PSMA-Targeted Radioligand Therapies in Advanced Prostate Cancer - Episode 2

PSMA PET Imaging in Advanced Prostate Cancer

A discussion on the sensitivity and specificity of an emerging imaging modality, PSMA PET, in advanced prostate cancer.

Scott T. Tagawa, MD, MS, FACP: PSMA [prostate-specific membrane antigen] PET [positron emission tomography] has emerged as a very useful tool in several different scenarios. One of the most common uses is in the setting of biochemical recurrence after prior treatments—for example, rising PSA [prostate-specific antigen] [levels found] after primary radiation or a prostatectomy. The first generation of PET agents, such as choline C 11 and fluciclovine F 18, were more useful than CT [computed tomography] or MRI [magnetic resonance imaging], particularly at lower PSA levels, especially at a PSA level less than 1 ng/mL, and definitely at a PSA level less than 0.5 ng/mL. PSMA PET is approximately [twice] more sensitive. We do not have a lot of direct head-to-head data. There is a small, 50-patient, randomized, head-to-head data set, but also large sets—hundreds and, sometimes, thousands—of retrospective datapoint towards the same factor. PSA [testing] is both more sensitive and more specific than are existing PET modalities. It is certainly way more sensitive than other imaging modalities, such as CT or MRI.

There have been direct comparisons, such as in the proPSMA trial for patients with high-risk disease.

Another disease setting besides biochemical recurrence is the initial risk stratification of patients with higher risk disease, especially when considering any visible disease outside the prostate. Are we thinking about a prostatectomy alone or radiation to the prostate alone? If we can visualize these things outside the prostate, we believe that will lead to better outcomes. They do not yet have survival data, but it makes sense that when we know there is something outside the prostate, it may be useful.

Besides the proPSMA study that showed an improvement with PSMA PET over the standard CT, MRI, or bone scan imaging, we have 2 trials. One used gallium 68 PSMA-11 and was led by the UCLA [University of California, Los Angeles] and UCSF [University of California, San Francisco] groups. The other used [piflufolastat F 18] in the study of high-risk disease. The results showed very clearly that there is a strong positive predictive value with PSMA PET [imaging] in that setting. The negative predictive value has something to be desired.

Those 2 studies compared [PSMA PET] to surgery, so even though PSMA PET imaging is clearly an advance over what we had before, it is not as sensitive as the microscope. Very small lesions that might be picked up by a microscope may not be seen on PSMA PET, with a negative predictive value of around 40% as opposed to positive predictive values of 95% to 98% in those studies. That said, it does represent an advance. The subtleties are that there may be PSMA-positive lesions that are not removed at the time of surgery, because they’re outside of the lymph node–dissection template. That remains an ongoing area of study.