Oncological predictive value of the 2004 World Health Organisation grading classification in primary T1 non-muscle-invasive bladder cancer. A step forward or back?

OBJECTIVE: To compare the clinical reliability of the 1973 and 2004 World Health Organisation (WHO) classification systems in pT1 bladder cancer. PATIENTS AND METHODS: We retrospectively evaluated 291 consecutive patients who had pT1 high grade bladder cancer between 2004 and 2011. All tumours were simultaneously evaluated by a single uro-pathologist as high grade and G2 or G3. All patients underwent a second transurethral resection (TUR) and those confirmed with non-muscle-invasive bladder cancer at second TUR received bacille Calmette-Guérin. Follow-up included urine cytology and cystoscopy 3 months after second TUR and then every 6 months for 5 years. Univariate and multivariate analysis to determine recurrence-free survival (RFS) and progression-free survival (PFS) rates were performed using the Kaplan­Meier method with the log-rank test. RESULTS: G2 tumours were found in 124 (46.6%) and G3 in 142 (53.4%) patients. The mean (median; range) follow-up period was 31.1 (19; 1­93) months. The 5-year RFS rate was 39.1% for the overall high grade population, and 49.1 and 31.8% for G2 and G3 subgroups, respectively. The 5-year PFS was 82% for the overall high grade population and 89 and 73% for G2 and G3 subgroups, respectively. RFS (P < 0.002) and PFS (P < 0.001) rates were significantly different between the G2 and G3 subgroups. In multivariate analysis, only the grade assessed according to the 1973 WHO significantly correlated with both RFS (P = 0.003) and PFS (P < 0.001). CONCLUSION: The results suggest that the 1973 WHO classification system has higher prognostic reliability for patients with T1 disease. If confirmed, these findings should be carefully taken into account when making treatment decisions for patients with T1 bladder cancer.

Random biopsy: when, how many and where to take the cores?

PURPOSE: The optimal random prostate biopsy scheme (PBx) in the initial and repeated setting is still an issue of controversy. We performed an analysis of the recent literature about the prostate biopsy techniques. METHODS: We performed a clinical and critical literature review by searching MEDLINE database from January 2005 up to January 2014. Electronic searches were limited to the English language, and the keywords prostate cancer, prostate biopsy, transrectal ultrasound, transperineal prostate biopsy were used. RESULTS: Prostate biopsy strategy in initial setting. According to the literature and the major international guidelines, the recommended approach in initial setting is still the extended scheme (EPBx) (12 cores). However, there is now a growing evidence in the literature that (a) saturation PBx (>20 cores) (SPBx) might be indicated in patients with PSA <10 ng/ml or low PSA density or large prostate and (b) an individualized approach with more than 12 cores according to the clinical characteristics of the patients may optimize cancer detection in the single patient. Moreover, in the era of multi-parametric MRI (mpMRI), EPBx or SPBX may be substituted by mpMRI-targeted biopsies that have demonstrated superiority over systematic random biopsies for the detection of clinically significant disease and representation of disease burden, while deploying fewer cores. Prostate biopsy strategy in repeat setting. How and how many cores should be taken in the different scenarios in the repeated setting is still unclear. SPBx clearly improves cancer detection if clinical suspicion persists after previous biopsy with negative findings and is able to provide an accurate prediction of prostate tumour volume and grade. Nevertheless, international guidelines do not strongly recommended SPBx in all situations of repeated setting. In the active surveillance and in focal therapy protocols, the optimal schemes have to be defined. CONCLUSIONS: The course of PBx has changed significantly from sextant biopsies to systematic and from extended to SPBx schemes. The issue about the number and location of the cores is still a matter of debate both in initial and in repeat setting. At present, EPBx is sufficient in most of the cases to provide adequate diagnosis and prostate cancer characterization in the initial setting, while SPBx seems to be necessary in repeat setting. The PBx schemes are evolving also because the scenario in which a PBx is necessary is changing. Random prostate PBx do not represent the future, while imaging target biopsy are becoming more popular.

Ureteral endometriosis: proposal for a diagnostic and therapeutic algorithm with a review of the literature.

INTRODUCTION: The ureteral involvement in deep pelvic endometriosis in usually asymptomatic and might lead to a silent loss of renal function. As a matter of fact, the diagnosis and the treatment modalities are still a matter of debate. MATERIALS AND METHODS: We performed a literature review by searching the MEDLINE database for articles published in English between 1996 and 2010, using the key words urinary tract endometriosis, ureteral endometriosis, diagnosis and treatment. We found more than 200 cases of ureteral endometriosis (UE). RESULTS: The disease most commonly affects a single distal segment of the ureter, with a left predisposition in most of the patients. Two major pathological types of UE may be distinguished: intrinsic and extrinsic. The symptoms are usually nonspecific and owing to secondary obstruction. The diagnosis has to be considered as a step- by-step procedure, starting from physical examination to highly detailed imaging methods. Nowadays, the treatment is usually chosen according to the type of UE, the site lesion and the distance to the ureteral orifice, with the use of JJ stents remaining a matter of debate. CONCLUSIONS: A close collaboration between the gynecologist and the urologist is advisable, especially in referral centers. Surgical treatment can lead to good results in terms of both patient compliance and prognosis.

Unilateral positive biopsies in low risk prostate cancer patients diagnosed with extended transrectal ultrasound-guided biopsy schemes do not predict unilateral prostate cancer at radical prostatectomy.

UNLABELLED: Focal therapy is an emergent therapeutic option for prostate cancer. Focal therapy includes a variety of therapeutic approaches ranging from lesion treatment to sub-total gland treatment. In this context, an accurate selection of patients having unilateral prostate cancer is closely related to the success of these strategies, especially when a hemi-ablative approach is considered. As prostate cancer is often multifocal, the critical issue is whether it is possible to preoperatively predict a clinically significant unifocal and/or unilateral lesion with sufficient accuracy to recommend focal or hemi-ablative therapy, relying on clinical characteristics and pathological data derived from the biopsy. Our study clearly demonstrates that the prediction of unilateral prostate cancer is not accurate, based on preoperative variables (predictive accuracy 52.3%). Our study is the first study based on an extended biopsy template. Even in patients diagnosed with extended biopsy, the accuracy of the available predictors is far from the ideal prediction. To date, there is no way of correctly identifying patients who will harbour unilateral prostate cancer based on routinely available variables. OBJECTIVE: o establish the predictors of unilateral prostate cancer in a population of patients with low risk prostate cancer, diagnosed with extended biopsy and submitted to radical prostatectomy, potentially candidates for focal therapy. PATIENTS AND METHODS: The study included 321 consecutive patients with low risk (clinical stage T1, Gleason score 3 + 3 or less, prostate-specific antigen [PSA] < 10 ng/mL) unilateral prostate cancer diagnosed after extended biopsy who were subsequently treated with radical prostatectomy between 2002 and 2009 at a single institution. We evaluated the rate of unilateral prostate cancers at final pathology following radical prostatectomy, defined as pT2a or pT2b stage. Univariable and multivariable logistic regression analyses were used to identify predictors of unilateral prostate cancers. Predictive accuracy was assessed with estimates of the area under the receiver operating characteristic curve, which were subjected to 200 bootstraps to reduce overfit bias. RESULTS: At final pathology only 29.3% patients harboured unilateral prostate cancer. No significant differences in terms of age, preoperative PSA, prostate volume and percentage of positive cores were recorded between patients with unilateral prostate cancer and patients with more advanced stage (all P ≥ 0.07). Patients harbouring unilateral prostate cancer had a smaller number of positive biopsy cores (2.8 vs 3.2, P = 0.056) compared with patients with stage pT2c or higher at final pathology. Patients with unilateral prostate cancer had a higher rate of Gleason sum 6 compared with patients with more advanced pathological stage (pT2c or higher: 85.1% vs 65.6%; P = 0.002). On multivariable analyses, only the percentage of positive cores (odds ratio 0.57; P = 0.047) was an independent predictor of unilateral prostate cancer at radical prostatectomy, after controlling for age, PSA at diagnosis and prostate volume (all P ≥ 0.3). The newly developed model for identifying the presence of unilateral prostate cancer failed to achieve accurate prediction (area under the curve 52.3%). When only patients with a single positive core were considered, no differences in PSA and prostate volume were detected (all P ≥ 0.5) and a similar rate of unilateral prostate cancer was demonstrated (33.3% vs 28.4%; P = 0.5). CONCLUSIONS: In patients with unilateral low risk prostate cancer at biopsy, only one-third showed unilateral prostate cancer at radical prostatectomy. The number of cores and the number of positive cores represented independent predictors of unilateral prostate cancer. However, the accuracy of the multivariable model in predicting unilateral prostate cancer is low (52.3%), thus making prediction of unilateral prostate cancer extremely inaccurate. These results need to be taken into account in those cases where focal therapy is considered as a treatment of prostate cancer.

Diagnosis of isolated high-grade prostatic intra-epithelial neoplasia: proposal of a nomogram for the prediction of cancer detection at saturation re-biopsy.

UNLABELLED: Study Type--Diagnostic (case series). Level of Evidence 4. What's known on the subject? And what does the study add? Multifocality, age, PSA values, and biopsy protocols regarding the predictive value of high grade PIN have been discussed extensively in the literature. Our study developed for the first time a predictive nomogram that could be helpful for patient counselling and to guide the urologist to perform rPBX after an initial diagnosis of isolated HGPIN. OBJECTIVE: • To evaluate factors that may predict prostate cancer (PCa) detection after the initial diagnosis of high-grade prostatic intra-epithelial neoplasia (HGPIN) on prostate biopsy (PBx) with six to 24 random cores. PATIENTS AND METHODS: • We retrospectively evaluated 262 patients submitted from 1998 to 2007 to prostate re-biopsy (rPBx) after an initial HGPIN diagnosis in tertiary academic centres. • HGPIN diagnosis was obtained on initial systematic PBx with six to 24 random cores. • All patients were re-biopsied with a 'saturation' rPBx with 20-26 cores, with a median time to rPBx of 12 months. • All slides were reviewed by expert uropathologists. RESULTS: • Plurifocal HGPIN (pHGPIN) was found in 115 patients and monofocal HGPIN (mHGPIN) was found in 147 patients. • In total, 108 and 154 patients, respectively, were submitted to >12-core initial PBx and ≤12-core initial PBx. • Overall PCa detection at rPBx was 31.7%. PSA level (7.7 vs 6.6 ng/mL; P= 0.031) and age (68 vs 64 years; P= 0.001) were significantly higher in patients with PCa at rPBx. • PCa detection was significantly higher in patients with a ≤12-core initial PBx than in those with a >12-core initial PBx (37.6% vs 23.1%; P= 0.01), as well as in patients with pHGPIN than in those with mHGPIN (40% vs 25.1%; P= 0.013). • At multivariable analysis, PSA level (P= 0.041; hazards ratio, HR, 1.08), age (P < 0.001; HR, 1.09), pHGPIN (P= 0.031; HR, 1.97) and ≤12-core initial PBx (P= 0.012; HR, 1.95) were independent predictors of PCa detection. • A nomogram including these four variables achieved 72% accuracy for predicting PCa detection after an initial HGPIN diagnosis. CONCLUSIONS: • PCa detection on saturation rPBx after an initial diagnosis of HGPIN is significantly higher in patients with a ≤12-core initial PBx than those with a >12-core initial PBx and in patients with pHGPIN than in those with mHGPIN. • We developed a simple prognostic tool for the prediction of PCa detection in patients with initial HGPIN diagnosis who were undergoing saturation rPBx.

Diagnosis and treatment of bladder endometriosis: state of the art.

BACKGROUND: The bladder is the most common affected site in urinary tract endometriosis, being diagnosed during gynecologic follow-up. The surgical urological treatment might lead to good results. STUDY OBJECTIVE: To define the state of the art in the diagnosis and treatment of bladder endometriosis. METHODS: We performed a literature review by searching the MEDLINE database for articles published between 1996 and 2011, limiting the searches to the words: urinary tract endometriosis, bladderendometriosis, symptoms, diagnosis and treatment. RESULTS: Deep pelvic endometriosis usually involves the urinary system, with the bladder being affected in 85% of cases. The diagnosis has to be considered as a step-by-step procedure. Currently, the treatment is usually surgical, consisting of either transurethral resection or partial cystectomy, and eventually associated with hormonal therapy. The hormonal therapy alone counteracts only the stimulus of endometriotic tissue proliferation, with no effects on the scarring caused by this tissue. The overall recurrence rate is about 30% for combined therapies and about 35% for the hormonal treatment alone. CONCLUSIONS: The bladder is the most common affected site in urinary tract endometriosis. Most of the time, this condition is diagnosed because of the complaint of urinary symptoms during gynecologic follow-up procedures for a deep pelvic endometriosis: a close collaboration between the gynecologist and the urologist is advisable, especially in highly specialized centers. The surgical urological treatment might lead to good results in terms of patients' compliance and prognosis.

Prostate saturation biopsy following a first negative biopsy: state of the art.

INTRODUCTION: Saturation prostate biopsy (SPBx) has been initially introduced to improve prostate cancer (PCa) detection rate (DR) in the repeat setting. Nevertheless, the optimal number and the most appropriate location of the cores, together with the timing to perform a second PBx and the eventual modification of the PBx protocols according to the different clinical situations, are matters of debate. The aim of this review is to perform a critical analysis of the literature about the actual role of SPBx in the repeat setting. MATERIALS AND METHODS: We performed a systematic review of the literature since 1995 up to 2011. Electronic searches were limited to the English language, using the MEDLINE database. The key words 'saturation prostate biopsy' and 'repeated prostate biopsy' were used. RESULTS: SPBx improves PCa DR if clinical suspicion persists after previous biopsy with negative findings and provides an accurate prediction of prostate tumor volume and grade, even if the issue about the number and locations of the cores is still a matter of debate. CONCLUSIONS: At present, SPBx seems to be really necessary in men with persistent suspicion of PCa after negative initial biopsy and probably in patients with a multifocal high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. In the remaining situations, adopting an individualized scheme is preferable.

Clinical reliability of the 2004 WHO histological classification system compared with the 1973 WHO system for Ta primary bladder tumors.

PURPOSE: Histopathological grade remains the most important predictive factor for the prognosis of nonmuscle invasive bladder cancer. We defined the clinical reliability of the 2004 WHO and International Society of Urological Pathology histological classification system compared with that of the 1973 WHO system for Ta primary bladder tumors. MATERIALS AND METHODS: We evaluated 270 consecutive patients with a first episode of low grade pTa bladder cancer at transurethral resection of the bladder between 2004 and 2008. Grade was assigned by a single uropathologist simultaneously as low grade, and as G1 or G2 according to the 2004 and 1973 WHO classification systems, respectively. All patients received a single early prophylaxis instillation of 50 mg epirubicin as the only adjuvant treatment. Followup included urine cytology and cystoscopy 3 months after resection and every 6 months thereafter for 5 years. Univariate and multivariate analysis of recurrence-free and progression-free survival was done with the Kaplan-Meier method and the log rank test. RESULTS: Mean patient age was 67.3 years (median 67, range 27 to 91). Of the patients 50 were female (18.1%) and 220 (81.9%) were male. According to the 1973 system, grade was G1 in 87 patients (32.2%) and G2 in 183 (67.8%). Median followup was 25 months (mean 27.4, range 3 to 72). The 5-year recurrence-free survival rate was 49.4% for the low grade population, and 62% and 40% for the G1 and G2 groups, respectively (p = 0.004). The 5-year progression-free survival rate was 93% for the low grade population, and 97.6% and 93.3% for the G1 and G2 groups, respectively (p = 0.06). CONCLUSIONS: The 1973 WHO classification system predicted the risk of recurrence in primary pTa cases more accurately than the 2004 WHO system. Each classification had the same accuracy when predicting the risk of progression. Our study confirms the clinical reliability of the new histological classification in clinical practice from a prognostic point of view.

Role of imaging and biopsy to assess local recurrence after definitive treatment for prostate carcinoma (surgery, radiotherapy, cryotherapy, HIFU).

PURPOSE: Defining the site of recurrent disease early after definitive treatment for a localized prostate cancer is a critical issue as it may greatly influence the subsequent therapeutic strategy or patient management. METHODS: A systematic review of the literature was performed by searching Medline from January 1995 up to January 2011. Electronic searches were limited to the English language, and the keywords prostate cancer, radiotherapy [RT], high intensity focused ultrasound [HIFU], cryotherapy [CRIO], transrectal ultrasound [TRUS], magnetic resonance [MRI], PET/TC, and prostate biopsy were used. RESULTS: Despite the fact that diagnosis of a local recurrence is based on PSA values and kinetics, imaging by means of different techniques may be a prerequisite for effective disease management. Unfortunately, prostate cancer local recurrences are very difficult to detect by TRUS and conventional imaging that have shown limited accuracy at least at early stages. On the contrary, functional and molecular imaging such as dynamic contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI), offers the possibility of imaging molecular or cellular processes of individual tumors. Recently, PET/CT, using 11C-choline, 18F-fluorocholine or 11C-acetate has been successfully proposed in detecting local recurrences as well as distant metastases. Nevertheless, in controversial cases, it is necessary to perform a biopsy of the prostatic fossa or a biopsy of the prostate to assess the presence of a local recurrence under guidance of MRI or TRUS findings. CONCLUSION: It is likely that imaging will be extensively used in the future to detect and localize prostate cancer local recurrences before salvage treatment.

Anaesthesia in transrectal prostate biopsy: which is the most effective technique?

BACKGROUND: Prostate biopsy (PBx) techniques have changed significantly since the original Hodge's scheme, with an increase in the number and location of cores. These improvements have been realized in part because of the introduction of different local anaesthesia techniques. We critically analysed the literature discussing the role of anaesthesia techniques for use during PBx to find which technique provides the best pain relief for the patient and safety for the urologist. METHODS: We performed a literature review by searching the Medline database for articles published between January 2000 and March 2010. Electronic searches were limited to the keywords 'transrectal prostate biopsy' and 'anaesthesia'. RESULTS: Pain and discomfort perceived during PBx are the result of different anatomic factors: the introduction to and movement of the transrectal ultrasound probe in the rectum and the needle piercing the rectum and the prostate capsule. The anaesthesia techniques currently available can be divided into two groups: local (i.e. intrarectal lubricant agents, periprostatic nerve blocks, caudal blocks, pudendal nerve blocks, and their different combinations) and systemic (i.e. oral/intravenous drug administration and sedoanalgesia). CONCLUSIONS: The most effective anaesthesia technique for transrectal PBx performed in outpatient settings is the periprostatic nerve blocks with 1 or 2% lidocaine 10 ml, which is associated with intrarectal lubricant agents, especially in younger people. Nevertheless, the current choice of the anaesthesia technique still depends both on patient characteristics (age, prostate size, number and location of cores, anxious personality, need for re-biopsy) and, above all, the urologist's experience and habits.

Active surveillance for non-muscle invasive bladder cancer: A systematic review and pooled-analysis.

INTRODUCTION: One of the Non-Muscle Invasive Bladder Cancer (NMIBC) treatment options recently recommended by International Guidelines is represented by Active Surveillance (AS),. Herein we carried out a systematic review and pooled-analysis of currently available evidences in order to provide recommendations for daily urological practice. MATERIAL AND METHODS: The PubMed, EMBASE, and Coch rane Library databases were searched with the terms "Non-Muscle Invasive" or "pTa/pT1" and "Bladder Cancer" or "Bladder Tumor". A meta-analysis was conducted to estimate the pooled upstage rate (from pTa to pT1/T2), the pooled upgrade (from G1-2 to G3), the proportion of pts still in AS and the pooled AS failure rate across all studies. A random-effects model was used to derive the pooled effect sizes and the 95% confidence intervals (CIs). RESULTS: 7 studies were included, accounting for 558 patients (pts). AS failure rate was 67% (95%CI 44-84%) and 32% of pts were still on AS (14-56%) during a median AS time of 15,6 months. Progression to worst grade or stage was observed in 19% of pts (95%CI 11-30%). Upgrade to G3 and upstage to pT1 were observed in 44% (95%CI 13.6-79.8%) and 8% (95%CI 3.9-15.9%) respectively. CONCLUSIONS: AS for Low Grade NMIBC can be considered safe and feasible, even if only in clinical trial context. We encourage multicenters to perform randomized clinical trials to obtain data about the quality of life of pts on AS, which are scarce, and to rapidly make AS an integral part of daily urological practice as soon as possible.

Is extended and saturation biopsy necessary?

Prostate biopsy (PBx) techniques have significantly changed since the original Hodge's 'sextant scheme', which should now be considered obsolete. The feasibility of carrying out a biopsy scheme with a high number of cores in an outpatient setting is a result of the great improvement and efficacy of local anesthesia. Peri-prostatic nerve block with lidocaine injection should be considered the 'gold standard' because it provides the best pain relief to patients undergoing PBx. The optimal extended protocol should now include the sextant template with an additional 4-6 cores directed laterally (anterior horn) to the base and medially to the apex. Saturation biopsies (i.e. template with > or = 20 cores, including transition zone) should be carried out only when biopsies are repeated in patients where there is a high suspicion of prostate cancer. Complementary imaging methods (such as color- and power-Doppler imaging, with or without contrast enhancement, and elastography) could be used in order to increase the accuracy of biopsy and reduce the number of unnecessary procedures. Nevertheless, the routine use of these methods is still under evaluation.

Overview of the italian experience in surgical management of bladder cancer during first month of COVID-19 pandemic.

OBJECTIVE: Overview of bladder cancer (BC) management in Italy during the first month of the COVID-19 pandemic (March 2020) with head to head comparison of the data from March 2019, considered "usual activity" period. The aim is to analyze performance of different Italian Centers in North, Center and South, with a special eye for Lombardy (the Italian epicenter). PATIENTS AND METHODS: During April 2020, a survey containing 14 multiple-choice questions focused on general staffing and surgical activity related to BC during the months of March 2019 and March 2020 was sent to 32 Italian Centers. Statistical analysis was performed using IBM SPSS Statistics (v26) software. A Medline search was performed, in order to attempt a comparative analysis with published papers. RESULTS: 28 Centers answered, for a response rate of 87.5%. Most of the urology staff in the Lombardy region were employed in COVID wards (p = 0.003), with a statistically significant reduction in the number of radical cystectomies (RC) performed during that time (p = 0.036). The total amount of RC across Italy remained the same between 2019 and 2020, however there was an increase in the number of surgeries performed in the Southern region. This was most likely due to travel restrictions limiting travel the North. The number of Trans-Urethral Resection of Bladder Tumors (TURBT) (p = 0.046) was higher in Academic Centers (AC) in 2020 (p = 0.037). CONCLUSIONS: The data of our survey, although limited, represents a snap shot of the management of BC during the first month of the COVD-19 pandemic, which posed a major challenge for cancer centers seeking to provide care during an extremely dynamic clinical and political situation which requires maximum flexibility to be appropriately managed.

Does educational status affect a patient's behavior toward erectile dysfunction?

INTRODUCTION: Educational status has been investigated rarely as a potential factor affecting the behavior of patients with new onset erectile dysfunction (ED) toward seeking first medical help and subsequent compliance with prescribed phosphodiesterase type 5 inhibitor (PDE5) therapy. AIM: To test whether the educational status of patients with new onset ED and naïve to PDE5 therapy may have a significant impact on the delay before seeking first medical help (DSH) and compliance with the suggested PDE5. MAIN OUTCOME MEASURES: Assessing DSH and compliance with PDE5 in new onset ED patients according to their educational status by means of detailed logistic regression analyses. METHODS: Data from 302 consecutive patients with new onset ED and naïve to PDE5s were comprehensively analyzed. Patients were segregated according to their educational status into low (elementary and/or secondary school education) and high (high school and/or university degrees) educational levels. Complete data were available for 231 assessable patients. Univariate (UVA) and multivariate (MVA) logistic regression analyses addressed the association between educational status and DSH after adjusting for age, relationship status, and Sexual Health Inventory for Men score. Likewise, UVA and MVA were performed to test the association between educational status and patient compliance with PDE5 at the 9-month median follow-up. RESULTS: Median DSH was 24 months (range 1-350; mean 38.1 +/- 42.8). The lower the educational status, the shorter the DSH (P = 0.03). In contrast, a significantly (P < 0.0001) greater proportion of patients with a higher educational status showed compliance with the suggested PDE5 at the 9-month follow-up. Overall, educational status was not an independent predictor of either DSH or patient compliance with PDE5 therapy. CONCLUSIONS: After adjusting for other variables, our findings suggest that in new onset ED patients, educational status does not independently affect the DSH and patient compliance with PDE5 therapy.

[When the conservative treatment in high-risk non-muscle invasive bladder cancer patients should be abandoned]. / Quando rinunciare alla terapia conservativa nelle neoplasie vescicali ad alto rischio.

Despite the good quality of treatment expected with optimized transurethral resection (TUR) and adjuvant Bacillus Calmette-Guérin (BCG) regimen, many high-risk non-muscle invasive bladder cancer (NMIBC) patients recur and progress. According to the EORTC Tables of risk, cases with a score of 10-17 and those with a score of 7-23 should be considered as being at high risk of recurrence and progression, respectively. AUA and NCCN consider all T1 stage tumors, high grade Ta and CIS at high risk of recurrence and progression. Long-term follow-up shows that T1,G3 patients treated with BCG will suffer from up to 45% and 17% rate of recurrence and progression, respectively. Consequently, EAU, AUA and NCCN Guidelines for bladder cancer recommend radical cystectomy as a first treatment option for those patients who failed after two cycles of adjuvant BCG. However, to date, there is no definitive evidence that in this special subgroup of patients an early radical cystectomy is better than any additional salvage strategy, in terms of oncologic outcome. On the other hand, it is well accepted that radical cystectomy is burdened with consistent reduction of overall post-operative quality of life. The reluctance of patient to accept (and of surgeon to recommend) this major extirpative surgery may explain the reduced disease-free survival rate, well documented when radical cystectomy has been extremely delayed. Defining the criteria for the selection of BCG-failure patients for whom any conservative procedure should be definitively abandoned in favor of a timely radical cystectomy has become of critical importance. Recently, clinical, laboratory and pathologic acquisitions allowed the development of more accurate predictive factors for tumor progression in NMIBC. Among these factors, clinical type of BCG-failure, morphology and tumor growth patterns, pathologic sub-staging and immunohistochemistry will play a paramount role in decision-making with these patients in routine practice.

Prostate cancer gene 3 urine assay cutoff in diagnosis of prostate cancer: a validation study on an Italian patient population undergoing first and repeat biopsy.

OBJECTIVE: To determine an optimal prostate cancer gene 3 (PCA3) cutoff in predicting prostate cancer in Italian patients undergoing first or repeat biopsy. STUDY DESIGN: In this observational multicenter study 1246 men with elevated prostate specific antigen (PSA) and negative digital rectal examination, with prostate biopsy after PCA3 assessment, were divided into two groups submitted to PCA3 testing before or after previous negative biopsies. Ideal PCA3 cutoff was identified using area under the curve of the receiver operating characteristic analysis. Various cutoff values were used to determine the best predictive score. Univariate and multivariate logistic regression models compared age, PSA, free-PSA, and PCA3 score to predict prostate cancer. RESULTS: PCA3 cutoff 39-50 had the highest accuracy in the repeat biopsy group in which cutoff of 39 could have avoided 51.9% negative repeat biopsies, eventually missing 7.8% of cancers (all low risk); cutoff of 50 would have prevented 56.5% of negative repeat biopsies, missing 29 tumors (10.3%), 5 potentially aggressive. The PCA3 test performed poorly in the first biopsy group. CONCLUSION: We confirm the usefulness of PCA3 in Italian men with a previous negative biopsy. We achieved the best performance at a cutoff of 39. PCA3 did not perform better than PSA in non-biopsy-selected men.

Neoadjuvant short-term intensive intravesical mitomycin C regimen compared with weekly schedule for low-grade recurrent non-muscle-invasive bladder cancer: preliminary results of a randomised phase 2 study.

BACKGROUND: The schedule for intravesical chemotherapy administration has not been definitively established in patients with low-grade recurrent non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To assess both the feasibility and the efficacy of a short-term intensive schedule of neoadjuvant intravesical chemotherapy in patients with recurrent NMIBC. DESIGN, SETTING, AND PARTICIPANTS: A randomised phase 2 clinical study included 54 patients with recurrent NMIBC who were submitted to neoadjuvant chemotherapy intravesical instillations according to two different timing schedules. The study was performed at a tertiary care referral centre. INTERVENTION: Intravesical mitomycin C (MMC) 40 mg/40 ml was administered according to a schedule of either one instillation per week for 6 wk (group 1) or three instillations per week for 2 wk (group 2) prior to transurethral resection (TUR). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Local and systemic toxicity were investigated using the US National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 questionnaire at each instillation and the SF-36 questionnaire at randomisation and before TUR. A video-recorded cystoscopy and TUR were performed within 14 d after treatment completion. RESULTS AND LIMITATIONS: Groups 1 and 2 each were assigned 27 cases. Two patients (7.4%) in group 2 could not complete the scheduled treatment because of severe lower urinary tract symptoms. No statistically significant difference in SF-36 domain score was documented pre- and post-treatment between groups. Likewise, no statistically significant difference in treatment-related toxicity according to the CTCAE v.4 questionnaire was registered. Twelve patients (44.4%) in group 1 and 19 patients (70.4%) in group 2 (p=0.054) had complete tumour response. The small number of patients included represents the main limitation of the study. CONCLUSIONS: The intensive short-term schedule of neoadjuvant chemotherapy is safe and without additional toxicity compared with the weekly regimen. The increased ablative effect may be explained by the improved adherence of the scheduled timing to the duplication rate of tumour cells.

Prostate-specific antigen (PSA) isoform p2PSA significantly improves the prediction of prostate cancer at initial extended prostate biopsies in patients with total PSA between 2.0 and 10 ng/ml: results of a prospective study in a clinical setting.

BACKGROUND: Total prostate-specific antigen (tPSA), ratio of free PSA (fPSA) to tPSA (%fPSA), and PSA density (PSAD) testing have a very low accuracy in the detection of prostate cancer (PCa). There is an urgent need for more accurate biomarkers. OBJECTIVE: To compare the diagnostic accuracy of PSA isoform p2PSA and its derivatives in determining the presence of PCa at initial biopsy with the accuracy of other predictors in patients with tPSA 2.0-10 ng/ml. DESIGN, SETTING, AND PARTICIPANTS: We conducted an observational prospective study in a real clinical setting of consecutive men with tPSA 2.0-10 ng/ml and negative digital rectal examination who were scheduled for prostate biopsy at a tertiary academic center. INTERVENTION: Outpatient transrectal ultrasound-guided prostate biopsies were performed according to a standardized institutional saturation scheme (18-22 cores). MEASUREMENTS: We determined the diagnostic accuracy of serum tPSA, %fPSA, PSAD, p2PSA, %p2PSA [(p2PSA/fPSA)×100] and the Beckman Coulter Prostate Health Index (phi; [p2PSA/fPSA×√tPSA]). RESULTS AND LIMITATIONS: Overall, 107 of 268 patients (39.9%) were diagnosed with PCa at extended prostate biopsies. Statistically significant differences between patients with and without PCa were observed for age, prostate and transition zone volume, PSAD, %p2PSA, and phi (all p values<0.05). In univariate accuracy analysis, phi and %p2PSA were the most accurate predictors of PCa (area under the curve: 75.6% and 75.7%, respectively), followed by transition zone volume (66%), prostate volume (65%), patient age (63%), PSAD (61%), %fPSA (58%), and tPSA (53%). In multivariate accuracy analyses, both phi (+11%) and %p2PSA (+10%) significantly improved the accuracy of established predictors in determining the presence of PCa at biopsy (p<0.001). Although %p2PSA and phi were significantly associated with Gleason score (Spearman ρ: 0.303 and 0.387, respectively; p ≤ 0.002), they did not improve the prediction of Gleason score ≥7 PCa in multivariable accuracy analyses (p > 0.05). CONCLUSIONS: In patients with a tPSA between 2.0 and 10 ng/ml, %p2PSA and phi are the strongest predictors of PCa at initial extended biopsies and are significantly more accurate than the currently used tests (tPSA, %fPSA, and PSAD) in determining the presence of PCa at biopsy.