Male awareness of prostate cancer risk remains poor in relatives of women with germline variants in DNA-repair genes.

Abstract. Objective: The aim of this study is to evaluate male awareness of developing prostate cancer (PCa) in families with germline DNA-repair genes (DRG) variants. Materials and methods: Data were collected from a prospective, monocentric cohort study. The study was conducted in a university hospital with a multidisciplinary approach to the patient (collaboration of the Departments of Oncology, Urology, Pathology, Radiology, and Medical Genetics Laboratory). We recruited healthy males, relatives of families of women with breast or ovarian cancer who tested positive for pathogenic variants (PVs) or likely pathogenic variants (LPVs) in DRGs. A dedicated PCa screening was designed and offered to men aged 35 to 69 years, based on early visits with digital rectal examination (DRE), prostate health index (PHI) measurement, multiparametric magnetic resonance imaging (mpMRI) and, if necessary, targeted/systematic prostate biopsies. The primary endpoint was to evaluate the willingness of healthy men from families with a DRG variants detected in female relatives affected with breast and/or ovarian cancer to be tested for the presence of familial PVs. The secondary endpoints were the acceptance to participate if resulted positive and compliance with the screening programme. Results: Over 1256 families, of which 139 resulted positive for PVs in DRGs, we identified 378 'healthy' men aged between 35 and 69 years old. Two hundred sixty-one (69.0%) refused to be tested for DRG variants, 66 (17.5%) declared to have been previously tested, and 51 (13.5%) males were interested to be tested. Between those previously tested and those who accepted to be tested, 62 (53.0%) were positive for a DRG variant, and all of them accepted to participate in the subsequent surveillance steps. The main limitation is that is a single-centre study and a short follow-up. Conclusions: All men tested positive for a DRG variants agreed to go under the surveillance scheme. However, only 31% of 'men at risk' (i.e., relative of a DRG variant carrier) expressed their willingness to be tested for the familial DRG variant. This observation strongly supports the urgent need to implement awareness of genetic risk for PCa within the male population.

Same-day discharge for endoscopic enucleation of the prostate: a systematic review and meta-analysis.

PURPOSE: To systematically review studies focused on the feasibility and outcomes of outpatient endoscopic enucleation of the prostate for benign prostatic obstruction. METHODS: A literature search was conducted through December 2022 using PubMed/Medline, Web of Science, and Embase databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. Risk of bias assessment was performed according to the Newcastle-Ottawa Scale for case control studies. RESULTS: Of 773 studies, ten were included in the systematic review (n = 1942 patients) and four in the meta-analysis (n = 1228 patients). The pooled incidence of successful same-day discharge was 84% (95% CI 0.72-0.91). Unplanned readmission was recorded in 3% (95% CI 0.02-0.06) of ambulatory cases. In the reported criteria-selected patients submitted to SDD surgery, the forest plot suggested a lower rate of postoperative readmission (OR 0.56, 95% CI 0.34-0.91, p = 0.02) and complications (OR 0.69, 95% CI 0.48-1, p < 0.05) rates compared to standard protocols. CONCLUSION: We provide the first systematic review and meta-analysis on SDD for endoscopic prostate enucleation. Despite the lack of randomized controlled trials, we confirm the feasibility and safety of the protocol with no increase in complications or readmission rate in well-selected patients.

Techniques and outcomes of robot-assisted partial nephrectomy for the treatment of multiple ipsilateral renal masses.

BACKGROUND: Patients with multiple ipsilateral renal masses have an augmented risk of metachronous contralateral lesions and are likely to undergo repeated surgeries. We report our experience with the technologies currently available and the surgical techniques to preserve healthy parenchyma while guaranteeing oncological radicality during robot-assisted partial nephrectomy (RAPN). METHODS: The data were collected at three tertiary-care centers, where 61 patients with multiple ipsilateral renal masses were treated with RAPN between 2012 and 2021. RAPN was performed with da Vinci Si or Xi surgical system using TilePro (Life360; San Francisco, CA, USA), indocyanine green fluorescence and intraoperative ultrasound. Three-dimensional reconstructions were built in some cases preoperatively. Different techniques were employed for hilum management. The primary endpoint is to report intra- and postoperative complications. Secondary endpoints were the estimated blood loss (EBL), warm ischemia time (WIT) and positive surgical margins (PSM) rate. RESULTS: Median preoperative size of the largest mass was 37.5 mm (24-51) with a median PADUA and R.E.N.A.L. score of 8 (7-9) and 7 (6-9). One hundred forty-two tumors were excised, with a mean number of 2.32. The median WIT was 17 (12-24) minutes, and the median EBL was 200 (100-400) mL. Intraoperative ultrasound was employed in 40 (67.8%) patients. The rate of early unclamping, selective clamping and zero-ischemia were respectively 13 (21.3%), 6 (9.8%) and 13 (21.3%). ICG fluorescence was employed in 21 (34.42%) patients and three-dimensional reconstructions were built in 7 (11.47%) patients. Three (4.8%) intraoperative complications occurred, all classified as grade-1 according to EAUiaiC. Postoperative complications were reported in 14 (22.9%) cases with 2 Clavien-Dindo grade >2 complications. Four (6.56%) patients had PSM. Mean period of follow-up was 21 months. CONCLUSIONS: In experienced hands, with the employment of the currently available technologies and surgical techniques, RAPN can guarantee optimal outcomes in patients with multiple ipsilateral renal masses.

Are nephrometry scores accurate for the prediction of outcomes in patients with renal angiomyolipoma treated with robot-assisted partial nephrectomy? A multi-institutional analysis.

BACKGROUND: Prediction of complications and surgical outcomes is of outmost importance even in patients with benign renal masses. The aim of our study is to test the PADUA, SPARE and R.E.N.A.L. scores to predict nephron sparing surgery (NSS) outcomes in patients presenting with renal angiomyolipoma (RAML). METHODS: We retrospectively analyzed the clinical and pathological data of 93 patients with AML treated with robot-assisted partial nephrectomy (RAPN) at three tertiary care referral centers. Renal masses were classified according to the PADUA, SPARE and R.E.N.A.L. nephrometry scores. Surgical success was defined according to the novel Trifecta Score. Logistic regression models (LRM) were fitted to predict the achievement of novel Trifecta and the risk of high-grade Clavien-Dindo (CD) complication. The receiver operating characteristics (ROC) curve analysis was used to estimate the accuracy of LRMs. RESULTS: Of 93 patients, 66 (69.9%) were females; median tumor size was 42 (36-48) mm. Novel Trifecta was achieved in 79 patients (84.9%) and postoperative complications classified as CD>2 occurred in 7 (7.5%) patients. At univariate and multivariate LRMs all three nephrometry scores were significantly associated with novel Trifecta achievement. Similar findings were observed for the prediction of CD>2 complications. The AUCs to predict optimal surgical outcomes and CD>2 complications were 0.791 and 0.912 for PADUA, 0.767 and 0.836 for SPARE and 0.756 and 0.842 for RENAL Score, respectively. CONCLUSIONS: RAPN appears to be a feasible and safe surgical technique for the treatment of RAML. PADUA, SPARE and RENAL scores can be safely adopted to predict surgical outcomes, with the first one showing a higher accuracy.

Combination of AST to ALT and neutrophils to lymphocytes ratios as predictors of locally advanced disease in patients with bladder cancer subjected to radical cystectomy: Results from a single-institutional series.

BACKGROUND: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. OBJECTIVE: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). METHODS: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. RESULTS: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282-11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027-1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312-6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374-6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12-6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95-5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623-0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

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.

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.

Multi-institutional Retrospective Validation and Comparison of the Simplified PADUA REnal Nephrometry System for the Prediction of Surgical Success of Robot-assisted Partial Nephrectomy.

BACKGROUND: The use of a nephron-sparing surgery for the treatment of localized renal masses is being pushed to more challenging cases. However, this procedure is not devoid of risks, and the Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location (RENAL) and Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classifications are commonly employed in the prediction of complications. Recently, the Simplified PADUA REnal (SPARE) scoring system has been proposed with the aim to provide a more simple system, to improve its reproducibility to predict postoperative risks. OBJECTIVE: We aim to retrospectively validate and compare the proposed new SPARE system in a multi-institutional population. DESIGN, SETTING, AND PARTICIPANTS: The Transatlantic Robotic Nephron-sparing Surgery (TRoNeS) study group collected data from 737 patients subjected to robot-assisted partial nephrectomy (RAPN) between 2010 and 2016 at three tertiary care referral centers. Of these patients, 536 presented complete demographic and clinical data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Renal masses were classified according to the SPARE, RENAL, and PADUA nephrometry scores, and surgical success was defined according to the margin, ischemia, and complication scores. RESULTS AND LIMITATIONS: Of 536 patients, 340 were male; the median age was 61 (53-69) yr and preoperative tumor size was 30 (22-43) mm. The margin, ischemia, and complication score was achieved in 399 of cases (74.4%). All three nephrometry scores were significant predictors of surgical outcomes both in univariate and in adjusted multivariate logistic regression model analysis. In accuracy analysis, the area under the curve (AUC) of the SPARE scoring system (0.73) was significantly higher than those of the PADUA (0.65) and RENAL (0.68) nephrometry scores in predicting surgical success. CONCLUSIONS: The SPARE score appears to be a promising and reliable score for the prediction of surgical outcomes of RAPN, showing a higher accuracy relative to the traditional PADUA and RENAL nephrometry scores. Further, prospective studies are warranted before its introduction in clinical practice. PATIENT SUMMARY: The Simplified PADUA REnal (SPARE) score is a reproducible and simple nephrometry score, offering better predictive capabilities of surgical success and complications.

Intravesical gemcitabine as bladder-preserving treatment for BCG unresponsive non-muscle-invasive bladder cancer. Results from a single-arm, open-label study.

Background: There is an unmet alternative medical therapy for BCG unresponsive patients. Objective: To report efficacy of intravesical gemcitabine in NMIBC patients, who failed a previous course of BCG, or intolerant, and unwilling to undergo radical cystectomy (RC). Material and methods: This is an open-label, single-arm study, which enrolled patients showing a failure or were intolerant to BCG and unwilling to undergo the RC. Intravesical gemcitabine was administered once a week for six consecutive weeks and once a month for 12 months. The primary outcome was DFS defined as the lack of a tumor on cystoscopy and negative urine cytology. Secondary endpoint was safety defined according a grading of side effects. OS, PFS, and DFS were described with Kaplan-Meier method at 12 and 24 months. Results and limitations: Overall 36 patients were enrolled. The median follow-up was 27 months. The DFS was 68.75% at the end of induction phase and 44.44% and 31.66% at 12 and 24 months of, respectively. The PFS was 43.75%. The OS and CSS were 77.9% (95% CI 58.78%-88.92%) and 80.68% (95% CI 61.49%-90.96%), 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 (LUTS) and fatigue (G1-G2). Conclusion: Patients who presented an unresponsive-BCG recurrent NMIBC and unwilling to receive a RC, could benefit from intravesical gemcitabine as salvage organ-sparing treatment.

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

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

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

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

Managing chronic bladder diseases with the administration of exogenous glycosaminoglycans: an update on the evidence.

Although the pathophysiology of acute chronic cystitis and other 'sensory' disorders, i.e. painful bladder syndrome (PBS) or interstitial cystitis (IC), often remains multifactorial, there is a wide consensus that such clinical conditions may arise from a primary defective urothelium lining or from damaged glycosaminoglycans (GAGs). A 'cascade' of events starting from GAG injury, which fails to heal, may lead to chronic bladder epithelial damage and neurogenic inflammation. To restore the GAG layer is becoming the main aim of new therapies for the treatment of chronic cystitis and PBS/IC. Preliminary experiences with GAG replenishment for different pathological conditions involving the lower urinary tract have been reported. There is a range of commercially available intravesical formulations of these components, alone or in combination. Literature evidence shows that exogenous intravesical hyaluronic acid markedly reduces recurrences of urinary tract infections (UTIs). Patients treated with exogenous GAGs have fewer UTI recurrences, a longer time to recurrence and a greater improvement in quality of life. Exogenous intravesical GAGs have been used for the treatment of PBS/IC. Despite the limitations of most of the studies, findings confirmed the role of combination therapy with hyaluronic acid and chondroitin sulfate as a safe and effective option for the treatment of PBS/IC. To prevent and/or treat radiotherapy and chemotherapy induced cystitis, GAG replenishment therapy has been used showing preliminary encouraging results. The safety profile of exogenous GAGs has been reported to be very favourable, without adverse events of particular significance.

"En Bloc" Resection of Nonmuscle Invasive Bladder Cancer: A Prospective Single-center Study.

OBJECTIVE: To describe our "en bloc" technique for nonmuscle invasive bladder cancer (NMIBC), assess the quality of resection, and report the midterm oncological outcome. MATERIALS AND METHODS: This is an observational prospective longitudinal study, from June 2010 to February 2014, enrolling patients with clinically NMIBC, having tumors of ≤3 cm and ≤4 lesions who underwent electrical en bloc bladder resection. The primary study end point was recurrence-free survival. Secondary outcomes were feasibility, safety, the presence of detrusor muscle, and the recurrence rate at the first follow-up cystoscopy (3 months). Statistical analysis was complemented with multivariable analysis. RESULTS: Of 87 enrolled patients, 2 showed a nonurothelial carcinoma and 11 showed muscle invasive bladder carcinoma at the definitive pathology. The study cohort consisted of 74 transitional cell carcinoma NMIBC cases, mean age 71 years ± 8, presenting with a mean tumor diameter of 1.98 ± 0.59 cm and a median number of resected tumors per patients of 1 (range 1-4). The 2-year recurrence-free survival was 85.59%. All the en bloc resection of bladder tumor samples showed the presence of detrusor muscle and the recurrence rate at the first follow-up cystoscopy (3 months) was 5.4% (4/74). An extraperitoneal bladder perforation occurred in only one patient. At multivariable analysis, only gender and the presence of carcinoma in situ were independent predictors of recurrence. The midterm follow-up and the absence of a control group are the main limitations. CONCLUSION: Our findings confirmed the feasibility and safety of en bloc resection of bladder tumor, with a recurrence-free survival of 85% after 2 years.

Role of Penile Doppler US in the Preoperative Assessment of Penile Squamous Cell Carcinoma Patients: Results From a Large Prospective Multicenter European Study.

OBJECTIVE: To determine the role of penile Doppler ultrasound (PDU) compared with magnetic resonance imaging (MRI) in preoperative diagnostic evaluation of patients with penile squamous cell carcinoma. MATERIALS AND METHODS: A prospective analysis on patients presenting with clinical diagnosis of penile squamous cell carcinoma from 6 different European hospitals between 2012 and 2014 was carried out. Each patient who had planned an organ sparing approach underwent an MRI and PDU both with an artificial erection with prostaglandin E 1. Age, evidence of MRI or PDU corpora cavernosa infiltration, frozen section examination report, definitive pathological report, and surgical approach used per patient were recorded. Accuracy, precision, negative predictive value, sensitivity, and specificity were calculated. Outcomes were statistically evaluated. RESULTS: Two hundred patients were enrolled in the study. The mean age of the patients was 67.35 ± 15.45 (range 51-82). All of the patients were treated surgically. Of the 200 patients, 135 (67.5%) underwent a corpora sparing approach, whereas 65 had a partial penectomy because of the frozen section outcome. About corpora cavernosa infiltration, the definitive outcome confirmed the frozen section examination. PDU vs MRI accuracy was 96.5% vs 90.5%; precision was 92.6% vs 96%; sensitivity was 96.9% vs 73.8%, specificity was 96.2% vs 98.5%. Despite sensitivity (P <.05) no statistical evidence was found between ultrasound and MRI. CONCLUSION: PDU has a statistical similar outcome on detecting infiltration of corpora cavernosa and could be used as a less expensive tool to drive surgical strategy in patient with a diagnosis of penile squamous cell carcinoma.

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

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

Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study.

OBJECTIVES: To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients. PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. RESULTS: Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ), 440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese (BMI ≥30 kg/m(2) ). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score ≥7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided. CONCLUSION: In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer.

Clinical use of [-2]proPSA (p2PSA) and its derivatives (%p2PSA and Prostate Health Index) for the detection of prostate cancer: a review of the literature.

Prostate-specific antigen (PSA) is recognized as an organ-specific marker with low specificity and sensitivity in discriminating prostate cancer (PCa) from other benign conditions, such as prostatic hyperplasia or chronic prostatitis. Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as a new marker to accurately detect PCa. The aim of this systematic review was to discuss the available literature regarding the clinical validity and utility of p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index (PHI). A systematic search of the PubMed and Scopus electronic databases was performed in accordance with the PRISMA statement (http://www.prisma-statement.org), considering the time period from January 1990 to January 2014 and using the following search terms: proprostate specific antigen, proenzyme PSA, proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies have been published, but only 35 were considered for the qualitative analysis. These studies suggested that p2PSA is the most cancer-specific form of PSA, being preferentially expressed in PCa tissue and being significantly elevated in the serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements improve the specificity of the available tests (PSA and derivatives) in detecting PCa. Moreover, increasing PHI values seem to correlate with more aggressive disease. Some studies have compared p2PSA and its derivatives with other new biomarkers and found p2PSA to be significantly more accurate. Indeed, the implementation of these tests in clinical practice has the potential to significantly increase the physician's ability to detect PCa and avoid unnecessary biopsies, while also having an effective impact on costs. Further studies in large, multicenter, prospective trials are required to confirm these encouraging results on the clinical utility of these new biomarkers.

Relationship of chronic histologic prostatic inflammation in biopsy specimens with serum isoform [-2]proPSA (p2PSA), %p2PSA, and prostate health index in men with a total prostate-specific antigen of 4-10 ng/ml and normal digital rectal examination.

OBJECTIVE: To investigate the relationship between serum [-2]proPSA (p2PSA) and derivatives with chronic histologic prostatic inflammation (CHPI) in men undergoing prostate biopsy for suspected prostate cancer (PCa). METHODS: This nested case-control study resulted from an observational prospective trial for the definition of sensibility, specificity, and accuracy of p2PSA, %p2PSA, and Beckman Coulter Prostate Health Index (PHI), in men undergoing prostate biopsy, with a total prostate-specific antigen (PSA) of 4-10 ng/mL and normal digital rectal examination. CHPI was the outcome of interest and defined as the presence of moderate to large infiltration of lymphomononuclear cells with interstitial and/or glandular disruption in absence of PCa. p2PSA, %p2PSA, and PHI were considered the index tests and compared with the established biomarker reference standard tests: tPSA, fPSA, %fPSA. RESULTS: Of 267 patients subjected to prostate biopsy, 73 (27.3%) patients were diagnosed with CHPI. Comparing CHPI with PCa patients, %p2PSA and PHI were found to be significantly lower, whereas fPSA and %fPSA were significantly higher. %p2PSA and PHI were the most accurate predictors of CHPI at biopsy, significantly outperforming tPSA, fPSA, and %fPSA. On the contrary, no significant differences were found in PSA, p2PSA, and derivatives between CHPI and benign prostatic hyperplasia (BPH) patients. CONCLUSION: Our findings showed that p2PSA, %p2PSA, and PHI values might discriminate PCa from CHPI or BPH, but not CHPI from BPH, in men with a total PSA 4-10 ng/mL and normal digital rectal examination. p2PSA isoform and its derivatives could be useful in clinical decision making to avoid unnecessary biopsies in patients with CHPI and elevated tPSA value.