remiss in mentioning the key risk factor of tobacco use, and I will discuss that a little bit more towards the end of this podcast. Shifting gears, Dr. Vaishampayan, could we talk a little bit about some of the clinical strategies that are both established and emerging as they relate to the treatment of kidney cancer?

Dr. Vaishampayan: I think one of the biggest problems with kidney cancer has been that it is not typically symptomatic unless the mass involves the collecting system or causes blood in the urine. Obviously, hematuria or blood in the urine that’s noticed should not be ignored and should definitely be addressed by talking to your primary doctor initially, then eventually getting a referral to urology.

The kidney cancer burden has continued to increase. The incidence is increasing year after year, and there are multiple publications that report that both in the US, as well as in Europe, this cancer is rising in incidents. We are not quite clear on the exact causes, although Sam is going to talk a little bit about tobacco in genitourinary (GU) malignancies.

I also think we haven’t pinned down any exact risk factors except for genetic or germline testing, where we know that there is a hereditary predisposition towards specific types of kidney cancer. People under the age of 45 should definitely be considered for germline testing in case they have hereditary risk and predisposition mutations for risk of kidney cancer. It’ll definitely help the patients themselves, as well as potentially their family members, by doing early testing. As for screening, routine screening is not recommended as of now.

The good news is that the mortality specific to kidney cancer has been decreasing somewhat, and some of that is because of the advances in kidney cancer therapies. Both immune checkpoint therapies and anti-vascular therapies have shown a lot of promise. There are recently reports of even 80% or higher remission rates in a fair number of patients with metastatic kidney cancer receiving immune checkpoint therapy–based combinations. It is absolutely important to consider systemic therapy. Going ahead with surgery for metastatic disease is typically no longer considered the first step in management. It is important to consider systemic therapy first because of how effective the systemic therapy can be in this disease in producing responses as well as potentially long-term remission outcomes.

Dr. Kareff: Thanks so much for the intro to a little bit of the change in clinical paradigms. I reflect on my training even in residency under the guidance of Dr. Michael Atkins at Georgetown Lombardi. We have seen a lot of use of immunotherapy adjuvantly or in the metastatic setting, and now we’ve just seen a flurry of approvals. We have targeted therapies for von Hippel-Lindau (VHL) syndrome. As you alluded to already, we’ve seen the use of neoadjuvant chemoimmunotherapy combinations in some cases, and even this really exciting approval of pembrolizumab for high-risk adjuvant therapy as well. The field is rapidly expanding, and hopefully we’ll be seeing better outcomes as a result of these changing treatment paradigms.

Dr. Vaishampayan: I agree with you. I think the adjuvant therapy is actually a bigger leap because it potentially can cure an additional percentage of patients who have not been cured and who may have a high chance of relapse down the road. Even though at initial presentation their cancer is limited to the kidney, and they have had the nephrectomy, it does seem to help prevent a proportion of relapses and help treat micro-metastatic disease. The adjuvant approach helps cure a slightly increased proportion of patients. Then of course in metastatic disease, if patients are presenting with metastasis, with or without having received adjuvant therapy initially, there are still very effective therapies there also.

Dr. Kareff: Absolutely, there have definitely been a lot of exciting gains in the past few years. We’ll see what the next few years have in store for our patients as well. Shifting gears, I wanted to discuss a little bit about the environmental factors. We just had a great discussion on some of those germline mutations. We talked about the VHL-directed therapy approval as well, but unfortunately, the majority of genitourinary malignancies, especially kidney cancer, are related to environmental exposures.

Our team at the University of Miami recently presented a poster at the American Society of Clinical Oncology (ASCO) GU 2024, in which we were looking to quantify the burden of tobacco as it relates to the development of GU cancers like kidney and bladder cancer. We found some interesting trends in both malignancies focusing on kidney cancer. What we have seen is generally a decrease in the contribution of tobacco towards kidney cancer incidence, and this probably mirrors the decreased use of tobacco prevalence in the countries we studied in the Global Burden of Disease database. That being said, it’s still unacceptably high, right? We’re talking about mortality attributed to tobacco use in the excess of 40%.

We really need to make sure that we, along with our thoracic oncology colleagues, are really advocating for tobacco cessation in all of its uses and forms. Interestingly, I’ll just briefly notes in the topic of GU malignancies, the estimates of tobacco-induced mortality for bladder cancer in our study were still in excess of 50%. Again, it’s really just all the more cause for us to work with folks in public health and other allied oncology subspecialties for that tobacco cessation whenever possible.

Does anyone have any additional comments on kidney cancer as it relates to treatment or about this special awareness month?

Dr. Haque: I think as we highlighted for VHL with belzutifan, we have some treatments now for patients who have hereditary forms of kidney cancer, which can affect 5% to 8% of patients who have kidney cancer in general. You do have patients with a family history, so I think it is important to get screened, as Ulka mentioned.

The other point I’ll mention is that you can’t really have a talk about next steps without talking about artificial intelligence (AI). There are studies that have looked at the performance of AI in detecting kidney cancer. At least for radiologic outcomes, it is pretty good at distinguishing a benign from malignant tumor, but it’s not so good at distinguishing the subtypes of kidney cancer. For pathology and histology, we’re starting to see better performance for subtypes and grading. Even though we don’t have any sort of current screening for kidney cancer in general, and even though we don’t have any blood-based cancer screening, I think in the future, incorporating AI might be part of a patient’s primary prevention.

Dr. Kareff: Excellent. As we’ve discussed on this podcast previously, we’ve seen the adoption of AI in so many aspects of oncology practice, and I’m really excited to see how it’s integrated into diagnostic algorithms, as you mentioned. I also can’t help but share, when you were talking about the germline implications, I thought about the kind of dogmatic phrase we have in oncology, “Test and you shall find.” So, make sure that you advocate for that germline testing whenever necessary.

Dr. Vaishampayan: I would also say, pertinent to the AI topic, I think some subtle clinical points are going to be critical in making that prognostic determination or even predictive determination. So far, there are no standard tissue-based or blood-based biomarkers that are established for treatment or outcomes prediction in kidney cancer. The field is really ripe for research.

I would make this last plug that the majority of the advances that we’ve had in kidney cancer, and maybe all kinds of cancers, has been because of patients participating in clinical trials. Going forward, creating those rational clinical trials for patients and their family members, trying to find that cutting-edge therapy by participation in a clinical trial, is of paramount importance.

Dr. Kareff: Excellent point. That’s always something we should be discussing with our patients whenever the referral is feasible. As you well alluded to, it’s not just the therapeutic implications of the treatment, but there’s also additional discovery we can do, such as biomarker testing that leads to predictive or prognostic abilities. Whenever we can get tissue, whenever we can get clinical trial access, it’s always an excellent option for our patients.

Excellent, I want to thank you both for joining us today on this special edition of Kidney Cancer Awareness Month. I hope this episode gives both you and our viewers that little extra oomph when they see their next kidney cancer patient and as we work together to fight their disease. Thanks so much.

About the Speakers

Samuel Kareff, MD, MPH, is a Medical Oncologist and the Chief Hematology-Oncology Fellow at the University of Miami’s Sylvester Comprehensive Cancer Center and Jackson Memorial Hospital in Miami, Florida. He has special research interests in health advocacy, public policy, and the development of cancer therapies.

Waqas Haque, MD, MPH, is a third-year Internal Medicine Resident at New York University (NYU) in a Clinical Investigator Track. He recently matched to the University of Chicago for fellowship, which he will be beginning later in 2024. As a Clinical Investigator Track Resident, Dr. Haque has balanced his patient care work with a variety of research projects. During his fellowship training at University of Chicago,he plans to further his work in innovative clinical trial design, value-based care delivery to cancer patients, and clinical investigation.

Ulka Vaishampayan, MD, is a Professor of Internal Medicine and the Director of the Phase 1 Program at the University of Michigan Rogel Cancer Center. She is also the Chair of the Southwest Oncology Group (SWOG) Advanced Renal Committee, a member of the National Cancer Institute (NCI) Renal Task Force, and a board member of the Michigan Society of Hematology/Oncology. Dr. Vaishampayan specializes in the treatment of genitourinary malignancies, including prostate cancer, bladder cancer, and renal cell carcinoma, and her research focuses on translational drug development.

For More Information

American Association for Cancer Research (2024). March is Kidney Cancer Awareness Month. Available at: https://www.aacr.org/patients-caregivers/awareness-months/kidney-cancer-awareness-month/

Jani C, Kareff SA, Salazar AS & Sharma N (2024). Assessing tobacco-related mortality trends in genitourinary cancers: a 1990-2019 analysis. J Clin Oncol (ASCO GU Symposium Abstracts), 42(suppl_4). DOI:10.1200/JCO.2024.42.4_suppl.36

Transcript edited for clarity. Any views expressed above are the speakers’ own and do not necessarily reflect those of Oncology Data Advisor.

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