The new director of the Genitourinary Cancer Disease Management Group and brachytherapy at NYU Langone Health’s Perlmutter Cancer Center, Michael J. Zelefsky, MD, brings decades of expertise in using radiation therapy to treat people with prostate cancer. A world-renowned authority on treatment, Dr. Zelefsky has been instrumental in developing approaches that minimize the dose and duration of radiation therapy for patients with prostate cancer and reduce side effects to improve their quality of life.
Below he discusses his vision for personalized approaches to prostate cancer treatment, the advances in treating prostate cancer with radiation that he has been involved with, and more.
You were previously at Memorial Sloan Kettering Cancer Center (MSKCC) for many years. What attracted you to Perlmutter Cancer Center?
What attracted me to Perlmutter Cancer Center was the ability to give state-of-the-art, sophisticated radiotherapy treatment interventions, along with providing personal attention to the patient in a very welcoming and reassuring environment. In addition, there is a great deal of opportunity for multidisciplinary collaboration among urologists, medical oncologists, radiologists, and pathologists. All of this joint expertise will help us provide a very personalized approach to address the specific disease with which the patient presents.
When people go to their provider for prostate cancer discussions, it’s not that uncommon for their oncologist to offer them a very specific approach, which is typically one type of treatment that is mostly utilized in their practice. At NYU Langone, our program will provide a comprehensive armamentarium of the various types of treatments available to address and personalize the treatment.
There are some patients who will have better outcomes with just surgery, while there are others who will need radiation alone, without any other treatments. Some people will need radiation in combination with hormonal therapy, while other patients may need radiation and hormonal therapy combined with brachytherapy, which is an internal radiation therapy. And there are some patients who may need more sophisticated hormonal therapies together with their radiation.
These various types of treatment interventions, all of which are available at Perlmutter Cancer Center, are the tools at our disposal to personalize therapy.
What does this personalized approach mean for patients with prostate cancer?
In the treatment of many genitourinary diseases, such as prostate and bladder cancer, patients are presented with many options, and it can be extraordinarily overwhelming and daunting for them to be asked to choose a form of therapy. There are medical aspects, such as the patient’s overall cardiac health, that are related to the choice, and then there are disease-specific aspects of the prostate cancer that are linked to the selection of a therapy. There are clearly personal variables that are linked to treatment selection, among them psychological concerns, various anxieties a person may have, and specific personal preferences. Finally, there are aspects of quality of life and side effect profiles that are intimately associated with treatment selection. It is well known from many published studies that patients often make their decisions based on preferences to avoid a particular side effect, and they might select a particular therapy because one has a perceived advantage of less-serious side effects that could potentially impact their quality of life.
I see my focus and responsibility—and that of the team that I will be working with within the department managing diseases like prostate cancer—to factor in all those variables and have frank discussions with the patient as to what is important and how to best address the disease in the most effective way to address the cancer. At the same time, we want to minimize exposure of the radiation to normal tissues, such as the bladder, the rectum, and the nerve bundles that control sexual function, that could be associated with side effects. And that balance is a very delicate one. Fortunately, advanced radiotherapy interventions are now available with very sophisticated computer programs that help localize the radiation to as tight a possible region, which excludes as much of the normal tissue as possible with exquisite, pinpoint precision.
Opportunities for conformal radiotherapy, which shapes the radiation beams to hit the target with superb precision while at the same time avoiding normal tissue, are now available more than ever before. Personalizing the treatment program for the individual patient also has to factor in whether additional therapies connected to the radiation, such as the use of hormone therapy or other systemic treatments, are needed to help maximize the ability to get rid of the disease. At the same time, we need to ask, Could this be done without those additional treatments as well? That depends on the elements of the particular disease. Is it very aggressive or less aggressive? What do the radiographic images teach us about the disease? What is the genetic analysis and genomic sequencing of the cancer? By looking at those gene elements, what do they tell us about the disease that may guide and personalize the therapy? There’s no “one treatment fits all.” It really needs to be personalized and targeted to what the patient needs to address the disease and to maximize and maintain their quality of life.
Can you talk about some of the advances in treatment that you have been involved with that have benefited people with prostate cancer?
In my many years in the field, I have had the opportunity to see and be intimately involved in incredible and dramatic developments of radiotherapy delivery. I’ve witnessed major changes in how we’ve been able to deliver treatment so much more effectively and so much more safely.
Many years ago, radiation therapy was delivered to general areas of the pelvis, using estimations of where the prostate was located based on the bony anatomy. Then in the 1980s and early ’90s, CT scans were integrated with the treatment planning to help target the radiation more accurately. Later, with the advent of superfast computers and very sophisticated computer-based algorithms, radiation treatments were able to be planned in a way that the radiation beams could be shaped in the same 3D configuration of the actual prostate, juxtaposed to those normal tissues surrounding it. And that 3D image was what was used to map out treatments to help us become more conformal, more precise, more targeted. That ushered in the era of 3D conformal radiotherapy, which was followed by the movement toward intensity-modulated radiation, where the radiation beams at certain points can be more or less intense to shape the radiation so that it’s more concentrated where the tumor is located. As the beam gets closer and closer to the normal tissue, the intensity of the beam is modulated or changed. This helped further enhance the precision of radiation. My colleagues and I at MSKCC developed that approach and demonstrated that intensity-modulated conformal radiotherapy was associated with significantly fewer rectal side effects, such as rectal bleeding, and other side effects from treatment compared to the radiation approaches that were the standard of care at that time.
Intensity-modulated radiation became the standard of care throughout the world in terms of radiotherapy delivery for the treatment of prostate cancer. Then subsequently, I developed the stereotactic body radiotherapy (SBRT) program at MSKCC, where we aimed to reduce the burden of therapy on the patient by condensing the total number of treatments from 48 or so over the course of 9 or 10 weeks down to 5 treatments using the same radiation machines and the same intensity-modulated radiation treatment planning programs, but focusing the radiation with continued, exquisite precision and incorporating motion monitoring.
Motion monitoring means that we recognize that the prostate is moving during the actual treatment, because as people breathe and as their bladders fill up, even while on the treatment table, there are subtle movements of the prostate, which could affect our targeting. And if we want to target the prostate cancer, we need submillimeter accuracy. So with the help of motion monitoring, where we use imaging to see what movements are ongoing during the actual treatment delivery and make appropriate positional adjustments, it further enhances our accuracy. Motion monitoring facilitated the delivery of these radiation treatments in only five sessions by reducing the margins of the radiation beam around the target to be even tighter than before, because we had that comfort level of knowing where the prostate was at every point during the actual treatment and making the appropriate adjustments.
Today, we recognize the importance of MRI-guided linear accelerator (MRI-LINAC)–based therapy, where we can take MRI pictures right as the patient gets on the table, map everything in real time, and make appropriate adjustments by taking other MRI images during treatment, while the patient is on the table. This further enhances our precision and accuracy. With the advent of MRI-LINAC, which we plan to use more routinely in the Department of Radiation Oncology at NYU Grossman School of Medicine, we will have the opportunity to deliver very targeted forms of radiation and further intensify the dose to the locations where the MRIs show us the tumor is mostly concentrated.
Intensifying the focus of the radiation to where the imaging is showing us the tumor is lodged and concentrated is a new concept in radiation oncology. Having that information at hand will allow us to be more conformal and more precise. Potentially in the future, with the very strong radiology and imaging programs here at NYU Langone, we will be able to join the various disciplines together to allow us to see biologic-based imaging abnormalities on the newest and most sophisticated imaging tools that are becoming available. Incorporating all of that information into the planning software for radiation will make the radiation treatments even more effective and allow us to see those normal tissue structures so much more clearly, which will enable us to delineate them so we could spare them more effectively.
What do you plan to do with respect to treating patients with prostate cancer?
Among the goals that I have in the future would be to further build programs to decrease the dose of radiation that we routinely have given to patients and push those doses more toward the tumor to achieve more effective focal ablation therapies, where we target the radiation more specifically with the guidance of imaging. This will need to be studied in the future. We’ll also plan to develop nerve-sparing approaches, in which we identify the nerve bundles near the prostate that affect sexual function and reduce the dose to those structures as well.
And one other approach I am bringing to Perlmutter Cancer Center is to provide brachytherapy in conjunction with the five-treatment program to patients with more aggressive cancers that previously had been thought to be resistant to radiation. We are seeing incredible success with the combination of internal and external radiation for more aggressive tumors, which offers greater chances of eradication of the cancer.
All of these approaches couldn’t be done without the help of the medical physics team, which is extraordinarily important as partners of radiation oncologists, to develop these treatment planning programs in addition to the radiologists and the emerging new imaging information that is seen on very sophisticated, new kinds of scans. And of course, we work hand in hand with medical oncologists and urologists to provide the patient a multidisciplinary approach to addressing their disease.
What are your research plans?
The research that I plan to bring focuses on reducing the toxicities and side effects of therapies, and improving the side effect profiles using the enhancements of treatment planning and precise directed therapies. We also will explore genetic markers that may be associated with more or fewer side effects that could help personalize the therapy accordingly. There are new directions in certain biomarkers that may provide us with that additional information.
I’m planning to develop, together with the various disciplines at Perlmutter Cancer Center—including radiology, medical oncology, and urology—a radiogenomic pathway whereby studying the nuances of various imaging techniques in addition to genomic sequencing of the tumor can provide us much more information about the future behavior of the tumor and its responses to various therapies. And finally, there are various treatment programs that may further lessen the burden of therapy by either reducing the number of treatments needed with radiotherapy or looking at ways where in certain situations hormonal therapy may not be needed or more intensified hormonal therapy may be required to address particular aspects of the disease.
These are very exciting times for radiotherapy and the treatment of prostate cancer. Over the years, I’ve witnessed with my own eyes the evolution of treatment that has gone from relatively primitive to the most sophisticated, and it continues to evolve with the help of advanced imaging and computer-based planning and integrating other treatment disciplines. For that reason, it is an extraordinary honor for me to be involved in these next steps that I will be taking with my colleagues in the Department of Radiation Oncology, as well as the other incredibly strong disciplines here at NYU Langone, to make a difference for our patients.