In part one of CURE’s “Mind Over Matter: Cultivating a Resilient Mindset During Breast Cancer Treatment” webinar, Ricki Fairley, CEO of TOUCH, The Black Breast Cancer Alliance; Hayley Brown, director of partnerships and programs at TOUCH, The Black Breast Cancer Alliance; and Michelle Anderson-Benjamin, CEO and founder of The Fearless Warrior Organization, discussed mental resilience during one’s breast cancer journey.

 – Mental resilience during breast cancer treatment

The panel discussed mental resilience during breast cancer treatment, while sharing their personal experiences and perspectives on the topic.

 – Managing cancer treatment while maintaining personal and family responsibilities

Michelle Anderson-Benjamin talked about how she prioritizes her loved ones' needs throughout her cancer journey, while also becoming a mental health coach to help others in their own journey.

 – Cancer diagnosis, treatment and family support

Hayley Brown, Ricki Fairley’s daughter, reflected on her mother's mental stability during her cancer treatment, highlighting her positive attitude and determination throughout.

Ricki Fairley shared how her children also played a role in stepping in to help during cancer treatment, demonstrating resilience and adaptability on their side as well.

 – Cancer diagnosis and communication with family

Ricki Fairley shared her story of her diagnosis, and when she decided to tell her daughter of her diagnosis and what information she chose to withhold.

Hayley Brown shared how this may have led to emotional trauma after learning of her mother’s diagnosis.

 – Health disparities and cancer in the black community

As Black women, the panel discussed the stigma around mental health therapy in cancer treatment within the Black community.

The panel also discussed their personal family history of breast and prostate cancer, highlighting the importance of discussing health disparities in communities of color.

Lastly, the panel emphasized the need to start conversations at the table and push the agenda to address health disparities, rather than ignoring them.

For more news on cancer updates, research and education, don’t forget to 

Videos

In this on-demand webinar series, CURE partnered with TOUCH, The Black Breast Cancer Alliance to discuss mental resilience during one’s breast cancer journey.

Encouraging Patients to Have a Resilient Mindset During Breast Cancer

For patients with metastatic hormone-sensitive prostate cancer, what are the treatment options?

 Metastatic hormone-sensitive prostate cancer is a particular type or stage of prostate cancer in which the cancer has spread outside of the prostate—that's the metastatic term—and hormone-sensitive means that it hasn't yet been treated with androgen deprivation therapy [ADT] to lower testosterone and shut down the cancer cells, so it's presumed to be sensitive to that hormonal manipulation or decrease of testosterone that we cause with androgen deprivation therapy.

We see patients with all versions of metastatic hormone-sensitive prostate cancer, in that it can be de novo metastatic, meaning that from the time of diagnosis, the first time someone heard he had prostate cancer, it had spread outside of the prostate and was metastatic from the start. It can be recurrent metastatic hormone-sensitive prostate cancer, meaning that the patient was diagnosed with prostate cancer that was all in the prostate or just around the prostate in the past but it came back after initial treatment and now is metastatic and has spread outside. It can be a small amount of metastatic hormone-sensitive prostate cancer, with maybe one spot of metastatic spread into the bone or a lymph node outside of the prostate somewhere. Or it can be really high-volume metastatic hormone-sensitive prostate cancer, with many spots of areas of spread of prostate cancer outside of the prostate into other areas.

No matter where prostate cancer spreads, whether it's into the bone, liver, lungs or lymph nodes, it is still prostate cancer cells that are in those areas. Metastatic prostate cancer just means the cancer cells that used to be in the prostate picked up and have moved outside and now live somewhere else but there are still prostate cancer cells. We treat metastatic hormone-sensitive prostate cancer with various things, but the backbone of what we do is androgen deprivation therapy, lowering testosterone to starve those cancer cells wherever they are in the body [to] really shut them down.

We know, based on data from multiple clinical trials, that lowering testosterone with ADT alone is not enough to really shut down these cells effectively for as long as possible, and we can do better by adding on additional pills that can further decrease the testosterone signaling and, sometimes, by adding on chemotherapy to really use another form of medicines to attack even more intensely and aggressively. We use an understanding of how much prostate cancer has spread outside of the prostate to help us make some of these decisions with the use of chemotherapy added on to ADT and hormonal-targeting pills for people who have high-volume prostate cancer and de novo metastatic prostate cancer much more commonly than we do for low-volume prostate cancer or recurrent prostate cancer. To put that a little more clearly, we try to target more advanced or aggressive prostate cancer—de novo metastatic and high-volume metastatic cancer—by using more intensive therapies that include ADT, hormonal pills and, often, chemotherapy. Of course, this is only going to work in settings where the patient is actually well enough, strong enough and fit enough to get chemotherapy and wants to get chemotherapy. But that is the setting where we use triplet therapy with ADT, hormonal pills and chemotherapy to try to be really aggressive against the cancer.

When patients have recurrent prostate cancer or low amounts of prostate cancer, low-volume prostate cancer, we sometimes think about using just the ADT and the hormonal pills and sometimes even add on radiation to the prostate to try to use the tools that we can to have the best control of the cancer cells and hopefully the longest prolongation of survival for the person—we want to help the person live for as long as he possibly can. And we're always, no matter what we're choosing for treatment, trying to make sure that the therapies that we're choosing help the person feel as well as he can feel during treatment. We think a lot about which choices for therapy we want for an individual patient, and we talk with patients and make shared decisions about which approach might be best. But understanding the amount of cancer spread that's metastatic and understanding if it has come back after we've previously treated the prostate or is newly metastatic right out of the gate can help us make some of those decisions, as well as thinking about how the patient feels and what he wants in terms of his treatment.

Transcript is AI-generated and edited for clarity and readability.

A comprehensive review of treatment options for patients with metastatic hormone-sensitive prostate cancer.

Metastatic Hormone-Sensitive Prostate Cancer Treatment Options

 Androgen deprivation therapy, sometimes called ADT or hormonal therapy, is a way of treating prostate cancer that is used pretty ubiquitously or used pretty uniformly for patients when the cancer is more advanced or has spread outside of the prostate, perhaps even throughout the body. This form of treatment is not giving androgens or giving hormones but actually decreasing hormone levels, particularly testosterone, that male hormone that goes up in patients or individuals when they go through puberty, and is also the hormone that drives prostate cancer cells to grow, divide, spread and cause the trouble that they cause.

When we use androgen deprivation therapy, we are lowering testosterone levels typically by turning off the testes from making testosterone. This starves cancer cells, causing them to shut down, causing some to essentially self-destruct or die, and causing others to go into a deep hibernation state where they are not going to be able to grow, divide, spread and cause trouble. They just sort of sit still and shrink. And that from a patient perspective and from a doctor perspective is really important and is what we want. We want to shut it all down. There are other things that we can add that are more hormonal therapies to further decrease that testosterone from driving cancer cells. But the ADT, or androgen deprivation therapy, is really just shutting off the testes.

It's important to know that there are several types of ADT. Of course, one is a surgical type, so you can remove the part of the testes on both sides that makes testosterone, and that's a surgical procedure. But more commonly, people use medications to have ADT or use treatment with ADT. Those medications can either be GnRH agonists, which is just a type of a hormonal therapy that causes a surge in testosterone before it causes low levels. That needs to be considered when you're starting the treatment. The other kind, which is a GnRH antagonist, causes the testosterone levels to go down right away. Both of these are really effective ways of lowering testosterone. They are both used really commonly, and they both can be given as injections. The GnRH antagonist form can also be given as a pill. There are lots of different ways and options for us to cause androgen deprivation and to treat prostate cancer with hormonal deprivation therapy. It's important with talk to your doctor about which one might be right for you.

Alicia Morgans, MD, MPH, discusses androgen deprivation therapy and its role in treating prostate cancer.

Androgen Deprivation Therapy for Prostate Cancer

Advanced RCC: Safety and Efficacy of IO/TKI Combination Therapies

In terms of front-line therapies, as we just mentioned, there are multiple immunotherapy [IO] combinations. When we look at ipilimumab-nivolumab, this is the pure immunotherapy accommodation from an efficacy standpoint; it does prolong overall survival [OS] when compared with sunitinib in the metastatic setting.

Our longest follow-up data for this combination comes from CheckMate 214 [NCT02231749], which was a phase 3 trial with a five-year follow-up now showing improved survival outcomes. The VEGF [anti-vascular endothelial growth factor] IO combinations also have shown improvements in OS and of note improvements in early progression-free survival [PFS] compared with sunitinib. We recently had data from ASCO [the American Society of Clinical Oncology Annual Meeting] 2023 from KEYNOTE-426 [NCT02853331], which was the axitinib with pembrolizumab combination, showing improved OS as well as improved PFS.

Then in the CLEAR trial [NCT02811861], from lenvatinib with pembrolizumab, we also saw both improved OS as well as improved PFS compared with sunitinib. And then finally, the cabozantinib and nivolumab combination also has shown both OS and PFS compared with sunitinib. When we talk about side effects, we absolutely have to think about the toxicities of these treatments when we’re deciding on the right combination to use.

And when we talk about these treatments, I often tell our patients that immunotherapy activates the immune system wherever [it is] active in the patient’s body. So on the skin, it can cause a rash; in the GI [gastrointestinal] tract, it can cause colitis or diarrhea; and then rarely would it cause inflammation of the liver, lungs, or kidney themselves. And finally, endocrinology, so toxicities affect the endocrine organs. The most common of [these] is thyroiditis or the toxicity of the thyroid, either high levels or low levels of thyroid hormone, and then also toxicities involving the pituitary-adrenal glands and pancreas.

We watch all of those hormone factors very carefully during the course of treatment. Now, when we add in the anti–blood vessel blockade, and our anti-VEGF therapies, these treatments often affect the cardiovascular system in particular. About 50% of patients will develop some elevated blood pressure, hypertension over baseline, and then also hand-foot syndrome or a painful rash on the palms of the hands in the soles of the feet. Mouth ulcers or taste changes are also pretty particular for the anti-VEGF component of these combinations. There are some overlapping toxicities, such as the diarrhea and the elevated liver function that we also keep an eye on and try to tease apart whether they’re due to the anti-VEGF blockade or if they’re due to the immunotherapy.

There are four landmark studies that I’m going to go into with detail. One was called the CLEAR study. The CLEAR study was a Phase 3 randomized study where patients [had] advanced renal cell and Stage 4 kidney cancer, and the medications were lenvatinib, which is a TKI [tyrosine kinase inhibitor] we talked about. And the dance partner was known as pembrolizumab, which is immunotherapy. The patients were randomized to either that treatment or the comparison arm, [which was] was sunitinib. There was a third arm of lenvatinib and everolimus. But, for the sake of the conversation, all of the trials used sunitinib as the comparison arm, so we’re just going to talk about sunitinib vs lenvatinib and pembrolizumab.

It was very striking…as a cancer doctor, the thing I look for is, how does the cancer respond? What is the response rate? If we have 100 people, how many of those patients are going to respond to treatment? The second thing I look at is, if I start them on medication three months from now, because typically that’s when we do a scan, what is the chance that the cancer is going to shrink, i.e., respond, or is cancer going to get worse? And the last thing is, are there any spots remaining? Let’s call it a complete response. A complete response means if you have some spots on the CT scan, you undergo treatment, and then on future CT scans, there are no spots. The CT scan is how we look for cancer.

In the CLEAR study, it had the highest response rate. Close to 70 to 71 out of 100 people responded to this medication, which is phenomenal in terms of a complete response; 17 out of 100 people had a complete response, which is striking. What’s the chance of cancer three months from now after you start this treatment? Are you going to have to give bad news to the patient? That is called progressive disease. Progressive disease means that you start a treatment and later on, three months from now, when you do the CAT scan, what’s the chance that you’re going to end up giving that patient bad news? That’s called progressive disease. In the CLEAR study, progressive disease was only 5%, which means three months from now, if you do this regimen, 19 out of 20 people that are on this regimen will either have cancer remaining the same size, getting smaller, or disappearing. So that really moved the needle for me.

Now, the problem with the CLEAR study and the lenvatinib and the pembrolizumab is at what price? This is where the kidney doctors and cancer doctors like myself really have to roll up our sleeves and keep an eye on things, because even though you might get a better response, you also have more toxicity. One of the things that I look for is high blood pressure. I always talk to my patients about high blood pressure on this medication, and make sure they have blood pressure cuffs at home. [Another one] is diarrhea. We have to know about any diarrhea. We have to treat the diarrhea. And we can also do a lower dose for the diarrhea. And then thyroid conditions are something I think about. So that’s the CLEAR study. It’s got the highest CR [complete response], the highest response rates and the lowest progressive disease. But you have to think about the toxicities because the patients, if you don’t treat them in a good fashion, you could end up with a lot of side effects.

The second study is called the KEYNOTE-426. The KEYNOTE-426 also uses the backbone of TKI with an immunotherapy. The TKI they used in this study was axitinib. The medication for the immunotherapy was called pembrolizumab. In this study, in the KEYNOTE-426, the response rate was very high. It was [about] 60%. The CR was in the 11% to 12% range. Progressive disease was in the 10% to 15% [range]. But the one thing about this combination is axitinib has the shortest half-life. So for our patients, it tends to be if you have any side effects of the medication, it’s much easier to control because if you hold that medication for three days and it’s caused by the TKI pill, the side effects would go away. So it’s much easier to control, but you do lose some of that CR and so on. Now it’s hard to compare studies, so I’ll just look at the terms of each study and not really compare.

In terms of the third combination called the CheckMate-9ER [NCT03141177]. The CheckMate-9ER is also composed of two treatments, one TKI, which is cabozantinib, and the second is nivolumab, which is a checkpoint inhibitor. Now, cabozantinib is like the Swiss Army knife of all the different TKIs. It is used for a lot of different diseases. It’s got a great response. In many of the studies, cabozantinib is treated at 60 milligrams per kilogram for kidney cancer, but in this study was 40 mg and nivolumab was every two to four weeks, depending upon the dosing of 240 and 480. In terms of the CR, it was in the 11% to 12% range. So, very respectable. In terms of progressive disease, it was [about] 67%. So that’s very low. In terms of response rate, it was in the 57% to 58% range.

Now, the one thing that I look at in terms of this combination for my patients is they have some really good data. It’s called the health quality of life data, reporting how our patients do with medication, fatigue, whether it is a hand-foot condition, where your hands are red or your feet are red. So the health-related quality of life of this combination is very impressive. This is something I think about for our patients when I’m thinking about the health-related quality of life.

Expert perspectives on the decision-making process for selecting frontline systemic therapy for patients with advanced renal cell carcinoma.

Selecting Appropriate Treatments for Patients With Advanced RCC

 One of the toughest parts of being a kidney cancer doctor is we have four FDA-approved medication combinations to treat our patients who are diagnosed with Stage 4 kidney cancer. As I mentioned, the cancers spread to the lungs or the liver. Now, all four [treatments] have been through rigorous clinical trials, phase 3 trials with hundreds of patients, so they’re all effective. How do I determine which of those four treatments to give to the patients in front of me? As an oncologist and a cancer doctor, we’re all board certified in internal medicine, so we’re internists at the end of the day. So this is where we have to use our internal medicine background, i.e., primary care certification background.

The first decision I have to make is whether one of the four is a dual checkpoint inhibitor, i.e., immunotherapy alone. That’s called the nivolumab and ipilimumab. On the other side of the road are tyrosine kinase inhibitors [TKIs] and immunotherapy. When I see a patient, the first decision I have to make is, do I want to give an all-immunotherapy treatment or do I want to give an immunotherapy and a TKI?

Now let’s talk about the two immunotherapy combination treatments. Let’s say that the patient is symptomatic. Symptomatic means, as a physician, I’m looking at them and asking, do they have bone pain? Do they have abdominal pain? Whatever area the cancer is in, is there pain? Is their blood count low, i.e., their hemoglobin? We have something called the IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] criteria. Now what do the IMDC criteria say? The IMDC criteria say the first thing I look at as a physician is, does my patient lie on a couch most of the day because cancer is causing a lot of symptoms? We have something called performance status. If they’re moving around really well, they get a score of zero. You have to add up the points and each point tells you if it’s intermediate, poor risk versus favorable risk.

The other thing that I look at is the blood level, called the CBC [complete blood count]. The CBC includes all the cells in the blood test. If their hemoglobin is low, that is one point. Now if their white blood cell count is high or if the platelet count is high, they’re each worth one point. So I add up the points. If they have zero points, that’s called favorable risk. If they have one or two points, that’s called intermediate risk. The poor risk is they have three or more of those points. The other way I add points, I forgot to mention, is if somebody had their kidney cancer removed by surgery and they haven’t had treatment in over a year, that’s considered zero as well.

Now based on the IMDC criteria, and based on performance status, when the kidney was diagnosed, is it less than a year or more than a year, hemoglobin, and white blood cell count of platelets. I put them into three buckets: favorable risk where they have zero on all those points, intermediate where there’s one to two and then poor risk if they have three. Now the favorable risk, I don’t give anybody in the favorable risk immunotherapy. That study was negative, and the benefit doesn’t outweigh the risk there. For favorable risk, I do immunotherapy and a TKI. For the intermediate risk and the poor risk, I look at the patient’s symptoms, are they asymptomatic? Do they have a lot of pain because of the cancer in the bones? Is their liver abnormal? Are they having trouble breathing? These are the things I look for if they’re symptomatic of cancer. I use a TKI and an immunotherapy because the TKI is much faster at controlling the cancer. And for the patients who may not have any symptoms and may have a low burden of disease, are when I think about the dual checkpoint inhibitor.

 In first-line treatment of metastatic or advanced kidney cancer, we often think about a lot of patient characteristics. Do they fall under the risk prognostication category of favorable risk disease, where their tumor and their clinical symptoms are not what we call inflamed? [Or] are they more in the intermediate and poor risk factors, or [using] IMDC criteria in which patients tend to have more inflammatory markers like anemia or high neutrophils or high platelets, as well as high calcium levels, which is a surrogate for bone metastases.

Based on those categories is how we currently assign systemic treatments in the front-line setting, and several immunotherapies with VEGF [anti-vascular endothelial growth factor] combinations as well as pure immunotherapy combinations are available across these IMDC tumor risk factor types. There is a pure immunotherapy combination called ipilimumab and nivolumab, which is used more for intermediate and poor risk disease [with] more inflamed tumors, and then VEGF and immunotherapy combinations more for favorable-risk disease, but also approved across all IMDC disease types. Those types in particular are agents like axitinib with pembrolizumab, lenvatinib with pembrolizumab, axitinib with ipilimumab, and cabozantinib with nivolumab. All four of those combinations are approved in the front-line setting.

Some key factors when selecting patients for these front-line therapies include the tumor burden. How much disease do they have, what are they presenting with, and how symptomatic are they? Do we need to look for early disease control, or are we shooting for durable responses over time? And then finally, patient comorbidities and their ability to tolerate some of the side effects of our treatments. For example, some patients with baseline autoimmune disease may or may not wish to undergo the potential immunotherapies that might activate their underlying autoimmune disease. Those are the things that we really think about when we’re talking through the right treatment combination for each patient in our clinics.

A urologic oncology fellow provides a comprehensive overview of systemic therapy options for patients with prostate cancer.

Systemic Therapy for Prostate Cancer

This is a synopsis of an Educated Patient Sound Bites series featuring Alicia Morgans, MD, MPH, of Dana-Farber Cancer Institute; Rashid K. Sayyid, MD, MSc, of the University of Toronto; and Reginald Tucker-Seeley, MA, ScM, ScD, of ZERO Prostate Cancer.

Dr Rashid K. Sayyid discusses chemotherapy options docetaxel and cabazitaxel, which stabilize microtubules to inhibit cancer cell proliferation. He then covers immunotherapy with programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors, which prevent cancer cells from tricking the immune system.

The most commonly used treatment is androgen deprivation therapy, including luteinizing hormone-releasing hormone (LHRH) agonists to reduce testosterone production and gonadotropin-releasing hormone (GnRH) antagonists to immediately inhibit testosterone. Newer drugs also prevent adrenal testosterone production. Dr Sayyid explains testosterone promotes prostate cancer growth, so limiting levels fights proliferation.

Additional drug classes are then summarized, including sipuleucel-T immunotherapy whereby peripheral blood cells activate against antigens then reinject to target cancer, radium Ra 223 dichloride which emits alpha radiation to damage cancer cell DNA, and PARP inhibitors like olaparib, rucaparib, and talazoparib that prevent DNA damage repair prompting cancer cell death.

In total, Dr. Rashid K. Sayyid overviews major drug categories for treating prostate cancer - chemotherapy, immunotherapy, hormone therapy, therapeutic vaccines, alpha radiation, and PARP inhibitors.

*Video synopsis is AI-generated and reviewed by CURE editorial staff.

How do clinical trials and real-world evidence contribute to treatment decisions?

 Clinical trials are essentially ways that we, as physicians and scientists, try to understand which treatment or which approach to therapy or care of an individual is the best. We typically compare maybe 2 different treatment options or sometimes 3 treatment options and put them head-to-head to help us understand what is the best way to move forward for an individual type of patient or an individual patient. I would say that we are very conscious to make sure that all of the options that are compared in clinical trials are equally likely to help the patient. We don’t put patients in situations in clinical trials where they’re not really receiving the best therapy or care that they can get. I usually think of it as a comparison of the standard treatment vs the standard treatment plus something else. We don’t usually remove therapy or remove treatments from these kinds of trials unless our goal is to deintensify or reduce the intensity of the treatment because we think we’re overtreating people. There are trials that are made up that way. And certainly, that would be discussed as people are considering clinical trials and they’re making their choice to get involved.

One other important caveat is that when patients do get involved in clinical trials, evidence suggests that they actually do better on clinical trials in general than they do in standard treatment. Just enrolling in a clinical trial, participating in that process, and getting the extra care from the research team members can help you do better in the long run, which I think is a really wonderful bonus as you’re doing something that’s so altruistic, like participating in a clinical trial.

Another form of research and investigation that we do in medicine, and particularly in cancer care, is to look at groups of patients who are being treated in the real world with the standard therapies that we have using compilations of medical records or perhaps Medicare data or other database data to understand in that real-world setting how people are really doing and how they’re being treated, what complications they’re experiencing, and how well they’re doing on a particular therapy. And those real-world studies can be done without actually even engaging directly with the patient but by using data that’s already contributed through medical records that a patient is providing and the way that they’re actually being cared for in the clinic.

This kind of investigation is not burdensome to patients. It can be really challenging for clinical teams and investigation teams because they have to weed out a lot of noise as they’re trying to understand what’s going on in that kind of a data setup, but it can be a nice way to try to get an understanding of not just how people are doing when they are engaging in those clinical trials and putting in that extra effort and time, but also how they’re doing in clinics like mine, or like the one down the street, or the one in Tennessee where I used to work, or wherever it is throughout the world. People around the world may be treated slightly differently and our real-world cohorts can help us understand what geographic differences exist or what similarities exist, and how we can really raise the level of care for everybody to do our best.

Expert perspectives on how clinical trials and real-world evidence contribute to treatment decisions in prostate cancer.

Informing Prostate Cancer Treatment Decisions with Clinical Trials and Real-World Evidence

A comprehensive overview of systemic therapies available for the treatment of patients with advanced renal cell carcinoma.

Systemic Therapies in Advanced Renal Cell Carcinoma

Systemic treatments for kidney cancer have evolved over the past 20 years or so. First with cytokines in the 1990s to early 2000s. These were things like interferon alpha and high-dose IL-2 [interleukin 2] that really made a difference for a very small proportion of patients who responded to systemic inflammatory responses. We then understood more about the hypoxia signaling pathways and how clear cell kidney cancer develops, and therefore there was a whole era of small molecules. So oral drugs targeted to blocking blood vessel formation, what we call antiangiogenic agents, or you’ll hear sometimes anti-VEGF [anti-vascular endothelial growth factor] agents. And these are mostly pills that patients take to help block blood vessel formation. And then in the most recent era, the past six years or so, we've seen an advent of immune therapy modulators. So treatments that are really targeted to activate T cells in the patients to attack the cancer cells. These have made it into combination strategies for systemic therapies, both as pure immunotherapy combinations as well as in combination with blood vessel blockade or anti-VEGF strategies.

Kidney cancer has evolved in many ways for the benefit of our patients in the past 15 to 20 years. When I was in fellowship training to be an oncologist, we used an immune therapy approach known as IL-2. The rationale behind IL-2 was [that we gave] this medication to stimulate an immune response, but the side effects of the treatment are that the patient’s blood pressure can go low or cause a fast heart rate. So we had to admit them to the ICU [intensive care unit]. And if the blood pressure got too low, we had to give medications called pressers to increase their blood pressure. We don’t really use that as much as we used to because we have much better medications. But after the IL-2 generation, we went to a different class of medication called tyrosine kinase inhibitors [TKIs].

What are TKIs? TKIs are like a key to a lock. So we had these targeted therapy medications that come in pill form. The patient would swallow the pill, and the medication would get absorbed and get into the blood vessel. It would then go to the different areas where the cancer is, where the blood vessels are called vascular endothelial growth factor. So it goes to the area and decreases the blood flow called VEGF. So that’s one class of medication. The evolution of kidney cancer treatment went from IL-2 to TKIs. There are different medications such as sunitinib, which was a TKI. Then we had something called cabozantinib, and then we had lenvatinib and now we had tivozanib. That’s the class of TKIs that decrease the blood flow at the level where the cancer is.

Now, about six years ago, the clinical trial for immunotherapy matured in kidney cancer. The landmark study was called Checkmate 214 [NCT02231749]. And what Checkmate 214 said is that patients with kidney cancer respond well to medications called immunotherapy. Now, what’s immunotherapy? Immunotherapy is an infusion. It looks like an intravenous bag of normal saline fluid that goes into your arm. And inside that fluid is a protein specifically called a checkpoint inhibitor.

What does a checkpoint inhibitor do? I like to use analogies to make things easier. The way I think about it is that some of us watch 

and they have a force field to protect an area. So kidney cancers and all cancers develop a way to protect themselves, and that is called resistance. We have stuff in our bodies called T cells. There are a type of white blood cell, and their job is to kill cancer. So when cancers develop and become resistant, they develop a force field around themselves. So you have all these T cells trying to get in there, and they don’t even know it exists. So a new class of medications called checkpoint inhibitors was developed. And the checkpoint inhibitor … removes the force field. It removes the checkpoint. So now your own white blood cells, and the T cells realize that there’s cancer in your body, and it starts attacking the cancer.

Immunotherapy is not chemotherapy. Immunotherapy is harvesting your own immune system to kill the cancer. One of the things that happens when patients develop cancer is the cancer cells try to survive. It forces a force field around it to protect itself. And this immunotherapy removes the force field to use your own T cells to kill the cancer. So that’s one of the landmark studies. The first was the IL-2, the second was the TKI and then the third was immunotherapy. So now we’re in that era of [combining] the TKI and the immunotherapy as two different medications to combat the cancer cells of the kidney. That’s where we are right now. We’re in the era of what’s called dual treatments; one medication is TKI, which could be cabozantinib, lenvatinib or axitinib. And then it’s got a dance partner of pembrolizumab or nivolumab based on the studies that we’re going to talk about.

Experts in the field of kidney cancer discuss the risk stratification process for renal cell carcinoma and its effect on prognosis.

Renal Cell Carcinoma Prognosis and Risk Stratification

Just to go back and talk about some of the statistics of renal cell kidney cancer, patients’ diagnosis, prognosis and so on. One of the things that we have to think about is something called the five-year survival. This is published by SEER [the Surveillance, Epidemiology, and End Results] program that provides cancer statistics. The five-year relative survival, which means al-comers, everybody that’s diagnosed with kidney cancer, it’s 77%. So that’s part of your survival. Now, what about the number of new cases? [In the United States,] 80,000 to 82,000 people are diagnosed with kidney cancer, which is about 4% to 5% of all cancers. Now, what about deaths? On average, about 14,000 to 15,000 people, unfortunately, pass away from kidney cancer every year.

How do you stratify people into different groups? As a cancer doctor, we use something called stages. It essentially boils down to people wanting to know how bad their cancer is. So I tell my patients stage 1, stage 2, stage 3 and stage 4. The way we describe stage 1 is if the cancer inside the kidney is less than 7 centimeters. So it’s strictly a size criterion. If the cancer is greater than 7 centimeters, it’s stage 2. Stage 3 is if the cancer spreads. The kidneys have a lining around them. The example I give to my patients is if I put my hand in a glove and the glove covers up my hand; a kidney also has a lining around it, just like a glove around my hand. So if the roots of the kidney cancer spread into the lining, they call it a fat pad or adipose tissue or into the blood vessels; that’s considered stage 3. Stage 4 is if the cancer cells jump into blood vessels, go into the blood and spread to the lung, liver or bone. So that’s how we determine the different stages.

In terms of cure, [it] is technically here in 2023 for stage 4 kidney cancer; some of the patients I’ve had scans for stage 4, and all the cancers disappeared. So I’ve seen patients [who are] in remission. I’m not sure if we want to use the word “cure” because we still want to keep an eye on the patients. But typically that’s how we determine prognosis, and that’s with the five-year survival. Now, how does the local and distant metastasis impact the patient’s prognosis? If it’s distant metastatic disease, that means that there tends to be cancer in other places. … [We use] that example of a seed. It takes millions of cancer seeds to come together to form 1 centimeter. So on a CT scan or an MRI, if you see a 1-centimeter lesion, that tends to be millions of cancer cells stuck together. Therefore, chances are there’s microscopic cancer somewhere. Now, what’s the risk of recurrence? Depends on whether you get a treatment or not. And we’re going to talk about some of the clinical trials. There are different risks of recurrence based on the treatment. And that has to do with immunotherapy versus immunotherapy and a targeted medication.

In kidney cancer, we talk about localized regional disease with lymph node involvement or distant metastases spread to distant organs. For these patients, often the localized disease settings are treated with surgery. In those cases, the five-year relative survival rates per the SEER databases are quite high, about 93% in regional disease, so patients who have lymph node involvement. For example, these patients often have a five-year survival rate of around 72%. And for patients with distant metastatic disease, the 5-year relative survival rate is around 15%. These are based on SEER population data from all the patients who are currently diagnosed and treated in the United States. As our treatment options improve for metastatic disease, hopefully, the long-term survival rates will also improve for patients with metastatic disease.

Risk for recurrence varies based on histology as well as patient risk factors. Often these depend on the size and invasion at the time of tumor removal. So when we’re talking about post-op patients and their recurrence risk, these often involve both their clinical and pathologic features at the time of surgery. There are good risk modeling calculators that we use to think about risk for recurrence, but these are really tailored for each patient.