Robert Uzzo, MD, MBA, is president and CEO of Fox Chase Cancer Center in Philadelphia and serves as the G. Willing “Wing” Pepper Chair in Cancer Research, Professor of surgery at Temple University Health System, Senior Associate Dean and EVP of Cancer Services. He is a nationally recognized urologic oncologist and has been a leading investigator in many clinical trials with over 500 publications. His research primarily focuses on renal cell carcinoma (RCC). He is well known for developing the RENAL nephrometry score, used to delineate the complexity of renal tumor.
Dr David Ambinder: You have worked on many things in your career, including significant research into the management of the small renal mass, adjuvant therapy and the role of cytoreductive nephrectomy in RCC. Early in your career, you researched and developed the RENAL nephrometry score, which is not only helpful clinically to assist in surgical planning but also gives us a language to use in defining renal masses, discussing them in research, and communicating with other urologists and patients. Can you give us a brief history of the early development of the RENAL nephrometry score and how you first started to think about it?
Dr Robert Uzzo: The RENAL nephrometry score was designed to be a framework. During my training, I realized that there was a great deal of variation in medical decision making. That is why patients get so many opinions. In my reading outside of medicine, I decided two important concepts improve both education and care in medicine. The first is developing heuristics or frameworks and the second is standardizing those frameworks so care can be validated and generalized under various clinical scenarios.
When I was a resident, and then later a fellow, I tried to understand what goes into the decision to pursue a radical versus a partial nephrectomy since you could ask three excellent surgeons and get three different answers. How do urologists evaluate risks and benefits? How do they objectify and defend their clinical decisions? While understanding that care is complex with many nuances, we all realize that it is an issue if Dr. A recommends a partial nephrectomy while Dr. B might look at the same case and conclude “that can’t or shouldn’t be done!”.
There were many clinical factors being discussed in terms of whether they should have an impact on management, including pathology (i.e, multifocal disease), tumor location (i.e, proximity to vessels or collecting system), and other practical questions, including whether the kidney would maintain functionality after resecting a significant portion. At the time, all these clinical questions seemed like they went into every surgeon’s individual mental blender to come upon an answer. As a trainee, this created a struggle for me to understand how people were developing their recommendations. Much of the decision making at that time was based on anecdotal reports, key opinion leaders and other publications; but there was no standard, in other words it mainly depended on where one trained, their skill set and how they viewed the oncologic disease. This led me to try to understand how to standardize and create an objective framework to evaluate renal masses.
At the time, there was nothing out there. I looked at the literature to ask if other surgeons had a framework and realized that I might be able to learn from the liver surgeons who used the segmental anatomy of the liver. Their vocabulary for the various segments of the liver transmitted meaning into the difficulty of performing a partial hepatectomy. I spent a lot of time thinking about the anatomical considerations and thought, “Is there a way to do this that is equivalent to the segmental anatomy of liver?”
Like others, when I became an attending physician, I starting to struggle directly with those questions surrounding candidacy for a partial nephrectomy. At the time, there weren’t a lot of partial nephrectomies being done in the country outside of Cleveland and a select few other centers. So, while beginning to increase my volume of partial nephrectomies performed, I started to try to communicate how I made the decision. Then I started to develop and entertain different systems and adjusted accordingly.
Can you briefly tell us how you evaluated and ultimately chose to incorporate the components of the RENAL nephrometry score, and how you came up with the acronym?
I thought about factors that were important in my own decision making. Size was important, that’s where the “R”— for radius—comes in. “E” is for endophytic versus exophytic because people were deciding on whether to pursue a partial nephrectomy based on whether the tumor was endophytic or exophytic. There were a number of publications at the time suggesting the purely central or endophytic tumors were more aggressive. I thought, “Is that biologically true, or just convenient for those who want to do a radical?” Then, we thought about how close it was to the vasculature, collecting system, and renal sinus because this has staging implications, and that makes up the nearness or “N” component.
This was when laparoscopy nephrectomies were becoming popular, which is why we added the “A” component for anterior or posterior since flipping the kidney might prevent people from an MIS partial in the pre-robot days. We thought this might be useful—i.e, if it is posterior, maybe a retroperitoneal approach would be ideal, or in some cases, potentially one would not attempt a laparoscopic approach. “L” is to aid in describing the tumor “real estate”—or location—in the kidney using the polar lines of the kidney since polar partials seemed to be easier, especially the lower pole.
So, I had all these elements without the acronym and was struggling with how to frame it. I thought, it’s really about the “geometry of the kidney,” so I called it “nephrometry”. Dr. Alex Kutikov, who was a fellow at the time, was very instrumental with thinking some of this through with me and he came in one day and credited his wife for the acronym “RENAL”. We chose it out of poetic license even though it really should have been DENAL, with a D for diameter.
How does the RENAL nephrometry score differ from other renal nephrometry scoring systems?
Since the development of the RENAL score, many other scores have been developed for similar purposes, some of which are really good. Among these, my favorite is the contact surface area (CSA) score. The PADUA score was developed after RENAL and is basically the European version of the RENAL score with some minor tweaks.
The RENAL nephrometry score was first developed for surgical planning, but on PubMed there are >600 publications that use the nephrometry score. In a lot of ways, the nephrometry score provided a language for talking about renal cancer.
It is exciting to see how the score has developed and become a commonly used way for colleagues to discuss renal masses and describe them in research, as well to be able to define potentially more difficult masses (e.g., to interpret complication rates based on nephrometry score).
The score is also really helpful in talking with patients and explaining their disease. Some patients are coming in either for a primary evaluation or for a second opinion, and we are able to explain to them why their disease may or may not be best suited for a partial nephrectomy. Many patients want to know the thought process of their urologist, and for those patients, it is a really useful tool to explain it to them.
Many urologists calculate the nephrometry score themselves. Do the radiologists in your hospital system incorporate the RENAL nephrometry score into their imaging reports?
Many of the radiologists here do incorporate it into their readings, especially the radiologists who have been at Fox Chase for a long time. However, not all of them do. At times the attending urologist will input it themselves, and of course we keep a database of all the cases. There are current publications now seeing if AI can calculate the score for you when reading a CT or MRI.
What are your thoughts on how we might characterize renal masses in the next 10 years?
The nephrometry score was initially a radiographic tool, but I think radiomics is really much more important. Of course, it would be great to be able to distinguish cancer biology based on cancer radiomics, whether via molecular markers or aggregated data, potentially using artificial intelligence. I think that this is where the field may be headed – the ability to match biology to treatment decision making. Nephrometry is just a very early step in that direction.
David Ambinder, MD is a urology resident at New York Medical College / Westchester Medical Center. His interests include surgical education, GU oncology and advancements in technology in urology. A significant portion of his research has been focused on litigation in urology.