POSTED: February 12, 2020

PET Imaging + Prostate Cancer

Dr. Oliver Sartor, the Bernadine Laborde Professor of Cancer Research in the Medicine and Urology Departments of the Tulane School of Medicine, is one of the leading researchers in advanced prostate cancer today. He is also the editor-inchief of Clinical Genitourinary Cancer and the author of more than 300 scientific papers.

Prostatepedia spoke with him about PET imaging and prostate cancer.
Let’s start off by talking about PET scans. What are they, and what types are currently available?

Dr. Sartor: Positron emission tomography (PET) scans rely  on the positron, which is like a piece of antimatter. When the positron comes out, the opposite of an electron, it interacts with matter  in the body. When it collides, it gives off a signal that can be detected by a variety of devices. These PET imaging devices can localize things with great precision using a PET scan. But here’s where the confusion begins.

There is a whole variety of PET scans that are dependent on not only the isotope involved but the little carrier molecules that are biologically important, molecules that distribute the isotope in  a particular manner so that we  can detect a signal.

People talk about PET scans  as if there were only one,  but there are five different types. There’s fluorodeoxyglucose (FDG), Axumin (fluciclovine F 18), sodium  fluoride, choline, and prostatespecific membrane antigen  (PSMA) PET. People get totally confused about them. Which  PET scan are you talking about,  and who’s going to pay for it?

Right now, there’s only one  that’s reliably paid for, and it’s  only in recurrent cancer, and  that’s Axumin (fluciclovine F 18). Everything else is not reliably  paid for. For reference, UCLA charged approximately $2,700  for a PSMA PET.

If someone says they’re going  to get a PET scan for a cancer patient, what they generally  mean is a fluorodeoxyglucose (FDG), which is fancy terminology for labeled sugar. The traditional FDG PET uses F-18, which is an isotope of fluorine that will give  off a positron. The F-18 is stuck onto a sugar molecule, and it goes  wherever the sugar goes in the body. Many parts of the body,  such as the heart and brain,  are metabolically active under  many circumstances, and they  will have an uptake of the sugar, which can be detected by the  PET scan. This is also true for  many cancers. You can trace out a whole variety of cancers by following these little sugar tracers and seeing where they go.

Not all prostate cancer is metabolically active. Others,  like lung, esophageal, and testicular cancer can be metabolically active, and the prototype is probably  lung cancer, where FDG PET  scans are routine.

To the chagrin of many patients  and some physicians, FDG PET  is not approved for prostate cancer use. In fact, it is specifically excluded. If a doctor orders  an FDG PET, it’s going to be hard to have it reimbursed because it’s not FDA-approved.

Sodium fluoride PET is another form of scan. A naked fluoride molecule will go into bone and areas of active bony turnover exclusively, so it doesn’t go  where the cancer goes. The sodium fluoride PET scan doesn’t show tumor; it only shows turnover in bone. The turnover in bone can be augmented by the presence of tumor, but it can also be augmented by things like arthritis, inflammation, and almost anything that damages the bone, like  a fracture followed by healing.  It’s like a souped-up bone scan.

A choline PET scan uses a different isotope, including C-13, which  has a short half-life. Choline PETs were made famous in the United States through the Mayo Clinic  in Rochester because they got  FDA approval. Choline PET uses uptake by areas of inflammation,  so you can track out the cancer  in a more sensitive manner  by looking at the choline uptake. They’ve been able to demonstrate areas of metastasis when conventional imaging fails.

Axumin (fluciclovine F 18) is PET scan that is specifically FDAapproved for use in recurrent prostate cancer. Axumin (fluciclovine F 18) is more sensitive to finding cancer in lymph nodes than CAT  or bone scans. There’s not a lot  of data on the Axumin (fluciclovine F 18) uptake in bone, but it definitely can be taken up in bone.

What has everyone excited is the prostate-specific membrane antigen (PSMA) scan. There’s more than one kind of PSMA scan out there, but the one most commonly used is the gallium-68 isotope tracer.

The tracer is a small molecule that will bind to the antigen expressed in a number of prostate cancer cells, but it can be expressed elsewhere as well. If you look at  a PSMA scan, there’s a lot of uptake in the salivary glands and the lacrimal glands, which are the glands around the eye that make the tears. There’s also some uptake in the liver. The typical PSMA scan is a molecule that is excreted into the kidneys. You’ll see uptake in the kidneys and then the ureters and the bladder.

There are newer PSMA tracers that are not excreted in the kidney. This could be helpful for viewing the lower pelvis and around the bladder. If the bladder is filled  up with isotope, you’re not going  to see much, but there are new PSMA tracers that can be excreted in the liver instead of the kidneys. The PSMA-1007 can do that.

PSMA tracers used predominantly in Europe include PSMA-11 and PSMA-I&T, and they’re both typically bound to gallium-68. Dr. Martin G. Pomper at Johns Hopkins has invented a molecule called DCFPyL that is bound to F-18. It traces out PSMA uptake in accordance with the PSMA distribution tissue in salivary and lacrimal glands, and in the liver, bladder, and kidney. Some people prefer F-18 imaging to gallium-68, but they’re both good.

Currently, the PSMA scan is not FDA-approved, but comparative studies indicate that PSMA is more sensitive than choline. UCLA has published that it’s definitely more sensitive than Axumin (fluciclovine  F 18), which is the current FDAapproved scan.

What does sensitive mean,  exactly? Many studies show that the average patient who  is detectable to bone scan probably has a PSA of somewhere between 30 and 70. The PSMA scan  is typically positive at a PSA  of 0.5. That’s about 100 times  more sensitive than a bone scan.

CAT scans and MRI depend on cross-sectional imaging. If you’re going to define something on  a CAT scan or an MRI, it typically needs to be about a centimeter in size. People argue about the number of tumor cells present  in a centimeter of tumor, but it might approach a billion cells  in one centimeter of tumor.  On a CAT scan or MRI, you’re waiting until you get a billion  cells in one spot before you  detect anything. The PSMA  is probably about 50 times  more sensitive than CT or bone scan, or better.

How does this change treatment?

Dr. Sartor: The reason we’re interested in finding small tumors  is that you want to know if the cancer has spread and where it  has spread. The success of almost any local therapy, such as surgery or radiation, depends on knowing the location of the cancer. So, different scans might alter your treatment plan. Studies have shown that PSMA detects more cancer than previously suspected.

For example, imagine a patient  with Gleason 8 and PSA 20 who has a small nodule on their prostate, and so they’re clinical stage T3A. We know that if we treat these patients with surgery, the probability of their failing  could be around 50% depending on how many biopsies are positive. The surgery hasn’t failed if the cancer has already spread by the time we do the surgery. It’s the imaging that failed.

If you get a PSMA scan, you  might be able to avoid noncurative surgery. I hesitate to say “unnecessary” because surgery might have a positive effect.  But surgery here is noncurative because you have to do something more. The same is true for radiation. And if you’re using  a focal class of therapy, you want  to know where the cancer is in  the best possible way.
We don’t have all the scan data  that we need. Most of the Axumin (fluciclovine F 18), choline, and PSMA scans are done for patients who are recurring after initial definitive therapies. These are patients whose PSAs are rising after surgery or radiation, and that’s where most of the data originates from now.

We can use specialized radiation techniques such as stereotactic ablative radiotherapy (SABR)  or stereotactic body radiotherapy (SBRT) to delay rising PSA after treatment. There’s some data from a prospective randomized trial by Dr. Peter Ost in Belgium [Prostatepedia spoke with Dr. Ost in February, 2018] that shows that SABR/SBRT can delay the time to PSA progression. Folks at various centers have shown that, depending on what you radiate at the time of recurrence, if there’s one or more lesions, and where they’re located, about 30% of patients might have a complete remission of PSA after radiation  on PSMA-detected scanning.
Based on several data sets,  we typically find that, for those  with PSA between 0.5 and 1.0,  are about 60% positive on a PSMA PET. Lower than 0.5 PSA, only a minority of scans are positive. Above 1.0 PSA, the vast majority are positive. PSMA is probably a little better in the lymph nodes as compared to the bone, but there’s a lot more work that needs to be done regarding localization.

The bottom line is that PSMA  scans are the most sensitive current technology for finding cancer. They seem particularly helpful for cancer in the lymph nodes, and for those who have recurrent cancer because treatment plans depend upon the location  of the tumor, as determined  by scans.

The VISION trial is about to complete accrual in September, 2019. It’s a Phase III trial of PSMA617 with lutetium-177 for the treatment of advanced prostate cancer. This is a prospective randomized trial, now closed  to accrual, so you can’t pursue  it at this point. But it’s an important trial that will look at whether  or not PSMA lutetium-177 prolongs radiographic progression-free survival or overall survival in patients who’ve been pre-treated with things like Zytiga (abiraterone), Xtandi (enzalutamide), and Taxotere (docetaxel). It’ll probably take about a year to report. 

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