Tumor Board Reviewing T1N0M0 Prostate Cancer - CASE 3

October 27, 2021

In this Clinical Case-Based Learning Educational Program, a Virtual Tumor Board in Advanced Prostate Cancer, a case of a 79-year-old with a history of osteoarthritis, chronic lower back pain, and prostate cancer diagnosed in 2008 with T1N0M0 is presented, evaluated, and his treatment plan addressed.

Independent Medical Education Initiative Supported by Progenics Pharmaceuticals, Inc. a subsidiary of Lantheus Holdings, Inc.

Biographies:

Presenter: Geoffrey Sonn, MD Urologic oncologist, Assistant Professor of Urology and, by courtesy, of Radiology, Principal Investigator, Urologic Cancer Innovation Lab, Stanford Health Care, Stanford, California

Program Discussants:

Andrei H. Iagaru, MD, FACNM, Professor of Radiology - Nuclear Medicine, Chief, Division of Nuclear Medicine and Molecular Imaging, Director, Nuclear Medicine Residency Program, Co-Director, PET-MRI Research Program, Stanford University, Stanford, California

Alicia Morgans, MD, MPH Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts, Stanford, California

Hilary Bagshaw, MD, Radiation oncologist, Clinical Assistant Professor, Stanford Health Care




Read the Full Video Transcript

Geoffrey Sonn: Welcome to case three of our Advanced Prostate Cancer Virtual Tumor Board.

Present, Mr. David Garcia. This is a 79-year-old man with a history of arthritis, chronic lower back pain, and prostate cancer, diagnosed in 2008, based on an elevated PSA. His biopsy showed Gleason 3+4 prostate cancer, and he was treated with external beam radiation and six months of ADT. His PSA nadir was 1.2 and then increased to 9.3 in February of '18. Staging at that time was negative, and a biopsy showed recurrent cancer in the prostate. So he was treated with salvage whole-gland cryoablation. The PSA nadir then at 2.2 after cryotherapy, but subsequently began to rise again, reaching 4.6. He underwent staging with CT chest/abdomen/pelvis in December of 2020, and then continued to be monitored, as his PSA rose to seven, in February of '21. He then underwent a PyL PSMA PET, which we will show, shortly.

But before then, just for a bit of additional information, Mr. Garcia lives in an assisted living facility. He is a widower and has adult children and grandchildren who live far away. He remains relatively independent in his facility and has no other significant medical problems. So let's turn the case over to Andrei for review of his imaging.

Andrei Iagaru: Thank you, Geoff. So the first thing we are going to review is his bone scan. This did not identify, also, as metastatic disease. This is a good technique here because you see focal optic overlapping with the left forearm over the radius, so it's at the injection site, residual activity there. Is it something real, maybe a trauma? We do the additional spot views, to separate this area from the underlying bone. And this is clearly outside, so this is just a little bit of unflushed radiopharmaceutical in the IV line.

There are also some degenerative changes in the first carpometacarpal regions, as well as reactive changes in the right foot. So for all intents and purposes of staging or restaging for prostate cancer, this is negative for metastatic disease.

So let's go now to his PyL scan. We will review first the projection image. So we see the normal areas of uptake in the lacrimal, salivary glands. As well as indicated before, something that stands out is the presence of focal uptake in the prostate foci, and perhaps some unusual accumulation in the scrotal region. Is it urinary contamination or is it something real? Let's take a look.

As we scroll down, what also is seen, only on CT, is the presence of a couple of plump retroperitoneal lymph nodes below the left renal vessels. So by CT alone, those are suspicious. However, and perhaps because of the uptake in the adjacent duodenum, they do not seem to be conspicuous on the PET component of the exam.

As we advance toward the pelvis, we see the bladder, and in the posterior mid prostate, we have uptake that is in the region of prior markers. This focal uptake, it's highly suspicious for recurrent disease. And this is also a good case to illustrate that the activity in the bladder is not necessarily a problem. There are people who advocate for administering Lasix or placing a folic catheter. I think that the invasiveness of those procedures in elderly men with prostate cancer does not provide additional benefit over what we see on imaging. So clear uptake in this case, in the prostate.

And so, let's review also, the uptake in the scrotal region. It turns out that this is a low-grade uptake in the testis itself. It is not urinary contamination. This is incompletely evaluated on this exam. So a scrotal ultrasound would be recommended.

Probably because of the enlarged lymph nodes in the retroperitoneum that did not have PyL uptake, a follow-up exam was done one month later. So this is now shown at the top. And the PyL is shown at the bottom. On the [inaudible 00:04:29] there is more intense uptake in the testis. And let's remember, this is not process-specific either. This is an amino acid that goes wherever you have [inaudible 00:04:41] amino acid transporters, which are not always prostate cancer. It can be a variety of other entities. So even further suggestion for a scrotal ultrasound.

We see here as well, the presence of focal uptake in the prostate. This is of course confirming what we saw in PyL. And so I think that in the appropriate clinical scenarios, it should be biopsied for confirmation. However, in this particular case, those lymph nodes that were seen enlarged on the CT from PyL demonstrate focal uptake of axumin, which makes them even more concerning for metastatic prostate cancer. They also increased in size on CT slightly. So all this constellation of findings suggests recurrent disease in the prostate bed, as well as in higher [inaudible 00:05:28] lymph nodes and a finding of uncertain significance that should be followed up with a scrotal ultrasound in the testis. So with that back to you, Geoff.

Geoffrey Sonn: Great. Thank you, Andrei. So before we go on and discuss the next steps in management, let's review his case one more time. Again, a 79-year-old man was initially treated for Gleason 3+4 prostate cancer with radiation in six months of ADT in 2008. Later with salvage cryoablation, his PSA dropped after cryo but began to rise, now up to seven. And we have findings on imaging that suggest a subtle abnormality in one testicle, potentially a local recurrence within the prostate, and a couple of enlarged retroperitoneal lymph nodes that don't light up on PyL PSMA imaging but do light up on an axumin scan. So the question is how do we reconcile then all of these different sites of disease?

So maybe I'll just start from a urologic perspective, as I think about the testis, as well as the prostate. So with respect to the testis, the recommendation was made for an ultrasound, which was performed, that showed a mass in the testicle. The patient ended up undergoing an orchiectomy, both for diagnostic purposes, as well as potentially for therapy. And that ended up showing a Leydig cell tumor, which is unrelated to his prostate cancer. This is usually benign... about 90% of Leydig cell tumors are benign and they are both diagnosed and managed with orchiectomy. So at this point, there is nothing else to do for that.

With respect to the finding in his prostate, when I see this, I would think about other sites of disease, because that is really going to drive his overall outcome much more so than a local recurrence in the prostate. And in this case, with the retroperitoneal lymph nodes, those are quite concerning again for distant disease, which would make me less concerned about the prostate. And in fact, until I knew for sure that the things in the retroperitoneum were not real, I wouldn't even recommend a biopsy of the prostate. That's something that I would likely monitor, with the idea that if he goes on systemic therapy, that will confer some disease control in the prostate. But let me turn this over to Alicia to ask, how would you, if you were to see this patient in your clinic, address or further workup or potentially treat the concern for retroperitoneal lymph nodes?

Alicia Morgans: I think that's a great question. So he's an older man, so I would want to be very cautious with any intervention, but I would ask our radiology team, our interventionalists, whether they could get a biopsy of any of those nodes. Because they did look a little bit enlarged on the initial CT and Andrei did mention that by a month later, they already had become even larger. They were not massive, and he is an older gentleman, so I'm not sure if the interventional team would be able to access them and do so safely. But if they could, I think that would be the cleanest way to really diagnose metastatic disease. In which case we would have a conversation about what kind of systemic therapy would be ideal. But that's probably where I would start.

Geoffrey Sonn: Terrific. And any other thoughts? Andrei, comments about other common areas of false positive or false negatives on the PyL PET? What do we think about this discordance between the axumin and the PSMA PET?

Andrei Iagaru: It's cancer and it's biology. So it has a million ways of messing up with what we think we know. As we said, 90% of prostate cancers are PSMA positive. So that leaves us with at least 10% that are not. I think that the presence of uptake in the duodenum adjacent to the [inaudible 00:09:45] may pose a challenge for particular cases. The more we use PSMA, the more we will learn about the plethora of false positives. However, the typical prostate cancer lesions have very well-defined high focal uptake with CT correlates in many cases. And even if not, the sites of disease are punitive for the presence of metastatic prostate cancer. That being said, you can have inflammatory low-grade uptake. You can have multiple other [inaudible 00:10:15] And they are a little bit more anterior than we expect those to be.

You can have benign or malignant thyroid nodules that will show up, again, a variety of causes for this false positive. But in general, I think that interpreting a PSMA scan is not very complicated if you are aware of the pattern of spread for biochemically recurrent prostate cancer, as well as the potential for false positives. There are, of course, false positives with axumin, as well, as we, saw the finding in the testis. But those lymph nodes look to be too plump on CT and too focal in uptake to ignore. So I agree with what Alicia recommended, that they should be biopsied. And I think that IR should be able to get to those lymph nodes under CT guidance.

Geoffrey Sonn: Great. Thank you. And Hilary, any role for radiation in this case, either to the prostate and or to the retroperitoneal nodes?

Hilary Bagshaw: I think at this point, probably not. He's already had pelvic radiation. If he didn't have the nodes, maybe I'd offer him salvage brachytherapy, but those nodes are pretty high up. So it would be a pretty extensive external beam field. So I think I'd favor hormonal therapy and perhaps if he had persistent disease or one area growing, we could consider SBRT down the line, if he was doing really well. But given his age, et cetera, I think it would be a pretty extensive treatment. So I would not recommend it.

Geoffrey Sonn: Great. That's very reasonable. So it sounds like the consensus from the group at this point would be to attempt a biopsy of the retroperitoneal lymph nodes. And if those do confirm metastatic prostate cancer, a thoughtful discussion about whether to initiate ADT or continue to monitor for some period of time.
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