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 68 Ga-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 68 Ga-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 68 Ga-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, 68 Ga-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. 68 Ga-PSMA PET/CT is superior to 18 F / 11 Choline 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 177 Lu-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 68 Ga-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 223 Ra-chloride or androgen deprivation therapy) has to be explored, and prospective clinical multicenter trials with theranostics are warranted.