For the past several years, prostate cancer experts have been working toward developing a consensus on the appropriate role of PSMA PET imaging in clinical practice. For patients who undergo radical prostatectomy and experience disease progression, there is now widespread support for the use of PSMA PET together with computed tomography (CT) or magnetic resonance imaging, often referred to simply as PSMA PET, to help identify lesions within the prostate bed or at more distant sites. Salvage radiotherapy is potentially curative in the setting of recurrence within the prostate bed, and PSMA PET may be valuable for salvage radiotherapy treatment planning, as well. Prior to the 2023 SNMMI Annual Meeting, Sonni et al analyzed the patterns of prostate bed recurrence using gallium-68 (⁶⁸Ga)–PSMA PET in relation to the Radiation Therapy Oncology Group clinical target volumes, concluding that their findings should be incorporated into the redefinition of prostate bed contouring guidelines.

Moreover, contemporary guidelines have evolved to note the increased sensitivity and specificity of PSMA PET tracers compared with conventional imaging in a number of settings, including high-risk localized disease. Such guidelines now include PSMA PET as an alternative to standard imaging of bone and soft tissue, and more recent guidelines incorporate PSMA PET into the initial staging of unfavorable intermediate-risk T2b and GS7 and/or PSA 10-20 disease. 

Further, PSMA PET is now used to screen patients with metastatic castration-resistant prostate cancer (mCRPC) for tumoral PSMA expression to help identify those who may benefit from lutetium Lu 177 vipivotide tetraxetan (formerly referred to as ¹⁷⁷Lu-PSMA-617), a PSMA-targeted radioligand therapy that was approved by the US Food and Drug Administration in March 2022 for progressive, PSMA-positive mCRPC.

The role of PSMA PET imaging in prostate cancer will likely continue to evolve in step with the expanding knowledge base. Toward that end, several reports from the 2023 SNMMI Annual Meeting highlighted recent innovations and areas for further study. Some of the data on PSMA PET that were presented at the meeting pertained to the CRPC space, where the data on the prognostic value of PSMA PET have been limited. In poster P1138, the authors reported data from a retrospective, single-center, post hoc analysis of patients with CRPC from 6 prospective studies of PSMA PET/CT, exploring the prognostic value of PSMA PET/CT for outcomes among those who did not receive prior chemotherapy or radionuclide therapy but did receive prior androgen receptor signaling inhibitor therapy. The authors concluded that, in men with CRPC, PSMA PET/CT can provide prognostic value for radiological progression after systemic treatment. 

The regulation and function of PSMA in prostate cancer cells, including the regulation of PSMA expression specifically by the androgen receptor, remain poorly understood, so this is another area that is primed for further study. PSMA expression in mCRPC has been described as heterogeneous and dynamic, and researchers hope to improve our understanding of its levers and mechanics to optimize PSMA-based imaging and treatment. 

Kluge et al examined the association between antihormonal treatment status and ⁶⁸Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA-11) PET biodistribution in patients with prostate cancer (poster P688). In particular, they were interested in the possible impacts of androgen deprivation therapies (ADTs) on nontumorous, PSMA-expressing tissues and organs. In their retrospective analysis of 50 patients, after attempting to control for confounders, they found that the renal SUV_mean and SUV_peak values were significantly lower in the 25 patients who were on ADT at the time of imaging (ie, the treatment group) compared with the 25 patients who had no history of ADT (ie, the control group). Based on their data, the authors hypothesized that long-term ADT might modulate PSMA expression in a systemic fashion, an effect that they felt might be particularly relevant to investigational radioligand therapies that incorporate more potent, but toxic, agents (eg, actinium-225 [²²⁵Ac]–labeled PSMA conjugates).

The molecular heterogeneity of mCRPC is often cited as being contributory to challenges that are associated with achieving longer-term responses to targeted therapies, and this concept may extend to PSMA-based theranostics applications. That is, mCRPC can have heterogeneous PSMA expression and/or may harbor some sites of PSMA-negative disease that may not respond to PSMA-targeted therapy. Thus, there is a need to identify disease that may benefit from a different treatment strategy or may, perhaps, ultimately respond better to a combination of different treatment strategies. A number of reports from the 2023 SNMMI Annual Meeting highlighted the need for molecular imaging strategies that match the heterogeneity and dynamics of mCRPC, including poster P822. In this study, Behr et al were interested in learning whether whole-body diffusion-weighted imaging on PET/magnetic resonance imaging can be added to a PSMA PET scan to identify non-PSMA disease.