Real-world comparison of Docetaxel versus new hormonal agents in combination with androgen-deprivation therapy in metastatic hormone-sensitive prostate cancer descrying PSA Nadir ≤ 0.05 ng/ml as marker for treatment response.

PROPOSE: Using Docetaxel chemotherapy or new hormonal agents (NHT) to intensify upfront systemic therapy resulted in improved survival rates compared to androgen deprivation monotherapy (ADT). Hence, combination therapies have become the new standard of care (SOC) in metastatic hormone-sensitive prostate cancer (mHSPC). However, head-to-head trails comparing different therapies as well as treatment-guiding biomarkers are still lacking. Thus, the aim of the present study was to compare clinical outcomes of Docetaxel versus NHT therapy in the real-world setting as well as to elaborate biomarkers predicting clinical outcome. METHODS: We retrospectively assessed overall-survival (OS), progression-free survival 1 and 2 (PFS1/2) and time to progression (TTP) in 42 patients treated by either ADT + NHT or ADT + Docetaxel. In addition, we investigated clinical prognostic biomarkers. RESULTS: Our survival analysis revealed 3-year OS of 89.4% in the NHT group compared to 82.4% in the Docetaxel group. 3-year PFS1 was 59.6% in the NHT group compared to 32.2% in the Docetaxel group and the TTP was 53.8% vs 32.2% (pOS = 0.189; pPFS1 = 0.082; pTTP = 0.055). In addition, castration-resistance occurred more often in the Docetaxel group (78.6% vs 25%, p = 0.004). Interestingly, a PSA-Nadir ≤ 0.05 ng/ml during therapy was associated with increased survival rates (p < 0.001) while PSA levels at primary diagnosis had no influence on therapy outcome. Furthermore, a thyroid-stimulating hormone (TSH) increase during therapy was associated with improved clinical outcome (p = 0.06). CONCLUSION: We observed a trend towards a higher benefit of NHT as first-line treatment compared to Docetaxel in men with mHSPC. Of note, a PSA-Nadir ≤ 0.05 ng/ml or a TSH-increase during therapy were predictors for therapy response.

Effects of cycling and rowing on serum concentrations of prostate-specific antigen: A randomized study of 101 male subjects.

OBJECTIVE: To determine the effects if cycling and rowing on serum prostate-specific antigen (PSA) levels. METHODS: Male volunteers (n = 101), aged 20-80 (mean, 49.9) years were randomized to exercise at the first or second study visit. They performed 1 h of either cycling or rowing on a stationary machine. To determine exercise-induced effects on the PSA level, serum total PSA (tPSA) and free PSA (fPSA) concentrations were evaluated before and after exercise and another sampling was performed at the second study visit. Pre-exercise and postexercise tPSA and fPSA concentrations were compared using the Wilcoxon matched-pairs test. The results were analyzed using the Mann-Whitney U-test. RESULTS: A significant (p < 0.001) average increase in tPSA after exercise (1.14 ± 1.11 ng/ml to 1.24 ± 1.26 ng/ml [mean, +8.8%]) was observed after both cycling and rowing, without significant differences between the sports (p = 0.54). The exercise-induced increase in PSA concentration affected participants aged ≥50 years (difference, 0.16 ± 0.37; p < 0.001), but not those aged <50 years (difference, 0.01 ± 0.06; p = 0.23). The effect size was clinically irrelevant in all except two outliers, in whom a distinct increase of PSA level by averages of 1.80 ng/ml (+55%) for tPSA and 1.25 ng/ml (+227%) for fPSA following cycling was observed. CONCLUSION: Rowing and cycling generally do not have a clinically relevant effect on PSA levels. However, outliers exist. Our findings do not support abstaining from exercise during the days approaching PSA sampling.

Transurethral resection of the prostate in 85+ patients: a retrospective, multicentre study.

PURPOSE: To determine the safety and efficacy of transurethral resection of the prostate (TUR-P) in patients 85 years or older. METHODS: In this retrospective, multicentre study, patients equal or older than 85 years at the time of surgery (2015-2020) were included. Several pre-, peri- and postoperative parameters were collected. The main outcome criterion was spontaneous voiding with a post-void residual (PVR) volume < 100 ml at dismission and at 12 months after surgery. RESULTS: One hundred sixty-eight patients (median age: 87 years, interquartile range [IQR]: 86-89) were recruited. The patients took on average 5.2 permanent medications (3-8), 107 (64%) were anticoagulated preoperatively and neurological co-morbidities were present in 29 (17%). The indication for surgery was recurrent urinary retention in 66.3% (n = 110) with a mean retention volume of 849 ml. The mean PVR volume of the remaining 35% was 146 ml. Surgery was successfully completed in all patients. A perioperative surgical revision had to be performed in 3% and 13 patients (7.7%) required blood transfusion. After catheter removal, 85% of patients were able to void spontaneously with a PVR < 100 ml, and 14.3% were dismissed with a catheter. Twelve months data were available for 93 patients (55%). Of this cohort, 78 (83.9%) were able to void spontaneously with a PVR < 100 ml, 12 (12.9%) were on permanent catheterization. One patient (0.6%) died perioperatively. The only significant factor associated with an unsuccessful outcome was the number of permanent medications (6.8 vs. 5.0, p = 0.005). CONCLUSION: This retrospective multicentre study documents the safety and efficacy of TURP (monopolar and bipolar) in the old-old cohort.

The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration-resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up.

INTRODUCTION: A new therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) of heavily pre-treated patients lies in 177Lu-PSMA-617 radioligand therapy. METHODS: On the basis of PSMA-targeted 68Ga-PSMA-11 PET/CT, 32 consecutive mCRPC patients were selected for 177Lu-PSMA-617 therapy (6 GBq/cycle, 2 to 6 cycles, 6-10 weeks apart) and followed until death. Post-therapy whole-body (WB) dosimetry and 68Ga-PSMA-11 PET/CT data were compared and related to progression free and overall survival. RESULTS: 177Lu-PSMA-617 dosimetry after the first cycle indicated high tumor doses for skeletal (4.01 ± 2.64; range 1.10-13.00 Gy/GBq), lymph node (3.12 ± 2.07; range 0.70-8.70 Gy/GBq), and liver (2.97 ± 1.38; range 0.76-5.00 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 24 GBq. Any PSA decrease after the first cycle was found in 23/32 (72%), after the second cycle in 22/32 (69%), after the third cycle in 16/28 (57%), and after the fourth cycle in 8/18 (44%) patients. Post-therapy 24 h WB scintigraphy showed decreased tumor-to-background ratios in 24/32 (75%) after the first therapy cycle, after the second cycle in 17/29 (59%), and after the third cycle in 13/21 (62%) patients. The median PFS was 7 months and the median OS 12 months. In the group of PSA responders (n = 22) the median OS was 17 months versus 11 months in the group of non-responders (n = 10), p < 0.05. Decreasing SUVmax values were found for parotid (15.93 ± 6.23 versus 12.33 ± 4.07) and submandibular glands (17.65 ± 7.34 versus 13.12 ± 4.62) following treatment, along with transient (n = 6) or permanent (n = 2) xerostomia in 8/32 (25%) patients. In 3/32 patients, nephrotoxicity changed from Grade 2 to 3, whereas neither Grade 4 nephrotoxicity nor hematotoxicity was found. In most patients a good agreement was observed for the visual interpretation of the tracer accumulation between 24 h WB and PET/CT scans. However, no significance could be calculated for baseline-absorbed tumor doses and SUVmax values of tumor lesions. 5/32 (16%) patients showed a mixed response pattern, which resulted in disease progression over time. CONCLUSION: Serial PSA measurements and post-therapy 24 h WB scintigraphy seems to allow a sufficiently accurate follow-up of 177Lu-PSMA-617-treated mCRPC patients whereas 68Ga-PSMA-11 PET/CT should be performed for patient selection and final response assessment.

Correction to: The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration-resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up.

The author name Bernhard Nilica was inadvertently interchanged in the original version of this article.

Comparison of multiparametric and biparametric MRI of the prostate: are gadolinium-based contrast agents needed for routine examinations?

PURPOSE: To investigate, if and how omitting gadolinium-based contrast agents (GBCA) and dynamic contrast-enhanced imaging (DCE) influences diagnostic accuracy and tumor detection rates of prostate MRI. METHODS: In this retrospective study, 236 patients were included. The results of biparametric (bpMRI) and multiparametric magnetic resonance imaging (mpMRI) were compared using the PI-RADS version 2 scoring system. The distribution of lesions to PIRADS score levels, tumor detection rates, diagnostic accuracy and RoC analysis were calculated and compared to the results of histopathological analysis or 5-year follow-up for benign findings. RESULTS: Omitting DCE changed PI-RADS scores in 9.75% of patients, increasing the number of PI-RADS 3 scores by 8.89% when compared to mpMRI. No change of more than one score level was observed. BpMRI did not show significant differences in diagnostic accuracy or tumor detection rates. (AuC of 0.914 vs 0.917 in ROC analysis). Of 135 prostate carcinomas (PCa), 94.07% were scored identically, and 5.93% were downgraded only from PI-RADS 4 to PI-RADS 3 by bpMRI. All of them were low-grade PCa with Gleason Score 6 or 7a. No changes were observed for PCa ≥ 7b. CONCLUSION: Omitting DCE did not lead to significant differences in diagnostic accuracy or tumor detection rates when using the PI-RADS 2 scoring system. According to these data, it seems reasonable to use a biparametric approach for initial routine prostate MRI. This could decrease examination time and reduce costs without significantly lowering the diagnostic accuracy.

Retrospective analysis of the development of PIRADS 3 lesions over time: when is a follow-up MRI reasonable?

PURPOSE: Often PIRADS 3 findings are usually followed up with further MRIs of the prostate. Current guidelines do not state an optimal interval between the initial MRI and the follow-up MRI. The aim of this study was to find out if PIRADS 3 lesions evolve over time and to determine how long the optimal interval between initial MRI and follow-ups should be. METHODS: In this retrospective study, 141 consecutive patients were included who underwent at least one follow-up MRI after an initial PIRADS 3 finding. Changes in PIRADS score and the interval between the first and the follow-up MRI were recorded. An optimal duration was calculated. RESULTS: Of all patients, 76.6% had a change from PIRADS 3 to either 2 or 4 in the first follow-up MRI. Reclassifications to PIRADS 4 happened earlier than reclassifications to PIRADS 2 (after 366.5 ± 217.9 days and after 534.2 ± 253.0 days, respectively). An optimal point of time for a follow-up to distinguish between changes to PIRADS 2 versus PIRADS 4 turned out to be 379 days (12.4 months, AUC 0.734, p = 0.0001). Of all patients with a PIRADS 3 lesion 14.8% harboured a prostate carcinoma. CONCLUSION: Performing follow-up mpMRI rather than immediate biopsy may be beneficial for patients with PIRADS 3, as most lesions can be reclassified after a manageable period of time. Upgrades to PIRADS 4 seem to happen earlier and within fewer follow-ups than downgrades to PIRADS 2. The optimal interval for follow-up MRIs seems to be 12.4 months.

Early dynamic imaging in 68Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and prostate cancer lesions.

PURPOSE: PET/CT with 68Ga-labelled prostate-specific membrane antigen (PSMA)-ligands has been proven to establish a promising imaging modality in the work-up of prostate cancer (PC) patients with biochemical relapse. Despite a high overall detection rate, the visualisation of local recurrence may be hampered by high physiologic tracer accumulation in the urinary bladder on whole body imaging, usually starting 60 min after injection. This study sought to verify whether early dynamic 68Ga-PSMA-11 (HBED-CC)PET/CT can differentiate pathologic PC-related tracer uptake from physiologic tracer accumulation in the urinary bladder. METHODS: Eighty consecutive PC patients referred to 68Ga -PSMA-11 PET/CT were included in this retrospective analysis (biochemical relapse: n = 64; primary staging: n = 8; evaluation of therapy response/restaging: n = 8). In addition to whole-body PET/CT acquisition 60 min post injection early dynamic imaging of the pelvis in the first 8 min after tracer injection was performed. SUVmax of pathologic lesions was calculated and time-activity curves were generated and compared to those of urinary bladder and areas of physiologic tracer uptake. RESULTS: A total of 55 lesions consistent with malignancy on 60 min whole body imaging exhibited also pathologic 68Ga-PSMA-11 uptake during early dynamic imaging (prostatic bed/prostate gland: n = 27; lymph nodes: n = 12; bone: n = 16). All pathologic lesions showed tracer uptake within the first 3 min, whereas urinary bladder activity was absent within the first 3 min of dynamic imaging in all patients. Suvmax was significantly higher in PC lesions in the first 6 min compared to urinary bladder accumulation (p < 0.001). In the subgroup of PC patients with biochemical relapse the detection rate of local recurrence could be increased from 20.3 to 29.7%. CONCLUSIONS: Early dynamic imaging in 68Ga-PSMA-11 PET/CT reliably enables the differentiation of pathologic tracer uptake in PC lesions from physiologic bladder accumulation. Performance of early dynamic imaging in addition to whole body imaging 60 min after tracer injection might improve the detection rate of local recurrence in PC patients with biochemical relapse referred for 68Ga-PSMA-11 PET/CT.

The 68Ga/177Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUVmax values and absorbed dose estimates.

INTRODUCTION: A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Ten consecutive mCRPC patients were selected for 177Lu-PSMA617 therapy on the basis of PSMA-targeted 68Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging (68Ga-PSMA-HBED-CC and 18F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1 ± 0.3 GBq, range 5.4-6.5 GBq) given intravenously over 30 minutes, 9 ± 1 weeks apart. PET/CT scans were compared to 177Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed. RESULTS: 177Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4 ± 1.9 Gy/GBq; range 1.1-7.2 Gy/GBq), lymph node (2.6 ± 0.4 Gy/GBq; range 2.3-2.9 Gy/GBq) as well as liver (2.4 ± 0.8 Gy/GBq; range 1.7-3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18 ± 0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased 177Lu-PSMA617 and 68Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p < 0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions. CONCLUSION: Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following 177Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study.

Early PET imaging with [68]Ga-PSMA-11 increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence.

PURPOSE: PET/CT using 68Ga-labelled prostate-specific membrane antigen PSMA-11 (HBEDD-CC) has emerged as a promising imaging method in the diagnostic evaluation of prostate cancer (PC) patients with biochemical recurrence. However, assessment of local recurrence (LR) may be limited by intense physiologic tracer accumulation in the urinary bladder on whole-body scans, normally conducted 60 min post-tracer injection (p.i.). It could be shown on early dynamic imaging studies that 68Ga-PSMA-11 uptake in PC lesions occurs earlier than tracer accumulation in the urinary bladder. This study aims to investigate whether early static PET acquisition increases detection rate of local recurrence on 68Ga-PSMA-11 PET/CT in comparison to PET imaging 60 min p.i.. METHODS: 203 consecutive PC patients with biochemical failure referred to 68Ga-PSMA-11 PET/CT were analysed retrospectively (median prostate specific antigen (PSA) value: 1.44 ng/ml). In addition to whole-body PET/CT scans 60 min p.i., early static imaging of the pelvis was performed, starting at a median time of 283 s p.i. (range: 243-491 s). Assessment was based on visual analysis and calculation of maximum standardized uptake value (SUVmax) of pathologic lesions present in the pelvic area found on early PET imaging and on 60 min-PET scans. RESULTS: 26 patients (12.8%) were judged positive for LR on PET scans 60 min p.i. (median SUVmax: 10.8; range: 4.7-40.9), whereas 50 patients (24.6%) revealed a lesion suggestive of LR on early PET imaging (median SUVmax: 5.9; range: 2.9-17.6), resulting in a significant rise in detection rate (p < 0.001). Equivocal findings on PET scans 60 min p.i. decreased significantly with the help of early imaging (15.8% vs. 4.5% of patients; p < 0.001). Tracer activity in the urinary bladder with a median SUVmax of 8.2 was present in 63 patients on early PET scans (31.0%). However, acquisition starting time of early PET scans differed significantly in the patient groups with and without urinary bladder activity (median starting time of 321 vs. 275 s p.i.; range: 281-491 vs. 243-311 s p.i.; p < 0.001). Median SUVmax value of lesions suggestive of LR on early images was significantly higher in comparison to gluteal muscle, inguinal vessels and seminal vesicle/anastomosis (median SUVmax: 5.9 vs. 1.9, 4.0 and 2.4, respectively). CONCLUSIONS: Performance of early imaging in 68Ga-PSMA-11 PET/CT in addition to whole-body scans 60 min p.i. increases the detection rate of local recurrence in PC patients with biochemical recurrence. Acquisition of early PET images should be started as early as 5 min p.i. in order to avoid disturbing tracer activity in the urinary bladder occuring at a later time point.

Performance of PI-RADS version 1 versus version 2 regarding the relation with histopathological results.

PURPOSE: Aim of this study was to compare the diagnostic performance of PI-RADS version 1 (v1) and version 2 (v2) in the detection of prostate cancer (PCa). METHODS: Multiparametric MRIs (mpMRI) of 50 consecutive patients with biopsy proven PCa, which had originally been evaluated according to PIRADS v1, were now retrospectively re-evaluated, comparing PI-RADS v1 and v2. MpMRI data were evaluated in comparison with histopathological whole-mount step-section slides. MRI examinations included T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI. RESULTS: Overall PI-RADS v1 showed a significantly larger discriminative ability of tumor detection: PI-RADS v1 AUC 0.96 (95 % CI 0.94-0.98) and v2 AUC 0.90 (95 % CI 0.86-0.94). For peripheral zone lesions, PI-RADS v1 showed a significantly larger ability of PCa discrimination: v1 AUC 0.97 (95 % CI 0.95-0.99) and v2 AUC 0.92 (95 % CI 0.88-0.96). For transition zone lesions, PI-RADS v1 showed more discrimination: v1 AUC 0.96 (95 % CI 0.92-1.00) and v2 0.90 (95 % CI 0.83-0.97), but the difference was not significant. PI-RADS v2 resulted in significantly more false negative results (3 % in v1, 14 % in v2) and a comparable number of true positive results (82 % in v1, 80 % in v2). CONCLUSION: PI-RADS v2 uses a simplified approach, but shows a lower diagnostic accuracy. This could lead to a higher rate of false negative results with the risk of missing tumors within low PI-RADS score levels. Therefore, its use cannot be recommended unconditionally, and further improvement should be considered.

Evaluation of the 'Prostate Interdisciplinary Communication and Mapping Algorithm for Biopsy and Pathology' (PIC-MABP).

INTRODUCTION: Experience from interdisciplinary cooperation revealed the need for a prostate mapping scheme to communicate multiparametric MRI (mpMRI) findings between radiologists, urologists, and pathologists, which should be detailed, yet easy to memorize. For this purpose, the 'Prostate interdisciplinary communication and mapping algorithm for biopsy and pathology' (PIC-MABP) was developed. This study evaluated the accuracy of the PIC-MABP system. METHODS: PIC-MABP was tested and validated in findings of 10 randomly selected patients from routine clinical practise with 18 histologically proven cancer lesions. Patients received an mpMRI of the prostate prior to prostatectomy. After surgery the prostates were prepared as whole-mount step sections. Cancer lesions, which were found suspicious on mpMRI, were assigned to the according PIC-MABP sectors by a radiologist. MpMRI slides were masked and sent to seven urologists from different centres, providing only the PIC-MABP location of each lesion. Urologists marked the accordant regions. Then mpMRI slides were unmasked, and the correctness of each mark was evaluated. RESULTS: One hundred and seventeen of the 126 marks (93%) were correctly assigned. Detection rates differed for lesions >0.5 cc compared with lesions <0.5 cc (p < 0.005): 3/7 (43%) marks were correctly assigned in lesions <0.3 cc, 16/21 (76%) in lesions with 0.3-0.5 cc, and 98/98 (100%) in lesions >0.5 cc. Interobserver agreement was good for lesions >0.5 cc and poor for lesions <0.3 cc (Fleiss Kappa 1 vs. 0.0175). CONCLUSION: PIC-MABP seems to be a reliable system to communicate the location of mpMRI findings >0.5 cc between different disciplines and can be a useful guidance for cognitive mpMRI/TRUS fusion biopsy.

Hydronephrosis Predicts Successful Catheter Removal after Painful Urinary Retention - Preliminary Results of a Prospective Single Center Study.

INTRODUCTION: The study aims to identify candidates who can be managed conservatively after the first episode of spontaneous painful acute urinary retention (AUR). METHODS: A total of 20 patients with primary spontaneous painful AUR were prospectively included in the study. Twenty-four hours after AUR, the catheter was removed. When residual urinary volume was <100 ml, patients were referred without catheter, when residual urinary volume was ≥100 ml, the catheter was replaced and removed again at day 4, 7 or 10 after AUR, respectively. Receiver operating characteristic curves, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to assess predictors for successful catheter removal. RESULTS: Thirteen out of 20 (65%) patients had a successful catheter removal until day 10 after AUR. Among them 12 of 13 (93.2%) had a successful catheter removal until day 4 of AUR. Hydronephrosis urinary volume and Qmax at the time of AUR were significant numeric predictors for failure of successful catheter removal. In addition, we calculated a prediction model combing age + prostate volume + urinary volume + Qmax that highly predicts successful catheter removal (sensitivity 100%, specificity 69%, PPV 64%, NPV 100%). CONCLUSION: We found for the first time a significant association between hydronephrosis and successful catheter removal. Successful catheter removal until day 4 after AUR can safely be managed without immediate transurethral resection of the prostate.

(68)Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate?

PURPOSE: To assess the association between PSA levels, PSA kinetics and other factors and a pathological (68)Ga-PSMA PET/CT scan in patients with recurrent prostate cancer (rPCa) with biochemical relapse (BR) after radical therapy. METHODS: Seventy consecutive rPCA patients referred for (68)Ga-PSMA PET/CT, matching all the following criteria, were retrospectively evaluated: (a) previous radical prostatectomy or primary radiotherapy with curative intent; (b) BR or persisting high PSA levels after primary treatment; and (c) complete clinical and imaging information. The mean ± SD PSA level was 3.5 ± 5.3 ng/mL (median 1.7, range 0.2 - 32.2 ng/mL), the mean ± SD PSA doubling time (PSAdt) was 6.5 ± 5.5 months (median 5.5, range 1.3 - 31.6 months), and the mean ± SD PSA velocity was 7.9 ± 20.5 (median 2.1, range 0.2 - 147.5 ng/mL/year). Statistical analysis was performed to assess which factors were associated with the detection of rPCa on (68)Ga-PSMA PET/CT. RESULTS: (68)Ga-PSMA PET/CT was positive in 52 of 70 patients (74.2%). In 30 patients (42.8%) lesions limited to the pelvis were detected. Distant lesions were observed in 8 of patients (11.4%). Local plus systemic lesions were detected in 14 patients (20%). PSA level (p = 0.017) and PSAdt (p = 0.0001) were significantly different between PET-positive patients (higher PSA level, shorter PSAdt) and PET-negative patients (lower PSA, longer PSAdt). ROC analysis showed that PSAdt 6.5 months and PSA 0.83 ng/mL were optimal cut-off values. In multivariate analysis PSAdt was associated with (68)Ga-PSMA PET/CT positivity. (68)Ga-PSMA PET/CT was positive in 17 of 20 patients (85%) with PSA <2 ng/mL and PSAdt <6.5 months, and in 3 of 16 patients (18.7%) with PSA <2 ng/mL and PSAdt ≥6.5 months. CONCLUSION: The great potential of (68)Ga-PSMA PET/CT in patients with rPCa and BR was confirmed. PSA and PSAdt were valuable predictors of pathological (68)Ga-PSMA PET/CT findings.

Multiparametric magnetic resonance imaging/transrectal ultrasound fusion targeted biopsy of the prostate: preliminary results of a prospective single-centre study.

PURPOSE: To evaluate multiparametric magnetic resonance imaging/transrectal ultrasound (mpMRI/TRUS) fusion targeted biopsy (TB) of the prostate for prostate cancer (PCa) diagnosis. PATIENTS AND METHODS: From April 2013 to January 2014, 53 men were included in this prospective single-centre study. The degree of PCa suspicion from mpMRI findings was classified according to the PI-RADS scoring system. Of these, 50 patients underwent both an mpMRI/TRUS fusion TB and a 10-core systematic biopsy (SB) of the prostate and were eligible for analysis. RESULTS: 225 targeted and 500 systematic cores were included in this study. PCa was histologically confirmed in 52.0% of patients (26/50), whereas TB revealed PCa in 46.0% (23/50) and SB in 36.0% (18/50). TB identified PCa in 16.0% of all patients (8/50) that were missed by SB. All told, the targeted core was 2.8 times more likely to be PCa-positive than the systematic core (29.3 vs. 10.4%). CONCLUSIONS: mpMRI/TRUS fusion TB of the prostate is safe, practicable and may improve PCa diagnosis using fewer biopsy cores compared to SB.

Identification of functionally active, low frequency copy number variants at 15q21.3 and 12q21.31 associated with prostate cancer risk.

Copy number variants (CNVs) are a recently recognized class of human germ line polymorphisms and are associated with a variety of human diseases, including cancer. Because of the strong genetic influence on prostate cancer, we sought to identify functionally active CNVs associated with susceptibility of this cancer type. We queried low-frequency biallelic CNVs from 1,903 men of Caucasian origin enrolled in the Tyrol Prostate Specific Antigen Screening Cohort and discovered two CNVs strongly associated with prostate cancer risk. The first risk locus (P = 7.7 × 10(-4), odds ratio = 2.78) maps to 15q21.3 and overlaps a noncoding enhancer element that contains multiple activator protein 1 (AP-1) transcription factor binding sites. Chromosome conformation capture (Hi-C) data suggested direct cis-interactions with distant genes. The second risk locus (P = 2.6 × 10(-3), odds ratio = 4.8) maps to the α-1,3-mannosyl-glycoprotein 4-ß-N-acetylglucosaminyltransferase C (MGAT4C) gene on 12q21.31. In vitro cell-line assays found this gene to significantly modulate cell proliferation and migration in both benign and cancer prostate cells. Furthermore, MGAT4C was significantly overexpressed in metastatic versus localized prostate cancer. These two risk associations were replicated in an independent PSA-screened cohort of 800 men (15q21.3, combined P = 0.006; 12q21.31, combined P = 0.026). These findings establish noncoding and coding germ line CNVs as significant risk factors for prostate cancer susceptibility and implicate their role in disease development and progression.

Comparison of real-time elastography and multiparametric MRI for prostate cancer detection: a whole-mount step-section analysis.

OBJECTIVE: The purpose of this study was to compare prostate cancer detection rate of real-time elastography (RTE) with that of multiparametric MRI to evaluate the advantages and disadvantages of the two methods. SUBJECTS AND METHODS: Thirty-nine patients with biopsy-proven prostate cancer underwent both RTE and multiparametric MRI to localize prostate cancer before radical prostatectomy. RTE was performed to assess prostate tissue elasticity, and hard lesions were considered suspicious for prostate cancer. Multiparametric MRI included T2-weighted MRI, diffusion-weighted MRI (DWI), and contrast-enhanced MRI (CE-MRI) with an endorectal coil at 1.5 T. After radical prostatectomy, whole-mount step sections of the prostate were generated, and the prostate cancer detection rates with both modalities were analyzed for cancer lesions measuring 0.2 cm3 or larger. RESULTS: Histopathologic examination revealed 61 cancer lesions. RTE depicted 39 of 50 cancer lesions (78.0%) in the peripheral zone and 2 of 11 (18.2%) in the transitional zone. Multiparametric MRI depicted 45 of 50 cancer lesions (90.0%) in the peripheral zone and 8 of 11 (72.7%) in the transitional zone. Significant differences between the two modalities were found for the transitional zone and anterior part in prostates with volumes greater than 40 cm3 (p<0.05). Detection rates for high-risk prostate cancer (Gleason score≥4 and 3) and cancer lesions with volumes greater than 0.5 cm3 were high for both methods (93.8% and 80.5% for RTE, 87.5% and 92.7% for multiparametric MRI). Volumetric measurements of prostate cancer were more reliable with T2-weighted MRI than with RTE (Spearman rank correlation, 0.72 and 0.46). CONCLUSION: RTE and multiparametric MRI depicted high-risk prostate cancer with high sensitivity. However, multiparametric MRI seems to have advantages in tumor volume assessment and for the detection of prostate cancer in the transitional zone and anterior part within prostates larger than 40 cm3.

Long-term follow up of renal anastomosing hemangioma mimicking renal angiosarcoma.

Anastomosing hemangioma of the kidney is a very rare neoplasm, currently 19 cases have been reported in the literature. First described in 2009, histopathologically anastomosing hemangioma is similar to aggressive angiosarcoma. No long-term follow-up data of anastomosing hemangioma have been described yet. Here, we present the case of a healthy 56-year-old man diagnosed in 2002 with a 7 × 5-cm anastomosing hemangioma mimicking an aggressive renal angiosarcoma. The patient underwent nephrectomy and has been followed up disease free for 13 years.

Real-World Evidence of Triplet Therapy in Metastatic Hormone-Sensitive Prostate Cancer: An Austrian Multicenter Study.

INTRODUCTION: Two randomized trials demonstrated a survival benefit of triplet therapy (androgen deprivation therapy [ADT]) plus androgen receptor pathway inhibitor [ARPI] plus docetaxel) over doublet therapy (ADT plus docetaxel), thus changing treatment strategies in metastatic hormonesensitive prostate cancer (mHSPC). PATIENTS AND METHODS: We conducted the first real-world analysis comprising 97 mHSPC patients from 16 Austrian medical centers, among them 79.4% of patients received abiraterone and 17.5% darolutamide treatment. Baseline characteristics and clinical parameters during triplet therapy were documented. Mann-Whitney U test for continuous or X²-test for categorical variables was used. Variables on progression were tested using logistic regression analysis and tabulated as hazard ratios (HR), 95% confidence interval (CI). RESULTS: Of 83.5% patients with synchronous and 16.5% with metachronous disease were included. 83.5% had high-volume disease diagnosed by conventional imaging (48.9%) or PSMA PET-CT (51.1%). While docetaxel and ARPI were administered consistent with pivotal trials, prednisolone, prophylactic gCSF and osteoprotective agents were not applied guideline conform in 32.5%, 37%, and 24.3% of patients, respectively. Importantly, a nonsimultaneous onset of chemotherapy and ARPI, performed in 44.3% of patients, was associated with significantly worse treatment response (P = .015, HR 0.245). Starting ARPI before chemotherapy was associated with significantly higher probability for progression (P = .023, HR 15.781) than vice versa. Strikingly, 15.6% (abiraterone) and 25.5% (darolutamide) low-volume patients as well as 14.4% (abiraterone) and 17.6% (darolutamide) metachronous patients received triplet therapy. Adverse events (AE) occurred in 61.9% with grade 3 to 5 in 15% of patient without age-related differences. All patients achieved a PSA decline of 99% and imaging response was confirmed in 88% of abiraterone and 75% of darolutamide patients. CONCLUSIONS: Triplet therapy arrived in clinical practice primarily for synchronous high-volume mHSPC. Regardless of selected therapy regimen, treatment is highly effective and tolerable. Preferably therapy should be administered simultaneously, however if not possible, chemotherapy should be started first.

Somatic mutations throughout the entire mitochondrial genome are associated with elevated PSA levels in prostate cancer patients.

The genetic etiology of prostate cancer, the most common form of male cancer in western countries, is complex and the interplay of disease genes with environmental factors is far from being understood. Studies on somatic mitochondrial DNA (mtDNA) mutations have become an important aspect of cancer research because these mutations might have functional consequences and/or might serve as biosensors for tumor detection and progression. We sequenced the entire mitochondrial genome (16,569 bp) from 30 prospectively collected pairs of macrodissected cancerous and benign cells from prostate cancer patients and compared their genetic variability. Given recent concerns regarding the authenticity of newly discovered mtDNA mutations, we implemented a high-quality procedure for mtDNA whole-genome sequencing. In addition, the mitochondrial genes MT-CO2, MT-CO3, MT-ATP6, and MT-ND6 were sequenced in further 35 paired samples from prostate cancer patients. We identified a total of 41 somatic mutations in 22 out of 30 patients: the majority of these mutations have not previously been observed in the human phylogeny. The presence of somatic mutations in transfer RNAs (tRNAs) was found to be associated with elevated PSA levels (14.25 ± 5.44 versus 7.15 ± 4.32 ng/ml; p = 0.004). The level and degree of heteroplasmy increased with increasing tumor activity. In summary, somatic mutations in the mitochondrial genome are frequent events in prostate cancer. Mutations mapping to mitochondrial tRNAs, ribosomal RNAs, and protein coding genes might impair processes that occur within the mitochondrial compartment (e.g., transcription, RNA processing, and translation) and might finally affect oxidative phosphorylation.