Andrew J. Armstrong, MD, MSc: This is a rapidly changing area of medicine that continually gets updated in our NCCN [National Comprehensive Cancer Network] Guidelines. The purpose of imaging in early disease is 2-fold. One is to assess patients with lower-risk disease as far as their candidacy for radical vs observational or active surveillance treatment initially.

Even before we get to treatment, many men can undergo multiparametric MRI of the prostate as part of their screening, simply based on having an elevated PSA [prostate-specific antigen]. Imaging is moving earlier into the disease algorithm to inform on where to place a needle for diagnostic biopsy purposes and risk stratification purposes, and to help make decisions on whether treatment is needed or active surveillance is appropriate for lower-risk men. We recommend imaging, particularly MRIs of the prostate, even for lower-risk patients—that’s now recommended in the 2022 NCCN guidelines—to help inform on that patient’s risk of progression, risk of relapse, and identify ideal candidates for surveillance.

The other purpose of imaging is in higher-risk men to identify patients who may have disease outside of the prostate, either extracapsular extension, seminal vesicle invasion, lymph node, or more distant metastases. This is where conventional imaging often fails patients. Conventional imaging typically means CT, MRI, and technetium-99m bone scan. This form of imaging tends to be insensitive for the detection of metastases.

This is where PSMA [prostate-specific membrane antigen]–based imaging modalities can be helpful with improved sensitivity. These types of tests are FDA approved in this higher-risk setting, but they’re not perfect either. We know that these tests suffer from false negatives because men can have small-volume lymph node metastases under 5 mm that go undetected even by PSMA PET, but they’re certainly better than conventional imaging. That’s where this has also been incorporated into NCCN algorithms. The challenge has been to get insurance to follow these guidelines and incorporate more advanced PET imaging into newly diagnosed settings. Most men in the United States are getting more conventional imaging and using it to make treatment decisions based on local therapy or systemic therapy.

As we’re incorporating PSMA PET imaging as our dominant form of PET imaging in prostate cancer, we’re learning about some of the nuances. For example, there are some normal tissues in the body that can uptake or express PSMA: the salivary glands, the submandibular and lacrimal glands, small peripheral ganglia, old rib fractures, sarcoidosis, Paget disease, and even lung cancer. Other metastatic tumors can also express PSMA in their neovasculature. There are some strong caveats to a positive test where biopsies are often recommended to confirm a lesion and that it’s prostate cancer before acting on it. For example, we’ve seen many patients with isolated rib lesions not have prostate cancer. Maybe it's an old healing fracture. I’ve had patients with an isolated PSMA PET–positive lung nodule that’s been biopsied that turned out to be lung cancer.

Not everything that expresses PSMA or is detected on PSMA PET is prostate cancer, but it does have much-enhanced sensitivity, probably in the 80% range. One of the major limitations as I’ve mentioned is that you can have very small lesions that are under 5 mm that are invisible even on PSMA PET. They lack diagnostic performance in tiny metastatic lesions. What we do at the PET imaging is an even more important question in [light of]the fact that the sensitivity is still an issue and has an impact on the outcome of patients who undergo PET-directed therapies.

Transcript edited for clarity.