Dr. J. Stephen Jones highlights the emergence and evolution of cryotherapy in urology

J. Stephen Jones, MD, FACS

Urology Times® is celebrating its 50th anniversary in 2022. To mark the occasion, we are highlighting 50 of the top innovations and developments that have transformed the field of urology over the past 50 years. In this installment, J. Stephen Jones, MD, FACS, discusses the development of cryotherapy for the treatment of kidney and prostate cancers. Jones is president and CEO of Inova Health System.

Please provide an overview of the development of cryotherapy in kidney and prostate cancer.

Interestingly, I was a little bit of a critic when cryotherapy first came out, especially for prostate cancer. I thought that the science had not been developed yet for determining whether it was safe and effective, and I thought it was a little bit commercially driven at first. But after about 5 years, I started to see presentations at scientific forums where people were collecting the data, both for kidney cancer and, more importantly to my career, prostate cancer, and I saw that they were promising enough that I went and trained in Norfolk, Virginia with Robert Given, [MD, FACS]. But what I did see was the science was starting to develop and people were collecting data on it. In about 2003, I learned more and then very cautiously started a database, at first institutionally and eventually, I was asked to assume responsibility for the COLD [Cryo On-Line Data] Registry database in which we collected thousands of cases. From that, we were able to see circumstances where we thought it was effective and circumstances where we thought it wasn't the right treatment. I volunteered to lead COLD Registry based on agreement that a) I would receive no compensation to minimize conflict of interest, and b) that I and an independent board had full control of access and publication of the data—whether favorable or not.

What makes cryotherapy an innovation in urology?

Cryotherapy was the first energy source that we were able to ablate tissues with in either the kidney or prostate and understand what that ablation would do. Throughout the years, I've said it's not hard to destroy tissue; it's hard to destroy tissue without destroying other things around [the cancer]. And cryotherapy happened to have a narrow enough margin, from the point where it was completely lethal, which you needed for the cancer, to the location where it was not at all lethal. It happened to have a reasonable range for that. There are multiple other energy sources that may be developed over time that would do that, so I don't think it's so much the energy source as much as cryotherapy happened to be the first one that we had with enough use, and enough of us who were looking at it and trying to understand it, and were able to develop data to drive decisions on it.

What other benefits did cryotherapy confer for patients?

The surgical morbidity from cryoablation is pretty limited. It's typically percutaneous, or at minimum, laparoscopically guided for the kidney. It's pretty quick and doesn't require major disruption of tissue. Now, that wasn't enough of an advantage that by any stretch that I would have said that it would be the right treatment for every patient. I think that would be completely the wrong message. If you take a 75-year-old very healthy man with significant high-grade disease, if that person has a normal life expectancy, that cancer is still going to, in all likelihood, kill him if not treated. We know that surgery in that setting is associated with significant morbidity. Cryotherapy allows a less invasive option, especially for the patient that either doesn't want or can't have radiation. Cryosurgery is a way that we could completely kill that tissue in significant numbers of those men. We published data regarding the ability in older patients, for example, to have curative therapy for high-grade disease. The other example is that focal therapy was possible with cryotherapy and certainly was not feasible initially surgically. To this day, focal therapy with surgery is not very feasible, but cryosurgically, you can ablate part of the gland and leave the remainder. Finally, there is the setting of salvage treatment after failed radiation therapy. We know that salvage surgery is associated with poor disease outcomes, probably because most patients are treated too late. There are also severe and sometimes crippling morbidities, including fistula. We showed in hundreds of salvage cryoablation patients that were able to have local disease control at least, acceptable morbidity, and fistula rates well below 1% when performed by expert hands. Certainly, it's not an operation that one wants to dabble in; it's one that only someone who does it a lot should be doing.

Where does cryotherapy fit in the armamentarium today?

It goes back to the fact that it's not hard to destroy tissue. You can name dozens of different modalities that will destroy the tissue. I'm not aware that any has shown an improvement over cryotherapy, although, again, there is no doubt that there are going to be plenty of companies that are going to want to create tissue-destroying technologies. I'm not saying that any of them is specifically better or again, that I think the cryotherapy is the only form of ablation. Picking an energy source and determining how to limit its morbidity is probably the right approach with any of the energy sources that have or will come forward.

Any other thoughts on cryotherapy for our audience?

My observation is that these innovations come along, and there are scientific drivers and there are business drivers; I think we shouldn't be naive to that. I think that early on, cryotherapy, was associated with too much of the commercial vs the scientific. Over time, what I tried to do was to drive the scientific and have no interest in what the commercial ramifications were. But by the same token, when there are technologies that come along that have significant commercial drivers behind them, they will indeed get pushed. It's our responsibility as a specialty to ensure that we scientifically evaluate those and judge their value based on their merit, and not on the commercial side.