Improvements in Surgical Technique Offer Better QOL in Kidney Cancer

Farshid Sadeghi, MD

City of Hope Phoenix

Multidisciplinary collaboration from surgical surgeons to intervention radiologists is crucial for the optimal treatment of kidney cancer. Although there have been no practice-changing technological advances in recent years, progress in technique and knowledge has improved outcomes for a wider group of patients, according to Farshid Sadeghi, MD.

In a conversation with CancerNetwork^® during Kidney Cancer Awareness Month, Sadeghi, a urologic oncologist and medical director of Genitourinary Center at City of Hope Phoenix, spoke on standard surgical treatment practices, recent therapeutic developments, and some notable areas of focus in terms of research in the kidney cancer space.

Importantly, Sadeghi offered advice to other multidisciplinary care teams in the kidney space.

“Always work together. Try to always keep up with all the data out there, both in the urology space and the medical oncology space. More importantly, work with your colleagues because they can educate you, and you can educate them more than any textbook or journal can,” Sadeghi concluded.

CancerNetwork^®: What does kidney care look like at City of Hope?

Sadeghi: We have a multidisciplinary approach for managing patients with kidney cancer. We treat patients from the earliest stage—stage 1—to advanced-stage and metastatic disease. We cover the full gamut. The physicians who are intimately involved with managing patients [with kidney cancer] are myself and urologic oncologists; I offer surgical management.

We have an interventional radiologist who treats kidney cancers with ablative technologies and medical oncologists who support us after surgery and treat patients with metastatic disease. That’s generally how kidney cancer should be treated anywhere across the country.

Have there been any recent updates in the surgical kidney space is of interest?

The main updates are just improvements in technique. Robotic partial nephrectomy, for example, has been around for at least 15 years, and, in my practice, it has been around for almost 19 years. However, as we’ve become more facile with robotics, there are now new tools [in terms of] robotic technology. We’re treating patients we wouldn’t have treated with a robot before.

That’s hugely important, because you take patients who would have had a post-operative course that would have been fairly long in the old days. Now, because we’re doing the procedure robotically, they have a much more rapid recovery. We’re offering surgery to patients who previously would have been either excluded from receiving cytoreductive surgery or would have had more complications.

For example, we had a patient with a level 2 vena cava thrombus—kidney cancer that travels up the vena cava; it doesn’t go above the liver but it reaches up to the liver. Historically, you would have had to perform this major open operation; you have to open up the vena cava, extract the tumor thrombus, perform the nephrectomy, and close the vena cava. It’s a high-risk procedure, and it requires a very large incision.

However, because I’ve become better with robotic surgery and because the surgical oncologist and the vascular surgical oncologists are better, we did the entire case robotically. The largest incision we made was approximately 7 cm to extract the kidney and tumor thrombus together. The patient only stayed in the hospital for 3 days and could have actually gone home in 2 days, which would have been unheard-of before.

We also offer cytoreductive surgery when a cancer has metastasized. Historically, it has been shown in older data that if you remove the kidney in a patient with metastatic cancer, they may have a survival benefit. We offer the cytoreductive surgery, either laparoscopically or robotically. Because we’ve gotten better at it, we offer it to patients with larger tumors up to 18 cm. We do it laparoscopically, and because we’re only making a small incision to extract the kidney, the patients recover more quickly, and then they can go on to treatment a lot sooner than they did 15 or 20 years ago.

What have been the most notable recent changes in the standard of care in this space?

The big change has to do with the fact that for the last 10 to 15 years, we’ve had a lot more systemic therapies to offer patients with kidney cancer. We’ve been offering immunotherapy and multi-kinase inhibitors. Kidney cancer is not chemotherapy-responsive, so the standard chemotherapy that we give to [treat] bladder cancer and testicular cancer, kidney cancer does not respond at all.

It [does], however, respond to immunotherapy. The way I explain multi-kinase inhibitors to my patients is that [they] try to choke off blood supply to the cancer to prevent it from growing.

The big difference has to do with multiple randomized trials examining older drugs we use vs immunotherapy and multi-kinase inhibitors and using them in the adjuvant [setting]. If you have patients with aggressive kidney cancer, either high-stage or very high-grade, there’s a high degree of certainty they will develop metastases even if the pathologic features are favorable.

There have been trials assessing immunotherapy immediately after surgery. These are very valid trials because they weren’t open-label; they were placebo-controlled, double-blind randomized trials. They showed a survival benefit in patients who get immunotherapy immediately after surgery when they have advanced cancer without metastases rather than waiting for them to develop metastases as we used to and then giving them systemic therapy.

That, to me, is very exciting. Now, if I have a patient with advanced-stage cancer, rather than monitoring them until they progress after surgery, we can treat them and reduce the risk of the cancer coming back.

You were an early adopter of laparoscopic and robotic-assisted surgery. Are there any other recent technological developments with practice-changing potential?

Not yet, [although] there have been efforts. There have been improvements, but [they haven’t produced] huge changes. We used to do retroperitoneoscopic laparoscopic surgery, which blows up the space behind the kidney and [allows us to] do the surgery from behind the kidney. We’ve converted to using that technique with a robot. That’s just a conversion, and I’ve been doing that for 10 or 11 years, so it’s not very new.

When you perform a partial nephrectomy, you temporarily choke up the blood supply to the whole kidney, so you’re causing some warm ischemia [and] you’re potentially losing nephrons as you’re operating. There have been efforts to identify the blood vessels that selectively infuse the mass as opposed to whole kidney and to selectively clamp those blood vessels to protect the rest of the kidney. However, that idea has not been adopted across the country because it’s very difficult to intraoperatively identify where the blood flow is going.

The big missing piece in kidney cancer surgery is to figure out if there’s some type of dye we could administer to patients, the [disease] could be selectively infused relative to the rest of the kidney, which would help us selectively occlude the blood supply to the mass. More importantly, if we could identify where a mass’ margins are, we wouldn’t have to use our eyes to determine where to cut. We would have an identifying pigment dye or even fluorescence to tell us where that space is, so we know where to cut.

[However], from my standpoint, the vast majority of [recent] advancement has not been made in surgical technique; it has been made in when to operate, in using the appropriate systemic therapies, and in knowing when to wedge in surgery relative to systemic therapy.

What are some areas in this space that should be focused on in terms of research?

There are quite a few. [Firstly], we still don’t have any type of screening test for kidney cancers. Approximately 70% of kidney cancers are identified by chance alone. [This usually] means that a patient has an imaging study to work up some type of abdominal pain or kidney stone or a screening study for some other cancer such as prostate cancer and then we identify the kidney mass. [In the other] 30% of [kidney cancers], the mass has grown to the point where it has become symptomatic. It’d be useful to have some type of staging protocol or predictive tool as to why people develop kidney cancer.

Additionally, we have patients who receive surgery and then adjuvant therapy; some respond and some don’t. It’d be very useful if we had biomarkers or molecular markers that would help predict who is going to respond. [With that information], we might be able to alter therapy. Right now, we give immunotherapy in the adjuvant setting; maybe we would change that if we had molecular markers. [Maybe], for those patients we would give multi-kinase inhibitors in the adjuvant setting or give both immunotherapy and multi-kinase inhibitors up front. Having some kind of molecular marker or predictor of who will respond to therapy is a huge need.

Figuring out, from a surgical standpoint, how to give cold ischemia—how to ice the kidney during robotic surgery—would be a huge benefit. As we get better [at these surgeries], we are treating more complicated patients. When we have a lot of patients with a solitary kidney and a kidney mass, I’m still very conservative in those cases; I do open surgery. Why? Because I can ice the kidney and protect the nephrons as I operate. It’d be fantastic if we came up with a strategy for cold ischemia that worked reliably. That way, we could marry the benefits of cold ischemia with minimally invasive surgery.

How do multidisciplinary considerations factor into surgical kidney care?

It’s important to be humble as a surgeon; no matter how good you are, the location of the kidney cancer still predicts how well you’re going to resect it. There are kidney cancers that are endophytic or posterior that are just hard to access. There are 2 philosophies: One is to be conservative and only try to operate on those with a high degree of certainty. You know you’re going to take the mass out and leave the kidney behind. The other philosophy is: ‘We’re going to make an attempt. If it doesn’t work, we’ll convert to an open procedure or into a nephrectomy.’

The better approach is to consult with your interventional radiologist, put your heads together, and see who thinks they can more favorably access the mass or even work together. For example, we might have an anterior mass that is endophytic. The interventional radiologist might have difficulty accessing it percutaneously; I would have difficulty visualizing it, but we can work together.

I could go in laparoscopically, use a drop-in ultrasound to identify the mass, and then work with the interventional radiologist to then place cryotherapy needles into the mass. The goal should always be to try to preserve the kidney and avoid open surgery or surgery with more morbidity than you anticipate. There’s a benefit to working together to come up with the best strategy. I’m happy to say that’s what we do here [at City of Hope] almost all the time, and it’s also reflected in the number of percutaneous treatments we do.

I’m very honest with patients. I tell them that I can go in robotically, laparoscopically, or even [with] open access to the kidney. I tell them, ‘These are the drawbacks. You may want to consider cryotherapy for a percutaneous approach,’ and we’ll monitor them almost the same [regardless]. The protocol for surveillance is not very different for ablative treatments vs surgery. [Moreover], if the minimally invasive approach fails, we still have the option of doing the robotic surgery or even open surgery.

Additionally, the cytoreductive surgery is based on very old data. It’s based on interferon, which is something we never give anymore. So, we really don’t know [if using] these immunotherapies or combined therapies systemically for metastatic [disease] or if taking the kidney has a survival benefit. If you talk to medical oncologists, they say no.

I still think it might have some quality-of-life benefit, if not survival benefit. In my experience, in the patients I follow for metastatic disease whose kidneys have not come out, even though the metastases respond nicely, the kidney itself does not respond as well as one would expect. It’s also important for the medical oncologists and the urologist to work together to find out if there’s the window of opportunity to remove the kidney, especially with minimally invasive approaches that would not delay systemic treatment. That’s another way to have a multidisciplinary discussion on the treatment of kidney cancer.

The end goal should be a survival benefit and quality-of-life benefit. We have different experiences, we have different hats we wear here, and we’re very respectful of each other. We’re physically very close to each other; I walk two offices [down] to get to my interventional radiologist, and [I’m] two doors [away from] all my medical oncologists. We do medicine the old-fashioned way: we go up to each other and have a discussion, we put our heads together, and come up with what we think is the best for the patient.