Brian Helfand, MD, PhD

Brian, how do you define PSA [prostate-specific antigen] nadirs, because I think this is an important point, in the surgical patient and in the radiotherapy patient?

 Ultimately after surgery, when we take out the entire prostate, we’re really expecting that PSA to go to a value of undetectable, 0 [ng/mL]. There are certain definitions, because we use ultrasensitive assays, etc. For the most part, we want to see that at what an equivalent value is of 0 [ng/mL]. At our institution, that is less than 0.02, or less than 0.001 [ng/mL], which I have seen depending on the assay. If after surgery that level rises to a value of 0.2 [ng/mL], I think everyone would agree this is a common definition that would be considered a recurrence. There has been some evolution, especially for men with higher-risk disease, that if you’re using an ultrasensitive assay and you are seeing consecutive rises of that PSA before they’re actually getting to a value of 0.2 [ng/mL], most people would agree that that’s a recurrence as well. There is some devil in the details there, but certainly, I think if you’re going to walk away with this, the value of 0.2 [ng/mL] after a surgery would be considered a recurrence.

For radiation, it becomes a little trickier because we still have the prostate gland that’s in situ, and there is some benign tissue there, so there is for many patients, a level of PSA that exists. Your PSA will get down to some lowest value, or that nadir value. There have been various definitions that have been used throughout the years. I typically use what’s referred to as the Phoenix definition, which is a value of 2 ng/mL greater than their lowest value. Again, if you see consecutive rises at least a month apart, consistently rising more than would be expected, I also have some suspicion there that earlier intervention or recurrence may be warranted.

Judd, we know that in the surgical patient, that nadir happens quickly, usually within 6 months, if it’s going to get to the level that Brian was discussing. What about with the radiation? When do you start to say, “OK, I’m at 6 months, I’m at 12 months, or I’m at 18 months?” When do you feel comfortable? I think as Brian pointed out, it’s not going to go to less than .001 or less than .02 [ng/mL]. What does that time frame look like in the radiation patient?

 That’s a great question. In the classic teaching, in the era before androgen deprivation therapy [ADT] was used with radiation, the radiation therapy itself would sometimes take up to 18 months to clear the prostate cancer. Therefore, we’ve been always taught that you need to sometimes wait up to 18 months if it’s a patient who’s just receiving radiation, and you wouldn’t necessarily want to do a biopsy. You also have a PSA bounce phenomenon that sometimes can occur. Now, all the high-risk patients and many of the intermediate-risk patients are also receiving ADT with the radiotherapy. With the ADT, their PSA should go down generally more quickly, especially if you’re using an antagonist like Degarelix, or now the new oral option, relugolix. In general, the PSA typically nadirs, I see it nadir usually within 3 to 6 months in men who are getting hormone therapy with radiation.

The only additional point that I would make is that sometimes in guys who had low-risk or intermediate-risk disease and had a modern-era radical prostatectomy [RP] with aggressive nerve sparing, bladder neck sparing, and urethra sparing, we see low levels of PSA that are not cancer-related. Therefore, I agree with Brian that in the high-risk patients, you can jump on a PSA recurrence quickly, but I would caution the oncologists in our audience tonight that you must look at the RP pathology. Moreover, if it was not so bad pathology, and if the guy has a PSA of 0.13, or even 0.2 [ng/mL] a couple of years out, I tend to follow those patients because there is this phenomenon of benign glands at the margin. We know from the Mayo Clinic’s series and our work at Duke [Cancer Center], that honestly, sometimes up to 30% of patients can have this in long-term follow-up, a little bit of PSA in the system that’s not cancer-related.

Videos

Brian Helfand, MD, PhD, describes the ways in which the PSA nadir can be defined after definitive therapy and the implications of the definition used for patients with prostate cancer. 

Defining PSA Nadir After Definitive Therapy in Prostate Cancer 

Let’s go to the next polling question, please. For patients who do have a biochemical recurrence, initial therapy should always be androgen deprivation therapy. Is that true or false? Let me put that in context. When I’m saying androgen deprivation therapy, I am talking about either bilateral orchiectomy, or initiation of an LHRH [luteinizing hormone-releasing hormone] analogue.

Polling question 2: For patients who do have a biochemical recurrence, should initial therapy always be androgen deprivation therapy? We’ve got about 40% who said true and 60% who said false. Patients who have been definitively treated for prostate cancer, whether it’s surgery or radiation, in your practice, you’ve been doing a ton of radical prostatectomies for years. How do you generally follow those patients after surgery or after radiation? What is your standard protocol relative to monitoring these patients, in general?

 Well first off, thanks so much for inviting me to be part of this tonight; it’s really an honor to be here. I would say for most of my patients who have surgery, I’m typically seeing them back about every 3 months for the first year, and if they have particularly high-risk features, I might see them back every 3 or 4 months for the first 2 or 3 years. Most of the lower-risk patients end up coming back every 6 months for the first 2 or 3 years, and I like to see them annually, at least out to 10 years for my surgical patients. I try to see my own patients back. However, not all the patients do come back because some of them are a far distance away. I think as a surgeon, it’s important. I appreciate seeing my own patients, so most of my patients I try to encourage to come back. Even for the radiotherapy patients, we have a joint practice, and a multidisciplinary program. I work closely with a couple of academic radiation oncologists. We typically split the follow-up. Therefore, even if I refer a patient to radiation, many times, it’s been my patient, and I will alternate 6-month visits with the radiation oncologist for the first even 5 to 10 years.

Brian, is that your pattern at NorthShore University HealthSystem?

 I would say it’s very similar. Thank you also for the invitation, I think this is great. I have a similar protocol. In general, I check their PSAs [prostate-specific antigen levels] every 3 months for the first year, every 4 months for the second year, and every 6 months from there on out. I do that for several reasons. I like to continue that relationship and look at the outcomes. I keep track of all of that. Sometimes, the meaning of what a recurrence is, or how we interpret that once they get out into the real world, or when their primary care physician is looking at it, often gets construed. Therefore, a PSA value of 2 [ng/mL] will often be considered in that setting a good value, and so it’s potentially stopping that from happening.

Dr Judd Moul and colleagues discuss best practices for monitoring patients with prostate cancer after definitive therapy. 

Best Practices for Monitoring After Definitive Therapy in Prostate Cancer

® presentation titled, “Around the Practice.” Our emphasis tonight is going to be on the biochemical recurrence in the patient with prostate cancer. I’m Raoul Concepcion. I’m a urologist in Nashville, Tennessee. Joining me tonight is Dr Brian Helfand, chief of urology at NorthShore University HealthSystem, and associate professor at the University of Chicago in Illinois; Dr Munir Ghesani, chief of nuclear medicine at Mount Sinai Health System, and associate professor of radiology at the Icahn School of Medicine at Mount Sinai in New York City; and my friend, Dr Judd Moul, urologist at the Duke Cancer Center in Durham, North Carolina.

Thanks everybody for joining us tonight. As I said in my introduction, we’re going to discuss the significance of biochemical recurrence, BCR, elevated PSA [prostate-specific antigen]—all of those are synonymous terms—after definitive therapy for prostate cancer, and the management issues associated with these patients. We’re also going to review 2 patient cases and involve our audience by using an interactive online platform to answer several polling questions that will then be discussed by our distinguished panelists. Let’s go ahead and start

Polling question 1: What is your impression of the [percentage] estimate of patients who have been definitively treated for prostate cancer, either with radiation or surgery, who will subsequently develop a biochemical recurrence or a rising PSA? Is it less than 10%; is it 10% to 30%; is it 30% to 50%? Or is it greater than 50%? Go ahead, and we’ll start the polling. For the urologists in the audience and for Dr Moul and Dr Helfand, as well as probably Dr Ghesani, to some degree, this is a common challenge we all face when we’re dealing with patients who have definitively been treated. As you all know, everybody is concentrating on their PSA values. I’m looking at the answers here in the polls, and about 20% of the audience says less than 10%; 20% say 10% to 30%; we have 2 votes of 30% to 50%, and we have 1 vote of greater than 50%.

Judd, I’m going to let you answer polling question 1. In your mind, what percentage of patients who undergo definitive therapy, whether it’s radical prostatectomy surgery or radiation, generally what is the accepted number out there that’s ultimately going to have a biochemical recurrence?

 In the review articles that have been written, it’s about anywhere from one-third to 50%. I agree with the audience in the answer 30% to 50%.

Dr Raoul Concepcion leads a panel of experts in prostate cancer in setting the stage for case-based discussions of biochemical recurrence.

Brian Helfand, MD, PhD

Articles

Defining PSA Nadir After Definitive Therapy in Prostate Cancer

Best Practices for Monitoring After Definitive Therapy in Prostate Cancer

Rate of BCR in Prostate Cancer

Brian Helfand, MD, PhD

Articles

Defining PSA Nadir After Definitive Therapy in Prostate Cancer

Best Practices for Monitoring After Definitive Therapy in Prostate Cancer

Rate of BCR in Prostate Cancer

Defining PSA Nadir After Definitive Therapy in Prostate Cancer 

Rate of BCR in Prostate Cancer 