Advances in nuclear medicine and molecular imaging, such as prostate-specific membrane antigen positron emission tomography (PSMA PET), are improving the diagnosis, staging, treatment, and monitoring of patients with prostate cancer, particularly those with high-risk, localized disease. Preliminary response and progression criteria using PSMA PET/computed tomography (CT) imaging were presented at the recent ESMO Congress 2024.

Following this presentation, featured expert Matthew R. Smith, MD, PhD, was interviewed by Conference Reporter Associate Editor-in-Chief Christopher Ontiveros, PhD. Dr Smith’s clinical perspectives on this study are presented here.

Historically, the staging and restaging of prostate cancer to evaluate for metastatic disease included a ^99mTc-MDP bone scan to assess for bone metastasis and cross-sectional imaging with either CT or magnetic resonance imaging (MRI). Multiparametric prostate MRI has played an important role in guiding targeted biopsies for a prostate cancer diagnosis in the initial evaluation of patients with elevated prostate-specific antigen (PSA) levels. PSMA PET, a next-generation imaging approach for prostate cancer, is vastly more sensitive and specific for the detection of metastatic prostate cancer than conventional imaging with bone scan, CT scan, or MRI. With conventional imaging, we usually do not identify detectable disease—local or distant—until the patient’s PSA level is above 10 ng/mL. With PSMA PET/CT, we now routinely identify prostate cancer in patients with PSA levels of less than 2 ng/mL.

Additionally, with PSMA PET/CT, we can be more precise in our treatment recommendations than we could be previously with the limitations of conventional imaging. In the past, we had whole categories of patients for whom we were unable to provide precise recommendations. A classic situation was a patient who had had a prostatectomy and sometime later experienced a rise in PSA. The question would have then been whether the patient’s rising PSA level was due to an isolated local recurrence or a distant metastasis. If it was due to an isolated local recurrence, you might have offered radiation and ADT. But if it was due to a distant metastasis, treatment with radiation and ADT would not have made sense, and you would have considered other approaches. Now, PSMA PET has an important role in the identification of patients with prostate cancer who may be candidates for radioligand therapy with ¹⁷⁷Lu-PSMA-617, which is appropriate for some individuals with PSMA-avid metastatic castration-resistant prostate cancer.

There has been a broad adoption of PSMA PET, but the optimal use and interpretation of PSMA PET for response assessment as sequential imaging remain to be elucidated and are at least somewhat controversial. With that in mind, there was an interesting report presented at the ESMO Congress 2024 about the Prostate Cancer Working Group 4 (PCWG4) preliminary PSMA PET/CT criteria for response and progression assessments (abstract 1608P). In this report, the investigators found excellent agreement between the PSMA PET/CT response criteria and the older PCWG3 criteria, which used conventional imaging. The preliminary PCWG4 criteria with PSMA PET/CT were able to identify progression earlier than conventional imaging. Importantly, whether assessed by PCWG3 criteria or the preliminary PCWG4 criteria, radiographic progression-free survival was associated with overall survival. It is very reassuring to see, at least with this preliminary report, that the PSMA PET criteria appear to hold up as a predictor of overall survival.

PSMA PET has been rapidly adopted following its commercial introduction in the United States several years ago, and it has changed the management of prostate cancer in a dramatic way. It has become a routine part of the initial staging of prostate cancer for patients with high-risk, localized disease; is routinely used for restaging patients who have a rise in PSA level despite therapy; and has also been adopted for serial imaging to assess response and resistance to current therapies. PSMA PET/CT has largely replaced conventional imaging in some practices.