Objectives: To compare targeted, transperineal magnetic resonance imaging ( MRI )/ultrasound ( US )‐fusion biopsy to systematic transrectal biopsy in patients with previous negative or first prostate biopsy and to evaluate the gain in diagnostic information with systematic biopsies in addition to targeted MRI / US ‐fusion biopsies. Patients and Methods: In all, 263 consecutive patients with suspicion of prostate cancer were investigated. All patients were evaluated by 3‐T multiparametric MRI (mp MRI ) applying the European Society of Urogenital Radiology criteria. All patients underwent MRI / US ‐fusion biopsy transperineally (mean nine cores) and additionally a systematic transrectal biopsy (mean 12 cores). Results: In all, 195 patients underwent repeat biopsy and 68 patients underwent first biopsy. The median age was 66 years, median PSA level was 8.3 ng/ mL and median prostate volume was 50 mL . Overall, the prostate cancer detection rate was 52% (137/263). MRI / US ‐fusion biopsy detected significantly more cancer than systematic prostate biopsy (44% [116/263] vs 35% [91/263]; P = 0.002). In repeat biopsy, the detection rate was 44% (85/195) in targeted and 32% (62/195) in systematic biopsy ( P = 0.002). In first biopsy, the detection rate was 46% (31/68) in targeted and 43% (29/68) in systematic biopsy ( P = 0.527). In all, 80% (110/137) of biopsy confirmed prostate cancers were clinically significant. For the upgrading of Gleason score, 44% (32/72) more clinically significant prostate cancer was detected by using additional targeted biopsy than by systematic biopsy alone. Conversely, 12% (10/94) more clinically significant cancer was found by systematic biopsy additionally to targeted biopsy. Conclusions: MRI / US ‐fusion biopsy was associated with a higher detection rate of clinically significant prostate cancer while taking fewer cores, especially in patients with prior negative biopsy. Due to a high portion of additional tumours with Gleason score ≥7 detected in addition to targeted biopsy, systematic biopsy should still be performed additionally to targeted biopsy.

Objective: To compare multiparametric magnetic resonance imaging (mp MRI ) of the prostate and histological findings of both targeted MRI /ultrasonography‐fusion prostate biopsy ( PB x) and systematic PB x with final histology of the radical prostatectomy ( RP ) specimen. Patients and Methods: A total of 105 patients with prostate cancer ( PC a) histopathologically proven using a combination of fusion Pbx and systematic PB x, who underwent RP , were investigated. All patients had been examined using mp MRI , applying the European Society of Urogenital Radiology criteria. Histological findings from the RP specimen were compared with those from the PB x. Whole‐mount RP specimen and mp MRI results were directly compared by a uro‐pathologist and a uro‐radiologist in step‐section analysis. Results: In the 105 patients with histopathologically proven PC a by combination of fusion PB x and systematic PB x, the detection rate of PC a was 90% (94/105) in fusion PB x alone and 68% (72/105) in systematic PB x alone ( P = 0.001). The combination PB x detected 23 (22%) Gleason score ( GS ) 6, 69 (66%) GS 7 and 13 (12%) GS ≥8 tumours. Fusion PB x alone detected 25 (26%) GS 6, 57 (61%) GS 7 and 12 (13%) GS ≥8 tumours. Systematic PB x alone detected 17 (24%) GS 6, 49 (68%) GS 7 and 6 (8%) GS ≥8 tumours. Fusion PB x alone would have missed 11 tumours (4% [4/105] of GS 6, 6% [6/105] of GS 7 and 1% [1/105] of GS ≥8 tumours). Systematic PB x alone would have missed 33 tumours (10% [10/105] of GS 6, 20% [21/105] of GS 7 and 2% [2/105] of GS ≥8 tumours). The rates of concordance with regard to GS between the PB x and RP specimen were 63% ( n = 65), 54% ( n = 56) and 75% ( n = 78) in fusion, systematic and combination PB x (fusion and systematic PB x combined), respectively. Upgrading of the GS between PB x and RP specimen occurred in 33% ( n = 34), 44% ( n = 46) and 18% ( n = 19) in fusion, systematic and combination PB x, respectively. γ‐correlation for detection of any cancer was 0.76 for combination PB x, 0.68 for fusion PB x alone and 0.23 for systematic PB x alone. In all, 84% ( n = 88) of index tumours were identified by mp MRI ; 86% ( n = 91) of index lesions on the mp MRI were proven in the RP specimen. Conclusions: Fusion PB x of tumour‐suspicious lesions on mp MRI was associated with a higher detection rate of more aggressive PC a and a better tumour prediction in final histopathology than systematic PB x alone; however, combination PB x had the best concordance for the prediction of GS . Furthermore, the additional findings of systematic PB x reflect the multifocality of PC a, therefore, the combination of both biopsy methods would still represent the best approach for the prediction of the final tumour grading in PC a.

Background: The analysis aimed to compare the radiotracers [⁶⁸Ga]-Ga-PSMA-11 and [¹⁸F]-F-PSMA-1007 intraindividually in terms of malignant lesions, mi(molecular-imaging)TNM staging and presumable unspecific lesions retrospectively as used in routine clinical practice. Methods: A retrospective analysis of 46 prostate cancer patients (median age: 71 years) who underwent consecutive [⁶⁸Ga]-Ga-PSMA-11- and [¹⁸F]-F-PSMA-1007-PET/CT or PET/MRI within a mean of 12 ± 8.0 days was performed. MiTNM staging was performed in both studies by two nuclear medicine physicians who were blinded to the results of the other tracer. After intradisciplinary and interdisciplinary consensus with two radiologists was reached, differences in both malignant and presumable nonspecific tracer accumulation were analyzed. Results: Differences in terms of miTNM stages in both studies occurred in nine of the 46 patients (19.6%). The miT stages differed in five patients (10.9%), the miN stages differed in three patients (6.5%), and different miM stages occurred only in one patient who was upstaged in [¹⁸F]-F-PSMA-1007 PET. Concordant miTNM stages were obtained in 37 patients (80.4%). There was no significant difference between [¹⁸F]-F-PSMA-1007 and [⁶⁸Ga]-Ga-PSMA-11 in the SUV_max locally (31.5 vs. 32.7; p = 0.658), in lymph node metastases (28.9 vs. 24.9; p = 0.30) or in bone metastases (22.9 vs. 27.6; p = 0.286). In [¹⁸F]-F-PSMA-1007 PET, more patients featured presumable unspecific uptake in the lymph nodes (52.2% vs. 28.3%; p: < 0.001), bones (71.7% vs. 23.9%; p < 0.001) and ganglia (71.7% vs. 43.5%; p < 0.001). Probable unspecific, exclusively [¹⁸F]-F-PSMA-1007-positive lesions mainly occurred in the ribs (58.7%), axillary lymph nodes (39.1%) and cervical ganglia (28.3%). Conclusion: In terms of miTNM staging, both tracers appeared widely exchangeable, as no tracer relevantly outperformed the other. The differences between the two tracers were far more common in presumable unspecific lesions than in malignant spots. A routinely performed two-tracer study could not be shown to be superior. Since it seems at least challenging for most nuclear medicine departments to provide both [¹⁸F]-F-PSMA-1007 and [⁶⁸Ga]-Ga-PSMA-11, it appears reasonable to choose the PSMA radiotracer depending on local availability with attention to the greater occurrence of nonspecific bone findings with [¹⁸F]-F-PSMA-1007.

Objectives: To evaluate the value of multiparametric magnetic resonance imaging (mp MRI ) in the detection of significant prostate cancer ( PC a) and to compare transperineal MRI /ultrasonography fusion biopsy (fusPbx) with conventional transrectal systematic biopsy (sysPbx) in biopsy‐naïve patients. Patients and Methods: This multicentre, prospective trial investigated biopsy‐naïve patients with suspicion of PC a undergoing transperineal fusPbx in combination with transrectal sysPbx (comPbx). The primary outcome was the detection of significant PC a, defined as Gleason pattern 4 or 5. We analysed the results after a study period of 2 years. Results: The study included 214 patients. The median (range) number of targeted and systematic cores was 6 (2–15) and 12 (6–18), respectively. The overall PC a detection rate of comPbx was 52%. FusPbx detected more PC a than sysPbx (47% vs 43%; P = 0.15). The detection rate of significant PC a was 38% for fusPbx and 35% for sysPbx ( P = 0.296). The rate of missed significant PC a was 14% in fusPbx and 21% in sysPbx. ComPbx detected significantly more significant PC a than fusPbx and sysPbx alone (44% vs 38% vs 35%; P < 0.005). In patients presenting with Prostate Imaging Reporting and Data System ( PI ‐ RADS ) 4 and 5 lesions there was a higher detection rate of significant PC a than in patients presenting with PI ‐ RADS ≤3 lesions in comPbx (61% vs 14%; P < 0.005). Conclusions: For biopsy‐naïve men with tumour‐suspicious lesions in mp MRI , the combined approach outperformed both fusPbx and sysPbx in the detection of overall PC a and significant PC a. Thus, biopsy‐naïve patients may benefit from sysPbx in combination with mp MRI targeted fusPbx.

Prostate-specific membrane antigen (PSMA) is an essential molecular regulator of prostate cancer (PCa) progression coded by the FOLH1 gene. The PSMA protein has become an important factor in metastatic PCa diagnosis and radioligand therapy. However, low PSMA expression is suggested to be a resistance mechanism to PSMA-based imaging and therapy. Clinical studies revealed that androgen receptor (AR) inhibition increases PSMA expression. The mechanism has not yet been elucidated. Therefore, this study investigated the effect of activation and inhibition of androgen signaling on PSMA expression levels in vitro and compared these findings with PSMA levels in PCa patients receiving systemic therapy. To this end, LAPC4, LNCaP, and C4-2 PCa cells were treated with various concentrations of the synthetic androgen R1881 and antiandrogens. Changes in FOLH1 mRNA were determined using qPCR. Open access databases were used for ChIP-Seq and tissue expression analysis. Changes in PSMA protein were determined using western blot. For PSMA staining in patients’ specimens, immunohistochemistry (IHC) was performed. Results revealed that treatment with the synthetic androgen R1881 led to decreased FOLH1 mRNA and PSMA protein. This effect was partially reversed by antiandrogen treatment. However, AR ChIP-Seq analysis revealed no canonical AR binding sites in the regulatory elements of the FOLH1 gene. IHC analysis indicated that androgen deprivation only resulted in increased PSMA expression in patients with low PSMA levels. The data demonstrate that AR activation and inhibition affects PSMA protein levels via a possible non-canonical mechanism. Moreover, analysis of PCa tissue reveals that low PSMA expression rates may be mandatory to increase PSMA by androgen deprivation.