Radiologists and specialists in nuclear medicine have an evolving role in prostate cancer, with new tools emerging, such as prostate-specific membrane antigen–based positron emission tomography/computed tomography (PSMA PET/CT). With these newer imaging techniques, the expertise of the reader is key. The Europeans have had the luxury of working with PSMA-based PET/CT for quite some time, but many of us are just getting started here in the United States. The US Food and Drug Administration approved gallium-68 (⁶⁸Ga) PSMA-11 PET imaging in December 2020, followed by ¹⁸F-DCFPyL PSMA PET in May 2021. I think that there will be a role for these tools, beginning with biochemically recurrent patients and for staging purposes. Ultimately, it is my opinion that these newer PSMA-based imaging techniques will replace a lot of the conventional imaging for staging, for high-risk patients, for those with metastatic disease, and for those with castration-resistant prostate cancer (CRPC). 

PSMA is a theranostic biomarker, meaning that it is useful in both imaging and therapeutics, and there was quite a bit of discussion of targeted radioligand therapy with lutetium-177 (¹⁷⁷Lu)–PSMA-617 at the ESMO Congress 2021. Two trials are examining its use in distinct populations of patients with advanced prostate cancer (abstracts 647TiP and 648TiP), and you could say that what is old is new again with this treatment, as this is precisely how docetaxel got its start. That is, you begin with clinical trials in heavily pretreated patients with the most severe disease, and, if you see a benefit, you move to earlier points in the disease continuum. The phase 3 VISION study with ¹⁷⁷Lu-PSMA-617 was conducted in a heavily pretreated metastatic CRPC (mCRPC) population, and we saw that ¹⁷⁷Lu-PSMA-617 plus standard of care significantly prolonged overall survival (median, 15.3 vs 11.3 months) compared with the standard of care alone. That type of incremental gain is exactly what was seen with docetaxel initially. Now, the PSMAddition study (abstract 647TiP) is looking at patients with metastatic hormone-sensitive prostate cancer, and the PSMAfore study (abstract 648TiP) is looking at taxane-naive patients with progressive mCRPC. These are healthier patients, with better performance statuses, lower tumor burdens, and certainly fewer mutational changes, and the hope is that we will see even more substantial survival gains. In the past, when a treatment was successful in the most heavily pretreated patients with the most advanced disease, we have often found that it is much more effective at an earlier stage. So, those are exciting previews, and we look forward to seeing those completed studies and their results.

Although there is great excitement about advanced imaging and theranostics, I would also emphasize that if we do not carefully monitor patients as recommended in European and US guidelines, with whatever imaging modality is available, then we miss out on opportunities to recognize therapeutic windows, to identify the need to switch therapies, and to detect findings that guide the correct sequencing of therapies. There was a real-world analysis from Spain presented at the ESMO Congress 2021 that included more than 6000 men with CRPC (abstract 602P).. It showed that the metastatic status was unknown in approximately 47% due to a lack of the recommended imaging examinations. So, careful monitoring is needed, and we will have to learn how to use the novel PSMA PET/CT imaging as we start to layer in its use.