Is multiparametric MRI always needed in biopsy-naïve patients with abnormal digital rectal examination? A single-institutional experience combining clinical and micro-ultrasonography-based factors to optimize prostate cancer detection.

PURPOSE: To assess the diagnostic performance of microultrasound-targeted biopsy (microUSTBx) and systematic biopsy (SBx) in detecting clinically significant prostate cancer (csPCa) among men with abnormal digital rectal examination (DRE) and suspicious lesions at multiparametric magnetic resonance imaging (mpMRI), and to compare the diagnostic performance of this approach with a mpMRI-guided targeted biopsy (MTBx) plus SBx-based strategy. METHODS: Biopsy-naïve men with suspicious lesions at mpMRI and abnormal DRE were prospectively evaluated between October 2017 and January 2023. csPCa detection rate by microUSTBx plus SBx and MTBx plus SBx was assessed and then compared by McNemar's test. The added value of prostate-specific antigen density (PSAd) was also evaluated. RESULTS: Overall, 182 biopsy naïve men were included. MicroUSTBx plus SBx achieved comparable detection rate to MTBx plus SBx in diagnosis of ciPCa and csPCa (ciPCa: 9.3% [17/182] vs 10% [19/182]; csPCa: 63% [114/182] vs 62% [113/182]). MicroUSTBx outperformed MTBx (ciPCa: 5.5% [10/182] vs 6.0% [11/182]; csPCa: 57% [103/182] vs 54% [99/182]). Using microUSTBx plus SBx would have avoided 68/182 (37%) unnecessary mpMRI, while missing only 2/116 (1.7%) csPCa. The decision curve analysis of suspicious microUS plus PSAd ≥ 0.15 ng/ml showed higher net benefit in the ability to identify true positives and reduce the number of unnecessary prostate biopsy in this subcategory of patients. CONCLUSIONS: The combination of microUSTBx and SBx showed equal diagnostic performance to an mpMRI-based approach in biopsy-naïve patients with an abnormal DRE. The combination of this approach with PSAd maximize the diagnostic accuracy while lowering the need for unnecessary biopsies.

Diagnostic performance of microUltrasound at MRI-guided confirmatory biopsy in patients under active surveillance for low-risk prostate cancer.

BACKGROUND: Active surveillance (AS) represents a standard of care of low-risk prostate cancer (PCa). However, the identification and monitoring of AS candidates remains challenging. Microultrasound (microUS) is a novel high-resolution imaging modality for transrectal ultrasonography (TRUS). We explored the impact of microUS TRUS and targeted biopsies in mpMRI-guided confirmatory biopsies. METHODS: Between October 2017 and September 2021, we prospectively enrolled 100 patients scheduled for MRI-guided confirmatory biopsy at 1 year from diagnosis of ISUP 1 PCa. TRUS was performed using the ExactVu microUS system; PRI-MUS protocol was applied to identify suspicious lesions (i.e., PRIMUS score ≥ 3). All patients received targeted biopsies of any identified microUS and mpMRI lesions and complementary systematic biopsies. The proportion of patients upgraded to clinically significant PCa (defined as ISUP ≥ 2 cancer; csPCa) at confirmatory biopsies was determined, and the diagnostic performance of microUS and mpMRI were compared. RESULTS: Ninety-two patients had a suspicious MRI lesion classified PI-RADS 3, 4, and 5 in respectively 28, 16, and 18 patients. MicroUS identified 82 patients with suspicious lesions, classified as PRI-MUS 3, 4, and 5 in respectively 20, 50, and 12 patients, while 18 individuals had no lesions. Thirty-four patients were upgraded to ISUP ≥ 2 cancer and excluded from AS. MicroUS and mpMRI showed a sensitivity of 94.1% and 100%, and an NPV of 88.9% and 100%, respectively, in detecting ISUP ≥ 2 patients. A microUS-mandated protocol would have avoided confirmatory biopsies in 18 patients with no PRI-MUS ≥ 3 lesions at the cost of missing four upgraded patients. CONCLUSIONS: MicroUS and mpMRI represent valuable imaging modalities showing high sensitivity and NPV in detecting csPCa, thus allowing their use for event-triggered confirmatory biopsies in AS patients. MicroUS offers an alternative imaging modality to mpMRI for the identification and real-time targeting of suspicious lesions in AS patients.

Diagnostic accuracy of multiparametric MRI- and microultrasound-targeted biopsy in biopsy-naïve patients with a PI-RADS 5 lesion: a single-institutional study.

PURPOSE: To evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging (MRI)- and microultrasound (microUS)-guided targeted biopsy (TBx) in detecting prostate cancer (PCa) and clinically significant (cs) PCa among men with Prostate Imaging Reporting and Data System (PI-RADS 5) lesions and to compare this combined TBx (CTBx) strategy with CTBx plus systemic biopsy (SBx). METHODS: One hundred and thirty-six biopsy-naïve patients with PI-RADS 5 lesion at multiparametric MRI undergoing CTBx plus SBx were retrospectively evaluated. Analysis of diagnostic performance of microUS-TBx, MRI-TBx, CTBx, SBx and combined CTBx plus SBx was performed. Cost (downgrade, upgrade and biopsy core) to effectiveness (detection rate) was compared. RESULTS: CTBx achieved a comparable detection rate to CTBx plus SBx in diagnosis of PCa and csPCa (PCa: 78.7% [107/136] vs 79.4% [108/136]; csPCa: 67.6% [92/136] vs 67.6% [92/136]; p > 0.05) and outperformed SBx (PCa: 58.8% [80/136]; csPCa: 47.8% [65/136]; p < 0.001). Using CTB would have avoided 41.1% (56/136) unnecessary SBx, without missing any csPCa. The rate of any upgrading or csPCa upgrading was significantly higher by SBx than by CTBx [33/65 (50.8%) vs 17/65 (26.1%) and 20/65 (30.8%) vs 4/65 (6.15%), respectively, p < 0.05]. Considering csPCa detection rate, microUS showed high sensitivity and positive predictive value (94.6%, 87.9%, respectively), with lower specificity and negative predictive value (25.0% and 44.4%, respectively). At multivariable logistic regression models, positive microUS was identified as an independent predictor of csPCa (p = 0.024). CONCLUSIONS: A combined microUS/MRI-TBx approach could be the ideal imaging tool for characterizing primary disease in PI-RADS five patients, allowing SBx to be avoided.

Diagnostic Performance and Clinical Impact of PSMA PET/CT versus mpMRI in Patients with a High Suspicion of Prostate Cancer and Previously Negative Biopsy: A Prospective Trial (PROSPET-BX).

BACKGROUND: This prospective single-arm study is designed to compare in parallel 68Ga-PSMA PET/TRUS (transrectal or transperineal) fusion biopsy ("experimental test") with multiparametric MRI (mpMRI)/TRUS fusion prostate biopsy ("standard test") in men with a high suspicion of prostate cancer (PCa) after at least one negative biopsy. The primary objective was to evaluate the diagnostic performance of 68Ga-PSMA PET/TRUS fusion prostate biopsy in comparison to mpMRI/TRUS fusion prostate biopsy analyzed in parallel. Secondarily, we aimed to determine the relationship between the "experimental test" and the histopathological characteristics of the specimen, along with the clinical utility of the "experimental test" compared to the "standard test." SUMMARY: To test the superiority of 68Ga-PSMA PET/CT compared to mpMRI, we will enroll a minimum cohort of 128 patients. Inclusion criteria comprise: age >18 years; blood PSA level >4.0 ng/mL; free-to-total PSA ratio <20%; progressive rise of PSA levels in two consecutive blood samples despite antibiotics; serum blood tests suspicious for PCa; at least one previous negative biopsy; ASAP and/or high-grade PIN; negative digital rectal examination. All eligible patients will undergo 68Ga-PSMA PET/CT and mpMRI scans within 1 month's distance from each other, followed by biopsy session to be completed within 1 month's distance. Targeted TRUS fusion needle biopsy will be performed for all lesions detected with PET and mpMRI. The total duration of the study is 36 months. KEY MESSAGES: By comparing the "experimental test" and the "standard test" in parallel, we will be able to determine the superior diagnostic performance of 68Ga-PSMA PET/CT over mpMRI in detecting PCa, and in particular clinically significant PCa, in the specific cohort of patients with a high suspicion of PCa who are candidates to re-biopsy. The clinical impact of the "experimental test" will be subsequently analyzed in terms of the number of prostate biopsies that could be spared, time-consuming, patient friendliness, and cost-effectiveness.

Use of high-resolution micro-ultrasound to predict extraprostatic extension of prostate cancer prior to surgery: a prospective single-institutional study.

PURPOSE: We aim to evaluate the accuracy of micro-ultrasound (microUS) in predicting extraprostatic extension (EPE) of Prostate Cancer (PCa) prior to surgery. METHODS: Patients with biopsy-proven PCa scheduled for robot-assisted radical prostatectomy (RARP) were prospectively recruited. The following MRI-derived microUS features were evaluated: capsular bulging, visible breach of the prostate capsule (visible extracapsular extension; ECE), presence of hypoechoic halo, and obliteration of the vesicle-prostatic angle. The ability of each feature to predict EPE was determined. RESULTS: Overall, data from 140 patients were examined. All predictors were associated with non-organ-confined disease (p < 0.001). Final pathology showed that 79 patients (56.4%) had a pT2 disease and 61 (43.3%) ≥ pT3. Rate of non-organ-confined disease increased from 44% in those individuals with only 1 predictor (OR 7.71) to 92.3% in those where 4 predictors (OR 72.00) were simultaneously observed. The multivariate logistic regression model including clinical parameters showed an area under the curve (AUC) of 82.3% as compared to an AUC of 87.6% for the model including both clinical and microUS parameters. Presence of ECE at microUS predicted EPE with a sensitivity of 72.1% and a specificity of 88%, a negative predictive value of 80.5% and positive predictive value of 83.0%, with an AUC of 80.4%. CONCLUSIONS: MicroUS can accurately predict EPE at the final pathology report in patients scheduled for RARP.

The Microbiome of Catheter Collected Urine in Males with Bladder Cancer According to Disease Stage.

PURPOSE: The dogma that urine is sterile has been overturned and dysbiosis of the urinary microbiome has been linked to many urological disorders. We tested the hypothesis that the urinary microbial composition may be different between men with or without bladder cancer in catheter collected urines, bladder washouts and midstream voided urines, and may be dependent on tumor staging. MATERIALS AND METHODS: Liquid samples were collected from male patients with bladder cancer, and sex and age matched nonneoplastic controls. Total DNA was extracted and processed for 16S rRNA gene sequencing. Bioinformatic analysis for microbial classification was performed to assess diversity and variations. RESULTS: The urinary microbiome associated with catheter collected urine samples of patients with bladder cancer was characterized by a significantly increased abundance of Veillonella (p=0.04) and Corynebacterium (p=0.03), and decreased Ruminococcus (p=0.03) compared to controls, with differences exacerbating with disease progression. Compared to catheterized urines, bladder cancer washouts showed the specific increase of some taxa, like Burkholderiaceae (p=0.014), whereas midstream urines were enriched in Streptococcus (p <0.0001), Enterococcus (p <0.0001), Corynebacterium (p=0.038) and Fusobacterium (p <0.0001). CONCLUSIONS: The bladder is colonized by endogenous bacteria and microbial modifications characterize the microbiome of patients with bladder cancer. Different microbial compositions can be characterized by changing sampling strategy. These results pave the way for exploring new diagnostic and therapeutic options based on the manipulation of the bacterial community.

Feasibility, safety, and efficacy of ultrasound-guided transperineal laser ablation for the treatment of benign prostatic hyperplasia: a single institutional experience.

PURPOSE: To evaluate the feasibility, safety, and efficacy of ultrasound-guided transperineal laser ablation (TPLA) as a new minimally invasive surgical therapy (MIST) for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Under local anesthesia and conscious sedation up to two laser fibers for each prostatic lobe were inserted under US-guidance by a percutaneous approach. TPLA was performed using a continuous wave diode laser (SoracteLite-EchoLaserX4) able to generate a light-induced thermal heating and subsequent coagulative necrosis of the prostatic tissue. Patients were evaluated at 3, 6, and 12 months after TPLA. RESULTS: Twenty-two consecutive patients were prospectively enrolled (median age 61.9 years). All procedures were well tolerated and no procedural complications were recorded. Median catheterization time was 7 days, while the median hospitalization time was 1 day. Three out of twenty-two patients (13.6%) experienced acute urinary retention and two (9.1%) of them urinary tract infection requiring major antibiotic treatment. At 3, 6, and 12 months, median prostate volume significantly decreased by a - 21.3%, - 29%, and - 41%, respectively. At the same time point, median IPSS was 8 (- 63.6%), 5 (- 74%), and 6 (- 75%), while median QoL score was 1 in all the scheduled timepoints of follow-up. The median postoperative Qmax at 3, 6, and 12 months improved by + 57.8%, + 98%, and + 115.8%, respectively. Ejaculatory function was preserved in 21 out of 22 patients (95.5%). CONCLUSIONS: TPLA of the prostate appears to be a promising MIST for BPH. Long-term results and comparative studies against standard treatments are warranted before implementations of this technique in the urologist's armamentarium.

Retrotrigonal muscular layer sling associated with total anatomical reconstruction in robot-assisted radical prostatectomy and early continence.

BACKGROUND AND PURPOSE: Urinary continence (UC) represents the main non-oncological goal in patients undergoing robotic-assisted radical prostatectomy (RARP). To evaluate the efficacy in early UC achievement, we described a new sling technique using the retrotrigonal muscular layer (TZ sling) combined with total anatomical reconstruction (TAR). PATIENTS AND METHODS: We prospectively enrolled 407 consecutive prostate cancer (PC) patients undergoing RARP between May 2017 and January 2020. The first 250 patients underwent only TAR, while the following 157 patients TAR + TZ sling, by isolating and anchoring the retrotrigonal muscular layer to the pubic bone with 2 bilateral sutures. We defined UC as ≤ 1 pad/die, which was assessed after catheter removal at 1, 4 and 12wk using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. Sling-related operative time and post-operative complications were analyzed. RESULTS: In the TAR group, the UC rates at the 1, 4 and 12wk were 58%, 66% and 86%; in the TAR + TZ sling group 72%, 76% and 88%, respectively. A statistically significant difference was observed in the two groups at 1wk (p = 0.0049) and 4wk (p = 0.035) favoring the TZ sling surgical strategy. This difference in UC rates was lost at 12wk (p ≥ 0.05). No statistically significant differences in operative time, acute urinary retentions and other complication rates were observed between the two groups (p = NS). CONCLUSIONS: We have described a new, safe, feasible modification of RARP using a sling with the retrotrigonal muscular layer associated with TAR. We have demonstrated a statistically significant improvement in early UC rate in patients who are undergoing TAR and TZ sling compared to undergoing only TAR.

Clinical performance of Xpert Bladder Cancer (BC) Monitor, a mRNA-based urine test, in active surveillance (AS) patients with recurrent non-muscle-invasive bladder cancer (NMIBC): results from the Bladder Cancer Italian Active Surveillance (BIAS) project.

PURPOSE: To investigate the clinical performance of a new mRNA-based urine test, aiming to avoid unnecessary follow-up cystoscopy in patients under active surveillance (AS) for recurrent NMIBC. METHODS: This is a prospective cohort study enrolling patients with history of low-grade (LG) NMIBC, who developed a recurrence during the follow-up and underwent AS. Their urinary samples were analyzed by Xpert BC Monitor (Cepheid, Sunnyvale, CA, USA). The primary endpoint was to investigate if Xpert BC Monitor could avoid unnecessary cystoscopy during the follow-up period. Its sensitivity, specificity, PPVs and NPVs were calculated. A cutoff of 0.4 "linear discriminant analysis" (LDA) was optimized for the AS setting. RESULTS: The cohort consisted of 106 patients with a mean age of 72 ± 9.52 and a median follow-up from AS start of 8.8 (range 0-56.5) months. No statistically significant difference was found for the mean age, smoker status, lesion size, and number of lesions with a cutoff of 0.4. Of 106 patients, 22 (20.8%) were deemed to require treatment because of cystoscopic changes in size and/or number of lesions during the follow-up period. Using a cutoff value of < 0.4, 34 (33.7%) cystoscopies could be avoided due to low LDA value, missing 2/22 (9%) failures, none with high-grade (HG) NMIBC. Further research on larger population remains mandatory before its clinical use. CONCLUSION: Xpert BC Monitor seems to be a reliable assay, which might avoid unnecessary cystoscopies without missing HG NMIBC when its cutoff is optimized for the AS setting.

An increased body mass index is associated with a worse prognosis in patients administered BCG immunotherapy for T1 bladder cancer.

PURPOSE: The body mass index (BMI) may be associated with an increased incidence and aggressiveness of urological cancers. In this study, we aimed to evaluate the impact of the BMI on survival in patients with T1G3 non-muscle-invasive bladder cancer (NMIBC). METHODS: A total of 1155 T1G3 NMIBC patients from 13 academic institutions were retrospectively reviewed and patients administered adjuvant intravesical Bacillus Calmette-Guérin (BCG) immunotherapy with maintenance were included. Multivariable Cox regression analysis was performed to identify factors predictive of recurrence and progression. RESULTS: After re-TURBT, 288 patients (27.53%) showed residual high-grade NMIBC, while 867 (82.89%) were negative. During follow-up, 678 (64.82%) suffered recurrence, and 303 (30%) progression, 150 (14.34%) died of all causes, and 77 (7.36%) died of bladder cancer. At multivariate analysis, tumor size (hazard ratio [HR]:1.3; p = 0.001), and multifocality (HR:1.24; p = 0.004) were significantly associated with recurrence (c-index for the model:55.98). Overweight (HR: 4; p < 0.001) and obesity (HR:5.33 p < 0.001) were significantly associated with an increased risk of recurrence. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 9.9. For progression, we found that tumor size (HR:1.63; p < 0.001), multifocality (HR:1.31; p = 0.01) and concomitant CIS (HR: 2.07; p < 0.001) were significant prognostic factors at multivariate analysis (C-index 63.8). Overweight (HR: 2.52; p < 0.001) and obesity (HR: 2.521 p < 0.001) were significantly associated with an increased risk of progression. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 1.9. CONCLUSIONS: The BMI could have a relevant role in the clinical management of T1G3 NMIBC, if associated with bladder cancer recurrence and progression. In particular, this anthropometric factor should be taken into account at initial diagnosis and in therapeutic strategy decision making.

Active Surveillance for Low Risk Nonmuscle Invasive Bladder Cancer: A Confirmatory and Resource Consumption Study from the BIAS Project.

PURPOSE: We investigated predictive factors of failure and performed a resource consumption analysis in patients who underwent active surveillance for nonmuscle invasive bladder cancer. MATERIALS AND METHODS: This prospective observational study monitored patients with a history of pathologically confirmed stage pTa (grade 1-2) or pT1a (grade 2) nonmuscle invasive bladder cancer, and recurrent small size and number of tumors without hematuria and positive urine cytology. The primary end point was the failure rate of active surveillance. Assessment of failure predictive variables and per year direct hospital resource consumption analysis were secondary outcomes. Descriptive statistical analysis and Cox regression with univariable and multivariable analysis were done. RESULTS: Of 625 patients with nonmuscle invasive bladder cancer 122 with a total of 146 active surveillance events were included in the protocol. Of the events 59 (40.4%) were deemed to require treatment after entering active surveillance. Median time on active surveillance was 11 months (IQR 5-26). Currently 76 patients (62.3%) remain under observation. On univariable analysis only time from the first transurethral resection to the start of active surveillance seemed to be inversely associated with recurrence-free survival (HR 0.99, 95% CI 0.98-1.00, p = 0.027). Multivariable analysis also revealed an association with age at active surveillance start (HR 0.97, 95% CI 0.94-1.00, p = 0.031) and the size of the lesion at the first transurethral resection (HR 1.55, 95% CI 1.06-2.27, p = 0.025). The average specific annual resource consumption savings for each avoided transurethral bladder tumor resection was €1,378 for each intervention avoided. CONCLUSIONS: Active surveillance might be a reasonable clinical and cost-effective strategy in patients who present with small, low grade pTa/pT1a recurrent papillary bladder tumors.

68Ga-PSMA Positron Emission Tomography/Computerized Tomography for Primary Diagnosis of Prostate Cancer in Men with Contraindications to or Negative Multiparametric Magnetic Resonance Imaging: A Prospective Observational Study.

PURPOSE: 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography may represent the most promising imaging modality to identify and risk stratify prostate cancer in patients with contraindications to or negative multiparametric magnetic resonance imaging. MATERIALS AND METHODS: In this prospective observational study we analyzed 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography in a select group of patients with persistently elevated prostate specific antigen and/or Prostate Health Index suspicious for prostate cancer, negative digital rectal examination and at least 1 negative biopsy. The cohort comprised men with equivocal multiparametric magnetic resonance imaging (Prostate Imaging-Reporting and Data System, version 2 score of 2 or less), or an absolute or relative contraindication to multiparametric magnetic resonance imaging. Sensitivity, specificity and CIs were calculated compared to histopathology findings. ROC analysis was applied to determine the optimal cutoff values of 68Ga labeled prostate specific membrane antigen uptake to identify clinically significant prostate cancer (Gleason score 7 or greater). RESULTS: A total of 45 patients with a median age of 64 years were referred for 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography between January and August 2017. The 25 patients (55.5%) considered to have positive positron emission tomography results underwent software assisted fusion biopsy. We determined the uptake values of regions of interest, including a median maximum standardized uptake value of 5.34 (range 2.25 to 30.41) and a maximum-to-background standardized uptake value ratio of 1.99 (range 1.06 to 14.42). Mean and median uptake values on 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography (ie the maximum standardized uptake value or the maximum-to-background standardized uptake value ratio) were significantly higher for Gleason score 7 lesions than for Gleason score 6 or benign lesions (p <0.001). On ROC analysis a maximum standardized uptake value of 5.4 and a maximum-to-background standardized uptake value ratio of 2 discriminated clinically relevant prostate cancer with 100% overall sensitivity in each case, and 76% and 88% specificity, respectively. CONCLUSIONS: Our findings support the use of 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography for primary detection of prostate cancer in a specific subset of men.

High-Grade T1 on Re-Transurethral Resection after Initial High-Grade T1 Confers Worse Oncological Outcomes: Results of a Multi-Institutional Study.

INTRODUCTION: The aim of this multicenter study was to investigate the prognostic impact of residual T1 high-grade (HG)/G3 tumors at re-transurethral resection (TUR of bladder tumor) in a large multi-institutional cohort of patients with primary T1 HG/G3 bladder cancer (BC). PATIENTS AND METHODS: The study period was from January 2002 to -December 2012. A total of 1,046 patients with primary T1 HG/G3 and who had non-muscle invasive BC (NMIBC) on re-TUR followed by adjuvant intravesical Bacillus Calmette-Guerin (BCG) therapy with maintenance were included. Endpoints were time to disease recurrence, progression, and overall and cancer-specific death. RESULTS: A total of 257 (24.6%) patients had residual T1 HG/G3 tumors. The presence of concomitant carcinoma in situ, multiple and large tumors (> 3 cm) at first TUR were associated with residual T1 HG/G3. Five-year recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were 17% (CI 11.8-23); 58.2% (CI 50.7-65); 73.7% (CI 66.3-79.7); and 84.5% (CI 77.8-89.3), respectively, in patients with residual T1 HG/G3, compared to 36.7% (CI 32.8-40.6); 71.4% (CI 67.3-75.2); 89.8% (CI 86.6-92.3); and 95.7% (CI 93.4-97.3), respectively, in patients with NMIBC other than T1 HG/G3 or T0 tumors. Residual T1 HG/G3 was independently associated with RFS, PFS, OS, and CSS in multivariable analyses. CONCLUSIONS: Residual T1 HG/G3 tumor at re-TUR confers worse prognosis in patients with primary T1 HG/G3 treated with maintenance BCG. Patients with residual T1 HG/G3 for primary T1 HG/G3 are very likely to fail BCG therapy alone.

Oncological outcomes and complication rates after laparoscopic-assisted cryoablation: a European Registry for Renal Cryoablation (EuRECA) multi-institutional study.

OBJECTIVE: To assess complication rates and intermediate oncological outcomes of laparoscopic-assisted cryoablation (LCA) in patients with small renal masses (SRMs). PATIENTS AND METHODS: A retrospective review of 808 patients treated with LCA for T1a SRMs from 2005 to 2015 at eight European institutions. Complications were analysed according to the Clavien-Dindo classification. Kaplan-Meier analyses were used to estimate 5- and 10-year disease-free survival (DFS) and overall survival (OS). RESULTS: The median [interquartile (IQR)] age was 67 (58-74) years. The median (IQR) tumour size was 25 (19-30) mm. The transperitoneal approach was used in 77.7% of the patients. The median postoperative hospital stay was 2 days. In all, 514 patients with a biopsy-confirmed renal cell carcinoma (RCC) were available for survival analyses. The median (IQR) follow-up for the RCC-cohort was 36 (14-56) months. A total of 32 patients (6.2%) were diagnosed with treatment failure. The 5-/10-year DFS was 90.4%/80.0% and 5-/10-year OS was 83.2%/64.4%, respectively. A total of 134 postoperative complications (16.6%) were reported, with severe complications (grade ≥III) in 26 patients (3.2%). An American Society of Anesthesiologists score of 3 was associated with an increased risk of overall complications (odds ratio 2.85, 95% confidence interval 1.32-6.20; P = 0.005). CONCLUSIONS: This large series of LCA demonstrates satisfactory long-term oncological outcomes for SRMs. However, although LCA is considered a minimally invasive procedure, risk of complications should be considered when counselling patients.

Impact of stage migration and practice changes on high-risk prostate cancer: results from patients treated with radical prostatectomy over the last two decades.

OBJECTIVE: To evaluate the impact of year of surgery on clinical, pathological and oncological outcomes of patients with high-risk prostate cancer. PATIENTS AND METHODS: We evaluated 1 033 patients with clinically high-risk prostate cancer, defined as the presence of at least one of the following risk factors: preoperative prostate-specific antigen (PSA) level >20 ng/mL, and/or clinical stage ≥T3, and/or biopsy Gleason score ≥8. Patients were treated between 1990 and 2013 at a single institution. The year-by-year trends in clinical and pathological characteristics were examined. Multivariable Cox regression analysis was used to test the relationship between year of surgery and oncological outcomes. RESULTS: We observed a decrease over time in the proportion of patients with high-risk disease (preoperative PSA >20 ng/mL or clinical stage cT3). A trend in the opposite direction was seen for biopsy Gleason score ≥8 tumours. We observed a considerable increase in the median number of lymph nodes removed, which was associated with an increased rate of lymph node invasion (LNI). On multivariable Cox regression analysis, year of surgery was associated with a reduced risk of biochemical recurrence (hazard ratio [HR] per 5-year interval 0.90, 95% confidence interval [CI] 0.84-0.96; P = 0.01) and distant metastasis (HR per 5-year interval 0.91, 95% CI 0.83-0.99; P = 0.039), after adjusting for age, preoperative PSA, pathological stage, LNI, surgical margin status, and pathological Gleason score. CONCLUSIONS: In this single-centre study, an increased diagnosis of localized and less extensive high-grade prostate cancer was observed over the last two decades. Patients with high-risk disease who were selected for radical prostatectomy showed better cancer control over time. Better definitions of what constitutes high-risk prostate cancer among contemporary patients are needed.

Active surveillance for low-risk non-muscle-invasive bladder cancer: mid-term results from the Bladder cancer Italian Active Surveillance (BIAS) project.

OBJECTIVE: To report the oncological safety and the risk of progression for patients with non-muscle-invasive bladder cancer (NMIBC) included in an active surveillance (AS) programme after the diagnosis of recurrence. PATIENTS AND METHODS: This is a prospective study enrolling patients with history of pathologically confirmed low grade pTa-pT1a NMIBC and diagnosed with a tumour recurrence. Inclusion criteria consisted of negative urine cytology, presence of ≤5 lesions with a diameter of ≤10 mm, absence of carcinoma in situ (CIS) or persistent gross haematuria. The primary outcome of interest was adherence to AS. Need to proceed with treatment was defined as progression in number/dimension/positive cytology/symptoms (gross haematuria persistent) or any further intervention (resection or electro-fulguration). Finally, we assessed the up-grading and up-staging when transurethral resection of bladder tumour was performed. RESULTS: The study population consisted of 55 patients with a previous diagnosis of NMIBC (70 AS events) prospectively recruited since 2008. The mean patient age was 69.8 years. The median follow-up was 53 months. The median time patients remained under AS was 12.5 months. There was disease progression in 28 patients (51%). No patient progressed to muscle-invasive disease. In all, 15 patients (27.3%) had an increase in the number and/or size of the tumour, nine (16.4%) had haematuria, and four (7.3%) had a positive cytology. Only five (9%) patients in the whole series progressed to a high-grade tumour (Grade 3) or presented with associated CIS. The overall adherence to the follow-up schedule was 95%. CONCLUSION: Our data show that an AS protocol for NMIBC could be a reasonable option in a select group of patients with small, recurrent cancers.

Endorectal multiparametric 3-tesla magnetic resonance imaging associated with systematic cognitive biopsies does not increase prostate cancer detection rate: a randomized prospective trial.

PURPOSE: To investigate prostate cancer (PC) detection rate, employing endorectal multiparametric 3-tesla magnetic resonance imaging (MRI) driving subsequent cognitive systematic prostatic biopsy (CSPB) versus a homogenous group of patients who did not undergo endorectal MRI. MATERIALS AND METHODS: A series of patients with a first negative biopsy were enrolled in the study. Patients were randomized into two groups: Group A: patients underwent MRI and subsequent CSPB; Group B: patients that did not undergo MRI. Each patient underwent a 13-core sampling. Patients from Group A had four cores more for each MRI suspected lesion. The cancer detection rate was calculated for each group with regard to possible matches or mismatches between MRI evidence and pathological reports. RESULTS: Two hundred consecutive patients were investigated. Fifty out of 200 (25 %) patients had a diagnosis of PC, 24 in Group A and 26 in Group B. In Group A, 67 patients (67 %) were positive for suspected lesions at the MRI. The mismatch between MRI findings and the CSPB outcome was 61 % with an MRI-driven detection rate of 15 %. Group B detection rate was 26 % with no significant differences versus Group A (P = NS). Patient discomfort was higher in Group A (82 %). The accuracy of CSPB was 41 % with a positive predictive value of 22.3 %. This rate is lower in high-grade cancers (11.9 %). The cost-effectiveness was higher in Group A. CONCLUSIONS: Prostate cancer detection rate does not improve by CSPB. The accuracy of CSPB was lower in high-grade PC, and a higher cost was found with CSPB.

An observational study of the use of beclomethasone dipropionate suppositories in the treatment of lower urinary tract inflammation in men.

BACKGROUND: Nonbacterial prostatitis, together with chronic pelvic pain syndrome, accounts for 90-95 % of prostatitis cases. Anti-inflammatory medications are commonly used to reduce storage/inflammatory symptoms that can deteriorate quality of life. The purpose of this study was to observe the efficacy and safety of beclomethasone dipropionate rectal suppositories (Topster®) in inflammations of the lower urinary tract in men. METHODS: Patients underwent diagnostic and therapeutic protocols according to current evidence-based practice. Efficacy assessments: voiding parameters, perineal pain, International Prostate Symptom Score (IPSS), digital rectal examination (DRE). Adverse events and patient compliance were recorded throughout the study. RESULTS: One hundred eighty patients were enrolled, mean age 52 ± 14.97. Most frequent diagnosis: nonbacterial prostatitis (85 %). All patients completed visits 1 and 2. All patients were treated with beclomethasone dipropionate (BDP) suppositories, 136/180 also with Serenoa repens (SR) extract. Antibiotics were rarely required. 162/180 patients presented clinically significant improvements and terminated treatment. Mean change vs. baseline in voiding frequency: -3.55 ± 2.70 n/day in patients taking only BDP and -3.68 ± 2.81 n/day in those taking both BDP and SR (P<.0001 in both groups). Uroflowmetry improved significantly; change from baseline 3.26 ± 5.35 ml/s in BDP only group and 5.61 ± 7.32 ml/s in BDP + SR group (P = 0.0002 for BDP, P<.0001 for BDP + SR). Urine stream normal in 35 % of patients at visit 1 and 57.22 % of patients at visit 2. Mean change in perineal pain, on 0-10 VAS, -0.66 ± 2.24 for BDP only group (P = 0.0699) and -1.37 ± 2.40 for BDP + SR group (P<.0001). IPSS increased at visit 2. No adverse events were reported. For all parameters, none of the comparisons between groups was found to be statistically significant. CONCLUSION: This study confirmed the drug's good safety profile. We also observed an improvement in the main storage symptoms and clinical findings associated with lower urinary tract inflammation in patients treated with beclomethasone dipropionate suppositories.

Application and Uses of Electronic Noses for Clinical Diagnosis on Urine Samples: A Review.

The electronic nose is able to provide useful information through the analysis of the volatile organic compounds in body fluids, such as exhaled breath, urine and blood. This paper focuses on the review of electronic nose studies and applications in the specific field of medical diagnostics based on the analysis of the gaseous headspace of human urine, in order to provide a broad overview of the state of the art and thus enhance future developments in this field. The research in this field is rather recent and still in progress, and there are several aspects that need to be investigated more into depth, not only to develop and improve specific electronic noses for different diseases, but also with the aim to discover and analyse the connections between specific diseases and the body fluids odour. Further research is needed to improve the results obtained up to now; the development of new sensors and data processing methods should lead to greater diagnostic accuracy thus making the electronic nose an effective tool for early detection of different kinds of diseases, ranging from infections to tumours or exposure to toxic agents.

Clinical performance of serum isoform [-2]proPSA (p2PSA), and its derivatives %p2PSA and the Prostate Health Index, in men aged <60 years: results from a multicentric European study.

OBJECTIVES: To test the hypothesis that [-2]proPSA (p2PSA) and its derivatives are more accurate than total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA) and fPSA as percentage of tPSA (%fPSA) in detecting prostate cancer (PCa) in men aged <60 years. PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the PRO- PSA Multicentric European Study (PROMEtheuS) project. The primary outcomes were measures of sensibility, specificity and accuracy of serum p2PSA, p2PSA as percentage of fPSA (%p2PSA) and Beckman Coulter prostate health index (PHI) in men aged <60 years who had undergone a prostate biopsy. The potential reduction in the number of unnecessary biopsies and the characteristics of the potentially missed PCa cases were reported as secondary outcomes. Multivariate logistic regression models were complemented by predictive accuracy and decision-curve analyses. RESULTS: Of the 1036 patients enrolled in the PROMEtheus project, 238 (22.9%) were aged < 60 years. PCa was found in 67 subjects (28.1%); p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001) among these subjects, while no differences were found in tPSA, fPSA and %fPSA values. On univariate analysis, %p2PSA (area under the curve [AUC]: 0.704) and PHI (AUC: 0.7) were the most accurate predictors, and these significantly outperformed tPSA (AUC: 0.549), fPSA (AUC: 0.511) and %fPSA (AUC: 0.557) in the prediction of PCa at biopsy (P ≤ 0.001). In multivariate logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariate models by 6.3 and 7.6%, respectively (P ≤ 0.05). CONCLUSION: PHI and %p2PSA are more accurate than the reference standard tests in predicting PCa in young men.