68Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC): a prospective single-centre study in patients eligible for salvage therapy.

OBJECTIVES: The primary objective is to assess the efficacy of 68Ga-PSMA-11-PET/CT to detect recurrent location(s) in hormone-sensitive prostate cancer (PCa). Secondary objectives are (1) to evaluate changes in clinical management; (2) to determine which covariates independently predict positive scan; (3) to assess 68Ga-PSMA-11-PET/CT performance in different settings of PSA relapse. MATERIALS AND METHODS: Inclusion criteria include (1) histologically diagnosed PCa; (2) previous radical therapy; (3) proven biochemical recurrence (BCR) or biochemical persistence (BCP); (4) hormone-sensitive PCa (HSPC); (5) androgen deprivation therapy (ADT)-free for at least 6 months; (6) PSA < 1.5 ng/mL or any PSA in case of negative choline-PET/CT (n = 38). Changes in clinical management were defined by multidisciplinary tumour-board. Clinical settings were BCP (group-1, n = 25); first-time BCR (group-2, n = 121); BCR after salvage therapy (group-3, n = 77). RESULTS: Two hundred twenty-three (223) consecutive patients were enrolled: median PSA = 0.65 ng/mL (0.2-8.9) and median PSAdt = 9.3 months (0.4-144.6). 96.9% received RP as primary therapy. 68Ga-PSMA-11-PET/CT positivity rate was 39.9% (CI95% 33.5-46.7%). Disease confined to pelvis was detected in 23.3% of cases. At least one distant lesion was observed in 16.6% of cases. Secondary objectives are as follows: (1) changes in clinical management were observed in 34.5% of patients; (2) PSA, PSAdt and T stage > 3a were independent predictors (all p < 0.03); (3) 68Ga-PSMA-11-PET/CT positivity rate was 56% (in group 1, 36.3% in group 2, 40.3% in group 3. CONCLUSION: This study attested the overall good performance of 68Ga-PSMA-11-PET/CT to detect PCa locations in HSPC patients eligible for salvage therapy, influencing the therapy management in 35.4% of cases. Furthermore, patient characteristics are influencing factors of 68Ga-PSMA-11-PET/CT positivity rate and should be considered to reduce false negative scan.

Transperineal Free-hand mpMRI Fusion-targeted Biopsies Under Local Anesthesia: Technique and Feasibility From a Single-center Prospective Study.

OBJECTIVE: To evaluate the feasibility of "in-office" TPFBx under local anesthesia (LA). MATERIALS AND METHODS: We prospectively screened for eligibility data of 724 consecutive men undergoing either TPFBx (target and systematic cores) or TPSBx (systematic cores only) from September 2016 to June 2018 due to suspicion of prostate cancer (CaP), according to predefined exclusion criteria. RESULTS: We included 459 men (TPFBx n = 279 including n = 338 mpMRI lesions, Pi-RADS 4 in 63.6%; TPSBx n = 180). Median procedural time and maximum pain were 19 minutes and 5 numeric rating scale (NRS) points; pain was highest at the time of LA. Only 1 major complication occurred (Clavien 3a). Hematuria and hematospermia were frequent (72.6% and 54.2%). Vaso-vagal reactions and AUR were rare (0.7% and 0.4%). No cases of UTI and 1 case of fever were recorded. No significant changes in erectile and urinary functions were noted from baseline compared to 40 days after TPFBx (P = .86 and P = .89). In comparison with TPSBx the sole differences were pain during prostatic sampling (P = .03), duration of hematospermia (P <.0001) and procedural time (P <.001) all higher for TPFBx. Clinically significant (cs) CaP was detected in n = 150 (53.8%) patients in the TPFBx group (34.9%, 51.7%, and 75% of Pirads 3, 4, and 5, respectively). Addition of systematic cores detected n = 25 csCaP that were missed by targeted cores (17.4% of all csCaP). CONCLUSION: TPFBx under LA are feasible, yielding high tolerability, low complications, no impact on erectile and urinary function and good csCaP detection. Addition of systematic to targeted cores remains recommended. Further studies are needed to confirm our findings.

A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or "chemopromotion"?

BACKGROUND: Antioxidants effectiveness in prostate cancer (PCa) chemoprevention has been severely questioned, especially after the recent results of the Selenium and Vitamin E Cancer Prevention Trial. We present the results of a double-blind randomized controlled trial (dbRCT) on the pharmacokinetic, clinical, and molecular activity of dietary supplements containing lycopene, selenium, and green tea catechins (GTCs) in men with multifocal high grade prostatic intraepithelial neoplasia (mHGPIN) and/or atypical small acinar proliferation (ASAP). METHODS: From 2009 to 2014, we conducted a dbRCT including 60 patients with primary mHGPIN and/or ASAP receiving daily lycopene 35 mg, selenium 55 µg, and GTCs 600 mg, or placebo for 6 months. Pharmacokinetic analysis were performed with UV-Visible spectrophotometric assay under standard (SC) and accelerated (AC) conditions. Upon plasma lycopene concentrations falling within the expected range (1.2-90 mcg/l) and no side-effects of grade >1, study proceeded to phase II (n = 50). After unblinding of results, eight men (4 per arm, 2 without and 2 with PCa, respectively) were randomly selected and totRNA extracted from "non-pathological" tissues. MicroRNA profiling was performed with the Agilent platform. Raw data processing used R-statistical language and linear models for microarray analysis. RESULTS: Samples were stable except for lycopene, showing significant degradation (SC = 56%, AC = 59%) and consequently stabilized under vacuum in a dark packaging. Mean plasmatic lycopene concentration was 1,45 ± 0,4 µM. At 6 months, 53 men underwent re-biopsy and 13 (24.5%) were diagnosed with PCa (supplementation n = 10, placebo n = 3 [P = 0.053]). At a mean 37 months follow-up, 3 additional PCa were found in the placebo group. No significant variations in PSA, IPSS, and PR25 questionnaires were observed. Stronger modulation of miRNAs was present on re-biopsy in the supplementation group compared to the placebo, including: (i) overexpression of miRNAs present in PCa versus non-cancer tissue; (ii) underexpression of miRNAs suppressing PCa proliferation; (iii) detection of 35 miRNAs in PCa patients versus disease-free men, including androgen-regulated miR-125b-5p and PTEN-targeting miR-92a-3p (both upregulated). CONCLUSION: Administration of high doses of lycopene, GTCs, and selenium in men harboring HGPIN and/or ASAP was associated with a higher incidence of PCa at re-biopsy and expression of microRNAs implicated in PCa progression at molecular analysis. The use of these supplements should be avoided.

Inguinal versus subinguinal varicocele vein ligation using magnifying loupe under local anesthesia: which technique is preferable in clinical practice?

OBJECTIVES: To compare the intraoperative results of inguinal versus subinguinal varicocelectomy using magnifying loupe, in terms of vein ligation and arterial preservation, recurrence rate, and patient tolerability. METHODS: Ninety-nine patients were randomized to undergo a varicocele repair with an inguinal or a subinguinal approach under local anesthesia. Data concerning the number of veins ligated and arterial preservation were recorded during each procedure. The amount of intraoperative and postoperative pain was assessed by means of visual analogue scale (VAS) scores. The recurrence rate was documented by color Doppler ultrasound examination. RESULTS: The average number of ligated veins was 5.6 with a subinguinal dissection and 4.4 with the inguinal approach. Inadvertent injury of the spermatic artery occurred in 6 of 47 subinguinal and 3 of 50 inguinal dissections; the artery could not be identified during 2 subinguinal and 1 inguinal dissection. Recurrent varicocele was detected in 8% and 14.9% of patients after an inguinal and a subinguinal approach, respectively. The intraoperative VAS score was significantly higher in the inguinal than in the subinguinal patients (P = 0.008). CONCLUSIONS: In our hands, the inguinal approach to the spermatic cord showed a trend toward an easier preservation of the artery and a reduced incidence of persistent pathologic vein reflux. The subinguinal approach had a lower degree of intraoperative pain. On the whole, an inguinal repair might be preferable when magnifying loupe are used for varicocelectomy.