Impact of operator expertise on transperineal free-hand mpMRI-fusion-targeted biopsies under local anaesthesia for prostate cancer diagnosis: a multicenter prospective learning curve.

PURPOSE: Transperineal mpMRI-targeted fusion prostate biopsies (TPFBx) are recommended for prostate cancer diagnosis, but little is known about their learning curve (LC), especially when performed under local anaesthesia (LA). We investigated how operators' and institutions' experience might affect biopsy results. METHODS: Baseline, procedure and pathology data of consecutive TPFBx under LA were prospectively collected at two academic Institutions, from Sep 2016 to May 2019. Main inclusion criterion was a positive MRI. Endpoints were biopsy duration, clinically significant prostate cancer detection rate on targeted cores (csCDR-T), complications, pain and urinary function. Data were analysed per-centre and per-operator (with ≥ 50 procedures), comparing groups of consecutive patient, and subsequently through regression and CUSUM analyses. Learning curves were plotted using an adjusted lowess smoothing function. RESULTS: We included 1014 patients, with 27.3% csCDR-T and a median duration was 15 min (IQR 12-18). A LC for biopsy duration was detected, with the steeper phase ending after around 50 procedures, in most operators. No reproducible evidence in favour of an impact of experience on csPCa detection was found at operator's level, whilst a possible gentle LC of limited clinical relevance emerged at Institutional level; complications, pain and IPSS variations were not related to operator experience. CONCLUSION: The implementation of TPFBx under LA was feasible, safe and efficient since early phases with a relatively short learning curve for procedure time.

Event-free survival after 68 Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC) patients eligible for salvage therapy.

BACKGROUND/AIM: Prostate-specific-membrane-antigen/positron emission tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment. MATERIALS AND METHODS: This analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan-Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as death, radiological progression, or PSA recurrence after therapy. RESULTS: One-hundred and seventy-six (n = 176) patients were analyzed (median PSA 0.62 [IQR: 0.43-1.00] ng/mL; median follow-up of 35.4 [IQR: 26.5-40.3] months). The EFS was 78.8% at 1 year, 65.2% (2 years), and 52.2% (3 years). Patients experiencing events during study follow-up had a significantly higher median PSA (0.81 [IQR: 0.53-1.28] vs 0.51 [IQR: 0.36-0.80] ng/mL) and a lower PSA doubling time (PSAdt) (5.4 [IQR: 3.7-11.6] vs 12.7 [IQR: 6.6-24.3] months) (p < 0.001) compared to event-free patients. The Kaplan-Meier curves showed that PSA > 0.5 ng/mL, PSAdt ≤ 6 months, and a positive PSMA-PET result were associated with a higher event rate (p < 0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA > 0.5 ng/mL and PSAdt ≤ 6 months were statistically significant event-predictors in multivariate model (p < 0.001). CONCLUSION: Low PSA and long PSAdt were significant predictors of longer EFS. A lower incidence of events was observed in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.

Transperineal freehand multiparametric MRI fusion targeted biopsies under local anaesthesia for prostate cancer diagnosis: a multicentre prospective study of 1014 cases.

OBJECTIVE: To assess the outcomes of multiparametric magnetic resonance imaging (mpMRI) transperineal targeted fusion biopsy (TPFBx) under local anaesthesia. PATIENTS AND METHODS: We prospectively screened 1327 patients with a positive mpMRI undergoing TPFBx (targeted cores and systematic cores) under local anaesthesia, at two tertiary referral institutions, between September 2016 and May 2019, for inclusion in the present study. Primary outcomes were detection of clinically significant prostate cancer (csPCa) defined as (1) International Society of Urological Pathologists (ISUP) grade >1 or ISUP grade 1 with >50% involvement of prostate cancer (PCa) in a single core or in >2 cores (D1) and (2) ISUP grade >1 PCa (D2). Secondary outcomes were: assessment of peri-procedural pain (numerical rating scale [NRS]) and procedure timings; erectile (International Index of Erectile Function) and urinary (International Prostate Symptom Score) function changes; and complications. We also investigated the value of systematic sampling and concordance with radical prostatectomy (RP). RESULTS: A total of 1014 patients were included, of whom csPCa was diagnosed in 39.4% (n = 400). The procedure was tolerable (NRS pain score 3.1 ± 2.3), with no impact on erectile (P = 0.45) or urinary (P = 0.58) function, and a low rate of complications (Clavien-Dindo grades 1 or 2, n = 8; grade >2, n = 0). No post-biopsy sepsis was recorded. Twenty-two men (95% confidence interval [CI] 17-29) needed to undergo additional systematic biopsy to diagnose one csPCa missed by targeted biopsies (D1). ISUP grade concordance of biopsies with RP was as follows: k = 0.40 (95% CI 0.31-0.49) for targeted cores alone and k = 0.65 (95% CI 0.57-0.72; P < 0.05) overall. CONCLUSIONS: The use of TPFBx under local anaesthesia yielded good csPCa detection and was feasible, quick, well tolerated and safe. Infectious risk was negligible. Addition of systematic to targeted cores may not be needed in all men, although it improves csPCa detection and concordance with RP.

Pain in Men Undergoing Transperineal Free-Hand Multiparametric Magnetic Resonance Imaging Fusion Targeted Biopsies under Local Anesthesia: Outcomes and Predictors from a Multicenter Study of 1,008 Patients.

PURPOSE: Several transperineal biopsy series have proven feasibility under local anesthesia. However, there is a lack of large analyses detailing pain outcomes and factors influencing pain. MATERIALS AND METHODS: From 2016 to 2019 we performed a multicenter prospective study in men undergoing multiparametric magnetic resonance imaging-transperineal fusion biopsies (target+systematic cores) under local anesthesia. Primary outcomes were 1) pain scores (assessed through a 0 to 10-point numeric rating scale) and 2) identification of factors associated with severe pain. The secondary outcome was to evaluate pain influence on clinically significant prostate cancer target cores detection. RESULTS: We included 1,008 men undergoing transperineal fusion biopsies under local anesthesia. Mean±SD numeric rating scale pain scores were 3.9±2.1 at local anesthesia administration and 3.1±2.3 when performing biopsies. Pain was not associated with lower clinically significant prostate cancer detection on targeted cores (p=0.23 and p=0.47 depending on clinically significant prostate cancer definition). On multivariate analysis age (OR 0.96, 95% CI 0.94-0.99) and severe anxiety (OR 2.99, 95% CI 1.83-4.89) were a protective and risk factor, respectively, for severe biopsy pain. Procedural time was also associated with an increased risk of experiencing severe biopsy pain (OR 1.04, 95% CI 1.00-1.08). If aiming to test the possible effects of anxiety preventive measures on pain, an anxiety cutoff greater than 6 on a numeric rating scale would decrease to 13% the number of patients being treated while identifying 56% of those experiencing severe pain. CONCLUSIONS: Transperineal fusion biopsies under local anesthesia result in moderate pain. Pain does not influence clinically significant prostate cancer target detection. Patient anxiety predicts pain. A numeric rating scale based anxiety assessment may be used to identify those at higher risk for experiencing severe pain in men undergoing transperineal fusion biopsies.

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.

Systematic review of lower urinary tract symptoms/benign prostatic hyperplasia surgical treatments on men's ejaculatory function: Time for a bespoke approach?

Although ejaculatory dysfunction is common for patients undergoing benign prostatic hyperplasia surgery, no clear evidence is present to counsel men seeking to preserve ejaculation. Our aim was to evaluate ejaculatory dysfunction in relation to benign prostatic hyperplasia surgery. We carried out a web and manual search using MEDLINE and Embase including randomized controlled trials reporting ejaculatory dysfunction after benign prostatic hyperplasia surgery: 42 randomized controlled trials comprising a total of 3857 patients were included. Only one study had ejaculatory dysfunction as a primary outcome, and just 10 evaluated ejaculatory dysfunction before and after surgery. The definition of ejaculatory dysfunction was not standardized. Similarly, just seven studies used internationally validated questionnaires to address ejaculatory dysfunction. The reported rates of ejaculatory dysfunction after resectional electrosurgery, laser procedures, coagulation, ablation and implant techniques were assessed and compared. Transurethral resection of the prostate and recent laser procedures including holmium, thulium and GreenLight cause similar rates of ejaculatory dysfunction, occurring in almost three out of four to five men. Although providing less symptomatic benefit compared with transurethral resection of the prostate, transurethral incision of the prostate, transurethral needle ablation and transurethral microwave thermotherapy should be considered for men aiming to maintain normal ejaculation. UroLift is also a recent promising option for this category of patients. The vast majority of studies reporting ejaculatory dysfunction after benign prostatic hyperplasia surgery used poor methodology to investigate this complication. Future studies able to address clear hypothesis and considering ejaculatory dysfunction anatomical and pathophysiological features are required to develop ejaculation preserving techniques and to increase the evidence to counsel men aiming to preserve ejaculation.

Hyperthermia for non-muscle invasive bladder cancer.

Recurrent non muscle invasive bladder cancer (NMIBC) represents a therapeutic challenge, especially in the case of Bacillus Calmette Guerin (BCG)-failures. Chemohyperthermia (CHT) has been tested as adjuvant therapy in selected categories of patients with promising results. The aim of this systematic review is to explore the current role of CHT and its future perspectives. The review process was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. After the selection process, 30 articles were used in this review. Treatment with CHT is safe and quite well tolerated. CHT seems to be effective in low and intermediate risk bladder cancer. Moreover CHT could be offered to selected categories of high risk patients and BCG failures NMIBC. Further trials are needed in order to better identify the categories of patients which could benefit from this therapy and to standardise the right schedule of treatment.

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.