Overview of Nuclear Medicine Applications in Prostate Cancer
In the past few years, we’ve seen a spike in the number of prostate cancer cases. This increase has been the highest on record. Two major factors have contributed to this surge: more successful and earlier detection and the rising average lifespan. Prostate cancer is currently ranked as the second most common type of cancer in men and the fourth most common of all cancers.
According to the American Cancer Society, prostate cancer is the second largest cause of death from cancer in the United States. In 2022 alone, it’s estimated that about 268,490 new cases will be diagnosed and around 34,500 men will succumb to the disease. Looking at these numbers, we see that the average American man has about an 11% chance of being diagnosed with prostate cancer in his lifetime, and a 2.5% chance of dying from the disease.
The worldwide scenario isn’t much different. In 2020, over 1.4 million new cases of prostate cancer were recorded translating to 375,304 deaths. Prostate cancer has been labeled as the most frequently diagnosed type of cancer in 112 countries globally and is the leading cause of cancer-related deaths in 48 countries.
To lower the high rates of disability and death caused by prostate cancer, diagnosis needs to occur earlier, and treatments need to be more effective. Nuclear medicine, a specialized area of radiology, includes several innovative techniques for detecting prostate cancer, pinpointing its location, determining its stage (how advanced it is), and treating it using targeted therapy. We’ll provide more information about how nuclear medicine is reshaping prostate cancer management in the following review.
Anatomy and Physiology of Nuclear Medicine Applications in Prostate Cancer
The prostate is a small organ with muscle and gland tissue, found just beneath the bladder and at the start of the urethra. This organ has a role in controlling the flow of urine and preventing a condition called retrograde ejaculation, which is when semen enters the bladder instead of exiting the body. However, its main job is to make a helpful secretion for semen. This includes special chemicals like acid phosphatase, which releases energy from compounds in the semen, and prostate-specific antigen, which helps to thin the semen after ejaculation. Additionally, it creates transglutaminase, an enzyme that helps semen to liquidate, citric acid, zinc, and calcitonin to help sperm move more effectively.
The prostate is located in the pelvic area, right in front of the rectum and beneath a bony plate in the lower part of the pelvis called the inferior edge of the symphysis pubis. Its rounded top portion, or apex, faces downwards, while its bottom part, or base, sits beneath the neck of the bladder. This gland is connected to the pubis bone through puboprostatic ligaments, and its back is in contact with the rectum’s second section, while levator ani muscles touch its sides.
The prostate is made up of five sections, or lobes: two equal-sized side lobes, and the anterior, posterior, and median lobes. It is separated from a sheet of connective tissue at the back of the body by a network of veins and is covered by a thin capsule made of fibrous tissue. This capsule also contains muscle tissue that surrounds the urethra.
The prostate’s blood supply primarily comes from the internal iliac circulation, in particular, the internal pudendal, inferior vesical, and hemorrhoidal or middle rectal arteries. The prostatic artery, which comes from the inferior vesical artery, is generally 1 to 2 cm long before it splits into capsular and urethral branches. Veins in the prostate drain into the internal iliac veins from the prostatic venous plexus and the dorsal vein of the penis. The nerves in the prostate come from the pelvic plexus and inferior hypogastric plexus.
Why do People Need Nuclear Medicine Applications in Prostate Cancer
If someone has a high-risk prostate cancer which is serious and advanced (having a high Gleason score, T3a or higher, PSA level of 20 or greater, ISUP of 4 or higher), then removing the prostate through surgery and/or radiation therapy are the best treatments. Approximately 80% of patients won’t have cancer for 7 years after these treatments, however, up to half could have the cancer come back. The chance of survival for 5 years is nearly 100% if the cancer hasn’t spread to other parts of the body. However, if it has spread, that survival rate drops to 31%. Unfortunately, 12% of patients find out they have prostate cancer when it has already spread to the lymph nodes or other organs. Those with spread cancer are less likely to live long and are less likely to benefit from surgery or radiation.
CT and MRI, which are scanning machines, aren’t great at spotting small cancer growth in the lymph nodes because these machines depend solely on the size and physical features of the nodes. And nuclear medicine bone scans, which are tests using a small amount of radioactive material to diagnose bone changes or abnormalities, often need higher PSA levels (20 ng/mL or more) before they can reliably determine bone cancer. However, new advanced technologies provide a more sensitive and accurate detection of cancer that has spread, allowing for a more accurate staging (or determining the extent) of the prostate cancer. This improves the chances of selecting an effective treatment while avoiding unnecessary side effects, like avoiding surgery or radiation if the cancer has already spread.
Radioligands, which are radioactive compounds that bind to specific cells or proteins, are also used in managing advanced prostate cancer.
In the past, radiotherapeutic isotopes, which are a kind of radiation therapy, played a significant role in relief treatment of bone cancer pain. However, recently, radioligands that target a substance called prostate-specific membrane antigen (PSMA), found on the surface of most prostate cancers, have been successfully used.
PSMA is a type of protein that is highly present, up to 95% of the time, on prostate cancer cells, including more aggressive cancer that has spread. Prostate cancer that becomes resistant to hormone therapies usually increases the presence of PSMA, up to 1,000 times the normal level. These features make PSMA an excellent target for therapies and treatments that use radioactive pharmaceuticals, including for cases where the disease progresses, comes back, or if there are suspected cancer spread.
In 1996, the first PSMA-based PET imaging radioligand, a compound that radioactively ‘lights up’ cancer cells and known as Prostascint, was approved by the FDA. Although this was initially a major breakthrough, however, it had limitations. This compound could only attach to inactive, damaged cells and not live ones, the latter being the cells you want to target. The scanning images were also not great because of high background activity that interfered with accurately finding cancer cells.
This scenario radically changed on December 1, 2020, when the FDA approved the first small molecule PSMA-based radioligand, a compound that can bind to the PSMA targets living on cancer cells. This new development of small molecules that can reliably attach to active cancer cells opened up availability for imaging, restaging, and staging prostate cancer, even if the cancer is very small or has a low PSA level.
These PSMA-binding radioactive compounds are now widely used and recommended for initial staging, determining the extent of the disease, and early cancer detection. These radioactive compounds can be used as therapy in high-risk and advanced cases. It’s important to remember that about 5% of prostate cancers do not have PSMA, and so these compounds will not work in these individuals.
Tumors that don’t have PSMA usually have a poor prognosis. A protein called fibroblast activation protein (FAP) is frequently present in many solid tumors, including prostate cancer, and recent studies suggest that it might be a useful alternative tracer in patients with prostate cancer that do not have PSMA for both diagnostic imaging and therapeutic treatment.
How is Nuclear Medicine Applications in Prostate Cancer performed
Radiopharmaceuticals are special substances used for scans that help doctors see what’s happening inside the body. They should be made and used in a safe and correct way, following all necessary rules and guidelines.
Two popular imaging procedures are CT and MRI. Both are similarly effective at spotting when cancer cells have spread to the lymph nodes. But MRI has a bit of an edge when it comes to enhancing the contrast in images, which can be particularly useful for prostate and pelvic examinations. Both methods are also efficient at identifying cancer that has spread to the bones.
F-18-FDG is a type of scan often used for many types of cancer. Yet, it might not be the best choice for prostate cancer. That’s because prostate cancer cells metabolize (or process) glucose at a slower rate than other types of cancer, making it harder for F-18-FDG scans to detect them. Also, some noncancerous conditions can also light up in F-18-FDG scans, which could lead to false positive results. For these reasons, this type of scan is generally not recommended for screening prostate cancer.
Bone scans, on the other hand, are useful in spotting cancer that has spread to the bones. They are most useful in patients at a high risk for such spread, and can be used to monitor how well treatment is working. For some patients, a second type of test might be used if the results from the bone scan are unclear.
There are many ways to carry out a bone scan. One method is with a gamma camera-based bone scan. Before this procedure, patients aren’t required to go through any special preparations, but it does take a few hours from the time of injection to the actual imaging. A more technologically advanced method combines SPECT (single photon emission computed tomography) and CT (computerized tomography), improving the quality and accuracy of the images. In fact, it can spot bone metastases (cancer spread to the bones) at much lower levels of prostate-specific antigen (PSA), a substance made by cells in the prostate gland, compared to traditional bone scans.
A more modern version of these scans uses F-18-sodium fluoride and is usually carried out with a PET/CT scan. This scan reacts more sensitively to changes in bone metabolism compared to older scans, thus it allows for quicker imaging and provides 3D images fused with CT scans. This makes it easier for doctors to find and pinpoint the exact location of individual bone metastases.
Overall, the goal of these scans is to help doctors understand the progression of prostate cancer and guide the necessary treatments to manage it effectively. The right type of scan will depend on the individual’s clinical situation and the doctor’s professional judgment.
What Else Should I Know About Nuclear Medicine Applications in Prostate Cancer?
Modern imaging techniques using radionuclide PET scans (a type of radioactivity-based scan) and targeted treatments can greatly improve the management decisions for over half of patients with prostate cancer. This could lead to a better survival rate for people with advanced stages of the disease.
PSMA PET scans, a specific type of scan that detects prostate-specific membrane antigen, are superior to CT scans and standard bone scans in staging prostate cancer, which means determining how advanced it is.
It’s recommended that the PSMA-based imaging is done before starting hormone therapy, which is a common treatment for prostate cancer. The hormones help to stop the cancer cells from growing.
Ga-68-PSMA-11 and F-18-piflufolastat (also known as DCFPyL) PET scans are types of PSMA PET scans that have been shown to be more sensitive than C-11 choline or F-18 fluciclovine PET scans, especially in detecting prostate cancer even when PSA levels (Prostate-Specific Antigen; a substance produced by the prostate gland) are very low.
When a Ga-68-PSMA-11 or F-18 piflufolastat PSMA PET/CT scan is performed, a separate bone scan is not necessary.
Tc-99m-PSMA SPECT/CT, another type of scan that combines two imaging methods, can be a cost-effective alternative to the more expensive PET scans.
New imaging techniques are now available to better assess each patient’s prostate cancer, including its staging, course, and progress over time.
Nuclear medicine-based imaging (using radioactive substances) and treatments can significantly influence treatment planning, decision-making, the quality of life, and overall survival chances for patients with prostate cancer.