Publications by authors named "Giorgio Guazzoni"

208 Publications

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

World J Urol 2021 Apr 3. Epub 2021 Apr 3.

Department of Urology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy.

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.
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http://dx.doi.org/10.1007/s00345-021-03685-7DOI Listing
April 2021

Impact of chronic exposure to 5-alpha reductase inhibitors on the risk of hospitalization for COVID-19: a case-control study in male population from two COVID-19 regional centers of Lombardy (Italy).

Minerva Urol Nefrol 2021 Jan 13. Epub 2021 Jan 13.

Humanitas Clinical and Research Center - IRCCS -, Rozzano, Milano, Italy.

Background: There are sex differences in vulnerability to Coronavirus disease 2019 (COVID-19). The coronavirus S protein mediates viral entry into target cells employing the host cellular serine protease TMPRSS2 for S-protein priming. The TMPRSS2 gene expression is responsive to androgen stimulation and it could partially explain sex differences. We hypothesized that men chronically exposed to 5-alpha reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) have a lower risk of hospitalization for COVID-19.

Methods: This is a population-based case-control study on consecutive patients positive for SARS-CoV-2 virus who required hospitalization for COVID-19 (cases), age-matched to beneficiaries of the Lombardy Regional Health Service (controls). Data were collected by two high-volume COVID-19 regional centers of Lombardy (Italy). The primary outcome was to compare the prevalence of patients chronically exposed to 5ARIs, who required hospitalization for COVID-19, with the one of controls.

Results: Overall, 943 males were enrolled; 45 (4.77%) were exposed to 5ARI. COVID-19 patients aged >55 years under 5ARI treatment were significantly less than expected on the basis of the prevalence of 5ARI treatment among age-matched controls (5.57 vs. 8.14%; p=0.0083, 95%CI=0.75-3.97%). This disproportion was higher for men aged >65 (7.14 vs. 12.31%; p=0.0001, 95%CI=2.83-6.97%). Eighteen 5ARIs-patients died; the mean age of men who died was higher than those who did not: 75.98±9.29 vs. 64.78±13.57 (p<0.001). Cox-regression and multivariable models did not show correlation between 5ARIs exposure and protection against intensive care unit admission/death.

Conclusions: Men exposed to 5ARIs might be less vulnerable to severe COVID-19, supporting its use in disease prophylaxis.
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http://dx.doi.org/10.23736/S0393-2249.20.04081-3DOI Listing
January 2021

Multiparametric magnetic resonance imaging and clinical variables: Which is the best combination to predict reclassification in active surveillance patients?

Prostate Int 2020 Dec 28;8(4):167-172. Epub 2020 May 28.

Department of Urology, ASST Papa Giovanni XXIII, Bergamo, Italy.

Introduction & Objectives: We tested the role of multiparametric magnetic resonance imaging (mpMRI) in disease reclassification and whether the combination of mpMRI and clinicopathological variables could represent the most accurate approach to predict the risk of reclassification during active surveillance.

Materials & Methods: Three-hundred eighty-nine patients (pts) underwent mpMRI and subsequent confirmatory or follow-up biopsy according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol. Pts with negative (-) mpMRI underwent systematic random biopsy. Pts with positive (+) mpMRI [Prostate Imaging Reporting and Data System, version 2 (PI-RADS-V2) score ≥3] underwent targeted + systematic random biopsies. Multivariate analyses were used to create three models predicting the probability of reclassification [International Society of Urological Pathology ≥ Grade Group 2 (GG2)]: a basic model including only clinical variables (age, prostate-specific antigen density, and number of positive cores at baseline), an Magnetic resonance imaging (MRI) model including only the PI-RADS score, and a full model including both the previous ones. The predictive accuracy (PA) of each model was quantified using the area under the curve.

Results: mpMRI negative (-) was recorded in 127 (32.6%) pts; mpMRI positive (+) was recorded in 262 pts: 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. At a median follow-up of 12 months, 125 pts (32%) were reclassified to GG2 prostate cancer. The rate of reclassification to GG2 prostate cancer was 17%, 35%, 38%, and 52% for mpMRI (-), PI-RADS 3, 4, and 5, respectively ( < 0.001). The PA was 69% and 64% in the basic and MRI models, respectively. The full model had the best PA of 74%: older age ( = 0.023; Odds ratio (OR) = 1.040), prostate-specific antigen density ( = 0.037; OR = 1.324), number of positive cores at baseline ( = 0.001; OR = 1.441), and PI-RADS 3, 4, and 5 (overall  = 0.001; OR = 2.458, 3.007, and 3.898, respectively) were independent predictors of reclassification.

Conclusions: Disease reclassification increased according to the PI-RADS score increase, at confirmatory or follow-up biopsy. However, a no-negligible rate of reclassification was found also in cases of mpMRI (-). The combination of mpMRI and clinicopathological variables still represents the most accurate approach to pts on active surveillance.
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http://dx.doi.org/10.1016/j.prnil.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767935PMC
December 2020

Mitochondrial metabolic reprogramming controls the induction of immunogenic cell death and efficacy of chemotherapy in bladder cancer.

Sci Transl Med 2021 Jan;13(575)

Humanitas Clinical and Research Center-IRCCS, via Manzoni 56, 20089 Rozzano (Milan), Italy.

Although chemotherapeutic agents have been used for decades, the mechanisms of action, mechanisms of resistance, and the best treatment schedule remain elusive. Mitomycin C (MMC) is the gold standard treatment for non-muscle-invasive bladder cancer (NMIBC). However, it is effective only in a subset of patients, suggesting that, aside from cytotoxicity, other mechanisms could be involved in mediating the success of the treatment. Here, we showed that MMC promotes immunogenic cell death (ICD) and in vivo tumor protection. MMC-induced ICD relied on metabolic reprogramming of tumor cells toward increased oxidative phosphorylation. This favored increased mitochondrial permeability leading to the cytoplasmic release of mitochondrial DNA, which activated the inflammasome for efficient IL-1β (interleukin-1β) secretion that promoted dendritic cell maturation. Resistance to ICD was associated with mitochondrial dysfunction related to low abundance of complex I of the respiratory chain. Analysis of complex I in patient tumors indicated that low abundance of this mitochondrial complex was associated with recurrence incidence after chemotherapy in patients with NMIBC. The identification of mitochondria-mediated ICD as a mechanism of action of MMC offers opportunities to optimize bladder cancer management and provides potential markers of treatment efficacy that could be used for patient stratification.
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http://dx.doi.org/10.1126/scitranslmed.aba6110DOI Listing
January 2021

How Can the COVID-19 Pandemic Lead to Positive Changes in Urology Residency?

Front Surg 2020 24;7:563006. Epub 2020 Nov 24.

Department of Urology, IEO European Institute of Oncology IRCCS, Milan, Italy.

The COVID-19 outbreak, in a few weeks, overloaded Italian hospitals, and the majority of medical procedures were postponed. During the pandemic, with hospital reorganization, clinical and learning activities performed by residents suffered a forced remodulation. The objective of this study is to investigate how urology training in Italy has been affected during the COVID-19 era. In this multi-academic study, we compared residents' training during the highest outbreak level with their previous activity. Overall 387 (67.1%) of the 577 Italian Urology residents participated in a 72-h anonymous online survey with 36 items sent via email. The main outcomes were clinical/surgical activities, social distancing, distance learning, and telemedicine. Clinical and learning activity was significantly reduced for the overall group, and after categorizing residents as those working only in COVID hospitals, both "junior" and "senior" residents, and those working in any of three geographical areas created (Italian regions were clustered in three major zones according to the prevalence of COVID-19). A significant decrease in outpatient activity, invasive diagnostic procedures, and endoscopic and major surgeries was reported. Through multivariate analysis, the specific year of residency has been found to be an independent predictor for all response modification. Being in zone 3 and zone 2 and having "senior" resident status were independent predictors associated with a lower reduction of the clinical and learning activity. Working in a COVID hospital and having "senior" resident status were independent predictors associated with higher reduction of the outpatient activity. Working in zone 3 and having "senior" resident status were independent predictors of lower and higher outpatient surgical activity, respectively. Working in a COVID hospital was an independent predictor associated with robotic surgical activity. The majority of residents reported that distance teaching and multidisciplinary virtual meetings are still not used, and 44.8% reported that their relationships with colleagues decreased. The COVID-19 pandemic presents an unprecedented challenge, including changes in the training and education of urology residents. The COVID era can offer an opportunity to balance and implement innovative solutions that can bridge the educational gap and can be part of future urology training.
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http://dx.doi.org/10.3389/fsurg.2020.563006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732553PMC
November 2020

Midterm follow-up (3 years) confirms and extends short-term results of intravesical gemcitabine as bladder-preserving treatment for non-muscle-invasive bladder cancer after BCG failure.

Urol Oncol 2021 03 23;39(3):195.e7-195.e13. Epub 2020 Oct 23.

Department of Urology, Humanitas Clinical and Research Center - IRCCS, Milan, Italy. Electronic address:

Background: There is a high demand for bladder sparing therapies in patients who do not respond to bacillus Calmette-Guérin (BCG).

Objective: To report the mid-term results of intravesical gemcitabine in non-muscle-invasive bladder cancer (NMIBC) patients, who failed BCG and who were unwilling to undergo radical cystectomy (RC).

Material & Methods: This is an extended confirmatory open-label, single-arm study, which enrolled consecutive patients who failed BCG or were BCG intolerant and unwilling to undergo the RC (histologically confirmed Tis (CIS), T1 high grade or multifocal Ta high grade of the urinary bladder). Intravesical gemcitabine was administered once a week for 6 consecutive weeks and once a month for 12 months. The primary outcome was disease-free survival (DFS) defined as the lack of tumor on cystoscopy and negative urine cytology. The secondary endpoint was safety, defined according a grading of side effects. overall survival, progression-free survival and DFS were described with Kaplan-Meier method at 12, 24, and 36 months.

Results And Limitations: Overall 46 patients were enrolled. The mean follow-up was 40 months. The DFS was 69.05% at the end of induction phase and 32.69% at 36 months. The progression-free survival at 36 months was 65.38%. The overall survival and cancer specific survival were 66.97% (95% confidence interval 47.25%-80.70%) and 78.71% (95% confidence interval 59.16%-89.66%), respectively. There was no life-threatening event or treatment related death (grade 4 or 5). The most common mild and moderate adverse events reported were urinary symptoms (lower urinary tract symptoms) and fatigue (G1-G2).

Conclusion: Intravesical gemcitabine seemed to represent a valid and safe alternative at 3 years follow-up for patients who failed BCG and were unwilling to undergo RC.
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http://dx.doi.org/10.1016/j.urolonc.2020.09.017DOI Listing
March 2021

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

World J Urol 2020 Oct 28. Epub 2020 Oct 28.

Department of Urology, Humanitas Mater Domini, Via Gerenzano 2, 21053, Varese, Castellanza, Italy.

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.
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http://dx.doi.org/10.1007/s00345-020-03500-9DOI Listing
October 2020

Diagnostic Accuracy of Microultrasound in Patients with a Suspicion of Prostate Cancer at Magnetic Resonance Imaging: A Single-institutional Prospective Study.

Eur Urol Focus 2020 Oct 14. Epub 2020 Oct 14.

Department of Urology, Humanitas Clinical and Research Center, Rozzano, Italy.

Background: Multiparametric magnetic resonance imaging (MRI) represents the gold standard for the diagnosis of clinically significant prostate cancer (csPCa). The search for alternative diagnostic techniques is still ongoing.

Objective: To determine the accuracy of microultrasound (microUS) for the diagnosis of csPCa within prospectively collected cohort of patients with a suspicion of prostate cancer (PCa) according to MRI.

Design, Setting, And Participants: A total of 320 consecutive patients with at least one Prostate Imaging Reporting and Data System (PIRADS) ≥3 lesion according to MRI were prospectively enrolled.

Intervention: All patients received microUS before prostate biopsy using the ExactVu system; the Prostate Risk Identification using microUS (PRI-MUS) protocol was used to identify targets. The urologists were blinded to MRI results until after the microUS targeting was completed. All patients received both targeted (based on either microUS or MRI findings) and randomized biopsies.

Outcome Measurements And Statistical Analysis: The sensitivity and specificity of microUS to determine the presence of csPCa (defined as at least one core with a Gleason score ≥7 PCa) were determined. Multivariable logistic regression analysis was fitted to determine the predictors of csPCa.

Results And Limitations: Clinically significant PCa was diagnosed in 116 (36.3%) patients. The sensitivity and negative predictive value of microUS for csPCa diagnosis were 89.7% and 81.5%, while specificity and positive predictive value were 26.0% and 40.8%, respectively. A combination of microUS-targeted and randomized biopsies would allow diagnosing the same proportion of csPCa as that diagnosed by an approach combining MRI-targeted and randomized biopsies (n = 113; 97.4%), with only three (2.6%) csPCa cases diagnosed by a microUS-targeted and three (2.6%) by an MRI-targeted approach. In a logistic regression model, an increasing PRI-MUS score was an independent predictor of csPCa (p ≤ 0.005). The main limitation of the current study is represented by the fact that all patients had suspicious MRI.

Conclusions: Microultrasound is a promising imaging modality for targeted prostate biopsies. Our results suggest that a microUS-based biopsy strategy may be capable of diagnosing the great majority of cancers, while missing only few patients with csPCa.

Patient Summary: According to our results, microultrasound (microUS) may represent an effective diagnostic alternative to magnetic resonance imaging for the diagnosis of clinically significant prostate cancer, providing high sensitivity and a high negative predictive value. Further randomized studies are needed to confirm the potential role of microUS in the diagnostic pathway of patients with a suspicion of prostate cancer.
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http://dx.doi.org/10.1016/j.euf.2020.09.013DOI Listing
October 2020

Stereotactic Body Radiation Therapy for Intermediate-risk Prostate Cancer With VMAT and Real-time Electromagnetic Tracking: A Phase II Study.

Am J Clin Oncol 2020 09;43(9):628-635

Departments of Radiotherapy and Radiosurgery.

Objectives: Stereotactic body radiation treatment represents an intriguing therapeutic option for patients with early-stage prostate cancer. In this phase II study, stereotactic body radiation treatment was delivered by volumetric modulated arc therapy with flattening filter free beams and was gated using real-time electromagnetic transponder system to maximize precision of radiotherapy and, potentially, to reduce toxicities.

Materials And Methods: Patients affected by histologically proven prostate adenocarcinoma and National Comprehensive Cancer Network (NCCN) intermediate class of risk were enrolled in this phase II study. Beacon transponders were positioned transrectally within the prostate parenchyma 7 to 10 days before simulation computed tomography scan. The radiotherapy schedule was 38 Gy in 4 fractions delivered every other day. Toxicity assessment was performed according to Common Terminology Criteria for Adverse Events (CTCAE), v4.0.

Results: Thirty-six patients were enrolled in this study. Median initial prostate-specific antigen was 7.0 ng/mL (range: 2.3 to 14.0 ng/mL). Median nadir-prostate-specific antigen after treatment was 0.2 ng/mL (range: 0.006 to 4.8 ng/mL). A genitourinary acute toxicity was observed in 21 patients (dysuria grade [G] 1: 41.7%, G2: 16.7%). Gastrointestinal acute toxicity was found in 9 patients (proctitis G1: 19.4%, G2: 5.6%). Late toxicity was mild (genitourinary toxicity G1: 30.6%; G2: 8.3%; gastrointestinal toxicity G1: 13.9%; G2: 19.4%). At a median follow-up time of 41 months, 3 biochemical recurrences were observed (2 local recurrences, 1 distant metastasis). Three-year biochemical recurrence-free survival was 89.8% (International Society of Urologic Pathology Grade Group 2: 100%, Grade Group 3: 77.1%, P=0.042).

Conclusion: Ultrahypofractionated radiotherapy, delivered with flattening filter free-volumetric modulated arc therapy and gated by electromagnetic transponders, is a valid option for intermediate-risk prostate cancer.
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http://dx.doi.org/10.1097/COC.0000000000000721DOI Listing
September 2020

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

J Urol 2021 Jan 28;205(1):86-93. Epub 2020 Aug 28.

Humanitas Clinical and Research Center, Rozzano, Milan, Italy.

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 (p=0.04) and (p=0.03), and decreased (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 (p=0.014), whereas midstream urines were enriched in (p <0.0001), (p <0.0001), (p=0.038) and (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.
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http://dx.doi.org/10.1097/JU.0000000000001336DOI Listing
January 2021

The Use of Multiparametric Magnetic Resonance Imaging for Follow-up of Patients Included in Active Surveillance Protocol. Can PSA Density Discriminate Patients at Different Risk of Reclassification?

Clin Genitourin Cancer 2020 Dec 4;18(6):e698-e704. Epub 2020 May 4.

Department of Urology, ASST Papa Giovanni XXIII, Bergamo, Italy; University of Milano-Bicocca, School of Medicine and Surgery, Monza, Italy.

Introduction: The objective of this study was to test Prostate Imaging Reporting and Data System (PI-RADS) classification on multiparametric magnetic resonance imaging (mpMRI) and MRI-derived prostate-specific antigen density (PSAD) in predicting the risk of reclassification in men in active surveillance (AS), who underwent confirmatory or per-protocol follow-up biopsy.

Materials And Methods: Three hundred eighty-nine patients in AS underwent mpMRI before confirmatory or follow-up biopsy. Patients with negative (-) mpMRI underwent systematic random biopsy. Patients with positive (+) mpMRI underwent targeted fusion prostate biopsies + systematic random biopsies. Different PSAD cutoff values were tested (< 0.10, 0.10-0.20, ≥ 0.20). Multivariable analyses assessed the risk of reclassification, defined as clinically significant prostate cancer of grade group 2 or more, during follow-up according to PSAD, after adjusting for covariates.

Results: One hundred twenty-seven (32.6%) patients had mpMRI(-); 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. The rate of reclassification to grade group 2 PCa was 16%, 22%, 31%, and 39% for mpMRI(-) and PI-RADS 3, 4, and 5, respectively, in case of PSAD < 0.10 ng/mL; 16%, 25%, 36%, and 44%, in case of PSAD 0.10 to 0.19 ng/mL; and 25%, 42%, 55%, and 67% in case of PSAD ≥ 0.20 ng/mL. PSAD ≥ 0.20 ng/mL (odds ratio [OR], 2.45; P = .007), PI-RADS 3 (OR, 2.47; P = .013), PI-RADS 4 (OR, 2.94; P < .001), and PI-RADS 5 (OR, 3.41; P = .004) were associated with a higher risk of reclassification.

Conclusion: PSAD ≥ 0.20 ng/mL may improve predictive accuracy of mpMRI results for reclassification of patients in AS, whereas PSAD < 0.10 ng/mL may help selection of patients at lower risk of harboring clinically significant prostate cancer. However, the risk of reclassification is not negligible at any PSAD cutoff value, also in the case of mpMRI(-).
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http://dx.doi.org/10.1016/j.clgc.2020.04.006DOI Listing
December 2020

Prospective Evaluation of Ga-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography in Primary Prostate Cancer Diagnosis.

Eur Urol Focus 2020 Apr 17. Epub 2020 Apr 17.

Urology Department, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.

Background: Positron emission tomography (PET)/computed tomography (CT) with Ga-labeled prostate-specific membrane antigen ligand (Ga-PSMA) may represent the most promising alternative to multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) diagnosis.

Objective: To test the diagnostic performance of Ga-PSMA PET/CT in this clinical context.

Design, Setting, And Participants: From January 2017 to December 2018 we prospectively enrolled 97 patients with persistently elevated prostate-specific antigen and/or Prostate Health Index score, negative digital rectal examination, and previous negative biopsy. We also included patients with either negative mpMRI or contraindications to or positive mpMRI but previous negative biopsy.

Intervention: Patients underwent 68Ga-PSMA PET/CT with additional pelvic reconstruction.

Outcome Measurements And Statistical Analysis: The primary endpoint of the study was the diagnostic performance of Ga-PSMA PET/CT in detecting malignant lesions and clinically significant PCa (Gleason score [GS] ≥7).

Results And Limitations: Ga-PSMA PET/transrectal ultrasound fusion biopsy was performed in 64 of 97 patients (66%) for 114 regions of interest (ROIs). Forty patients (41%) had already undergone mpMRI with either a negative result for PCa (n = 15; 22 ROIs) or a positive mpMRI result but a previous negative biopsy. According to pathology, 23 patients (36%) had evidence of PCa: eight (16 ROIs) with GS 6, 13 (21 ROIs) with GS 7 (3 + 4 or 4 + 3), one (2 ROIs) with GS 8, and one (2 ROIs) with GS 10. Clinically significant PCa was identified in four patients with previous negative mpMRI (25%). PET/CT demonstrated PCa in seven patients (14 ROIs) with previous positive mpMRI and negative biopsy. The median maximum standardized uptake value (SUVmax) and median SUV ratio were significantly higher for PCa lesions than for benign lesions (p <  0.001). Optimal cutoff points obtained for SUVmax (>5.4) and SUV ratio (>2.2) could identify clinically significant PCa with accuracy of 81% and 90%, respectively.

Conclusions: In our cohort of patients with high suspicion of cancer,Ga-PSMA PET/CT was capable of detecting malignancy and accurately identifying clinically relevant PCa.

Patient Summary: Positron emission tomography/computed tomography with a Ga-labeled ligand for prostate-specific membrane antigen is capable of detecting prostate cancer in patients with a high suspicion of cancer and a previous negative biopsy.
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http://dx.doi.org/10.1016/j.euf.2020.03.004DOI Listing
April 2020

Type 2 diabetes mellitus predicts worse outcomes in patients with high-grade T1 bladder cancer receiving bacillus Calmette-Guérin after transurethral resection of the bladder tumor.

Urol Oncol 2020 05 12;38(5):459-464. Epub 2020 Mar 12.

Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy.

Objectives: The aim of this multicenter study was to investigate the prognostic role of type 2 diabetes mellitus (T2DM) comorbidity in a large multi-institutional cohort of patients with primary T1HG/G3 non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB).

Materials And Methods: A total of 1,172 patients with primary T1 HG/G3 who had NMIBC on re-TURB and who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance were included. Endpoints were recurrence-free survival and progression-free survival.

Results: A total of 231 (19.7%) of patients had T2DM prior to TURB. Five-year recurrence-free survival estimates were 12.5% in patients with T2DM compared to 36% in patients without T2DM, P < 0.0001. Five-year PFS estimates were 60.5% in patients with T2DM compared to 70.2% in patients without T2DM, P = 0.003. T2DM was independently associated with disease recurrence (hazard ratio = 1.41; 95% confidence interval = 1.20-1.66, P < 0.001) and progression (hazard ratio = 1.27; 95% confidence interval = 0.99-1.63, P < 0.001), after adjusting for other known predictive factors such as tumor size, multifocality, T1G3 on re-TURB, body mass index, lymphovascular invasion, and neutrophil-to-lymphocytes ratio.

Conclusions: Given the potential implications for management, prospective validation of this finding along with translational studies designed to investigate the underlying biology of such an association are warranted.
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http://dx.doi.org/10.1016/j.urolonc.2020.02.016DOI Listing
May 2020

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.

World J Urol 2020 Sep 5;38(9):2215-2220. Epub 2019 Nov 5.

Department of Urology, Istituto Clinico Humanitas IRCCS-Clinical and Research Hospital, via Manzoni 56, 20089, Milan, Rozzano, Italy.

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.
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http://dx.doi.org/10.1007/s00345-019-03002-3DOI Listing
September 2020

Comparison of the Diagnostic Accuracy of Micro-ultrasound and Magnetic Resonance Imaging/Ultrasound Fusion Targeted Biopsies for the Diagnosis of Clinically Significant Prostate Cancer.

Eur Urol Oncol 2019 05 25;2(3):329-332. Epub 2018 Oct 25.

Department of Urology, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy.

Multiparametric magnetic resonance imaging (mpMRI) and MRI/ultrasound (US) fusion targeted biopsies are an increasingly popular alternative to randomized biopsies, but adoption of this technique has been limited owing to its additional costs and complexity. High-resolution micro-ultrasound (micro-US) is a real-time US-based imaging modality that allows real-time targeted prostate biopsies using the Prostate Risk Identification Using Micro-Ultrasound risk identification protocol. We compared the diagnostic accuracy of micro-US targeted biopsies (index test) and MRI/US fusion targeted biopsies (reference standard test) in detecting clinically significant prostate cancer (csPC), defined as Gleason ≥7 disease, in a prospectively collected cohort of 104 patients with suspected PC defined according to prostate-specific antigen, digital rectal examination, and the presence of at least one Prostate Imaging-Reporting and Data System ≥3 lesion at mpMRI. PC was diagnosed in 56 patients (54%) and csPC in 35 (34%). Micro-US sensitivity for csPC detection was 94%, with 33/35 csPC cases correctly identified. The negative predictive value was 90%, while the positive predictive value was 40% and the specificity was 28%. Of the 61 targeted zones concordant between micro-US and mpMRI, 24 were csPC. Discordant targeted lesions led to csPC discovery by micro-US in three cases and mpMRI in four cases. Both techniques missed one case for which csPC was diagnosed by systematic biopsies only. PATIENT SUMMARY: According to the results of our preliminary trial, micro-ultrasound may provide additional information regarding the presence or absence of clinically significant prostate cancer (PC) in patients with suspected PC. Further studies are warranted to investigate how this new imaging modality can best be leveraged within the PC diagnostic pathway.
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http://dx.doi.org/10.1016/j.euo.2018.10.001DOI Listing
May 2019

Pathological Outcomes for Patients Who Failed To Remain Under Active Surveillance for Low-risk Non-muscle-invasive Bladder Cancer: Update and Results from the Bladder Cancer Italian Active Surveillance Project.

Eur Urol Oncol 2018 10 5;1(5):437-442. Epub 2018 Jun 5.

Department of Urology, Istituto Clinico Humanitas IRCCS, Clinical and Research Hospital, Rozzano, Italy.

Background: It has been shown that active surveillance (AS) is feasible and effective in a subset of patients with recurrent low-grade (LG) non-muscle-invasive bladder cancer (NMIBC).

Objective: To update a previous preliminary series and investigate pathological outcomes for patients who failed to remain on AS.

Design, Setting, And Participants: Prospective observational cohort study started in February 2008, and currently still active, at a tertiary university hospital, including patients with pathologically confirmed NMIBC who experienced recurrence during follow-up.

Intervention: AS monitoring consisted of cytology and in-office flexible cystoscopy every 3 mo for the first year, and every 6 mo thereafter.

Outcome Measurements And Statistical Analysis: The primary endpoint was pathological results for patients who failed to remain on AS. The secondary outcome was an update of clinical results from our previous series. Data were complemented by descriptive statistical analysis and univariable and multivariable proportional hazards Cox regression.

Results And Limitations: Overall, 167 patients were included. Of 181 AS events, 61 (33.7%) were deemed to require treatment because of positive cytology (n=10), gross haematuria (n=11), and increases in the tumour number (n=15), or size (n=17), or both (n=8). The median time on AS was 12 mo (interquartile range 4-26). Pathological specimens from AS failures did not show any malignancy in 20 cases. Histopathology identified urothelial hyperplasia and oedema, submucosal vascular ectasia, mucosal erosion, polypoid cystitis, von Brunn nest hyperplasia, and squamous metaplasia. The time from first transurethral resection to AS start was inversely associated with recurrence-free survival (hazard ratio 0.97, 95% confidence interval 0.96-1.00; p=0.024). The study lacks statistical subanalyses focusing on patients with failure and negative neoplastic pathological outcomes.

Conclusions: AS might be a reasonable strategy in patients presenting with small LG pTa/pT1a recurrent bladder tumours. Approximately 30% of patients deemed to have AS failure did not harbour any neoplastic lesion, strengthening the role of AS.

Patient Summary: Patients with small low-grade pTa/pT1a recurrent papillary bladder tumours could benefit from an active surveillance protocol with no significant risk of pathological progression to muscle-invasive cancer.
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http://dx.doi.org/10.1016/j.euo.2018.05.006DOI Listing
October 2018

Systemic Inflammatory Markers and Oncologic Outcomes in Patients with High-risk Non-muscle-invasive Urothelial Bladder Cancer.

Eur Urol Oncol 2018 10 13;1(5):403-410. Epub 2018 Jul 13.

Division of Urology, European Institute of Oncology, Milan, Italy.

Background: Serum levels of neutrophils, platelets, and lymphocytes have been recognized as factors related to poor prognosis for many solid tumors, including bladder cancer (BC).

Objective: To evaluate the prognostic role of the combination of the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR) in patients with high-risk non-muscle-invasive urothelial BC (NIMBC).

Design, Setting, And Participants: A total of 1151 NMIBC patients who underwent first transurethral resection of the bladder tumor (TURBT) at 13 academic institutions between January 1, 2002 and December 31, 2012 were included in this analysis. The median follow-up was 48 mo.

Intervention: TURBT with intravesical chemotherapy or immunotherapy.

Outcome Measurements And Statistical Analysis: Multivariable Cox regression analysis was performed to identify factors predictive of recurrence, progression, cancer-specific mortality, and overall mortality. A systemic inflammatory marker (SIM) score was calculated based on cutoffs for NLR, PLR, and LMR.

Results And Limitations: The 48-mo recurrence-free survival was 80.8%, 47.35%, 20.67%, and 17.06% for patients with an SIM score of 0, 1, 2, and 3, respectively (p<0.01, log-rank test) while the corresponding 48-mo progression free-survival was 92.0%, 75.67%, 72.85%, and 63.1% (p<0.01, log-rank test). SIM scores of 1, 2, and 3 were associated with recurrence (hazard ratio [HR] 3.73, 7.06, and 7.88) and progression (HR 3.15, 4.41, and 5.83). Limitations include the lack of external validation and comparison to other clinical risk models.

Conclusions: Patients with high-grade T1 stage NMIBC with high SIM scores have worse oncologic outcomes in terms of recurrence and progression. Further studies should be conducted to stratify patients according to SIM scores to identify individuals who might benefit from early cystectomy.

Patient Summary: In this study, we defined a risk score (the SIM score) based on the measurement of routine systemic inflammatory markers. This score can identify patients with high-grade bladder cancer not invading the muscular layer who are more likely to suffer from tumor recurrence and progression. Therefore, the score could be used to select patients who might benefit from early bladder removal.
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http://dx.doi.org/10.1016/j.euo.2018.06.006DOI Listing
October 2018

Predictive factors for progression of patients with carcinoma in situ of the bladder at long-term follow-up: pure versus non-pure CIS.

Minerva Urol Nefrol 2019 Aug 28;71(4):406-412. Epub 2019 May 28.

Department of Urology, Humanitas Clinic IRCCS, Rozzano, Milan, Italy.

Background: The aim of this study was to identify the predictive factors for progression defined as any event that shifted the management of the disease from a bladder sparing approach, by comparing patients with pure versus non-pure carcinoma in situ (CIS) of the bladder.

Methods: A retrospective analysis was carried out in consecutive patients affected by newly-diagnosed pure CIS and non-pure CIS (excluding cases with concomitant muscle invasive cancer). All patients were enrolled a in our institution from 1998 to 2010. Data was prospectively collected. Main end point was progression-free survival.

Results: Overall, 149 patients with CIS were identified for the analysis. A total of 98 patients had pure CIS (66%). Median follow-up was 103 months (range: 40-206 months). Progression occurred in 29 patients (19%). A total of 30 patients died during the follow-up (20%). In 13 cases (9%), the death was cancer specific. Progression-free survival estimate was 181 months (95% CI: 169-193 months) and 154 months (95% CI: 133-176 months) respectively for pure and non-pure CIS population (P=0.03). Among examined variables (age, gender, symptoms, smoking habit, ASA score, number of bacillus Calmette-Guérin [BCG] instillations), multivariate analysis disclosed that only CIS type was an independent predictor of progression (P=0.03) with a relative risk of 0.37 in favor of pure CIS.

Conclusions: Pure and non-pure CIS are efficiently treated by BCG therapy combined with trans-urethral resection and/or radical cystectomy, with relatively low rate of progression. CIS type was the only significant predictor of progression.
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http://dx.doi.org/10.23736/S0393-2249.19.03254-5DOI Listing
August 2019

Is Robot-assisted Surgery Contraindicated in the Case of Partial Nephrectomy for Complex Tumours or Relevant Comorbidities? A Comparative Analysis of Morbidity, Renal Function, and Oncologic Outcomes.

Eur Urol Oncol 2018 05 15;1(1):61-68. Epub 2018 May 15.

ORSI Academy, Melle, Belgium; Department of Urology, Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium.

Background: Available comparisons between open partial nephrectomy (OPN) and robot-assisted partial nephrectomy (RAPN) are scarce, incomplete, and affected by non-negligible risk of bias.

Objective: To compare RAPN and OPN.

Design, Setting, And Participants: This was an observational study of 472 patients diagnosed with a cT1-2cN0cM0 renal mass and treated with RAPN or OPN assessed in two prospective institutional databases.

Outcome Measurements And Statistical Analysis: The study outcomes were morbidity, complications, warm ischaemia time, renal function, positive surgical margins, and oncologic outcomes. Propensity score matching for age at diagnosis, gender, Charlson comorbidity index, preoperative estimated glomerular filtration rate (eGFR), single kidney status, tumour size and side, total PADUA score, any individual PADUA score item, and year of surgery was used to account for baseline confounders. The effect of surgical approach was estimated using linear and logistic regressions for continuous and categorical outcomes. An interaction test was used for subgroup analyses.

Results And Limitations: Relative to OPN, RAPN was associated with lower rates for overall (21% vs 36%; p<0.0001) and major (3% vs 9%; p=0.03) complications. This benefit was consistent in patients with high PADUA scores, high CCI, large tumours, and low preoperative eGFR (all p>0.05, interaction test). No difference between the groups was observed for warm ischaemia time, postoperative and 1-yr eGFR, and positive surgical margins (all p>0.05). After median follow-up of 41 mo, there was no difference between the groups for the 5-yr rates of local recurrence-free, systemic progression-free, and disease-free survival (all p>0.05).

Conclusions: RAPN is associated with overall better perioperative morbidity and lower rates of complications, regardless of characteristics such as tumour complexity and patient comorbidity status. Functional and oncologic outcomes are equal after RARP and OPN.

Patient Summary: Robot-assisted partial nephrectomy is associated with a better morbidity profile than open partial nephrectomy (OPN) and provides the same cancer control and renal function preservation observed after OPN.
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http://dx.doi.org/10.1016/j.euo.2018.01.001DOI Listing
May 2018

Assessing the Feasibility and Accuracy of High-resolution Microultrasound Imaging for Bladder Cancer Detection and Staging.

Eur Urol 2020 06 10;77(6):727-732. Epub 2019 Apr 10.

Department of Urology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.

Background: Magnetic resonance imaging (MRI) has been proposed as a staging tool for bladder cancer (BC), but its use has been limited by its high costs and limited availability. Microultrasound (mUS) is a novel technology capable of providing high-resolution images of the prostate.

Objective: To test the feasibility of high-resolution mUS in patients diagnosed with BC and its ability to differentiate between non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC).

Design, Setting, And Participants: This is an observational prospective study performed in 23 patients with a diagnosis of primary BC scheduled for an endoscopic treatment.

Surgical Procedure: Micro-US was performed before transurethral resection of bladder tumor using the ExactVu system with an EV29L 29-MHz side-fire transducer (Exact Imaging, Markham, Canada).

Measurements: The endpoints were to test the feasibility, describe the normal bladder wall anatomy, identify the lesions, and compare the mUS findings with the histopathological results.

Results And Limitations: Micro-US was accurate in differentiating the three layers of the bladder wall in all cases. Bladder cancers were clearly identified as heterogeneous structures protruding from the normal bladder wall. In 14 cases the lesions appeared confined to the lamina propria, and in all cases NMIBC was confirmed by the final pathological report. In the other patients, the lesions seemed to extend into the muscular layer, but MIBC was confirmed in five out of seven cases (71.4%) from the pathologist. The small sample size was the main limitation of the current study.

Conclusions: Our findings showed that mUS is able to differentiate the bladder wall layers and identify the bladder cancer stage. Further studies with a larger population and imaging correlation with MRI are warranted before its introduction in clinical practice.

Patient Summary: In this report, a new imaging technique was tested for the characterization of bladder cancer. Microultrasound appears to be feasible and capable of discriminating between superficial and invasive tumors.
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http://dx.doi.org/10.1016/j.eururo.2019.03.044DOI Listing
June 2020

p2PSA for predicting biochemical recurrence of prostate cancer earlier than total prostate-specific antigen after radical prostatectomy: an observational prospective cohort study.

Minerva Urol Nefrol 2019 Jun 28;71(3):273-279. Epub 2019 Jan 28.

Department of Urology, Humanitas Clinical Institute IRCCS, Clinical and Research Hospital, Rozzano, Milan, Italy.

Background: There is an unmet clinical need for more biochemical specific tests that may detect clinically significant recurrent PCa at an early stage after radical prostatectomy (RP). Our purpose is to test the hypothesis that p2PSA (Index test) detects prostate cancer relapse (BCR) earlier than the current Reference Standard Test (total prostate-specific antigen [tPSA]) in patients who underwent RP for localized PCa.

Methods: This is an observational, prospective, cohort, follow-up study in patients subjected to RALP (robotic assisted laparoscopic radical prostatectomy) for clinically localized PCa from January 2013 to July 2013 at a high-volume Institution (450 average RP/year). A blood sample, for tPSA and p2PSA, was prospectively drawn after 3, 6, and 12 months and then every 6 months during the following two years. The primary outcome is to determine whether or not kinetics in rising of p2PSA significantly anticipates the tPSA kinetics. Exploratory data analysis was used to identify relationship between different variables.

Results: Over 134 patients 20 BCRs were detected according to tPSA cut-off. Five patients showed a contemporary increase of tPSA and p2PSA, 11 presented a p2PSA increase earlier than tPSA increase (13.9 months ±9.7). In four patients, the increase of PSA was not associated with a p2PSA>0.8 pg/mL. The correlation between tPSA and p2PSA according to Sperman's rho coefficient was statistically significant at 3, 6, 18 and 30 months: 0.416 (P<0.01), 0.255 (P<0.01), 0.359 (P<0.01) and 0.413 (P<0.01) respectively. When subjects were stratified according to stage/grade and margins (positive vs. negative), patients with higher stage and positive surgical margins could be considered the target categories. The low rate of observed BCR and high rate of p2PSA false positive are the main limitations.

Conclusions: The current findings showed that p2PSA might be more sensitive than tPSA in detecting earlier BCR within 3-year follow-up. Further studies with a longer follow-up and larger population remain mandatory before considering p2PSA for clinical decision-making.
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http://dx.doi.org/10.23736/S0393-2249.19.03279-XDOI Listing
June 2019

Predictors of Residual T1 High Grade on Re-Transurethral Resection in a Large Multi-Institutional Cohort of Patients with Primary T1 High-Grade/Grade 3 Bladder Cancer.

J Cancer 2018 20;9(22):4250-4254. Epub 2018 Oct 20.

Division of Urology, European Institute of Oncology, Milan, Italy.

The aim of this multi-institutional study was to identify predictors of residual high-grade (HG) disease at re-transurethral resection (reTUR) in a large cohort of primary T1 HG/Grade 3 (G3) bladder cancer patients. A total of 1155 patients with primary T1 HG/G3 bladder cancer from 13 academic institutions that underwent a reTUR within 6 weeks after first TUR were evaluated. Logistic regression analysis was performed to assess the association of predictive factors with residual HG at reTUR. Residual HG cancer was found in 288 (24.9%) of patients at reTUR. Patients presenting residual HG cancer were more likely to have carcinoma in situ (CIS) at first resection (p<0.001), multiple tumors (p=0.02), and tumor size larger than 3 cm (p=0.02). Residual HG disease at reTUR was associated with increased preoperative neutrophil-to-lymphocytes ratio (NLR) (p=0.006) and body mass index (BMI)>=25 kg/m. On multivariable analysis, independent predictors for HG residual disease at reTUR were tumor size >3cm (OR = 1.37; 95% CI: 1.02-1.84, p=0.03), concomitant CIS (OR 1.92; 95% CI: 1.32-2.78, p=0.001), being overweight (OR= 2.08; 95% CI: 1.44-3.01, p<0.001) and obesity (OR 2.48; 95% CI: 1.64-3.77, p<0.001). A reTUR in high grade T1 bladder cancer is mandatory as about 25% of patients, presents residual high grade disease. Independent predictors to identify patients at risk of residual high grade disease after a complete TUR include tumor size, presence of carcinoma in situ, and BMI >=25 kg/m.
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http://dx.doi.org/10.7150/jca.26129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277616PMC
October 2018

Early Catheter Removal After Robot-assisted Radical Prostatectomy: Results from a Prospective Single-institutional Randomized Trial (Ripreca Study).

Eur Urol Focus 2020 03 7;6(2):259-266. Epub 2018 Nov 7.

Urology, Humanitas Clinical and Research Hospital, Rozzano, Milan, Italy.

Background: The adoption of robotic technology in the treatment of prostate cancer (PCa) could lead to improvement in outcomes.

Objective: To evaluate feasibility, to compare functional outcomes, and to assess the economic benefits of removing catheter on the postoperative day (POD) 3 versus POD 5 after robot-assisted radical prostatectomy (RARP).

Design, Setting, And Participants: From September 2016 to May 2017, patients selected to undergo RARP for clinically localized PCa at a high-volume center were prospectively randomized into group 1 (POD 3; n=72) versus group 2 (POD 5, n=74).

Intervention: All patients underwent RARP with anatomical posterior and anterior reconstruction.

Outcome Measurements And Statistical Analysis: The primary endpoint was to compare acute urinary retention (AUR) and urinary leakage rate in the two groups. The secondary endpoints were early and mid-term postoperative functional outcomes assessed through questionnaires (ICIQ-MLUTS, IPSS), early continence rate, and postoperative pain/discomfort (visual analog scale score). The economic impact of early catheter removal was also assessed.

Results And Limitations: AUR was reported in two (1.4%) cases, one for each study group (p=0.9). One case of vesicourethral leakage was reported (0.7%) in group 1. Urethral discomfort and pain at discharge was significantly higher in group 2 (p=0.03). In our clinical practice, POD 3 catheter removal approach would determine a saving of approximately €80 000 and 405 d of hospitalization yearly. The main limitation is the small sample size.

Conclusions: Early catheter removal after RARP does not lead to an increase in perioperative complications. No negative effect on early and mid-term functional outcomes was observed. A significant impact on saving economic resources was reported.

Patient Summary: We demonstrated that early catheter removal has no negative effect on spontaneous voiding, complications, or urinary continence recovery after robot-assisted radical prostatectomy.
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http://dx.doi.org/10.1016/j.euf.2018.10.013DOI Listing
March 2020

A Multicentre Evaluation of the Role of the Prostate Health Index (PHI) in Regions with Differing Prevalence of Prostate Cancer: Adjustment of PHI Reference Ranges is Needed for European and Asian Settings.

Eur Urol 2019 04 2;75(4):558-561. Epub 2018 Nov 2.

Department of Urology, Erasmus MC, Rotterdam, The Netherlands.

Asians have a lower incidence of prostate cancer (PC). We compared the performance of the Prostate Health Index (PHI) for 2488 men in different ethnic groups (1688 Asian and 800 European men from 9 sites) with PSA 2-20ng/ml and PHI test and transrectal ultrasound-guided biopsy results available. Of these, 1652 men had PSA 2-10ng/ml and a normal digital rectal examination and underwent initial biopsy. The proportions of PC (Gleason ≥6) and higher-grade PC (HGPC, Gleason ≥7) across different PHI ranges were compared. The performance of PSA and PHI was compared using the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA). Among Asian men, HGPC would be diagnosed in 1.0%, 1.9%, 13%, and 30% of men using PHI thresholds of <25, 25-35, 35-55, and >55, respectively. At 90% sensitivity for HGPC (PHI >30), 56% of biopsies and 33% of Gleason 6 PC diagnoses could have been avoided. Among European men, HGPC would be diagnosed in 4.1%, 4.3%, 30%, and 34% of men using PHI thresholds of <25, 25-35, 35-55, and >55, respectively. At 90% sensitivity for HGPC (PHI >40), 40% of biopsies and 31% of Gleason 6 PC diagnoses could have been avoided. AUC and DCA confirmed the benefit of PHI over PSA. The benefit of PHI was also seen at repeat biopsy (n=397) and for PSA 10-20ng/ml (n=439). PHI is effective in cancer risk stratification for both European and Asian men. However, population-specific PHI reference ranges should be used. PATIENT SUMMARY: The Prostate Health Index (PHI) blood test helps to identify individuals at higher risk of prostate cancer among Asian and European men, and could significantly reduce unnecessary biopsies and overdiagnosis of prostate cancer. Different PHI reference ranges should be used for different ethnic groups.
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http://dx.doi.org/10.1016/j.eururo.2018.10.047DOI Listing
April 2019

Validation of Neutrophil-to-lymphocyte Ratio in a Multi-institutional Cohort of Patients With T1G3 Non-muscle-invasive Bladder Cancer.

Clin Genitourin Cancer 2018 12 6;16(6):445-452. Epub 2018 Jul 6.

Department of Urology, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Weill Cornell Medical College, New York, NY.

Introduction: The aim of this multicenter study was to investigate the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and to validate the NLR cutoff of 3 in a large multi-institutional cohort of patients with primary T1 HG/G3 non-muscle-invasive bladder cancer (NMIBC).

Patients And Methods: The study period was from January 2002 through December 2012. A total of 1046 patients with primary T1 HG/G3 who had NMIBC on re-transurethral bladder resection (TURB) who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance from 13 academic institutions were included. Endpoints were time to disease, and recurrence-free (RFS), progression-free (PFS), overall (OS), and cancer-specific survival (CSS).

Results: A total of 512 (48.9%) of patients had NLR ≥ 3 prior to TURB. High pretreatment NLR was associated with female gender and residual T1HG/G3 on re-TURB. The 5-year RFS estimates were 9.4% (95% confidence interval [CI], 6.8%-12.4%) in patients with NLR ≥ 3 compared with 58.8% (95% CI, 54%-63.2%) in patients with NLR < 3; the 5-year PFS estimates were 57.1% (95% CI, 51.5%-62.2%) versus 79.2% (95% CI, 74.7%-83%; P < .0001); the 10-year OS estimates were 63.6% (95% CI, 55%-71%) versus 66.5% (95% CI, 56.8%-74.5%; P = .03); the 10-year CSS estimates were 77.4% (95% CI, 68.4%-84.2%) versus 84.3% (95% CI, 76.6%-89.7%; P = .004). NLR was independently associated with disease recurrence (hazard ratio [HR], 3.34; 95% CI, 2.82-3.95; P < .001), progression (HR, 2.18; 95% CI, 1.71-2.78; P < .001) and CSS (HR, 1.65; 95% CI, 1.02-2.66; P = .03). The addition of NLR to a multivariable model that included established features increased its discrimination for predicting of RFS (+6.9%), PFS (+1.8%), and CSS (+1.7%).

Conclusions: Pretreatment NLR ≥ 3 was a strong predictor for RFS, PFS, and CSS in patients with primary T1 HG/G3 NMIBC. It could help in the decision-making regarding intensity of therapy and follow-up.
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http://dx.doi.org/10.1016/j.clgc.2018.07.003DOI Listing
December 2018

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

World J Urol 2019 Mar 10;37(3):507-514. Epub 2018 Jul 10.

Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy.

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.
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http://dx.doi.org/10.1007/s00345-018-2397-1DOI Listing
March 2019

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

Urol Int 2018 4;101(1):7-15. Epub 2018 Jul 4.

Department of Urology, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1159/000490765DOI Listing
January 2019

Long-term outcomes of high-grade T1 bladder cancer treated with intravesical bacillus Calmette-Guérin: experience of a single center.

Minerva Urol Nefrol 2018 Oct 3;70(5):501-508. Epub 2018 Jul 3.

Department of Urology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy -

Background: To assess the outcomes of patients with high-grade (HG) pT1 bladder cancer (BC) treated with intravesical BCG therapy.

Methods: The study population consisted of 185 patients with HG pT1 BC treated between 1998 and 2010. We aimed to determine recurrence-free (RFS) and progression-free survival (PFS), as well as the predictors of RFS and PFS.

Results: Overall, 143 (77.3%) patients were males. Median age was 72 years (IQR: 66-78). Tumor size was ≥3 cm in 100 (54.1%) individuals. Most patients had single tumors (125; 67.6%). Primary, progressive and recurrent patterns of presentation were observed in 146 (78.9%), 21 (11.4%), and 18 (9.7%) cases, respectively. After 2nd-look TURB, 127 (68.6%) patients had no residual disease, 44 (23.8%) had Ta/CIS, and 14 (7.6%) had T1 HG BC. Twenty-two (11.9%) patients experience early recurrence after BCG. Of these, 12 patients (54.5%) were diagnosed with Ta/CIS, while 10 (45.5%) were diagnosed with HG pT1 BC. The median follow-up was 93 months (IQR: 63-147). Ten-year RFS and PFS rates were 69.6 and 79.2%. In multivariable Cox regression models, female gender (HR=2.41; P=0.001), progressive (HR=2.03; P=0.030) and recurrent (HR=3.87; P<0.001) pattern of presentation emerged as independent predictors of RFS, while age ≥70 years (HR=2.13; P=0.027), presence of multiple tumors (HR=2.06; P=0.019), and early recurrence (HR=3.88; P<0.001) emerged as independent predictors of PFS.

Conclusions: Intravesical BCG appears to be an effective treatment for HG pT1 BC. Caution should be used in patients aged ≥70 years, with multiple tumors or experiencing early recurrence.
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http://dx.doi.org/10.23736/S0393-2249.18.03042-4DOI Listing
October 2018

Innovative Diagnostic Methods for Early Prostate Cancer Detection through Urine Analysis: A Review.

Cancers (Basel) 2018 Apr 18;10(4). Epub 2018 Apr 18.

Politecnico di Milano, Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Piazza Leonardo da Vinci 32, 20133 Milan, Italy.

Prostate cancer is the second most common cause of cancer death among men. It is an asymptomatic and slow growing tumour, which starts occurring in young men, but can be detected only around the age of 40–50. Although its long latency period and potential curability make prostate cancer a perfect candidate for screening programs, the current procedure lacks in specificity. Researchers are rising to the challenge of developing innovative tools able of detecting the disease during its early stage that is the most curable. In recent years, the interest in characterisation of biological fluids aimed at the identification of tumour-specific compounds has increased significantly, since cell neoplastic transformation causes metabolic alterations leading to volatile organic compounds release. In the scientific literature, different approaches have been proposed. Many studies focus on the identification of a cancer-characteristic “odour fingerprint” emanated from biological samples through the application of sensorial or senso-instrumental analyses, others suggest a chemical characterisation of biological fluids with the aim of identifying prostate cancer (PCa)-specific biomarkers. This paper focuses on the review of literary studies in the field of prostate cancer diagnosis, in order to provide an overview of innovative methods based on the analysis of urine, thereby comparing them with the traditional diagnostic procedures.
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http://dx.doi.org/10.3390/cancers10040123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923378PMC
April 2018

Ga Prostate-specific Membrane Antigen PET/CT for Primary Diagnosis of Prostate Cancer: Complementary or Alternative to Multiparametric MR Imaging.

Radiology 2018 05;287(2):725-726

† Humanitas Clinical and Research Hospital, via Manzoni 56, 20089 Rozzano (Milan), Italy.

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http://dx.doi.org/10.1148/radiol.2017172607DOI Listing
May 2018