Revised Guidelines Helping to Advance Kidney Cancer Care

Robert G. Uzzo, MD

Management of patients with localized kidney cancer became a more uniformed, guided, and evidence-based approach earlier this year with revised guidelines individually developed by the American Society of Clinical Oncology (ASCO), American Urological Association (AUA), and the American College of Radiology (ACR).

Specifically, the guidelines are for treatment of patients with small renal masses, with an emphasis on biopsy and risk stratification to better improve outcomes.

“Use the guidelines; that is the biggest takeaway,” said Robert G. Uzzo, MD. “The guidelines were developed by panels of experts across multiple disciplines; they included pathologists, nephrologists, interventional radiologists, and patient advocates, as well. There is no doubt, and the data are increasingly clear, that if you use the guidelines you deliver better care.”

OncLive: What did you discuss in your lecture regarding localized kidney cancer?

What are the specifics of those guidelines?

Uzzo, chair, Department of Surgical Oncology, G. Willing "Wing" Pepper Chair in Cancer Research, Fox Chase Cancer Center, lectured on localized kidney cancer management during the 2017 OncLive^® State of the Science Summit^TM on Renal Cell Carcinoma and Bladder Cancer. In an interview at the event, he honed in on recent guidelines that have impacted clinical practice and ongoing biomarker research in the field.Uzzo: The management of localized kidney cancer is increasingly complicated. Over the course of the last couple of years, we have developed more guidelines. It is not just a matter of when the surgery ought to be or how it’s going to be performed if surgery is indicated. We spoke about excision, ablation, and observation as the most common paradigm for [how] you should treat kidney cancer. What I spoke about is what ASCO, AUA, and ACR say about that. I should disclose that I was part of all 3 of those guidelines. There is an increased emphasis on biopsy to determine and risk stratify prior to any plans for excision, ablation or even observation. The use of percutaneous biopsy, particularly core biopsy as a risk-stratifying tool, is an important aspect. Many physicians believe that biopsy is associated with a risk of tumor spillage which, fortunately, is not the case. It is more anecdotal and older data. Biopsy does not seem to be associated with a higher risk of tumor dissemination or seeding.

There is an emphasis on the functional aspects of the management of kidney cancer and an increased understanding that kidney disease can be induced by both medical and surgical events. Also, using the baseline designation of chronic kidney disease not only with glomerular filtration rate but also the amount of proteinuria preoperatively and then following it postoperatively. That is a new aspect of the guidelines.

There is also a renewed emphasis on partial nephrectomy for appropriate management whenever feasible. It is certainly for stage T1, increasingly T1b, and some T2 tumors. It is more in the relative and absolute settings, but sometimes in the elective settings, as well.

Where does surgery fit into the future treatment landscape of kidney cancer?

[We’re not only looking at] active surveillance and risk stratification for tumor risks but also comorbidities, life expectancy, and some of the risks that patients incur just when going to surgery. We’re balancing those risks when making appropriate decisions—empowering patients to understand all of those aspects of decisions, and, not just when the surgery ought to be, but balancing all of those risks to see who should be excised, ablated, or observed. Surgery will always have an important role in the management of kidney cancer until we have completely effective systemic therapies, which we don’t. As systemic therapies grow more effective, then surgery [will have] less of a role. If you have a systemic therapy that can cure metastatic kidney cancer, then surgery is going to have a small role. However, we're not even close to that.

Where are we currently with biomarker research?

Where all of this goes is to risk stratification. We need a better understanding that some kidney cancers are never destined to metastasize and are better to be [observed]. With genomic profiling and improved biomarkers, perhaps we will have a better idea. The role of surgery is getting refined, just like it is with all malignancies. Organ-sparing surgeries are becoming increasingly emphasized, and the complexities of minimally invasive surgery are being emphasized. Biomarkers for kidney cancer currently don’t exist. There are a number of serological markers that people have looked at—neutrophil counts, lymphocyte counts and ratios, C-reactive proteins, and other types of serum biomarkers—that are easy to measure but are not sensitive or specific enough.

What are the biggest unmet needs in this field?

There are other biomarkers that people are looking at, such as immunohistochemical stains, but this all goes ultimately to either the genetic level or protein level. Ultimately, the most effective biomarker will be something that is easily collected—like in the blood—and something that is easily measured and has a high sensitivity and specificity. That is always a trade-off there. But as we understand the mutational heterogeneity of kidney cancer, those biomarkers will come soon thereafter. A biomarker is the biggest pressing unmet need, because without it you can’t stratify risk. Beyond that, there is an awareness that there are trade-offs with these decisions. Ten to 20 years ago, kidney cancer management was very reactive. You saw mass and you removed it. In many cases, you may have helped, and in some you may have hurt because the biology of that tumor may never have been destined to metastasize.

However, the reason we did it [that way] was because there weren’t many systemic therapies. I don’t mean to imply wonderful systemic therapies, but we have active agents. We have a lot of them, and combinations are doing a much better job than anything we had a decade ago. As we work in partnership with our medical oncology colleagues, adjuvant therapy, neoadjuvant therapy, and using some immunologically active agents is the multimodal approach that we'll be using a lot more of in patients with locally advanced or metastatic disease. For those patients with localized disease, active surveillance combined with biomarkers is what the future holds.