PSMA Testing and Precision Medicine in Prostate Cancer: Today, Tomorrow, and Beyond

By Alex Pozdnyakov, MD, Zachary Bessette - Last Updated: February 8, 2023

GU Oncology Now spoke with Alex Pozdnyakov, MD, a diagnostic radiology resident at McMaster University, about the current utility and potential application of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging in prostate cancer.

Can you provide a brief background on PSMA PET imaging in prostate cancer? What is the current utility and capability of such imaging?

Dr. Pozdnyakov: PSMA PET is an emerging nuclear medicine molecular imaging modality that primarily targets the PSMA receptors on the prostate cancer cells. It is a sensitive and specific way to detect prostate cancer cells, which are localized in various tissues in the body. One of the main challenges that existed before the emergence of PSMA PET was detecting metastatic disease in lymph nodes and at distant sites. With PSMA PET, the idea is to target this particular receptor with a radioligand—such as      Gallium-68—to identify where the disease has metastasized. Then, we can adjust the treatment approach for patients who have early metastatic disease.

Which patients should be undergoing PSMA PET imaging, and do you believe it is being overutilized, underutilized, or utilized appropriately?

Dr. Pozdnyakov: There are different stages at which PSMA PET imaging can be used. One of the stages that my research focuses on is during biochemical recurrence. After the initial treatment of prostate cancer, rising prostate-specific antigen (PSA) levels in the blood suggest biochemical recurrence. It is often difficult to localize the disease, but PSMA PET can help to localize biochemical recurrence so that the treatment can be targeted. In particular, this helps to guide metastasis-directed treatment, such as radiation therapy or metastasis-directed surgery

Another stage at which patients can receive PSMA PET imaging is during initial staging to detect any occult metastatic disease and subsequently guide the treatment approach for initial management. Specifically, this influences decisions on the extent of prostatectomy and pelvic lymph node dissection, and it helps to identify distant metastatic disease early.

Additionally, another area where PSMA PET can be applicable is in decision-making with regard to PSMA antigens like Lutetium-177-PSMA-617 radioligand therapy. This approach utilizes targeted delivery of radiation via radioligand that binds to PSMA-expressing cells.

How have PSMA PET imaging results impacted treatment decisions and management of patients?

Dr. Pozdnyakov: Many clinicians are changing their management decisions based on PSMA PET results. I’m involved in a systematic review with the team of researchers from the University of Toronto concerning clinical outcomes after PSMA PET imaging. We’ve found that more than 50% (56.4%) of patients have their treatment changed based on the findings of initial PSMA PET, which demonstrates the role it plays in current management decisions.

Within the next few years, I expect we’ll see improvements in survival outcomes. In our systematic review, we’ve tried to determine if there has been any significant overall survival benefit. But given that most of the PSMA PET studies have been published within the past 5 years, it is too soon to tell. Time will tell if mortality and morbidity from prostate cancer will be improved by PSMA PET utilization in the diagnostic and treatment management pathways.

What is the ceiling for PSMA PET imaging in prostate cancer? What is the most potential that PSMA PET imaging has for the prostate cancer treatment landscape?

Dr. Pozdnyakov: One of the limitations of PSMA PET imaging is that not all prostate cancer expresses PSMA molecularly. Some prostate cancer can be occult on the PSMA PET scan because the cancer cells simply don’t express PSMA in the first place. In this situation, PSMA PET would not be the optimal diagnostic imaging modality. Also, it’s important to note that with PSMA PET—like with a lot of molecular imaging and nuclear imaging scans—certain tissues, such as lacrimal glands, salivary glands, epithelium of the duodenum, and renal tubules, express higher levels of avidity on PSMA PET. This may limit detection of metastasis in those tissues. However, the expression levels of PSMA in those tissues are still lower in comparison with prostate cells.

How is PSMA PET imaging likely to evolve in the next 5 to 10 years? How will its capabilities and utility change?

Dr. Pozdnyakov: Right now, one of the areas of interest is looking at other cancers that might express this antigen. Though the name implies it is prostate-specific, there is evolving research to see whether PSMA is expressed in other malignancies, particularly in those organs that have shown baseline PSMA expression. There is ongoing research into gastrointestinal cancers, neuroendocrine cancers, and glioblastoma. However, this research is in the early stages, and it will be very interesting to see in the upcoming years whether PSMA PET can be applicable in other cancers or if its utility lies solely in prostate cancer.

Additionally, I’d like to highlight that in our systematic review, we’ve found that using PSMA PET for guiding radiation therapy in prostate cancer has been associated with complete biochemical response and biochemical-free survival in patients with prostate cancer who already had biochemical recurrence. Approximately 60% (60.2%) of patients had biochemical recurrence-free survival in 20 months of follow-up, and also almost 25% (23.3%) of patients had complete biochemical response at a median follow-up of 11 months after treatments that were guided by PSMA PET.