External Validation of the IMPROD-MRI Volumetric Model to Predict the Utility of Systematic Biopsies at the Time of Targeted Biopsy.

Background: The aim of this study was to validate externally a nomogram that relies on MRI volumetric parameters and clinical data to determine the need for a standard biopsy in addition to a target biopsy for men with suspicious prostate MRI findings. Methods: We conducted a retrospective analysis of a prospectively maintained database of 469 biopsy-naïve men who underwent prostate biopsies. These biopsies were guided by pre-biopsy multiparametric Magnetic Resonance Imaging (mpMRI) and were performed at two different institutions. We included men with a PIRADSsv 2.1 score from 3 to 5. Each patient underwent both an MRI-ultrasound fusion biopsy of identified MRI-suspicious lesions and a systematic biopsy according to our protocol. The lesion volume percentage was determined as the proportion of cancer volume on MRI relative to the entire prostate volume. The study's outcomes were iPCa (Gleason Grade Group 1) and csPCa (Gleason Grade Group > 1). We evaluated the model's performance using AUC decision curve analyses and a systematic analysis of model-derived probability cut-offs in terms of the potential to avoid diagnosing iPCa and to accurately diagnose csPCa. Results: The nomogram includes age, PSA value, prostate volume, PIRADSsv 2.1 score, percentage of MRI-suspicious lesion volume, and lesion location. AUC was determined to be 0.73. By using various nomogram cut-off thresholds (ranging from 5% to 30%), it was observed that 19% to 58% of men could potentially avoid undergoing standard biopsies. In this scenario, the model might miss 0% to 10% of diagnosis of csPCa and could prevent identifying 6% to 31% of iPCa cases. These results are in line with findings from the multi-institutional external validation study based on the IMPROD trial (n = 122) and the MULTI-IMPROD trial (n = 262). According to DCA, the use of this nomogram led to an increased overall net clinical benefit when the threshold probability exceeded 10%. Conclusions: This study supports the potential value of a model relying on MRI volumetric measurements for selecting individuals with clinical suspicion of prostate cancer who would benefit from undergoing a standard biopsy in addition to a targeted biopsy.

Oncological outcomes of whole-gland cryoablation in patients with prostate cancer and high risk of lymph node invasion.

Purpose: Prostate cryoablation has been proposed as an alternative to radical prostatectomy for men with localized prostate cancer (PCa); however, it is limited by the lack of data regarding oncological outcomes and the impossibility of performing a lymph node dissection. The aim of this study was to assess if whole-gland cryoablation is oncologically safe, especially for patients in whom pelvic lymph node dissection would be necessary. Materials and Methods: After institutional review board approval, we identified 102 patients who underwent whole-gland prostate cryoablation between 2013 and April 2019. Lymph node invasion (LNI) probability was computed using Briganti nomogram, and a 5% cutoff probability was used to stratify the population in two groups. Biochemical recurrence after procedure was assessed using Phoenix criteria. Multiparametric magnetic resonance imaging, (CT), and bone scan or choline positron-emission tomography/CT were performed for the detection of distant metastases. Results: Seventeen (17%) patients were treated for a low-risk PCa, 48 (47%) patients were at intermediate-risk PCa, and 37 (36%) patients were at high-risk PCa. Patients with a probability of LNI >5% (n = 46) exhibited higher prostate-specific antigen (PSA), PSA density, ISUP Grade Group, CT stage, and european association of urology (EAU) risk. Recurrence-free survival rates at 3 years' follow-up were 93%, 82%, and 72%, respectively for low-, intermediate-, and high-risk patients. At a median follow-up of 37 months (17-62), additional treatment and metastasis-free survival were 84% and 97%, respectively. No differences in oncological outcomes were found in patients with a probability of LNI above and below 5%. Conclusions: Prostate whole-gland cryoablation can be considered a safe procedure with acceptable outcomes in low- and intermediate-risk patients. A high preoperative risk of nodal involvement could not be considered an exclusion criterion to perform cryoablation. Further studies are required.

Treatment of localized prostate cancer in elderly patients: the role of partial cryoablation.

PURPOSE: To evaluate oncological outcomes of partial gland cryoablation (PGC) for localized prostate cancer (PCa) in a cohort of elderly patients who required an active treatment. METHODS: Data from 110 consecutive patients treated with PGC for localized PCa were collected. All patients underwent the same standardized follow-up with serum-PSA level and digital rectal examination. Prostate MRI and eventual re-biopsy were performed at twelve months after cryotherapy or in case of suspicion of recurrence. Biochemical recurrence was defined according to Phoenix criteria (PSA nadir + 2 ng/ml). Kaplan-Meier curves and Multivariable Cox Regression analyses were used to predict disease progression, biochemical recurrence- (BCS) and additional treatment-free survival (TFS). RESULTS: Median age was 75 years (IQR 70-79). PGC was performed in 54 (49.1%) patients with low-risk PCa, 42 (38.1%) with intermediate risk and 14 (12.8%) high risk. At a median follow-up of 36 months, we recorded a BCS and TFS of 75 and 81%, respectively. At 5 years, BCS was 68.5% and CRS 71.5%. High-risk prostate cancer was associated with lower TFS and BCS curves when compared with low-risk group (all p values < .03). A PSA reduction < 50% between preoperative level and nadir resulted as an independent failure predictor for all outcomes evaluated (all p values < .01). Age was not associated with worse outcomes. CONCLUSIONS: PGC could be a valid treatment for low- to intermediate PCa in elderly patients, when a curative approach is suitable in terms of life expectancy and quality of life.

Foggia Prostate Cancer Risk Calculator 2.0: A Novel Risk Calculator including MRI and Bladder Outlet Obstruction Parameters to Reduce Unnecessary Biopsies.

Risk calculator (RC) combining PSA with other clinical information can help to better select patients at risk of prostate cancer (PCa) for prostate biopsy. The present study aimed to develop a new Pca RC, including MRI and bladder outlet obstruction parameters (BOOP). The ability of these parameters in predicting PCa and clinically significant PCa (csPCa: ISUP GG ≥ 2) was assessed by binary logistic regression. A total of 728 patients were included from two institutions. Of these, 395 (54.3%) had negative biopsies and 161 (22.11%) and 172 (23.6%) had a diagnosis of ISUP GG1 PCa and csPCa. The two RC ultimately included age, PSA, DRE, prostate volume (pVol), post-voided residual urinary volume (PVR), and PIRADS score. Regarding BOOP, higher prostate volumes (csPCa: OR 0.98, CI 0.97,0.99) and PVR ≥ 50 mL (csPCa: OR 0.27, CI 0.15, 0.47) were protective factors for the diagnosis of any PCa and csPCa. AUCs after internal validation were 0.78 (0.75, 0.82) and 0.82 (0.79, 0.86), respectively. Finally, decision curves analysis demonstrated higher benefit compared to the first-generation calculator and MRI alone. These novel RC based on MRI and BOOP may help to better select patient for prostate biopsy after prostate MRI.

One-Day Prostate Cancer Diagnosis: Biparametric Magnetic Resonance Imaging and Digital Pathology by Fluorescence Confocal Microscopy.

In this prospective observational study, we tested the feasibility and efficacy of a novel one-day PCa diagnosis path based on biparametric magnetic resonance (bpMRI) and digital pathology by fluorescence confocal microscopy (FCM). Patients aged 55-70 years scheduled for PBx due to increased PSA levels (3-10 ng/mL) and/or abnormal digitorectal examination were enrolled. All patients underwent bpMRI and PBx with immediate FCM evaluation of biopsy cores. Patients were asked to fill out a dedicated Patient Satisfaction Questionnaire. Patients' satisfaction rates and concordance between digital pathology and standard HE evaluation were the outcomes of interest. Twelve patients completed our one-day PCa diagnosis path. BpMRI showed suspicious lesions in 7 patients. Digital pathology by FCM identified PCa in 5 (41.7%) of the 12 patients. Standard pathology confirmed the diagnosis made through digital pathology in all the cases. At a per patient level, high concordance between the methods was achieved in Gleason Grading (4 out of 5 patients). The level of agreement in the number of positive cores was lower but did not affect the choice of treatment in any of the 5 PCa cases. At a per core level, the agreement was very high for the diagnosis of anyPCa (96.2%) and csPCa (97.3%), with a k coefficient of 0.90 and 0.92, respectively (near perfect agreement). In conclusion, one-day PCa diagnosis by FCM represents a feasible, reliable, and fast diagnostic method that provides significant advantages in optimizing time and resources, leading to patients having a higher quality standard of care perception.

Bioptic prostatic inflammation correlates with false positive rates of multiparametric magnetic resonance imaging in detecting clinically significant prostate cancer.

INTRODUCTION: The aim of this article was to determine the impact of bioptic prostatic inflammation (PI) on the false positive rate of multiparametric magnetic resonance imaging (mp-MRI) in detecting clinically significant prostate ancer (csPCa). MATERIAL AND METHODS: Our prostate biopsy database was queried to identify patients who underwent mp-MRI before PB at our institution. A dedicated uropathologist prospectively assessed bioptic PI using the Irani scores. We evaluated the association between mp-MRI findings, bioptic Gleason grade (GG) and aggressiveness of PI, and PCa detection. RESULTS: In total, 366 men were included. In patients with Prostate Imaging Reporting and Data System (PIRADS) 4-5 lesions, the csPCa (GG ≥2) rate was significantly higher in those with low-grade than in those with high-grade PI (36% vs 29.7%; p = 0.002), and in those with low-aggressive than in those with high-aggressive PI (37.7% vs 30.1%; p = 0.0003). The false positive rates of PIRADS 4-5 lesions for any PCa were 34.2% and 57.8% for low- and high-grade PI, respectively (p = 0.002); similarly, they were 29.5% and 59.4% for mildly and highly-aggressive PI (p = 0.0003). Potential study limitations include its retrospective analysis and single-center study and lack of assessment of the type of PI. CONCLUSIONS: Bioptic PI directly correlates with false positive rates of mp-MRI in detecting csPCa. Clinicians should be aware that PI remains the most common pitfall of mp-MRI.

Intraoperative Digital Analysis of Ablation Margins (DAAM) by Fluorescent Confocal Microscopy to Improve Partial Prostate Gland Cryoablation Outcomes.

Partial gland cryoablation (PGC) aims at destroying prostate cancer (PCa) foci while sparing the unaffected prostate tissue and the functionally relevant structures around the prostate. Magnetic Resonance Imaging (MRI) has boosted PGC, but available evidence suggests that ablation margins may be positive due to MRI-invisible lesions. This study aimed at determining the potential role of intraoperative digital analysis of ablation margins (DAAM) by fluoresce confocal microscopy (FCM) of biopsy cores taken during prostate PGC. Ten patients with low to intermediate risk PCa scheduled for PGC were enrolled. After cryo-needles placement, 76 biopsy cores were taken from the ablation margins and stained by the urologist for FCM analysis. Digital images were sent for "real-time" pathology review. DAAM, always completed within the frame of PGC treatment (median time 25 min), pointed out PCa in 1/10 cores taken from 1 patient, thus prompting placement of another cryo-needle to treat this area. Standard HE evaluation confirmed 75 cores to be cancer-free while displayed a GG 4 PCa in 7% of the core positive at FCM. Our data point out that IDAAM is feasible and reliable, thus representing a potentially useful tool to reduce the risk of missing areas of PCa during PGC.

PSA Density Help to Identify Patients With Elevated PSA Due to Prostate Cancer Rather Than Intraprostatic Inflammation: A Prospective Single Center Study.

The association between PSA density, prostate cancer (PCa) and BPH is well established. The aim of the present study was to establish whether PSA density can be used as a reliable parameter to predict csPCa and to determine its optimal cutoff to exclude increased PSA levels due to intraprostatic inflammation. This is a large prospective single-center, observational study evaluating the role of PSA density in the discrimination between intraprostatic inflammation and clinically significant PCa (csPCa). Patients with PSA ≥ 4 ng/ml and/or positive digito-rectal examination (DRE) and scheduled for prostate biopsy were enrolled. Prostatic inflammation (PI) was assessed and graded using the Irani Scores. Multivariable binary logistic regression analysis was used to assess if PSA density was associated with clinically significant PCa (csPCa) rather than prostatic inflammation. A total of 1988 patients met the inclusion criteria. Any PCa and csPCa rates were 47% and 24% respectively. In the group without csPCa, patients with prostatic inflammation had a higher PSA (6.0 vs 5.0 ng/ml; p=0.0003), higher prostate volume (58 vs 52 cc; p<0.0001), were more likely to have a previous negative biopsy (29% vs 21%; p=0.0005) and a negative DRE (70% vs 65%; p=0.023) but no difference in PSA density (0.1 vs 0.11; p=0.2). Conversely in the group with csPCa, patients with prostatic inflammation had a higher prostate volume (43 vs 40 cc; p=0.007) but no difference in the other clinical parameters. At multivariable analysis adjusting for age, biopsy history, DRE and prostate volume, PSA density emerged as a strong predictor of csPCA but was not associated with prostatic inflammation. The optimal cutoffs of PSA density to diagnose csPCa and rule out the presence of prostatic inflammation in patients with an elevated PSA (>4 ng/ml) were 0.10 ng/ml2 in biopsy naïve patients and 0.15 ng/ml2 in patients with a previous negative biopsy. PSA density rather than PSA, should be used to evaluate patients at risk of prostate cancer who may need additional testing or prostate biopsy. This readily available parameter can potentially identify men who do not have PCa but have an elevated PSA secondary to benign conditions.

Prospective Validation of Pentraxin-3 as a Novel Serum Biomarker to Predict the Risk of Prostate Cancer in Patients Scheduled for Prostate Biopsy.

PURPOSE: To test and internally validate serum Pentraxin-3 (PTX3) levels as a potential PCa biomarker to predict prostate biopsy (PBx) results. MATERIALS AND METHODS: Serum PSA and serum PTX3 were prospectively assessed in patients scheduled for PBx at our Institution due to increased serum PSA levels or abnormal digital rectal examination. Uni- and multivariable logistic regression analysis, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA), were used to test the accuracy of serum PTX3 in predicting anyPCa and clinically significant PCa (csPCa) defined as Gleason Grade (GG) ≥ 2. RESULTS: Among the 455 eligible patients, PCa was detected in 49% and csPCa in 25%. During univariate analysis, PTX3 outperformed other variables in predicting both anyPCa and csPCa. The addition of PTX3 to multivariable models based on standard clinical variables, significantly increased each model's predictive accuracy for anyPCa (AUC from 0.73 to 0.82; p < 0.001) and csPCa (AUC from 0.79 to 0.83; p < 0.001). At DCA, PTX3, and PTX3, density showed higher net benefit than PSA and PSA density and increased the net benefit of multivariable models in deciding when to perform PBx. CONCLUSIONS: Serum PTX3 levels might be of clinical utility in predicting prostate biopsy results. Should our findings be confirmed, this novel reflex test could be used to reduce the number and burden of unnecessary prostate biopsies.

Combined Use of Prostate-specific Antigen Density and Magnetic Resonance Imaging for Prostate Biopsy Decision Planning: A Retrospective Multi-institutional Study Using the Prostate Magnetic Resonance Imaging Outcome Database (PROMOD).

BACKGROUND: Previous studies suggested that prostate-specific antigen (PSA) density (PSAd) combined with magnetic resonance imaging (MRI) may help avoid unnecessary prostate biopsy (PB) with a limited risk of missing clinically significant prostate cancer (csPCa; Gleason grade group [GGG] >1). OBJECTIVE: To define optimal diagnostic strategies based on the combined use of PSAd and MRI in patients at risk of prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of the international multicenter Prostate MRI Outcome Database (PROMOD), including 2512 men having undergone PSAd and prostate MRI before PB between 2013 and 2019, was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Rates of avoided PB, missed GGG 1, and csPCa according to 10 strategies based on PSAd values and MRI reporting scores (Prostate Imaging Reporting and Data System [PI-RADS]/Likert/IMPROD biparametric prostate MRI Likert). Decision curve analysis (DCA) was used to statistically compare the net benefit of each strategy. Combined systematic and targeted biopsies were used for reference. RESULTS AND LIMITATIONS: According to DCA, the best strategy in biopsy-naive patients was #7 (PI-RADS/Likert 4-5 or PI-RADS/Likert 3 if PSAd >0.2), which avoided 41.2% PBs while missed 44% of GGG 1 and 10.9% of csPCa cases. From a clinical standpoint, however, strategies with a lower risk of missing csPCa included #10 (PI-RADS/Likert 4-5 or PI-RADS 3 if PSAd >0.10 or PSAd >0.2), which avoided 27% PBs while missing 24.4% GGG 1 and 4% csPCa cases, or #5 (PI-RADS/Likert 3-5 or PSAd>0.15), which avoided 14.7% PBs while missing 9.3% GGG 1 and 1.7% csPCa cases. Similar results were found in patients with a previous negative biopsy. This study is limited by its retrospective nature, and no central review of MRI and histopathological findings. CONCLUSIONS: Combined PSAd and MRI findings allows individualization of the decision to perform PB on the basis of the risk of missing PCa that both patients and clinicians are ready to accept to avoid this procedure. PATIENT SUMMARY: We compared several biopsy strategies based on a combination of prostate magnetic resonance imaging findings and prostate-specific antigen density, providing a readily available tool for each center and practicing urologist to counsel patients about their individual risk of significant prostate cancer.

Mini invasive approaches in the treatment of small renal masses: TC-guided renal cryoablation in elderly.

BACKGROUND: Today, the goal of surgery is to achieve oncological efficacy with the lowest complication rate. Computed Tomography (CT)-guided cryoablation is proposed as a safe and effective technique. We report, our series of small renal masses treated with cryoablation in elderly (> 70 years). METHODS: From May 2014 to April 2019, 32 patients with median (IQR) age of 75.5 years (range 71-80) with small renal masses (< T1a) diagnosis, clinical anesthesia contraindications to nephron-sparing surgery or patient's will previous informed consent have been selected at our Urology Department. All patients underwent CT-guided cryoablation, preceded by needle biopsy. The cryoablation consisted in a procedure with an argon/helium gas-based system under local anesthesia. The follow-up included CT abdomen at 3, 6 and 12 months. The definition of incomplete treatment was the persistence of the lesion contrast enhancement (CE) at the end of the scan; the definition of relapse was the appearance of the CE to the 6-month control CT. RESULTS: The median follow-up was 30 months (IQR 1-59). The median size of the tumor was 3.85 cm (IQR 1.6-4.5). All patients underwent lesion biopsy resulting in diagnosis of Renal Cell Carcinoma (RCC) in 29 patients (90.7%) and oncocytoma in 3 patients (9.3%). A median of 2 cryoprobes (IQR 1- 3) was used and 2/3 cycles of freeze-thaw of the duration of 10 minutes or 5 minutes were performed. Complications were: 3 asymptomatic transitional perirenal effusion, 2 lumbar pain well-controlled by analgesic drug. Hospital stay was 2 days (range 1-3). No case showed incomplete treatment and local relapse or metastates at the CT abdomen-pelvis with contrast medium at 12 months. CONCLUSIONS: This study shows the efficacy and safety of percutaneous cryoablation of small renal masses in elderly population. The procedure is easy to perform, with low complication rates and well tolerated by the elderly patients.

Modulation of complement activation by pentraxin-3 in prostate cancer.

Pentraxin 3 (PTX3) is an essential component of the innate immune system and a recognized modulator of Complement cascade. The role of Complement system in the pathogenesis of prostate cancer has been largely underestimated. The aim of our study was to investigate the role of PTX3 as possible modulator of Complement activation in the development of this neoplasia. We performed a single center cohort study; from January 2017 through December 2018, serum and prostate tissue samples were obtained from 620 patients undergoing prostate biopsy. A group of patients with benign prostatic hyperplasia (BPH) underwent a second biopsy within 12-36 months demonstrating the presence of a prostate cancer (Group A, n = 40) or confirming the diagnosis of BPH (Group B, N = 40). We measured tissue PTX3 protein expression together with complement activation by confocal microscopy in the first and second biopsy in group A and B patients. We confirmed that that PTX3 tissue expression in the first biopsy was increased in group A compared to group B patients. C1q deposits were extensively present in group A patients co-localizing and significantly correlating with PTX3 deposits; on the contrary, C1q/PTX3 deposits were negative in group B. Moreover, we found a significantly increased expression of C3a and C5a receptors within resident cells in group A patient. Interestingly, C1q/PTX3 deposits were not associated with activation of the terminal Complement complex C5b-9; moreover, we found a significant increase of Complement inhibitor CD59 in cancer tissue. Our data indicate that PTX3 might play a significant pathogenic role in the development of this neoplasia through recruitment of the early components of Complement cascade with hampered activation of terminal Complement pathway associated with the upregulation of CD59. This alteration might lead to the PTX3-mediated promotion of cellular proliferation, angiogenesis and insensitivity to apoptosis possible leading to cancer cell invasion and migration.

Does Multiparametric Magnetic Resonance of Prostate Outperform Risk Calculators in Predicting Prostate Cancer in Biopsy Naïve Patients?

BACKGROUND: European Association of Urology (EAU) guidelines recommend using risk-calculators (RCs), imaging or additional biomarkers in asymptomatic men at risk of prostate cancer (PCa). OBJECTIVES: To compare the performance of mpMRI, a RC we recently developed and two commonly used RC not including mpMRI in predicting the risk of PCa, as well as the added value of mpMRI to each RC. DESIGN SETTING AND PARTICIPANTS: Single-center retrospective study evaluating 221 biopsy-naïve patients who underwent prebiopsy mpMRI. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients' probabilities of any PCa and clinically significant PCa (csPC, defined as Gleason-Score ≥3 + 4) were computed according to mpMRI, European Randomized Study of Screening for Prostate Cancer RC (ERSPC-RC), the Prostate Biopsy Collaborative Group RC (PBCG-RC) and the Foggia Prostate Cancer RC (FPC-RC). Logistic regression, AUC, and Decision curve analysis (DCA) were used to assess the accuracy of tested models. RESULTS AND LIMITATION: The FPC-RC outperformed mpMRI in diagnosing both any PCa (AUC 0.76 vs 0.69) and csPCa (AUC 0.80 vs 0.75). Conversely mpMRI showed a higher accuracy in predicting any PCa compared to the PBCG-RC and the ERSPC-RC but similar performances in predicting csPCa. At multivariable analysis predicting csPCa and any PCa, the addition of mpMRI findings improved the accuracy of each calculator. DCA showed that the FPC-RC provided a greater net benefit than mpMRI and the other RCs. The addition of mpMRI findings improved the net benefit provided by each calculator. CONCLUSIONS: mpMRI was outperformed by the novel FPC-RC and showed similar performances compared to the PBCG and ERSPC RCs in predicting csPCa. The addition of mpMRI findings improved the diagnostic accuracy of each of these calculators.

Preliminary outcomes of the European multicentre experience with the ZSI 375 artificial urinary sphincter for treatment of stress urinary incontinence in men.

INTRODUCTION: The ZSI 375 is a new artificial urinary sphincter utilised in men suffering from stress urinary incontinence (SUI). We present the first European multicentre study on the effectiveness of ZSI 375. MATERIAL AND METHODS: This study was conducted in a retrospective, non-randomized format in centres across Europe. Between May 2009 and December 2014, ZSI 375 was fitted in 109 SUI patients following radical prostatectomy, transurethral resection of prostate (TURP), rectal surgery and high intensity focused ultrasound (HIFU). Patients with history of pelvic radiotherapy or previous surgical treatment for incontinence or stricture were excluded from the series. Follow-up was completed by December 2016. The key outcome measures included overall improvement and complication rates. RESULTS: A total of 109 patients in 10 European centres were recruited and had the ZSI 375 device implanted. The average patient age was 72 years old. The indication for the majority of patients was incontinence following radical prostatectomy (100/109 patients, 91.74%). On average, patients were incontinent for 48.6 months prior to treatment. All patients used ≥4 pads daily at baseline and thus were classified as suffering from 'severe incontinence'. The average follow-up until the final visit was 43 months. The pad usage decreased to 0.84 on average by the last visit. There were no reported cases of device infection. A total of 9 patients had urethral cuff erosion (8.25%),which was the most common complication in this series. A further 3 men (2.75%) experienced mechanical failure requiring subsequent device reimplantation. The implantation of the ZSI 375 device was considered successful in 92.66% of patients. CONCLUSIONS: The ZSI 375 is an effective surgical treatment option in men with severe stress urinary incontinence.

Prognostic and therapeutic role of HER2 expression in micropapillary carcinoma of the bladder.

Micropapillary carcinoma of the bladder (MPBC) is a variant type of infiltrating urothelial carcinoma, which portends a poor biological behavior in terms of disease stage at first diagnosis and clinical outcome; its peculiar morphology raises issues concerning the ability of tumor detection by imaging techniques and proper biopsy procedure, and the appropriate treatment for non-muscle infiltrating and muscle-infiltrating MPBC remains a matter of debate. On the basis of its established prognostic and therapeutic role in breast and gastro-esophageal cancer in the first instance, the human epidermal growth factor receptor-2 (HER2) has been investigated in selected case series of MPBC over the last 10 years. The aim of the present review was to summarize the existing evidence on HER2 status in MPBC, and to discuss its present and future utility in risk assessment and treatment choice of this uncommon, yet aggressive, disease.

Human Epidermal Growth Factor Receptor 2 in Non-Muscle Invasive Bladder Cancer: Issues in Assessment Methods and Its Role as Prognostic/Predictive Marker and Putative Therapeutic Target: A Comprehensive Review.

Although human epidermal growth factor receptor 2 (HER2) plays a prognostic and predictive role in breast and gastric cancer, its function in bladder cancer (BC) is still controversial. A comprehensive review of the literature has been carried out. An electronic search of databases from PubMed, Scopus, Google Scholar was implemented. The search terms were: "BC," "bladder carcinoma," "bladder neoplasm," "human epidermal growth factor 2," "HER2," "HER-2," "c-erbB-2," "c-erbB2," "erbB-2," "erbB2," "neu," "marker," "biomarker," and "prognosis". Results of the review consented to (a) summarize the available data on HER2 a predictor of recurrence and/or progression free survival on univariate and multivariate analysis, (b) explore the related issues in assessing HER2 status on these tumor samples, since they may severely impair its predictive function, and (c) report the state-of-the art of HER2 as a putative therapeutic target in BC and especially non-muscle invasive BC. HER2 stands out for being a prognostic factor as well as a therapeutic target in various cancers. Data from the literature concerning its use in BC provide conflicting results, probably due to the inherent complexity of BC biology. Efforts should be made to establish a suitable tumor-specific scoring system, and to assess single drugs' efficacy in well-designed clinical trials.

Morphological and Immunohistochemical Biomarkers in Distinguishing Prostate Carcinoma and Urothelial Carcinoma: A Comprehensive Review.

The differential diagnosis between high-grade prostate carcinoma and infiltrating urothelial carcinoma (UC) in transurethral resection prostate specimens as well as cystoprostatectomy specimens may often be challenging due to morphologic and clinical overlap of the 2 entities. Such distinction has critical therapeutic and staging consequences, yet it is hampered by both issues in morphology and by the low accuracy rates of single immunohistochemical markers, as reported in literature. This review aims to provide a comprehensive analysis of the available morphological and immunohistochemical parameters, which may allow to discriminate between prostate carcinoma and urothelial carcinoma in the proper clinical context and to discuss their diagnostic applications in daily practice.

Combined Plaque Incision, Buccal Mucosa Grafting, and Additional Tunica Albuginea Plication for Peyronie's Disease.

INTRODUCTION: Surgery remains the gold standard for treatment in stable patients with penile deformity associated to Peyronie's disease (PD). AIM: To evaluate the long-term results of plaque incision and buccal mucosa grafting (BMG), with or without additional tunica albuginea plication (TAP), in the correction of severe penile curvatures secondary to PD. METHODS: 72 patients with severe curvature caused by PD, normal erections, and stable disease entered this prospective study. Preoperatively, they underwent penile duplex ultrasounds with measurement of curvature and length of affected side. All procedures were carried out by 1 surgeon. Patients were seen at 1, 3, 6, and 12 months postoperatively, then yearly. Subjective outcome was assessed by the Sexual Encounter Profile (SEP) questionnaire, and objective outcome was assessed by an intracavernous injection (ICI) test performed within the first year for evaluating penile rigidity, straightness, and length. MAIN OUTCOME MEASURE: Long-term outcomes include penile straightening, penile shortening, and sexual satisfaction. RESULTS: Mean curvature was 71.32 ± 17.6° (range 40-110); 33 (45.8%) patients had a 2-sided curvature with a mean second curvature of 33.79 ± 12.2° (range 10-60). Additional TAP was needed in 60% of patients for complete straightening or graft stretching. All patients resumed unassisted intercourse 1 month after surgery; 4 (5.5%) refused follow-up, claiming excessive penile shortening. In the remaining 68, the ICI test showed no recurvature, shortening, or de novo erectile dysfunction. At mean follow-up of 62.01 ± 34.3 months (range 12-135), all were able to obtain an erection (SEP-1), 97.1% to penetrate (SEP-2), and 89.7% to successfully complete intercourse (SEP-3); 80.9% of them were satisfied with erection hardness (SEP-4) and 86.8% were overall satisfied (SEP-5), with the main reason for dissatisfaction being expectation of better length and rigidity. CONCLUSION: BMG, with or without TAP, provides excellent long-term results and is safe and reproducible, representing a valuable treatment option for PD, but great care should be taken in patient counseling to avoid unrealistic expectations. Cormio L, Mancini V, Massenio P. Combined Plaque Incision, Buccal Mucosa Grafting, and Additional Tunica Albuginea Plication for Peyronie's Disease. Sex Med 2019;7:48-53.

Development and Internal Validation of Novel Nomograms Based on Benign Prostatic Obstruction-Related Parameters to Predict the Risk of Prostate Cancer at First Prostate Biopsy.

The present study aimed to determine the ability of novel nomograms based onto readily-available clinical parameters, like those related to benign prostatic obstruction (BPO), in predicting the outcome of first prostate biopsy (PBx). To do so, we analyzed our Internal Review Board-approved prospectively-maintained PBx database. Patients with PSA>20 ng/ml were excluded because of their high risk of harboring prostate cancer (PCa). A total of 2577 were found to be eligible for study analyses. The ability of age, PSA, digital rectal examination (DRE), prostate volume (PVol), post-void residual urinary volume (PVR), and peak flow rate (PFR) in predicting PCa and clinically-significant PCa (CSPCa)was tested by univariable and multivariable logistic regression analysis. The predictive accuracy of the multivariate models was assessed using receiver operator characteristic curves analysis, calibration plot, and decision-curve analyses (DCA). Nomograms predicting PCa and CSPCa were built using the coefficients of the logit function. Multivariable logistic regression analysis showed that all variables but PFR significantly predicted PCA and CSPCa. The addition of the BPO-related variables PVol and PVR to a model based on age, PSA and DRE findings increased the model predictive accuracy from 0.664 to 0.768 for PCa and from 0.7365 to 0.8002 for CSPCa. Calibration plot demonstrated excellent models' concordance. DCA demonstrated that the model predicting PCa is of value between ~15 and ~80% threshold probabilities, whereas the one predicting CSPCa is of value between ~10 and ~60% threshold probabilities. In conclusion, our novel nomograms including PVR and PVol significantly increased the accuracy of the model based on age, PSA and DRE in predicting PCa and CSPCa at first PBx. Being based onto parameters commonly assessed in the initial evaluation of men "prostate health," these novel nomograms could represent a valuable and easy-to-use tool for physicians to help patients to understand their risk of harboring PCa and CSPCa.

Safety and efficacy of abiraterone acetate in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: an Italian multicenter "real life" study.

BACKGROUND: To evaluate the safety and efficacy of abiraterone acetate (AA) in the "real life" clinical practice for men with chemotherapy-naïve metastatic castration-resistant prostate. METHODS: A consecutive series of patients with mCRPC in 9 Italian tertiary centres treated with AA was collected. Demographics, clinical parameters, treatment outcomes and toxicity were recorded. The Brief Pain Inventory scale Q3 was tracked and patient treatment satisfaction was evaluated. Survival curves were estimated by the method of Kaplan-Meier and Cox regression and compared by the log-rank test statistic. RESULTS: We included 145 patients (mean age 76.5y). All patients were on androgen deprivation therapy. Patients had prior radiotherapy, radical prostatectomy, both treatments or exclusive androgen deprivation therapy in 17%, 33%, 9% and 40%, respectively. 57% of the patients had a Gleason score higher more than 7 at diagnosis. 62% were asymptomatic patients. The median serum total PSA at AA start was 17 ng/mL (range 0,4-2100). The median exposure to AA was 10 months (range 1-35). The proportion of patients achieving a PSA decline ≥50% at 12 weeks was 49%. Distribution of patient satisfaction was 32% "greatly improved", 38% "improved", 24% "not changed", 5.5% "worsened". Grade 3 and 4 toxicity was recorded in 17/145 patients 11.7% (70% cardiovascular events, 30% critical elevation of AST/ALT levels). At the last follow-up, median progression free and overall survival were 17 and 26.5 months, respectively. Both outcomes significantly correlated with the presence of pain, patient satisfaction, PSA baseline and PSA decline. CONCLUSIONS: The AA is effective and well tolerated in asymptomatic or slightly symptomatic mCRPC in a "real life" setting. The survival outcomes are influenced by the presence of pain, patient satisfaction, baseline PSA and PSA decline. TRIAL REGISTRATION: The study was retrospectively registered at ISRCTN as DOI: 10.1186/ISRCTN 52513758 in date April the 30th 2016.