Prostate cancer is one of the most common cancers and one of the leading oncologic causes of death in men in western countries. In these patients, particularly in those with aggressive, metastatic or castration-resistant prostate cancer (mCRPC), the levels of prostate-specific membrane antigen, also called glutamate carboxypeptidase type II and abbreviated as PSMA, are elevated up to 1000 times the normal value and are inversely correlated with the levels of androgens [1]. These receptors are a highly potent target in the diagnosis and treatment of patients with prostate tumors. Therefore, radionuclides targeting these peptides, such as [⁶⁸Ga]Ga-PSMA-11 ligand positron emission tomography (⁶⁸Ga-PSMA PET), which is widely applied as a non-invasive molecular method for imaging prostate cancer, and [¹⁷⁷Lu]Lu-PSMA-617 radio-ligand therapy (PSMA-RLT), which has emerged as a valuable treatment in patients with mCRPC, are currently available. Although this novel therapy has not yet been approved for clinical use, it has been successfully administered to patients with mCRPC, based on the results of numerous studies ^[2][3][4][5][2,3,4,5]. Despite encouraging favorable outcomes of these trials on the efficacy and safety of PSMA-RLT ^[2][6][2,6], this therapy is presently used in mCRPC patients only as a last therapy option when other available standard medical procedures have failed to show clinical improvement. The therapeutic protocol in many centers, however, is quite heterogenous with treatments differing between two to six cycles of 3.7–9.3 GBq PSMA-RLT every 6 to 8 weeks [7]. Most recently, the TheraP study, a multicenter, unblinded, randomized phase 2 trial involving 11 centers in Australia, demonstrated a more frequent PSA response in mCRPC men treated with PSMA-RLT than in patients receiving cabazitaxel at the same stage of the disease. In addition, the results of this study reported fewer serious adverse events in men treated with PSMA-RLT than with cabazitaxel [8].

2. Response Rate and Clinical Clinical Effects of SEffects of Second PSMA-RLT Course

TIn Table 2, the laboratory parameters of the entire studied mCRPC patients before and 1 month after the third last cycle of the second course of PSMA-RLT applied every 4 weeks have been compared. The PSA levels of the treated patients decreased significantly after three cycles of PSMA-RLT compared with baseline, median PSA 40.8 (range 0.87–1358 µg/L) vs. 20.2 (range 0.6–1926 µg/L),  p = 0.002. Overall, 26 out of 43 (60.5%) patients demonstrated any decrease in PSA levels, 18 out of 43 (42%) had a PSA decline of ≥50%, and 8 of 43 (19%) patients showed a PSA decrease of ≥80%. The percentage of the PSA decline after both treatment courses of highly standardized PSMA-RLT, each three cycles with a 4-week interval, in all patients studied are depicted in Figure 1.