By Dr. Stefano Fanti (IT) – Nuclear Medicine Unit, IRCSS Azienda Ospedaliero Universitaria di Bologna
This article reflects the highlights of the lecture Dr. Stefano Fanti (IT) will be giving during the Special Session EAU, EANM, ESMO and ESTRO, at EAU22. This meeting will be taking place in the eURO Auditorium 2 (Grey Area) on Saturday 2 July, from 14:00 – 15:30 CEST.
Prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PCa) cells, and several PSMA ligands for PET imaging are now available worldwide. The use of PSMA PET is currently suggested by several international guidelines for investigating PCa in different clinical settings , and in particular for recurrent PCa. There is an amount of published data suggesting that PSMA-based radioligands carry the highest diagnostic value in the imaging of PCa. 
The nuclear medicine community has come a long way since the first in-human applications of 68Ga-PSMA-11, which date back to 2012. Prospective, randomised clinical trials incorporating PSMA imaging will probably soon be published; their results are needed to provide even more robust evidence of its role in improving patient outcome. Imaging of recurring PCa after radical treatment aims at treatment changes and thus possibly a better clinical outcome.
PSMA PET demonstrated higher sensitivity than 11C-choline or 18F-fluciclovine PET in this setting [3,4], and scan positivity increases with higher PSA values. A common limitation of PSMA PET for this purpose is the lack of robust validation of PSMA PET positive findings, and lack of accurate evaluation of its impact on outcome, since most of the data are retrospective or with a short median follow-up time. Nonetheless, it is evident that among all available imaging methods, PSMA PET is clearly superior, both for the higher accuracy and for the possibility to study with a single examination the local recurrence (prostatic bed), the lymph nodes, the bone and the other metastases.
A number of publications confirm a significant impact of PSMA PET at least on clinical management. A meta-analysis investigating the impact of PSMA PET on management of biochemical recurrent patients (11 studies, 908 patients) reported changes in 54% of patients, although substantial heterogeneity among the included studies was noted .  According to the EAU Guidelines, PSMA PET is the most sensitive imaging modality to detect metastasis in this patient setting and should be offered to patients with a PSA higher than 0 .2 ng/mL after RP ; another setting where PSMA PET is actually recommended by EAU Guidelines is persistence of PSA after radical prostatectomy.
In a large single-arm, multicentre prospective study, 635 patients with biochemical recurrence after radical prostatectomy (41%), radiation therapy (27%), or both (32%) were enrolled, with the main aim of evaluating the positive predictive value and the detection rate of PSMA PET.  PSMA PET showed recurrent PCa in 75% of patients; the positive predictive value was 0.84 in the 87 patients validated by histopathology and 0.92 in the 217 patients validated by the composite reference standard. As expected, the PSMA PET detection rate was associated with increased PSA values, ranging from 38% in patients with a PSA lower than 0.5 ng/mL to 97% in those with a PSA higher than 5.0 ng/mL.
In castration-resistant PCa (CRPC), the number of available treatments is steadily rising over ADT, but in this setting, conventional imaging (CI) is still recommended despite PSMA PET’s emergence as a more accurate imaging modality. A multicentre retrospective study including 200 patients with PSA >2 .0 ng/mL, negative conventional imaging and high risk for metastasis, reported PSMA PET positive in 196/200 (98%) of patients . Overall PSMA PET showed pelvic diseases in 44%, including 24% with local prostate bed recurrence and distant metastasis in 55% despite negative CI . The overall accuracy of PSMA PET was 95% for osseous lesions and 60% for soft-tissue lesions.
According to these results, it may be suggested that PSMA PET leads to an earlier detection of metastasis compared with CI and a change of clinical subtype, which may trigger earlier or different treatments. However, if and how this could impact on patient outcome in terms of overall survival and quality of life has yet to be determined and further studies are warranted.
This article first appeared in the June/July 2022 Congress edition of European Urology Today.