In this interview, Ardeshir (Art) Rastinehad, DO, discusses the current state of focal therapy in prostate cancer, the role of fusion biopsy in pushing the treatment forward, and what institutions looking to implement focal therapy should know.
Focal therapy confers myriad advantages in prostate cancer treatment but is currently limited to the clinical trial setting. In this interview, Ardeshir (Art) Rastinehad, DO, discusses the current state of focal therapy in prostate cancer, the role of fusion biopsy in pushing the treatment forward, and what institutions looking to implement focal therapy should know. Rastinehad is system director for prostate cancer at Northwell Health and vice chair at the Smith Institute for Urology at Lenox Hill Hospital in New York, New York.
It's still considered investigational. Most of the work being done around the world is done in trials and through registries to track outcomes. There is limited long-term data supporting the use of focal therapy, but it is an area of extreme interest.
When taking a high-level look at prostate cancer, there are several questions that arise. First, are we finding the best patients that actually need treatment and also identifying patients that would be best served by active surveillance? A recent survey presented at this year’s American Urological Association Annual Meeting has found that less than 55% of patients with low-risk prostate cancer are being offered active surveillance. Second, once we determine which patients need treatment, we need to determine which treatment is best suited for them, taking into account their goals of treatment, such as quality of life and oncologic control.
Next, how do we risk-stratify these patients to different treatment options, including active surveillance? In some cases, patients will have focal disease that we're able to identify through high-quality MRI imaging of the prostate, biomarkers, or germline- or somatic mutation testing. After a thorough diagnostic workup of patients with localized prostate cancer, 20% to 40% may be candidates for focal therapy. The cornerstone of today’s approach to focal therapy rests on high-quality multiparametric MRIs of the prostate and MR/US (magnetic resonance/ultrasound) fusion-guided prostate biopsy. After this approach, we may be able to better identify men that don't have to have their prostate removed or radiated and help them avoid the risks of incontinence and erectile dysfunction.
In the past 5 years, focal therapy as a research topic has really exploded. Almost every major urologic organization is featuring programs on focal therapy. In 2019, to meet this demand, the focal therapy group collaborated with the Endourological Society and created the Focal Therapy Society with Dr Thomas Polascik as the president. That has helped to bring every single major research group and academic clinician, and even private researchers, under 1 umbrella. That's what's really been exciting. In the beginning, a lot of the groups were segmented or isolated by technology and vendor. Now, everyone is under 1 organization working together with a common goal of researching and investigating the use of focal therapy.
In that spirit, we have also created the Focal Therapy Registry, which is an international collaborative to look at post-market approval of focal therapy technologies for tissue ablation, to really track this and look at the outcomes with respect to quality-of-life metrics as well as oncologic outcomes. At every major meeting around the world, the Focal Therapy Society sends representatives to build awareness as well as foster discussion and build collaboration on an international level.
Before we get to technologies, let's discuss how patients are given a diagnosis. At our institution, Smith Institute for Urology, an MRI is ordered on every patient with a suspected or elevated PSA (prostate-specific antigen) level or suspicion of prostate cancer. From that, they go through what is called the rapid diagnostic pathway, which is a quick, streamlined approach so every step is clearly outlined, and patients aren't wondering what's going to happen next. We try to make it easier because we found that it takes about 8 to 12 weeks for a man to go through the diagnostic process and maybe find out the PSA was elevated due to some other reason than prostate cancer. We at the Smith Institute for Urology at Lenox Hill, Northwell Health felt that this timeline wasn't acceptable, so we collaborated with some of our colleagues in the United Kingdom, including Dr Hashim Ahmed at Imperial College London, England, and we're rolling out the Northwell Health Rapid Diagnostic Pathway. This approach decreases wait times, helps better stratify a patient’s prostate cancer level of disease, and can help us identify men for focal therapy. Our flagship research project was in nanomedicine, with nanoparticle-directed ablation for prostate tumors, which has been published in PNAS (Proceedings of the National Academy of Sciences of the United States of America) and other publications. That trial is moving forward very well and it's in at least 6 sites around the country.
We are also a research site for Philips Healthcare; our collaboration at Northwell Health started in 2012 and has been very productive. We were the first site in the world to validate the original MR/US fusion technology developed at the NIH. Currently, through our collaboration with Sam Coons’ research team from Philips Healthcare, we've developed MR/US fusion ablation-planning software, which is reaching FDA approval within the month. What's nice about this is that the expertise in 3D-guided focal therapies that I have developed over my career is not needed when you can use this software application to help physicians visualize a 3D-treatment plan and perform ablations. This technology is agnostic, which means it can work with multiple treatment modalities.
In some cases, if a patient has a recurrence, we can treat the spot again, which is similar to our history with renal focal therapy, which is considered a part of the standard of care today. We're 1 of 2 test sites in the world developing this technology. The technology was borne out of Dr Peter Pinto [MD; Investigator and faculty member, Urologic Oncology, National Cancer Institutes of Health, NIH, Bethesda, Maryland] and Dr Brad Wood’s [MD; director, Center for Interventional Oncology and chief of Interventional Radiology, NIH, Bethesda, Maryland] work with the National Institute of Health in 2008. We developed a platform so a urologist without an intense imaging background or experience can pick up focal therapy and provide it to their patients and perform trials in their local hospitals. We've done that trial for cryoablation with Philips Healthcare using UroNav guidance technology. As for other modalities, we also offer high-intensity focused ultrasound (HIFU) for hemiablation and focal ablation of prostate tissue. Finally, most recently, we're in collaboration with AngioDynamics and the Society of Urologic Oncology to offer irreversible electroporation of prostate tissue.
To create a strong focal therapy program, you must have an expert at every level that collaborates well. We have dedicated prostate imaging–specialized radiologists, pathologists, MR technologists, and urologists trained in focal therapy at Northwell Health.
As I mentioned before, fusion biopsy really was developed with the idea of using multiparametric MRI to risk-stratify patients for prostate cancer. If you can’t see it, how are you going to sample it? In the past, people used to try to use their mind's eye (cognitive biopsy) to sample the area of the prostate in that region. We know that it's not as effective as a using a targeting technology. The first targeting technology was developed out of the NIH with Dr Pinto and Dr Wood's group, which I was a part of, as well as Dr Peter Choyke [MD; Investigator and chief, Molecular Imaging, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland] and Dr Baris Turkbey [MD; chief, Molecular Imaging, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. That was the core group of people that really helped launch this technology. We had the first publication in the field on this.
We can sample an area of the prostate and go back and resample it if we had to. The system creates a 3D map that can help guide us to those areas as well as know the exact area of the prostate sampled on biopsy. This helps us assess how well we are interpreting MRIs of the prostate. The next obvious question is, can we use that same information to plan a treatment? Can we put a needle there that would facilitate the treatment? Can we guide the ablation technology to destroy that specific area of the prostate and then use that information from those treatments to confirm that we did it later on? That's why you have patients that are now very familiar with fusion biopsy technology. Patients ask the question, “If you can biopsy the area, why can't you just treat the spot? Why do I have to have my entire prostate removed or radiate the whole thing?” Yes, we know that prostate cancer is a multifocal disease. However, the implication is that a cohort of patients could have a focal treatment and we can observe the rest of the prostate for new disease arising with the use of imaging and biopsy if needed. Essentially, they are in a modified active-surveillance plan. Patients are interested in the concept of focal therapy because they hope to avoid the adverse events of typical whole-gland therapy, which are erectile dysfunction and stress urinary incontinence. Those are the things that challenge patients today.
If you look at the literature, 40% of patients have treatment regret after being treated for prostate cancer because they feel like their quality of life was affected so much that the treatment was not worth it. I really feel patients are going to drive this work forward. But as surgeon-scientists, we have to critically evaluate this new approach and do these things on trial. Some people do this off trial. I'm not here to critique that; we're just trying to collect high-quality data and demonstrate that we're moving forward in a scientific manner to prove this concept to be a viable medical treatment, because if we do, it'll become an option for many more men and obtain recognition from the Centers for Medicare & Medicaid Services. We'll have long-term data to support its use. With HIFU, there are significant long-term data showing that you can successfully ablate prostate tumors and have equivalent oncologic outcomes to prostatectomy. We need more data, but that's the direction that it's heading. That's why fusion biopsy laid the foundation for our evolution into focal therapy, without a doubt.
Everything has really changed for us in medicine because of COVID-19. I think focal therapy fits in well because it's a same-day outpatient procedure. Patients don't stay in a hospital; they don't have multiple touch points like radiation. Some are even treated without the need for a urinary catheter; add to that fewer adverse events. But what are you giving up when you say, "fewer adverse events?" Maybe oncologic control long-term, but no one really knows. When you're looking at the incidence of metastatic disease, it’s 3% to 5% for Gleason 7 prostate cancer at 15 years and cancer death rates less than 5%. That means 95% of patients will be fine over the long-term. We don't have that data for focal therapy; that's just looking at long-term prostatectomy data. We can compare the gene signatures for similar patients that are undergoing focal therapy and compare that to prostatectomy. So we may have some idea what the outcome should be, and if there's a deviation from expected events, we can understand that maybe focal therapy was not the ideal choice for that type of patient.
Probably more than 90% of patients will be served fine long-term with focal therapy. We're just trying to work hard to identify and make sure we know who those patients are. No man wants to get his cancer treated and not have high-quality erections or leak urine. We're trying to find that "middle path," as Dr Mark Emberton would say, between whole-gland therapy and active surveillance. Early on, a lot of providers were treating Gleason 6 disease and calling that focal therapy. We know in the history of prostate cancer that true Gleason 6 prostate cancer is not a malignant disease that's going to progress. It's just, unfortunately, with the technology we have today, we're not able to always identify that disease subset as optimally as we would want to.
There's a hardware issue, and there's a skills issue. The first barrier is, how do you identify patients? That has to be done with high-quality multiparametric MRI imaging. The problem is that not all prostate MRI is created equal. That's a challenge we deal with on a regular basis. It takes time. Time is money. The longer your scan is, the higher the cost to your institution, because everyone's paid the same amount for a good scan or a bad scan from a reimbursement point of view, which is a challenge. Hopefully, the American College of Radiology will come up with new minimum standards for prostate MRI specifically, but we haven't seen that to date. It's been talked about, but it hasn't been implemented. So first is how we screen more efficiently and effectively identify men that need a biopsy. If you have a biomarker, risk-stratify the patient that it can help. But at the end of the day, if you're going to perform a focal therapy treatment or a hemigland ablation, you need high-quality imaging for the planning. You can't get around that fact.
The second part is targeted biopsy. Cognitive biopsy is not going to cut it because you're not going to have a record of exactly where each core was. It's a learning process; you have to have this feedback loop that goes into critiquing your technique. No one's perfect. Not every biopsy will come out perfect. Sometimes, a standard biopsy will find cancer that was not visualized on the MRI, and you have to go back and ask yourself, was it my technique? Was it the interpretation of the MRI? Or was it the technique or the MRI quality that led us to miss this specific area? Then you can develop a treatment plan based on these 3D data with high-quality multiparametric MR imaging of the prostate. Those are the first 2 major hurdles.
I think what we need a clinician to understand is that there has to be a complete care-cycle database tool created for men at risk for prostate cancer and those diagnosed, treated, and their long-term oncologic outcomes. We are working with industry, Philips Healthcare, to create such a full care-cycle platform and feel that it will improve patient outcomes and also be able to assess the full cost of prostate cancer care for a health system. This may be very useful in the value-based reimbursement space. It's exciting to see this rolled out. Fourth, and finally, what technology do you pick? Each technology has its pros and cons. But even inside the same technology, the data you look at—how they use the technology—can affect their patient-specific outcomes and oncologic control. We're not curing cancer. No one really cures prostate cancer; we just control it, because there's always a risk of biochemical recurrence, and it's high regardless of the disease state. Or did we just control cancer to hopefully decrease the risk of progression to metastatic disease, which could affect our patients?
Implementing the technology, you must have the key skill set. I have completed two IR (interventional radiology) fellowships to help implement these new therapies. My second fellowship was with Dr Brad Wood’s team at the NIH. This is where I learned this technology. We teach this today; we have a fellowship in interventional urology here at Northwell Health, which is exciting. We're training the next generation of surgeons to be able to use these technologies. There are other focal therapy fellowships around the world, which is also very exciting. Imperial College London and University College London have them. UCLA has one as well. But a deficit that we see is people's ability as a urologist or a person using this technology to be able to span the gamut of interventional radiology procedures, urologic oncology, and diagnostic radiology. When I came out of training, this was so new. In 2011, I realized that I had to have all 3 skill sets. That's why I spent every week learning how to read an MRI from Dr Turkbey and Dr Choyke. I spent time with Dr Turkbey learning MRI physics. I spent time with Dr Wood and Dr Pinto helping develop the fusion biopsy technology, which is actually the foundation for the majority of the focal therapy technology imagery that we have today. And of course, completing a Society of Urologic Oncology fellowship at the National Cancer Institute helped me understand the biology of cancer.
They have to create that multidisciplinary team that must include a dedicated radiologist that comes to the treatments. The radiologists need to understand their role in the treatment of these patients. When we launched the nanoparticle trial, I spoke to the principal investigators at different sites. I told them, your radiologist has to come see these procedures to understand the implications of what they do and the impact on patient outcomes. A lot of times, I don't think radiologists really get that experience because they're just reading films. Once they show up and they see a couple of procedures, they realize the impact of what they're doing and why their role in it is so crucial to the team’s success.
Number two is you have to figure out how to critically evaluate yourself. Are you doing the right thing on a consistent basis? That's a challenge, and understanding the technology and having a mechanism to create a feedback loop to complete the evaluation is key. To pick an ablation technology, you have to pick one that you feel offers a good safety profile, good oncologic outcomes, as well as not cost prohibitive. How much does it cost to implement? A lot of this stuff's not reimbursed. It can be sponsored by industry, your institution, or others charge cash. Cryoablation is covered by insurance, and that is probably the easiest one to start with. It's the one that urologists have the most experience with. You can actually see what you're doing, because the ice ball is easily visualized on ultrasound, and since most fusion technology is guidance based on ultrasound, it makes an easy starting point. No one technology fits all. You need to have a recipe book where you pull out 1 technology for a location of a tumor in 1 area versus another.
I want people to get involved. Join the society, come to the meetings, talk to people. We have a mentoring system where you can have the opportunity to speak to leaders in the field to help start your own program. Our next meeting will be June 2022. The Focal Therapy Society has a hands-on meeting run by Dr Arvin George, but due to COVID-19, it was postponed this year. Dr George’s meeting is more of a community-based approach with hands-on courses teaching these new technologies. By supporting the society, it helps grow the whole field.