An interview with Russell Szmulewitz, MD, associate professor of medicine and a leader of the clinical and experimental therapeutics program at the Comprehensive Cancer Research Center at the University of Chicago School of Medicine. Interviewed by Daniel Tennenbaum, MD, chief resident at the Maimonides Medical Center urology residency program in Brooklyn, New York.
This is the first part of a two-part conversation with Dr. Szmulewitz. Watch part two of this interview here.
Dr. Daniel Tennenbaum:
My name is Daniel Tennenbaum. I’m a chief resident at the Maimonides Medical Center urology residency program in Brooklyn, New York. Today, I’m speaking with Dr. Russell Szmulewitz, associate professor of medicine and a leader of the clinical and experimental therapeutics program at the Comprehensive Cancer Research Center at the University of Chicago School of Medicine, as well as a program leader of the Genital Urinary Oncology Program.
After completing his medical school education at the university of Chicago, Dr. Szmulewitz completed an internal medicine residency at the NYU Langone Medical Center before returning to the University of Chicago for his oncology fellowship. His clinical focus is on the treatment of patients with advanced prostate cancer with particular expertise in the use of leading edge hormonal, targeted, and immunotherapies.
We’re fortunate to have Dr. Szmulewitz here today to discuss PSMA PET/CT scans in the setting of advanced prostate cancer. Dr. Szmulewitz, welcome and thank you for joining us today.
Dr. Russell Szmulewitz:
Thanks for having me, Daniel.
First off, Dr. Szmulewitz, can you please define for our audience what high risk prostate cancer is?
So high risk prostate cancer is generally defined for patients who have clinically localized disease, meaning we don’t think that it has spread outside of the prostate or pelvis, and it’s defined as any of the following, either higher grade, grade four or five disease, a large lesion, that would be defined as T3 or higher, or patients with a high PSA at the time of diagnosis.
And you mentioned that this is localized disease. Is that different than advanced prostate cancer?
Advanced prostate cancer is, I would say, an informal definition that’s used often clinically and often encompasses both locally advanced disease that might need medication in addition to surgery or radiation, as well as metastatic disease, disease that has spread.
Sure. Thank you for defining that. While we’re on the subject of defining what we’re talking about today, can you also please just describe for us what exactly PSMA PET is as both the technology and how we use it?
Yeah. Thanks. So it’s an impressive technology and I guess we should probably break it down into its various pieces. So PET scans in general are imaging modalities in which a radio isotope that is lightly radioactive, not dangerously so, but is slightly radioactive, is injected intravenously. It distributes throughout the body. And depending on what the actual tracer is, it localizes differently. So there are multiple different types of PET scans. The most common PET scan is FDG, fluorodeoxyglucose, which measures metabolic activity and is often used in oncology, just generally speaking.
PSMA PET scanning is the newest type of PET scan that we have and it’s specific for prostate cancer. What it is, is a tracer that is a ligand. It binds a cell surface protein called PSMA. So PSMA is on the service of prostate cancer and there are different ligands which bind to PSMA and those ligands are linked to a radioactive element. So there are several different types of PSMA PET scans and there are different brands of PSMA PET scans, and they vary both by the ligand and by their radioactive tracer, but they basically have equivalent performance and are used interchangeably in large part.
I suppose it’s worth asking then, what are the advantages of using this PSMA technology compared to standard cross-sectional imaging? Has it helped in diagnosis, therapeutics?
So there are multiple applications, and I think that the biggest thing to know is that PSMA PET scans are remarkably more sensitive than cross-sectional imaging or technician bone scan, which is an older radio tracer that’s used to show bone activity and bone turnover. And so the conventional imaging, when we say conventional imaging in prostate cancer, we’re typically talking about a combination of cross sectional imaging, like a CAT scan or an MRI and nuclear medicine technician bone scan. Now, PSMA PET scanning is an order of magnitude more sensitive, and it is more specific, meaning that if it’s positive on a PSMA PET scan, we’re very confident that it’s prostate cancer and it picks up things that a cross-sectional or conventional image just is unable to pick up.
The question is, is that good? And why is that good? It could be helpful and a few different places, and I would say that there are three applications of PSMA PET scanning. One is in patients with localized high risk disease. So we talked about high risk at the onset of our discussion, and PSMA PET scans can be used in that setting to aid in the identification of early spread from the prostates to the regional lymph nodes or beyond.
I would say the most common is the second application, which is in patients who have a rising PSA after definitive therapy. So after surgery or radiation that was meant to be curative, if their PSA is rising, cross-sectional, conventional imaging is not sensitive at all and is almost never positive, but PSMA PET scanning is much more sensitive. And it depends on the PSA, but that’s probably the most common application, meaning to detect and localize recurrence after our primary therapy. The third application, and maybe we can talk about it later, is prior to and in association with therapeutics. There are PSMA directed therapeutics that rely on a PET scan to confirm that the prostate cancer makes the target, the PSMA target.
Okay. That sounds incredibly fascinating. I definitely want to find out more about that therapeutic availability later in our discussion. What are some of the indications for pursuing a PSMA PET, or for that matter, a contraindication? Are there any clinical circumstances where one would want to avoid a PSMA PET?
So I’ll start with that question. I don’t think there are any strong contraindications to PSMA PET imaging. It’s a safe test. But you should probably make sure your insurance will cover it before you do it, because it’s an expensive test. And so if it’s not covered, I would say that that would be a contraindication, because to pay out of pocket would be quite a bit. I would say the indications for use are in those three modalities I said. There’s the FDA approved indications for Gallium 68 PSMA-11 PET scanning, which is branded by another brand, that is indicated for localized high risk disease as well as recurrent and prior to therapy. So some urologists who are seeing high-risk disease are ordering PSMA PET scans as part of their initial staging. And what we know from studies is that does add to our knowledge about what’s going on locally and will identify occult early metastases in a small but significant population.
And sometimes that changes management, meaning that if a patient was about to have surgery and now they have a PET scan that shows that they have a small thing outside of where they would normally have it removed, then sometimes those patients are now shunted towards other modalities. What we don’t know in full disclosure is whether that decision change is in the patient’s best interest or improves long term outcome, meaning that the test hasn’t been out long enough to know the impact of the increase in our diagnostic information and how those changes are impacting patients’ health long term.
I’m sure it’ll take a number of years until we’re able to determine that.
Yeah. I would say the biggest place that it’s being used and really changing practice is in the biochemical recurrent state, so in the rising PSA. What many people, including myself, are doing is getting these PET scans. And then if there’s a focal recurrent outside of the prior radiation field or outside of the prostatectomy bed and things like that, then we’re using other modalities like focal radiotherapy to target those focal recurrences with the hopes of either salvaging a cure, or at the very least delaying the time before which we need to give systemic hormonal therapies. And there have been a couple of studies, studies that have showed us that such an approach, meaning PSMA PET identification of focal recurrence then followed by stereotactic body radiotherapy does delay the time before which you have to start systemic therapy, which for most patients is a good thing.
Absolutely. Anytime you have the opportunity to avoid starting what may end up being lifelong therapy, I’m sure most patients appreciate that. I did want to circle back for a moment to the list of three opportunities to use this PSMA technology. Out of curiosity, whether at your own institution or amongst your colleagues that you’ve discussed this technology in your conference, have you noticed any increase in PSMA PET/CT use prior to definitive therapy, prior to radiation, prior to prostatectomies?
I would say that we have noticed an increase. Our surgical oncology, urologic oncology colleagues that are seeing high risk or very high risk in particular prostate cancer are inclined to get them. It will help with surgical planning often, or it might shut a patient from surgery to radiation and hormonal therapy, which has different morbidity associated with it. So I think it’s definitely being done more often. What I have been telling… We have a multidisciplinary clinic here that sees patients with very high risk disease, and so I will see them concurrently with our urologic oncologists. And what I tell them is that, “We can get this test and it might show us something, but that doesn’t mean that we know exactly what to do with that knowledge and it doesn’t mean that we should definitely change what we’re planning on doing.” Now, if we see multiple spots outside the prostate, then yes, it does change management.