Renal biopsy may alter management in high-risk patients

The role of biopsy in renal masses is evolving. For large renal masses in particular, new data suggest biopsy may change the management of patients with certain high-risk features, according to E. Jason Abel, MD, assistant professor of urology at the University of Wisconsin School of Medicine and Public Health Madison. Dr. Abel discusses biopsy’s role in small and large renal masses, associated risks, and when patients can be safely observed. Dr. Abel was interviewed by Urology Times Editorial Consultant J. Brantley Thrasher, MD, professor and chair of urology at the University of Kansas Medical Center, Kansas City.

Let’s start by discussing the small renal tumor. In the past, conventional wisdom was that a biopsy doesn’t add very much information. If you’ve already decided that a tumor needs treatment based on imaging, then doing a biopsy will only potentially cause a complication or lead to an indeterminate result. In your mind, which patients should be offered percutaneous biopsy for small renal masses today? 

That’s an excellent question. I do think we should at least discuss renal mass biopsy with the vast majority of patients who have small renal masses. The biopsy informs patients and improves the decision-making process for treatment. Biopsy ultimately provides more information that allows the surgeon to provide better informed consent for treatment.

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Given that about 20% of small renal tumors are benign in almost all surgical series, it’s difficult to make the argument that you can decide if a patient needs treatment based on imaging alone. Simply, biopsy allows identification of some patients with benign tumors, who may be spared unnecessary treatment. Biopsy is especially valuable for older patients with comorbidities or for patients who are poor candidates for nephron-sparing techniques.

Finally, serious complications from percutaneous biopsy are rare in experienced centers, especially when compared to the possible complications from treatment.

Next: "Imaging has certainly improved the detection of lipid-poor angiomyolipomas but is not perfect."

Doesn’t improved imaging give us a better idea of whether a tumor might be an oncocytoma or angiomyolipoma, most of which are not renal cell cancers in the first place? Or do you still think there are places where we might benefit from biopsy for identifying benign versus cancerous masses?

Lipid-poor angiomyolipomas and oncocytomas are two tumors that comprise the majority of benign tumors in surgical series. Imaging has certainly improved the detection of lipid-poor angiomyolipomas but is not perfect. If we can identify lipid-poor angiomyolipomas or oncocytomas from biopsy, contemporary studies have demonstrated that treatment can usually be avoided for these benign tumors. However, in younger patients with larger tumors, most experts would agree there’s less of a role for biopsy.

Large renal masses demonstrate significant heterogeneity in radiological appearance. A multiquadrant technique samples cores from multiple enhancing areas in tumors, whereas standard technique obtains tissue from asingle location. (Source: Reprinted from the Journal of Urology, Vol. 194, page 887, Copyright 2015, with permission from Elsevier.)

How about women in childbearing years? Would you limit biopsy in those cases too?

Biopsy is not appropriate for everyone and the decision should be made for each patient individually. However, I think it’s important to realize that biopsy is one way to avoid the morbidity associated with overtreatment of small renal masses. Overtreatment is associated with a decrease in renal function and increased cost of treatment. The potential risks associated with biopsy are very small, and it does provide more information to help patients make decisions.

What are those risks? When you’re doing informed consent with patients, what do you tell them?

The risk is probably dependent on the institutional experience. In our last 700 patients, we’ve had less than 1% incidence of Clavien III complications-those requiring additional treatment. Most complications are related to bleeding and less than 1% of patients will require blood transfusion or angioemobolization.

Next: "The practice of urologists performing biopsies is encouraging."

Practicing urologists may be concerned about sending a patient to interventional radiology to do the biopsy and have the urologist take care of the complication. There’s also a concern about the radiologist doing cryotherapy or a percutaneous treatment right in the suite. Does this remain in our purview as urologists?

Definitely. At our institution, we have a close relationship with our radiology department and communicate about patients frequently. Improving future patient outcomes is really dependent on cooperation across disciplines. However, it’s important that urologists continue to maintain ownership of these patients because we are trained to understand the tumor biology of kidney cancer and we follow these patients for years to observe the natural history of renal masses. The practice of urologists performing biopsies is encouraging.

A gross pathology specimen demonstrates distinct pathologic diagnoses among different regions of large renal cell carcinoma. (Source: Reprinted from the Journal of Urology, Vol. 194, page 889, Copyright 2015, with permission from Elsevier.)

If you believe by imaging that you’re looking at a small, percutaneous tumor, how does biopsy help you risk-stratify patients?

For the patient who has a very limited life expectancy and a very small tumor, it’s probably not helpful to identify whether or not a tumor is cancerous since it will not likely affect their life expectancy. In very young patients, biopsy is also probably not as helpful.

But there are a lot of gray areas, since most patients with renal cell cancer are in their 60s or 70s and are healthy but have some comorbidities or borderline renal function. Patients may choose different treatments if they know that they have a benign tumor or a malignancy. If patients understand that they have cancer, some would feel more comfortable consenting to surgery.

Next: "I have had many patients in their 70s ask if a mass can be just followed instead of treating it. What do you tell them?"

I’ve had a few older patients who are not in great shape say that if they have cancer, they need to identify that for their cancer insurance policy; that’s one of the reasons to do a biopsy. Also, I have had many patients in their 70s ask if a mass can be just followed instead of treating it. What do you tell them?

The minority of small renal masses will be aggressive tumors. But if you identify an aggressive tumor in an older patient, you may be more likely to treat it. If you identify a grade 4 or sarcomatoid tumor, even when it’s 2 or 3 centimeters, you may offer aggressive treatment to an older comorbid patient.

Patients also tell me they’ve read that aggressive cancer can actually spread cancer along the needle tract. What do you tell them?

That is a very rare, almost theoretical risk with modern techniques. We struggle sometimes with explaining rare events because we can’t define the exact risk. We have not seen tumor seeding our institution in the last 20 years, and there have been very limited reports of it. It’s a theoretical concern, but we know that biopsy tract seeding is a rare event for any cancer that involves doing a biopsy, such as prostate cancer.

When you have an upper pole or lower pole tumor that may be extending into a calix or coming from the calix, do you use an endoscopic approach first before placing needles in those tumors?

Yes. More central tumors and those we suspect are urothelial cancers are approached ureteroscopically rather than percutaneously.

Next: How do you see percutaneous biopsy fitting into the large heterogeneous class of renal masses?

How do you see percutaneous biopsy fitting into the large heterogeneous class of renal masses?

In the management of locally advanced and metastatic renal cell cancer, there is not a lot of data to guide us how to use biopsy. For large, locally advanced but non-metastatic tumors, extended lymph node dissection certainly benefits some patients but may also be associated with increased morbidity.

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Several groups have identified poor prognostic factors for patients who harbor lymph node metastases, including advanced clinical stage, high Fuhrman grade, clear cell renal cell cancer, necrosis in the specimen, and sarcomatoid features. If the primary tumor demonstrates these high-risk features from biopsy, the surgeon has that information prior to surgery, and you can discuss more aggressive surgery preoperatively with the patient.

We know these large heterogeneous renal tumors frequently have areas with different tumor grades and rare aggressive pathologic features, such as sarcomatoid de-differentiation. Prior studies of large renal mass using a standard biopsy technique to obtain multiple cores from a single site may be prone to error from sampling. We presented data at the 2015 AUA annual meeting using a novel multiquadrant technique that obtains multiple samples from different sites in large tumors. Using this technique, we demonstrated a higher detection rate of sarcomatoid features, increasing sensitivity from 11% in prior studies to about 85%, and we had no higher rate of complications with this technique.

In patients with advanced disease, the medical oncologists are asking us to debulk the tumor before immunotherapy. In those cases, is there any reason to proceed with a biopsy?

Even with newer therapies, there’s certainly a role for cytoreductive nephrectomy in many patients. However, we know from population-based studies that less than half of patients with metastatic disease undergo a cytoreductive nephrectomy; biopsy definitely has a role in identifying metastatic disease in those patients. Subtyping and getting those patients into appropriate treatment is important because some of the treatments work better than others for clear cell carcinoma.

In patients with metastatic disease, renal mass biopsy using a multiquadrant technique demonstrated fewer non-diagnostic biopsies.

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In the future, biopsy may be increasingly utilized to identify metastatic renal cell cancer patients who are unlikely to benefit from nephrectomy. For example, metastatic renal cell cancer patients with sarcomatoid de-differentiation in the primary tumor are known to have exceptionally poor survival and may not benefit from cytoreductive surgery.

Next: "I think we need to continue to be aggressive with cytoreductive surgery."

At our institution, medical oncologists often question whether a patient is a good candidate for cytoreductive nephrectomy simply because their tumor is advancing so quickly. They advise watching it for another 3 to 6 months. Is biopsy helpful in those cases, or are you simply watching the biological growth of such a tumor?

In metastatic patients, biopsy establishes a diagnosis for histologic subtype of renal cell cancer. In patients with non-clear cell subtypes for whom there are not great systemic treatments, surgery remains a viable option. I think we need to continue to be aggressive with cytoreductive surgery, including nephrectomy, metastasectomy, and lymph node dissection. Despite the development of newer and better systemic therapies, most patients continue to have very poor outcomes, and surgery will be important for the foreseeable future in the treatment of metastatic renal cell cancer.

One other argument against biopsying large masses is that, in many cases, it leads to non-diagnostic results. How often does that happen in your series?

We presented another study at the 2015 AUA annual meeting evaluating patient and tumor characteristics that were predictive of non-diagnostic findings from biopsy. Factors that may increase non-diagnostic rate are: tumor size, radiologic enhancement, the presence of cystic features, and the distance from the tumor to the skin. We reported a non-diagnostic rate of about 15%, which is similar or less than other large series.

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The lack of consensus definitions for “non-diagnostic” biopsy is a source of considerable variability in reported biopsy diagnostic rates. It is important to note that the definition of non-diagnostic should also include biopsies that have only normal renal tissue and have likely “missed the target.” These findings should not be interpreted as benign.

In large renal masses with a standard biopsy technique (multiple cores from one site), approximately 10% to 11% of biopsies are non-diagnostic. Using the multi-quadrant technique to sample several sites within large tumors decreased the non-diagnostic rate to 0% in our experience.

Next: "I think biopsy is relevant to anyone who sees patients with incidental renal masses."

You work at a major institution where people are doing this a lot. How is this relevant to the average private practitioner in a community hospital?

I think biopsy is relevant to anyone who sees patients with incidental renal masses, although experience is definitely helpful to get the best results. To maintain good quality of care, discussing the approach to renal mass biopsy with your abdominal or interventional radiologist is important. If the urologist is performing a biopsy in the office, I think it’s important to carefully plan the procedure and begin with less anatomically complex lesions. It’s certainly reasonable to expect good results with renal mass biopsy, just as we do with other complex office procedures.

We know that partial nephrectomies for small renal masses are not done very often by private practitioners. They’re simply doing a radical nephrectomy. If you’re going to approach that surgery laparoscopically, would there be a reason to do a biopsy at the time and potentially avoid a nephrectomy?

I think we should always use nephron-sparing and minimally invasive approaches when feasible. If a urologist sees a patient with a small central renal tumor and feels that the patient will need a radical nephrectomy for treatment, biopsy can be especially helpful. In most patients with benign masses such as oncocytoma, active surveillance is a better choice compared to radical nephrectomy.

Next: "We really believe it’s an advantage to have the pathologic diagnosis before the procedure."

The average urologist might consider doing a biopsy laparoscopically prior to definitive treatment. Would you recommend that approach?

We really believe it’s an advantage to have the pathologic diagnosis before the procedure. Unfortunately, frozen pathology is not always reliable and establishing the diagnosis in patients treated with ablation is critical so that we know how to follow patients afterward. Historically, many patients were treated with thermal ablation without a biopsy, which makes it difficult to follow these patients clinically afterward.

I’ve looked at some of the cryotherapy series and some radiofrequency ablation (RFA) series. It appears that results with cryo might be a little better than with RFA, but our interventional radiologists are doing RFA in their suite. Do you favor one or the other at your institution?

It’s a difficult question because we don’t have head-to-head, prospective, randomized studies. We actually do a lot of microwave ablation. Microwave is similar to radiofrequency ablation, but it’s a little bit more powerful and it provides a bit of a coagulation effect. Institutionally, we favor microwave ablation and we have good results. Patients who are young with no medical comorbidities are not generally selected for ablation.

Next: "If you do ablation, how are you following those patients afterwards?"

If you do ablation, how are you following those patients afterwards?

We do MRIs post ablation in most patients. Especially in younger patients, there’s a concern about limiting radiation exposure. There’s not high-quality, evidence-driven data guiding us on the best methods to follow patients post ablation, but we generally obtain abdominal MRI or CT, and obtain labs/chest imaging similar to patients after surgery.

If you have some rim enhancement in that lesion, are you going back and doing biopsies or just following?

To ensure there is no viable tumor present after ablation, we may biopsy the ablation bed at about 9 months. With no viable tumor, we can extend the interval between surveillance MRI or CT. Another approach is to follow with serial imaging at shorter intervals.

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