Judd W. Moul, MD

Let’s go to the second case, which is slightly different. We’re probably going to get into a discussion more to everybody’s point when we’re talking about a patient with much lower levels of PSA [prostate-specific antigen]. In this next case, in March 2016, a 64-year-old African American man presents to urology with a PSA of 5.8 ng/mL, and his DRE [digital rectal examination] is negative. The patient underwent multiparametric MRI of the prostate. He has a 66.3 volume gland and has a PI-RADS [prostate imaging reporting and data system] 4 lesion to the right peripheral zone measuring 1.5 cm. The patient undergoes mechanical fusion biopsy and 2 of 3 cores to the target area. Again, that is a PI-RADS 4 lesion, right peripheral zone, and he shows Gleason Group 3, 4+3, and then 3 of 12 systematic biopsies shows Gleason Group 4, 4+4, in the mid-left peripheral zone. He’s got a multifocal disease, not only in the right peripheral zone but also in the mid-left peripheral zone.

Staging work-up, bone scan and CT once again is negative. In this case, the patient opted for external beam radiation therapy, but he refused. As most of us know, patients with higher-risk prostate cancer should get 2 years of androgen deprivation therapy [ADT] along with their radiotherapy. However, the patient refused ADT because of the potential adverse-effect profile. He finishes his external beam therapy in 2016. These are the following PSAs dating from June 2017 and October 2017, and as you can see, he has this slow rise in PSA. For the first polling question, based on this PSA kinetics, would you restage the patient at this point? Yes or no? He finished radiotherapy in 2016. He had a PSA of 0.8 in June of 2017, and a PSA of 1.7 in June of 2018. On this PSA kinetics, would you restage the patient at this point? Yes or no? Looks like the polling is getting ready to conclude.

There is 1 question in the queue, which I’ll get to. According to the audience, basically 80%—the vast majority—say they would go ahead and restage as close to 90%. What imaging modality would you use to restage this patient? [The options are] technician bone scan and CT, whole-body MRI, Fluciclovine, gallium PSMA [prostate-specific membrane antigen], or C-11 choline, if you were going to restage? There is a question in the queue that somebody in the audience asked, just so we comment on this, the biochemical recurrence of 0.2 occurred 39 months after prostatectomy, and 6 years after prostatectomy the PSA is 0.62.

How can I balance the hope to get local treatment of oligometastatic tumors if found soon with the newest scans against the risk of more systemic metastases if I waited until all tumors can be seen? We’re probably going to answer this question with the role of imaging, so sit tight just for a second. The audience for this case—close to 60%—chose fluciclovine; 14% chose gallium PSMA, and 30% basically stuck with bone scan CT. I’m assuming that’s probably because of availability. Dr Moul, this is a patient whose PSA is low. He’s still below 2, but his doubling time looks to be under a year. How do you look at these patients? How do PSA values influence your choice of scans? Is it the value? Is it the doubling time? Is it the availability? How do you look at PSA relative? Does that impact your choice of scans?

 This is an interesting case, as you said. Technically, this gentleman does not meet the ASTRO [American Society for Therapeutic Radiology and Oncology] Phoenix definition of recurrence because his PSA is still below. If I walked in the exam room and he was in poor health, and if I perceive that his life expectancy is going to be less than 10 years, I might reassure him and say “Sir, your PSA is still below 2, so you haven’t met the definition of recurrence. We’re just going to keep an eye on things, and I’ll follow you closely and see you again in 6 months.” On the other hand, his nadir was poor.

We know from data way back with Frank Crights back in your neck of the woods, Raoul. He used to say that even with radiation, if the PSA didn’t nadir at 0.2 or less, then it was ultimately going to be a failure. You could argue this in 2 ways. If he’s in poor health, I would probably observe him. If he was in robust health or I perceived he had a greater than 10-year life expectancy, I would work him up. An Axumin fluciclovine scan would be an ideal imaging test. That’s what we would use at Duke because that’s what we have. If I got pushback from the insurance companies, I might have to order the bone scan and CT first.

Videos

Dr Raoul Concepcion leads a panel discussion on a case of a 64-year-old man with multifocal prostate cancer treated with IMRT who refused ADT. 

Case 2: 64-Year-Old Man With Multifocal Prostate Cancer Post-IMRT

Dr Ghesani, educate us. You deal with this a lot, and you understand. You have a tracer, and then there are nuances to this based on half-life. Gallium has a particular half-life, and F-18 [fluorine-18] has a particular half-life. Obviously, choline has a particular half-life. How does that impact and how does that play out potentially, as these scans are made more available to the general practitioner, the community urologist and oncologist? What are the factors there that the practitioners need to know that are the nuanced differences between those tracers?

 I would like to make 2 more points that I just started thinking about as Brian and Judd mentioned those items. I would like to add on those as well. As Brian referenced, there are data that show there’s less than 20% sensitivity for combination of bone scans and CT [computerized tomography] scans in the setting of biochemical recurrence. There’s even a bigger problem, which is that in the small minority of the patients where the scans pick up the disease, it’s misleading because it does not fully clarify the extent of disease. Therefore, if you superficially look at it, you will see about 20% or less benefit. But in fact, even a subgroup of those patients does not benefit because their disease has not been properly delineated. They may have disease that was picked up only in part by the CT and bone scans, and you may end up targeting your treatment and not recognizing that there may be disease outside what the CT and bone scan did not pick up. 

For that reason, it will be important to work with the CMS [Centers for Medicare & Medicaid Services] and other providers, and we are aggressively working in various societies by collaborating with one another to make these points clear. Hopefully, soon, these requirements for bone scans and CT scans will not be there. The second point I wanted to mention was in that polling question, the item about other, and this brings back to your question about all different options. There is also fluorine-18 FDG [fluorodeoxyglucose], which is the most used agent for most other cancers. It has been shown that for most cancers in the prostate it does not work, but with a very high Gleason score, they have very high level of glucose metabolism. Therefore, in a select and small subgroup of patients who have known to have a very high Gleason score, when they recur, one should also consider the possibility of FDG PET [positron emission tomography scan] or CT because in that subgroup, it is going to be very powerful.

Regarding your question about how we should choose. At the current level, the fluorine-18 half-life of 2 hours is readily available all around. It will be easy for the sides. Even after bone scan and CT scans have been negative, you have gone through the peer-to-peer and have an approval of fluciclovine, which would be the most used agent across the country at this time. For those sites that have the availability of gallium PSMA [prostate-specific membrane antigen] through the cross-referencing IND [investigational new drug] or clinical trials, but those would be mostly major academic centers. They can consider using gallium or fluorine PSMA-based agents. For small sites—the Mayo Clinic, for example—where the C-11 choline was first developed, they can with cyclotron availability produce in a large batch, and we know that sites like the Mayo Clinic are doing a large number of carbon-11 PSMA scans.

That is a limitation, isn’t it? The half-life of the C-11 is so short that they can’t…

 You can’t ship it a distance. To any of you, we know that fluciclovine Axumin is approved. It is approved in patients who have been treated for prostate cancer and have a rising PSA [prostate-specific antigen]. Correct me if I’m wrong, but doesn’t that include patients on active surveillance whose PSA [is rising]? Can you make the argument that active surveillance is a treatment and if they have a rising PSA, you could get fluciclovine? Have any of you tried that?

 You can make that argument. I don’t think it’s correct. I’ve seen it done, and it’s not really the FDA indication. What they mean is that interventions with curative intent, or subsequent hormone therapy that the patient is progressing. However, active surveillance was not part of that initial approval indication. Having said that, in the world many things are done whether there’s evidence or not evidence for that. Therefore, we don’t generally monitor our active surveillance patients with that.

Munir Ghesani, MD, an expert in nuclear medicine, describes the factors that differentiate available tracers and provides guidance on tracer selection. 

Considerations for Tracer Selection to Assess Biochemical Recurrence in Prostate Cancer 

If that patient presented today, and came to you as a second opinion, is bone scan and CT your choice still? Describe to me what other imaging modalities you might consider.

 Thank you again for inviting me. It’s an honor and privilege to be on this panel. With regard to the current day and age, the answer to this also will depend on which geographic region you are in, because there are certain agents that are approved that are widely available, and there are others that have more limited availability, because of either half-life limitation of the agent, or the way the FDA approval has been structured. Let me expand on that. Going back first to your question, the bone scan and the CT scan would not be the standard of care now, because there are other options. These options include the PET [positron emission tomography scan]/CT agents or PET MRI, if there are certain geographic regions that have it available. The most widely available agent right now is the fluciclovine, which is a fluorine-18–based agent. It has a half-life of close to 2 hours. Therefore, for most commercial radiopharmacies around the country, there is a network sufficient that if there is any PET scanner in any geographic region in the country, they will have access to fluciclovine.

There are a few other agents, such as C-11 choline, which is available and approved. However, because of its half-life, the availability is going to be limited very close to a cyclotron, or most of the times, the sites that have a cyclotron can access that agent. As of November, or December of 2020, the very first PSMA [prostate-specific membrane antigen] agent was approved by the FDA, and that is the gallium PSMA agent. That has the approval primarily through UCLA [the University of California, Los Angeles] and UCSF [the University of California, San Francisco]. However, UCLA and UCSF have been kind enough not to hold onto the IND [investigational new drug] proprietarily, so there is access if there is a cross reference to the IND for the sites that are doing the studies and have approached the FDA to cross reference it. Finally, there are many other PSMA agents that are available through the clinical trials. So, if any one of the sites is participating in these trials, there is access to those PSMA agents that are still not approved by the FDA. However, we’ll discuss them later during our subsequent discussions on the imaging side, but that is also an available access through the clinical trials.

Perfect. We’re going to go to a second polling question. I think the audience has already seen this. If this patient presented today, and assuming you would re-stage the patient, what imaging modality would you choose? Dr Ghesani gave a nice and brief summary on this. Would the audience continue to do their first restaging technetium bone scan and CT of the abdomen and pelvis, with and without IV [intravenous] contrast, whole body MRI, fluciclovine, gallium PSMA PET, C-11 choline, or other? This will give us [an idea about], as Dr Ghesani said, what’s available out there in your various marketplaces, because it’s not equal around the country. I think your point is very well taken. I don’t think a lot of people realize that when the gallium PSMA scan was approved, that it was specifically for UCLA and UCSF.

Looking at the polling question, we’ve got about 23%, a quarter, would still do bone scan, CT. Nobody would do a whole-body MRI. Close to 50% is going to use fluciclovine. Finally, 30% are going to do gallium PSA [prostate-specific antigen]. Judd, what do you have over there at Duke [Cancer Center]?

 I really appreciated Munir’s comments. I think from an academic standpoint, he’s right on target. The problem is, at least in the trenches where I’m at in North Carolina, a lot of times insurance carriers will not cover the Axumin [fluciclovine] scan until you’ve done the bone scan and CT. Often, I don’t know if Brian’s running into that in Chicago, but you order it, and then I’ll get a call to do a peer-to-peer [discussion], which is never really a peer-to-peer, it’s someone on the other end who doesn’t really know what they’re talking about, but that’s another story. They will say, “Have you done a bone scan and a CT? We need to see a negative bone scan and a CT before we’ll pay for the Axumin.” I don’t know, that needs to change, because it’s a waste of money. Nevertheless, that’s what we’re facing in early 2021.

 I think that most clinicians, and certainly insurance companies, don’t necessarily recognize that the sensitivity of a bone and CT scan is very limited. Historically, as you said, and back even in the early to mid-2000s, and even today, we order these tests. However, half of it’s out of necessity to meet insurance standards, but the sensitivity, at levels less than 10, and less than 20 [ng/mL] certainly, are poor. Moreover, it’s been studied and suggested that up to 90% of scans at that level will be negative, but nonetheless, that’s our gold standard for what we compare against. When those studies came out, it was because choline was being FDA approved at the time, and you needed a PSA level recurrence of about 2 [ng/mL], at minimum.

Therefore, a lot of these insurance companies adopted a level that said, “Hey, not only would you have to get a CT and a bone scan first, but I want to see your patients’ PSA level at about 2 [ng/mL] before we’re going to approve that.” There is some variability there, and certainly Medicare is better, but it’s frustrating. The point here is that if we can locate that disease and we can treat this at volumes when the tumor is still small, certainly, patients are going to have better outcomes.

Post-surgery, there have been many trials that say if you treat patients at an early time, when their PSA values are between 0.2 and 0.5 [ng/mL], they’re going to do better than if we wait until those values are higher. We typically want to get these types of what we call next-generation imaging scans, or these PET/CT scans, whether it’s fluciclovine or a PSMA scans, at earlier levels, which we believe help patients better. I agree with Judd that often, I must go through those hoops, although it’s a futile exercise and extra radiation exposure to the patient. From there, the patients become frustrated because I don’t hide my angst for these hoops. But I think it’s the way that we get the right scans these days.

An expert panel reacts to polling data on choice of imaging modalities for patients with prostate patients after definitive therapy and share their insights about best practices.  

Imaging Modalities for Evaluating Biochemical Recurrence in Prostate Cancer 

Here’s our first case; pay attention to the dates here. In 2010, we have a 58-year-old white male who presents to urology with a PSA [prostate-specific antigen] of 15 ng/mL, normal DRE [digital rectal examination]. He undergoes a TRUS [transrectal ultrasound] guided biopsy, and shows 5/12 cores positive, all Gleason group 2, which as many of you know, now has been broken out as 3+4 [Gleason grade group 2 (3+4)]. Additionally, the staging work-up, bone scan CT was negative. The patient underwent robotically assisted radical prostatectomy, and surgical pathology shows a pathologic T3a, so he had capsular involvement. Again, all Gleason grade 2; surgical margins and seminal vesicles were negative. Six months post-operation, his PSA was 0.8 [ng/mL]. Then, the patient relocates for his job and has no follow-up. Let’s go to the next slide.

He returns to the area in 3 years, and he has a PSA of 8.3 [ng/mL] now. Remember, his nadir, his 6-month PSA after surgery was 0.8 [ng/mL]. He’s completely asymptomatic. He undergoes a work-up, restaging, and he has a bone scan and CT scan, which are negative for metastatic disease. To the audience, would you start this patient on ADT [androgen deprivation therapy]? Again, he had a radical prostatectomy, pathologic T3, Gleason [group] 3+4, asymptomatic, PSA was 0.8 at 6 months, and now the PSA is 8.3 [ng/mL], completely asymptomatic. Let’s see here, two-thirds of the audience say they would start ADT; 17% said no; 16% to 17% said there’s not enough information.

Raoul Concepcion, MD, presents the case of a 58-year-old man who had a radical prostatectomy 6 months prior and discusses how aspects of the case influence treatment selection. 

Judd W. Moul, MD

Articles

Case 2: 64-Year-Old Man With Multifocal Prostate Cancer Post-IMRT

Considerations for Tracer Selection to Assess Biochemical Recurrence in Prostate Cancer

Imaging Modalities for Evaluating Biochemical Recurrence in Prostate Cancer

Case 1: 58-Year-Old Man 6 Months Post-Radical Prostatectomy

Judd W. Moul, MD

Articles

Case 2: 64-Year-Old Man With Multifocal Prostate Cancer Post-IMRT

Considerations for Tracer Selection to Assess Biochemical Recurrence in Prostate Cancer

Imaging Modalities for Evaluating Biochemical Recurrence in Prostate Cancer

Case 1: 58-Year-Old Man 6 Months Post-Radical Prostatectomy

Considerations for Tracer Selection to Assess Biochemical Recurrence in Prostate Cancer 

Imaging Modalities for Evaluating Biochemical Recurrence in Prostate Cancer 

Case 1: 58-Year-Old Man 6 Months Post-Radical Prostatectomy 