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When it comes to radiation therapy, there is plenty for patients with kidney cancer to discuss with their care teams, as Susan Poteat, 

Poteat is a medical physicist specializing in radiation therapy, as was her husband, who died approximately 15 months ago after living with metastatic kidney cancer for 15 years. She spoke with CURE® about some of the things that patients need to keep in mind and conversations they should have with their care teams about radiation therapy.

When discussing a study on stereotactic ablative body radiotherapy (SABR), Poteat noted that “there are multiple terms that get used to describe [the act of] using many, many beams of radiation to tightly focus on a small target and be able to give a large dose there,” stating that some may be more familiar, for example, with SBRT, or stereotactic body radiotherapy.

“I do encourage patients to remember that it is skill-dependent — just like you wouldn't have a difficult surgery done at a community hospital, you shouldn't have SABR done at a community hospital in general,” she said. “... A lot of community hospitals have experience using SABR in lung [cancer] and there's usually nothing too delicate nearby, but when we start talking about in the abdomen, there are a lot of radiosensitive tissues there and a lot of special considerations. So, I think [patients] should talk to their oncologist in some cases about using SABR in their course of treatment, but they also should talk to their oncologist about where's the nearest academic center with an outstanding radiotherapy program.”

The use of SABR, Poteat said, has “a very, very clear space for patients who get just a few brain [metastases],” stating kidney cancer metastasizes to the brain for approximately 30% of patients.

Additionally, Poteat said, “we have a lot of patients who are doing very, very well on their drug treatment, and then there's this one spot that pops up, it's developed some sort of resistance, it's growing on multiple scans. If everything else is going well, the patient can very likely extend their time on that particular drug by ablating that single place that's the bad actor and is growing.”

“Community physicians may not bring that [strategy] up,” she said. “So, it's appropriate for patients to ask about that. And ask who they could ask for a referral to radiation therapy and go talk to someone who's knowledgeable about that.”

“I do think, more than anything else, knowing that your medical oncologist may not think about whether radiation would help the current thing that just popped up for you [is important],” Poteat said. “And it's OK to ask, ‘Is there any point in me talking to a radiation oncologist about this?’ He's very likely going to refer you for a bone [metastasis] or brain [metastasis]. But there are other times in your care path [when] you might wonder [about radiation], and it's fine to ask.”

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

An expert explains what patients need to keep in mind and what conversations they should be having with their care teams.

What Patients With Kidney Cancer Need to Know About Radiation Therapy

An expert said that he is optimistic about the future use of biomarkers in the kidney cancer space. 

What Are Biomarkers and How Are They Used in Kidney Cancer? 

Not all patients with kidney cancer need to undergo extensive biomarker testing with the current treatments available, but Dr. David A Braun said that he is optimistic about the future of biomarker testing for this patient population.

According to the American Cancer Society, “biomarkers are genes, proteins or other substances that can be tested for to reveal important details about a person's cancer.” Oftentimes, biomarkers can be used to determine more personalized treatments for patients or lend insight into their prognosis.

The most common biomarker used in the kidney cancer space is determining whether patients’ disease have sarcomatoid or rhabdoid histology, which could indicate that patients are more likely to respond to immunotherapy or other targeted therapies, explained Braun, who is an assistant professor of Medicine at Yale Cancer Center.

 to discuss the current and future use of biomarkers in patients with kidney cancer.

Not all kidney cancer patients undergo extensive biomarker testing, meaning genomics and transcriptomics. And these sorts of things. But I think the real answer is they shouldn't at this stage.

I'm really optimistic about biomarkers. I think they play an important role, and I think we'll see lots of developments in the years to come. But if we were to sit here and say, ‘Today, how does this affect my practice? Monday morning in the clinic, how's this going to affect that kidney cancer patient in front of me?’

Really, the only biomarker at this point that's actionable is not something new, it's not advanced. It doesn't catch headlines, but it's looking under the microscope and understanding the histology. And particularly for kidney cancer, it's having sarcomatoid or rhabdoid histology. Those features are really suggestive of something that's much more likely to respond to immunotherapy and much less likely to respond to other targeted therapies. And so again, where my hope is, [that] we'll eventually enter an era where sequencing and single-cell approaches will have really utility and I think we will get there. But where we are right now, it's really the histology that looking at a microscope that plays the biggest role in terms of biomarkers.

Transcript was edited for clarity and conciseness.

'No Stupid Questions' for Newly Diagnosed Patients With Cancer

Finding a patient support group could be essential after being diagnosed with kidney cancer, explained Dr. Rachel Giles, chief executive officer of the International Kidney Cancer Coalition.

In a recent interview, Giles explained that the time after diagnosis can be extremely overwhelming for patients, as they navigate treatment options and side effects. By becoming educated about their disease and joining a group of individuals who have gone through something similar, this burden can be a bit easier to bear, Giles said.

It's all about getting the right information. And like I said, the most vulnerable time for a patient is after diagnosis when they have been told that they have cancer, in this case. And (regarding) the choice that they make the treatment that they start, there is a huge amount (of decisions) … often just a few short weeks. And in those that period of time, the patient has to become essentially an expert in their disease condition and figure out all the options plus perhaps what their doctors may not be telling them. So sometimes you have the guidelines that are approved in whatever country you are, and you need to compare that with what the options are, that are being provided, because some hospitals may leave out options. So we try and help that.

But typically, I tell patients to go find a patient organization; this will support you tremendously at all levels. They'll give you information, you'll find a peer-to-peer support system where you'll learn about your condition, and perhaps people can turn you on to ideas you've never even thought about. And also during treatment, of course, this is a very helpful resource because you actually have someone to turn to and say, “I am having a lot of diarrhea,” for example. “What products and what stores do you buy (medications to help) at?” It can be very specific and that's, that's tremendously useful information.

So I would tell patients to take the time to breathe in, breathe out. There's a lot of information out there, it's not impossible, but it is a lot of work, and it's hard to do when you're dealing with the impact of a problem, possibly an out-of-the-blue of a diagnosis.

In the situation of kidney cancer there, it's typically asymptomatic — you have no symptoms whatsoever. And you we found a lot of people, for example, were being diagnosed with the renal masses, as they call them during COVID, because they were going to get their lung CT. And the kidneys are behind the lungs. So that would come up in the imaging. And we had, I think, all the patient organizations in kidney cancer (space) got that huge uptake in phone calls, and requests for support because they didn't know what to do with these small renal masses. You know, we don't know if they're really going to be cancer or not what they are, it could take years before they become anything scary. But no one really knows and there's no guidelines for that.

So the idea is to just find your patient organization, try and find a partner. You know, some people get binders and actually put all the information into one place. Whatever works for you, is convenient, but do take the time to understand the information and ask questions. Don't be scared. There are no wrong answers, no stupid questions. And it's important to be aware that your options are what they are and that they're the right options, that they're guidelines that they're compliant to the guidelines, make sure that you're getting what you should be getting. And but typically, that's not a problem. It's just occasionally and just ask questions.

An expert stressed the importance of finding a patient support group and asking questions after being diagnosed with kidney — or any other form — of cancer. 

‘No Stupid Questions’ for Newly Diagnosed Patients With Cancer

Focused Radiation Has ‘Good Success’ for Metastatic Kidney Cancer

Though not curative, stereotactic radiation — which is a method of delivering radiation to precise locations within the body — is an effective treatment strategy for certain patients with metastatic kidney cancer and may be able to delay the need for taking drugs to treat the disease, according to Dr. Raquibul Hannan.

In a recent interview with CURE®, Hannan, who is the chief of Genitourinary Radiation Oncology Services at UT Southwestern Medical Center, discussed the use of stereotactic radiation in patients with metastatic kidney cancer.

“Those patients we had very good success by doing focused radiation to all sides of visible metastasis,” he said.

We first look and see if metastatic kidney cancer can be controlled with stereotactic radiation, and now we have published results that shows that more than 90% local control with stereotactic radiation, again with minimal toxicity for tumors that are metastatic and it could be metastatic to any part of the body.

But oftentimes you have patients with many number of metastasis So how do you integrate radiation or stereotactic radiation for those patients? That's the main question. So two places where we found application of this one is the oligometastatic setting. So when the kidney cancer patients are coming in with metastasis in one, two or three, or four or five sites only, and the patient's biology suggests that there are not a very aggressive biology such as IDTC, favorable and intermediate risk. So we know that these patients are not going to rapidly progress. Those patients we had very good success by doing focused radiation to all sides of visible metastasis.

We're not curing those patients. We know there are other sides of metastases that are unseen or are metastases that will eventually grow, and the patient will eventually need systemic therapy. However, by giving the radiation and controlling them temporarily, we delay the start of systemic therapy. We preserve the quality of life for these patients. And eventually when the patient do start systemic therapy, we think that the efficacy of the systemic therapy will not be compromised. So we have now published a retrospective study and a prospective small single arm phase 2 trial confirming these findings.

Stereotactic radiation is promising in treating patients with metastatic kidney cancer and may delay the time until patients need further treatment, an expert said. 

CAR-T cell therapy holds promise to become a standard of care for patients with advanced renal cell carcinoma (RCC) who experienced progression on checkpoint inhibitors and VEGF inhibitors, according to Dr. Michael Hurwitz.

Several clinical trials are ongoing in RCC, most of which involve therapies targeting CD70, as well as CAIX, AXL, ROR2, VEGFR2, MUC1 and c-MET.

“The ones I’m going to concentrate on today are the CAIX and CD70 (because) those are the only ones for which we have results,” noted Hurwitz, associate professor of internal medicine (medical oncology) at Yale School of Medicine in New Haven, Connecticut, in a presentation delivered during the 2023 International Kidney Cancer Symposium.

The first trial Hurwitz covered was that of a CAIX CAR-engineered T cell, results from which showed the importance of the “on-tumor, off-target effect.” Although CAIX is highly expressed in kidney cancer, it is also found in biliary epithelium. In the trial, half of patients in the first two cohorts had dose-limiting liver toxicity, but when an anti-CAIX antibody was administered to patients in the third cohort to mitigate the toxicity, no objective responses occurred.

An alternative target is CD70, Hurwitz said, with high expression across clear cell, papillary, sarcomatoid, chromophobe and translocation histologies.

Hurwitz first discussed the phase 1 COBALT-RCC trial, which evaluated CTX130 allogeneic CRISPR-Cas9–engineered CAR T cells in patients with advanced clear cell RCC.

“The advantages (of allogeneic products) are you don’t have to wait four weeks to get this into patients; the cells that you get are from healthy donors (with an) intact immune system, and you can make tons of it,” Hurwitz noted.

The trial evaluated four dose levels ranging from 3x107 to 9x108 CAR-T cells, but only one response was seen in the first dose level cohort. Nine patients experienced stable disease, translating to a disease control rate (DCR) of 77% (10 patients). By four months, only four patients remained in stable disease. The one patient with partial response reached complete response by month three and has sustained this response through month 18.

The product was also safe, with no side effects leading to dose limitations observed across any of the dose levels. Overall (14 patients), seven patients experienced grade 1/2 cytokine release syndrome (CRS) and four patients experienced infections (grade 1/2, 2 patients; grade 3 or higher, two patients).

“There were no instances of tumor lysis syndrome, infusion reactions, HLH, ICANS, GVHD or second malignancies,” Hurwitz noted.

Another allogeneic cell therapy, data from which were presented at the 2023 AACR Annual Meeting, has also generated excitement for the future of cellular therapy. In results from the phase 1 TRAVERSE trial, ALLO-316 demonstrated preliminary antitumor activity in patients with advanced or metastatic clear cell RCC.

The trial was similar to COBALT-RCC in that investigators evaluated an anti-CD70 allogeneic CAR T-cell therapy. However, the studies had several differences.

“They knocked out the T-cell receptor, so they wouldn’t recognize the recipient, and they knocked out CD52. The reason they did that is so they could use an anti-CD52 antibody, and that’s very immunosuppressive. They do that to make sure that these T cells stay around. They also knocked out CD70 because although CD70 is highly expressed in kidney cancer cells, it also is upregulated on active immune cells and they were worried about fratricide,” Hurwitz said.

The product was shown to be “pretty safe” Hurwitz said, although the rate of all-grade cytokine release syndrome was 58% (grade 3 or higher, 5%). In addition, among all patients who received ALLO-316 (19 patients), infusion-related reactions (all grade, 5%), neurotoxicity (all grade, 68%; grade 3 or higher, 11%), infection (all grade, 42%; grade 3 or higher, 21%) and prolonged grade 3 cytopenia (16%) occurred. Higher efficacy was seen with the product, Hurwitz said, with an objective response rate (ORR; percentage of patients whose disease shrinks or disappears from treatment) of 17% and a DCR of 89% among the 18 patients evaluable for efficacy.

Notably, in patients with CD70-positive disease (10 patients), the ORR was 30% and the DCR was 100%. Moreover, median progression-free survival (time from treatment until disease worsens or death) was five months in this population.

“They also showed that even 70 or 80 days out if they use a very strong conditioning regimen, the (cells) stayed around a long time. And we know that durability of response has to do with persistence of the cells,” Hurwitz said. Additionally, ALLO-316 was shown to eliminate CD70-positive host T cells, preventing allorejection and supporting persistence.

Hurwitz concluded by explaining that for CAR-T cell therapy to land in the kidney cancer armamentarium, several challenges will need to be addressed including persistence, antigen loss from therapy, tumor microenvironment toxicity and the inability to infiltrate the tumor.

“This (area of research) is exciting, there are some responses, (but) we’re not there yet. This is just the beginning because there are many different technologies that we can use to make these T cells much more effective,” he said.

While CAR-T cell therapy is showing promise in treating patients with advanced renal cell carcinoma, there is still more research that needs to be done in this arena. 

CAR-T Cell Therapy Is ‘Exciting’ in Advanced Kidney Cancer

With many surgical options available to treat patients with kidney cancer, it is important for patients to make informed discussions with the care team to understand what approach may be best for a patient’s disease type and stage.

According to the American Cancer Society, surgery is the most common treatment for patients with kidney cancer, and most people with early-stage disease (meaning stages 1, 2 and 3) can be cured with this approach. The primary goal of kidney cancer surgery is to remove or treat the cancer effectively while preserving kidney function and providing the best possible outcome and quality of life for the patient.

There are several different types of surgeries for kidney cancer, each with its specific indications and appropriateness based on the stage and characteristics of the cancer. Here are the main surgical options and when they are typically considered appropriate:

Partial Nephrectomy (Nephron-Sparing Surgery)

This type of surgery is appropriate for small to medium-sized tumors (T1 and some T2 tumors) that are confined to a specific area of the kidney. In addition, it is suitable when the tumor is in a location that allows for the preservation of kidney function.

It is the preferred option when the patient has only one kidney or has pre-existing kidney disease.

Compared with a partial nephrectomy, a radical nephrectomy, which is when the entire kidney is removed, is appropriate for larger tumors that have grown beyond the kidney's boundaries or when the cancer has invaded nearby structures.

This is recommended when the tumor is large, the kidney function is already compromised or there is evidence of cancer spreading outside the kidney.

These approaches are suitable for small- to medium-sized tumors (T1 and some T2 tumors) that are confined to the kidney and haven't spread to other organs. They are also preferred for patients who desire a less invasive approach, smaller scars, reduced postoperative pain and quicker recovery compared to open surgery.

With laparoscopic surgery, the surgeon makes a few small incisions (usually three to four) in the abdomen, and a thin tube called a laparoscope, equipped with a camera and light source, is inserted through one of the incisions. Other tools are inserted through the other incisions, allowing the surgeon the manipulate and remove the tumor.

Of note, robotic-assisted surgery is similar to laparoscopic surgery to uses robotic technology to enhance the surgeon’s precision and control.

These approaches may not be suitable for large tumors or those with complex locations that require more extensive surgical access.

This procedure is appropriate for small kidney tumors (T1a tumors) that are localized and haven't spread outside the kidney. In particular, it is suitable for patients who may not be eligible for traditional surgery due to medical conditions or poor overall health.

Cryotherapy, also known as cryoablation, is a minimally invasive procedure used to treat kidney cancer by freezing and destroying cancerous cells within the kidney. In contrast, radiofrequency ablation uses heat to destroy cancer cells within the kidney.

These approaches may not be recommended for large tumors or tumors in critical areas where preserving kidney function is essential.

This is often used as a pre-surgery treatment to shrink larger tumors and reduce blood loss during surgery and is appropriate when the tumor is too large for other treatments or when surgery alone may cause excessive bleeding. It can also be used as a palliative treatment to alleviate symptoms caused by larger tumors, even if the cancer cannot be completely removed.

With embolization, the surgeon blocks the blood supply to the tumor, which reduces the tumor’s blood flow and causes it to shrink, potentially alleviating symptoms.

Nephrectomy with Inferior Vena Cava Thrombectomy

This complex surgical approach is appropriate when the cancer has extended into the large vein that carries blood from the lower body to the heart. It is often considered for patients with advanced kidney cancer who require removal of the kidney and the tumor thrombus within the vein.

It is important to note that the appropriateness of each surgical option depends on the individual patient's condition, the stage of the cancer, the location and size of the tumor, and the overall health of the patient. Treatment decisions should be made after a thorough evaluation by a multidisciplinary team, including urologists, oncologists and other specialists.

With surgical techniques applicable to many stages of kidney cancer, it is important for patients to discuss these options with their cancer team to select the best approach for their disease.

Surgical Approaches May Treat Kidney Cancer of Various Stages

While prior research has shown that clonal hematopoiesis can be associated with blood cancers such as chronic myeloid leukemia or myelodysplastic syndrome, more recent data shows that it can also be a driver for cardiovascular disease in patients with cancer. The association between clonal hematopoiesis and death due to heart complications was particularly strong among patients with kidney cancer, explained Dr. Maxine Sun.

Sun, who is a scientist who focuses on genitourinary oncology at the Dana-Farber Cancer Center in Boston, recently presented her research on clonal hematopoiesis and cancer at the 2023 

“I found that in patients with various types of cancers, that it was associated ultimately with death from cardiovascular disease — mortality, or coronary artery cause-related mortality in patients diagnosed with cancer, and that this effect was particularly relevant for patients diagnosed with kidney cancer,” she explained in an interview at the conference.

Of note, prior research has shown that survivors of childhood cancer also tended to have a higher rate of clonal hematopoiesis than individuals without a cancer history.

Childhood Cancer Survivors Have Higher Rate of Aging-Related Mutations Than the General Population

My work relates to clonal hematopoiesis. I don't know if you've ever heard of that term before. It's a very interesting topic nowadays. (Clonal hematopoiesis is) basically when a mutation gains a survival advantage over other normal hematopoietic stem cells, and so it expands and becomes like a clonal expansion.

And so recently, in the last five or six years, clonal hematopoiesis has found to be a link with cardiovascular disease. So previously, it was an established driver for blood cancer. And very recently, so they found that it was associated with cardiovascular disease. And what's interesting in relation to the work that I did, was that within a UK Biobank, I looked at clonal hematopoiesis, and I found that in patients with various types of cancers, that it was associated ultimately with death from cardiovascular disease — mortality, or coronary artery cause-related mortality in patients diagnosed with cancer, and that this effect was particularly relevant for patients diagnosed with kidney cancer.

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In patients with cancer, clonal hematopoiesis was associated with cardiac toxicity and in increased risk of death due to heart conditions. 

Kidney Cancer

LIVING WITH CANCER

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