Who Benefits From Cytoreductive Nephrectomy? Q & A with Dr. Jose Karam 

By D’Ann George, PhD, Medical Writer

A nephrectomy is surgery to remove all or part of a kidney, but when someone has surgery to remove a kidney tumor that has metastasized (spread) to other areas, the name for the procedure is called a cytoreductive nephrectomy. In years past, this procedure provided the best option to prolong survival for people with metastatic renal cell carcinoma (mRCC) because no effective pharmaceutical treatments existed for this patient group. 

In recent years, fewer people with mRCC are receiving cytoreductive nephrectomy, largely due to the success of immunotherapies and targeted therapies as first-line systemic (non-surgical) treatments for metastatic disease. 

Nevertheless, some people still benefit from the procedure either before or after receiving systemic therapy, said Dr. Jose Karam, a kidney cancer expert and urologic oncologist at MD Anderson. Dr. Karam, who is also a member of the KCA’s Medical Steering Committee, explained when, why, and for whom he recommends cytoreductive nephrectomy today. 

Nephrectomy can help people with kidney cancer that is limited to the kidney reach No Evidence of Disease (NED) status. Can cytoreductive nephrectomy do the same for people who have mRCC?

If somebody has metastatic disease and we’re doing a nephrectomy in that setting, we’re generally just removing the kidney and the surrounding tissues, but we’re leaving behind the lung nodule, the liver nodule, the chest lymph node, or anywhere the cancer cells may have spread. So because of that, we call it cytoreductive, meaning remove as many cells as possible. Cyto means cells and reductive is decreasing the amount. But generally, cytoreductive nephrectomy is not done with a curative intent for the majority of mRCC patients, unfortunately. 

In clinic, I tell my patients that we cannot cure the vast majority of people with this surgery. But what we hope is to prolong the overall survival and improve the quality of life in select patients. 

For the KCA’s Patient Video Library, Dr. Eric Singer, currently of Ohio State University Comprehensive Cancer Center, discussed how patients can prepare for any kidney cancer surgery.

Is “debulking surgery” another name for cytoreductive surgery?

It is roughly equivalent. Debulking is removing the bulk of the tumor, which is kind of the same thing as cytoreductive nephrectomy. But debulking sounds a bit more medieval, I think, than cytoreductive – like you’re getting a shovel and just shoveling tumor out. I know it’s used for gynecological cancer a lot, but for urology generally we’ve all used cytoreductive nephrectomy. 

Who would you recommend cytoreductive surgery for? 

From a clinical practice standpoint, there are two ways to try to pick patients who might benefit [meaning living longer] from surgery. One of the ways is to use preoperative risk factors, meaning information that you have when the patient shows up to your clinic, that there are several ways to do that. There is not one set of perioperative risk factors. The fewer the risk factors, the more someone might benefit from cytoreductive surgery before systemic therapy. 

The second way to try to figure out who might benefit from surgery is not a static way like the first one I described– it’s more dynamic. We won’t do surgery first. We’ll refer them to [a medical oncologist who] will give them therapy, and then six months later, we reassess if the patient is responding to the therapy, feeling better, performance status improved and the bulk of their tumor is in the kidney and few metastatic areas. It all depends on the bulk of the tumor. There is data to say if you can remove more than 90% of the disease in the patient by doing the nephrectomy, it might help the patient. 

Could the surgery potentially make people more responsive to immunotherapy?

We don’t know. There is no specific data. Some people argue that it’s better to keep the primary tumor because it produces some antigens that help the immunotherapy work better. So it’s not clear. And it might be cancer dependent. It might work like that for some cancers, but not necessarily for kidney cancer. 

How do you know when cytoreductive nephrectomy is not a good option for someone?

If the patient is not responding to the best [systemic] therapy that we have, we know that these patients are not going to benefit from surgery. Let’s say they get the best medication we have today for three months, and all their tumors are still growing. There’s no point in doing surgery for these patients because we know we’re not going to help them. So we know from our data and other data that if I operate on a patient like this, their survival is the same as if I did not operate on them. So what’s the point of putting them through a big surgery? If they respond, that might encourage us to offer them surgery – as long as the bulk of the tumor is in the kidney. If the kidney tumor is [golf ball sized] but they have lung and liver lesions [the size of an orange], there’s no point just to take the kidney out and leave the majority of the disease outside the kidney. 

Have there been randomized clinical trials proving whether or not this surgery, when combined with systemic therapy, can prolong overall survival in people with mRCC?

Data for risk factors and response that helps us pick patients for surgery is mostly retrospective, which is less convincing evidence. Two recent trials – CARMENA and SURTIME – in the last five years have been prospective, which is more convincing and showed surgery does not help, but they used sunitinib, which is a drug we don’t use as much anymore. 

These trials do show a subgroup analysis where cytoreductive surgery might help patients – these are the ones who got medication for a while, responded, and then had surgery. These are patients that might benefit from cytoreductive surgery. That’s what we’ve been trying to do in selecting who we might help rather than offer surgery to everybody. 

Are there more recent randomized trials incorporating the use of immunotherapies combined with cytoreductive nephrectomy to see if this surgery adds any survival benefit over immunotherapy alone?

There are ongoing clinical trials with immunotherapy, but they will take several years to give us results. 

Who usually makes the call about whether or not–and when– to recommend this surgery to people? Is it the urologist, or the oncologist?

That’s a great question, and it depends on who the patient sees. If a patient sees the urologist first, that urologist might make that decision. If the patient sees the medical oncologist first, the medical oncologist makes that decision most of the time. 

The ideal setting, which is what we do in our center, is that the medical oncologist talks to the urologist and vice versa so that we both make the decision. Or we present the patient in our weekly [team meeting] to make sure that we’re not withholding surgery from somebody who might benefit from it and vice versa. We want to make sure we’re not doing surgery on somebody who we might not help.

Are there professional guidelines that help people make a decision regarding this surgery? 

There are guidelines, but the guidelines are, on purpose, kind of vague, to leave leeway for people to do what they think is best for the patient. The European Association of Urologists guidelines say if somebody has poor risk features, they should not have surgery. This is a strong recommendation. All the other recommendations from the National Comprehensive Cancer Network guidelines are labeled as weak. They say if a patient, a surgical candidate, has clear cell cancer and they don’t have poor risk, then they should be considered for surgery in select patients.

It helps [to] communicate with the medical oncology team and say, “Hey, you have this patient, what do you think?” We go back and forth. Maybe we should do medications first and reassess for surgery later. Or, if a patient is young, healthy, and the vast majority of the tumor is in the kidney, let’s get the kidney out and focus on the small metastatic disease. Perhaps use radiation on a lung nodule and give systemic therapy later when they need it. It is a very nuanced approach. 

Do urologists performing this procedure remove only the kidney, or do they also take out smaller tumors outside the kidney?

When we say cytoreductive nephrectomy, we’re focusing on the abdomen. If there is metastasis to the adrenal gland or to lymph nodes right by the kidney, we take that with the kidney tumor. But cytoreductive nephrectomy does not include removing a lung portion or a portion of the pancreas at the same time–that’s a whole different concept.

What is the most important thing that you want people to know when making a decision whether or not to have this surgery?

Multidisciplinary work in patients with metastatic kidney cancer is extremely important. It shouldn’t be a one-person show. It should be really collaborative work between the medical oncologist and the urologic oncologist.