PSMA PET-CT Scans for Prostate Cancer: A More Accurate Way to Stage and Treat High-Risk and Recurrent Disease

What Is A PET-CT Scan?

A PSMA PET-CT scan is an imaging technique that detects clusters of prostate cancer cells anywhere in the body. In principle, it is just like a regular PET-CT scan, which also highlights cancerous areas within the body.

Dr. Asit Paul, hematologist-oncologist at the Massey Cancer Center, explains the regular PET-CT scan in the following words, “PET-CT is a hybrid imaging system that combines two different modalities to image cancers. In a PET scan, radioactive material is injected into the body, which travels through the bloodstream and preferentially accumulates in the cancer cells more than normal cells.”

He continues, “Once the radioactive compound is taken up by the cells, it provides imaging signals that are captured by highly sophisticated cameras. But PET scan does not provide a structural outline of the organ being imaged. A CT scan uses regular X-rays to outline the structure which is being imaged. As a result, we get composite images of cancer cells along with their structural outline.”

A regular PET-CT scan uses a molecule called 18F-fluorodeoxyglucose (FDG). This is essentially a glucose molecule tethered to a radiotracer (any material that can be detected based on its radioactivity). FDG is preferentially taken up by cancer cells in the body, as they tend to burn more glucose to fuel their growth than most of the other cells within the body.

This action by cancer cells is seen as bright areas on the PET portion of the scan. Then, PET imaging is combined with a high-resolution CT scan (obtained at the same time as the PET) to generate a combined image that precisely pinpoints the location of the cancer cells.

How Is A PSMA-PET Scan Different? What Are Its Benefits?

The FDG PET-CT scan, however, cannot easily pick up prostate cancer because FDG does not routinely bind to prostate cancer cells. To overcome this shortcoming, researchers designed different radiotracer drugs like 68Ga-PSMA-11 or 18F-DCFPyL, that seek out PSMA, a protein that is reliably present in high amounts on prostate cancer cells.

Once this drug binds to PSMA, it emits signals that identify the body’s PSMA-rich regions. Much like the FDG PET-CT scan, this information is combined with a CT scan to precisely highlight prostate cancer cells’ location(s) within the body.

These scans are revolutionary and have vastly changed the way modern medicine treats prostate cancer. However, they have limitations that people should be aware of.

Summarizing the need for a PSMA PET-CT scan, Dr. Paul says “The most used PET-CT is FDG PET-CT. FDG targets the property of increased glucose metabolism of cancer or other cells. Prostate cancers, unlike many other cancers, especially in early stages are slow growing and not very metabolically active.  Therefore FDG PET-CT may not provide the whole picture of cancer spread. PSMA PET-CT is different because it images different properties of cancer cells. PSMA is found in >80% of prostate cancer cells. As a result, it better depicts the distribution of cancer spread.”

He continues, “Multiple research studies have shown PSMA PET-CT has better accuracy and detection capability of prostate cancer than conventional CT scans and bone scans. As a result, a treatment plan can be changed based on PSMA PET-CT results. For example, PSMA PET-CT may detect cancer spread outside the prostate earlier than a conventional scan. Those patients may not benefit from prostate-directed radiation or prostate surgery. PSMA PET-CT can also help cancer doctors in treatment decisions when PSA is detectable but still too low to be detected by conventional scans.

RELATED: Pros and Cons of the PET/CT Scan

Limitations of PSMA PET-CT Scans

• Not all prostate cancer patients express PSMA. This scan will not detect cancer in these patients.
• Some areas with prostate cancer may be very small. Their radiotracer uptake may not be sufficient to be picked up by the scan. A patient with metastatic disease, therefore, can potentially be missed.
• PSMA may be expressed by other cancers, such as breast, bladder, colon, and kidney cancers. These may be erroneously diagnosed as prostate cancers, which can result in the patient receiving incorrect treatment.

Highlighting the limitations of the PSMA PET-CT scan, Dr. Paul says, “About 10% of prostate cancer may not be PSMA positive. Therefore, small percentages of prostate cancers might be missed by PSMA PET-CT. False positive PSMA uptake has been described in non-cancerous benign tumors as well as non-prostatic tissues that include blood vessels, soft tissue, neural tissues, and others. Normal distribution of PSMA is seen in salivary glands, liver, spleen, bowel, kidneys, and bladder. Therefore, reporting physicians should carefully interpret the scan.”

Side Effects of a PSMA PET-CT Scan

The PSMA PET-CT scan is a low-risk examination and is safe for most patients. However, some may experience side effects, such as:

• Headaches
• Taste changes
• Tiredness, among others.

These are temporary and will usually resolve within a few hours or days.

People can rarely experience allergic reactions to contrast, or radiotracer, drugs. These reactions can range from mild to serious, causing symptoms like:

• Itchy eyes.
• Wheezing
• Hives
• Nasal congestion
• Breathing difficulties.

These symptoms require immediate medical attention. A thorough review of your allergies and medications greatly minimizes this risk.

The scan also contributes to lifetime radiation exposure. For context, the amount of radiation you are exposed to during the scan is equivalent to the amount you will naturally experience through your environment over eight years. In other words, it is an extremely low level of radiation exposure.

WATCH: Metastatic Prostate Cancer Treatment Is Improving

How to Read a PSMA PET-CT Scan

The images from a PSMA PET-CT scan look like regular CT scan images on which areas with cancer are brightly highlighted in yellow.

However, normal tissues that are not cancerous but also express PSMA also appear bright on these images. Distinguishing cancer from normal tissues, therefore, requires specialized training.

So, it is best to review these images and what they mean with your doctor.

How Much Does a PSMA Pet Scan Cost?

The out-of-pocket cost of a PSMA PET-CT scan can vary widely, from just over $1,000 to almost $10,000.

Since its approval by the U.S. Food and Drug Administration (FDA), most of this cost may be covered by insurance providers for patients designated as high-risk for metastatic disease by the National Comprehensive Cancer Network (NCCN).

Your physician’s office or the examination facility will be able to provide you with the exact cost of your test, so be sure to ask for this.

Meanwhile, your insurance provider can help you understand what portion will be covered by your plan and if you will be responsible for covering any of the cost.

“PSMA PET-CT is covered by Medicare for certain indications. Private insurance should cover PSMA PET-CT, but coverage may vary based on indications and insurance plans,” says Dr. Paul.

Who Is a PSMA PET-CT Scan For?

Not everyone with prostate cancer requires a PSMA PET-CT scan. It is most appropriate for a patient with an increased risk of harboring metastatic disease, which happens when their cancer has spread throughout their body.

Most patients with prostate cancer only have localized disease. Their cancers are confined to their prostate glands.

The likelihood that they have disease elsewhere in the body is so low that they do not require additional imaging, such as the PSMA PET-CT scan, as this can expose them to unnecessary radiation and side effects without any benefits.

But those patients who have a high risk for metastatic disease, based on their lab work, disease history, and certain features seen in their initial biopsy are well suited for a PSMA PET-CT scan.

This scan can either rule out or diagnose metastatic disease, which is crucial as the extent of the disease dictates the most appropriate treatment options for them.

If their cancer has not spread, they can potentially be cured by targeted surgery or radiotherapy. If their cancer has spread, they may require more extensive treatments.

Some patients who have been previously treated, likely with surgery (prostatectomy) or radiation, can develop a recurrence of their cancer. This is usually picked up on lab work that measures prostate-specific antigen (PSA), which is a protein made in abnormal quantities by prostate cancer cells.

When this happens, it is called a biochemical recurrence and a PSMA PET-CT scan can be the key to identifying the areas and the extent of the recurrence.

These areas can then be targeted by specific treatments, such as radiation.

What to Expect When Getting A PSMA Pet Scan

Questions To Ask Your Doctor Prior To Your Exam:

• Discuss why you need a PSMA PET-CT scan with your physician.
• Discuss alternatives to the exam and how they compare to the PSMA PET-CT.
• Understand the benefits and the side effects of the scan.
• Share any concerns you have regarding the examination.
• Share the complete list of your current medications with your physicians.

Preparing For The Exam:

• You may be asked to follow a special diet in the days leading up to your examination. This may include a low-carbohydrate, no-sugar diet. However, some centers do not require any special preparation for the PSMA PET-CT scan.
• You may need lab work prior to your examination. Be sure to complete it as recommended as this can influence what you can or cannot receive during the procedure, such as intravenous (IV) contrast.
• You may take your routine medications prior to your examination unless your physician or the examination facility recommends otherwise.
• It may be helpful to wear loose-fitting, comfortable clothing on the day of the examination. Clothing without metal parts, such as zippers, is recommended to ensure the quality of the examination. You may be asked to change into a hospital gown if your clothing has metal parts.
• Metal accessories, such as eyeglasses and jewelry, will need to be removed prior to the examination. It may be helpful to leave these at home or with a loved one.
• You may be asked to complete screening and consent forms on the day of your examination. This ensures that you are aware of the benefits and the risks, and can tolerate the procedure safely.
• An IV line will be placed in your arm vein. This will be used to inject the radiotracer into your body.
• IV contrast may also be injected to visualize the veins in your body.
• Your examination facility will usually have its own set of preparation protocols for you. Be sure to obtain and adhere to it.

What Happens During The Exam

• A technologist will likely meet with you to ensure that you are appropriately prepared for your examination. You should use this encounter to discuss any of your remaining questions and concerns.
• The technologist will then guide you through the different steps of the examination. These will likely include an IV insertion, radiotracer injection, wait time to ensure radiotracer uptake by the cancer cells, and getting set up for and undergoing the imaging.
• The exam can take around two hours. The exact duration of your exam may vary by facility.
• The results of your examination will be available in a few days. These will likely be communicated to you by your physician.

After The Examination

• If you have any new signs and symptoms, such as itchy eyes, nasal congestion, or difficulty breathing, alert the facility staff immediately. If you experience these symptoms after you have departed the facility, visit your nearest emergency room or call 911.
• Await communication from your physician about the results of your examination.

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