Current status of theranostics in prostate cancer

The aim of this review is to report on the current status of prostate-specific membrane antigen (PSMA)-directed theranostics in prostate cancer (PC) patients. The value of ⁶⁸Ga-PSMA-directed PET imaging as a diagnostic procedure for primary and recurrent PC as well as the role of evolving PSMA radioligand therapy (PRLT) in castration-resistant (CR)PC is assessed. The most eminent data from mostly retrospective studies currently available on theranostics of prostate cancer are discussed. The current knowledge on ⁶⁸Ga-PSMA PET/CT implicates that primary staging with PET/CT is meaningful in patients with high-risk PC and that the combination with pelvic multi parametric (mp)MR (or PET/mpMR) reaches the highest impact on patient management. There may be a place for ⁶⁸Ga-PSMA PET/CT in intermediate-risk PC patients as well, however, only a few data are available at the moment. In secondary staging for local recurrence, ⁶⁸Ga-PSMA PET/mpMR is superior to PET/CT, whereas for distant recurrence, PET/CT has equivalent results and is faster and cheaper compared to PET/mpMR. ⁶⁸Ga-PSMA PET/CT is superior to ¹⁸F / ¹¹Choline PET/CT in primary staging as well as in secondary staging. In patients with biochemical relapse, PET/CT positivity is directly associated with prostate-specific antigen (PSA) increase and amounts to roughly 50% when PSA is raised to ≤0.5 ng/ml and to ≥90% above 1 ng/ml. Significant clinical results have so far been achieved with the subsequent use of radiolabeled PSMA ligands in the treatment of CRPC. Accumulated activities of 30 to 50 GBq of ¹⁷⁷Lu-PSMA ligands seem to be clinically safe with biochemical response and PERCIST/RECIST response in around 75% of patients along with xerostomia in 5-10% of patients as the only notable side effect. On the basis of the current literature, we conclude that PSMA-directed theranostics do have a major clinical impact in diagnosis and therapy of PC patients. We recommend that ⁶⁸Ga-PSMA PET/CT should be performed in primary staging together with pelvic mpMR in high-risk patients and in all patients for secondary staging, and that PSMA-directed therapy is a potent strategy in CRPC patients when other treatment options have failed. The combination of PSMA-directed therapy with existing therapy modalities (such as ²²³Ra-chloride or androgen deprivation therapy) has to be explored, and prospective clinical multicenter trials with theranostics are warranted.