Efficacy of hyperthermic intravesical chemotherapy (HIVEC) in patients with non-muscle invasive bladder cancer after BCG failure.

PURPOSE: To evaluate hyperthermic intravesical chemotherapy (HIVEC) efficacy regarding 1-year disease-free survival (RFS) rate and bladder preservation rate in patients with non-muscle invasive bladder cancer (NMIBC) who fail bacillus Calmette-Guérin (BCG) therapy. METHODS: This is a multicenter retrospective series from a national database (7 expert centers). Between January 2016 and October 2021, patients treated with HIVEC for NMIBC who failed BCG have been included in our study. These patients had a theoretical indication for cystectomy but were ineligible for surgery or refused it. RESULTS: A total of 116 patients treated with HIVEC and with a follow-up > 6 months were included in this study and retrospectively analyzed. The median follow-up was 20.6 months. The 12 month-RFS (recurrence-free survival) rate was 62.9%. The bladder preservation rate was 87.1%. Fifteen patients (12.9%) progressed to muscle infiltration, three of them having a metastatic disease at the time of progression. Predictive factors of progression were T1 stage, high grade and very high-risk tumors according to the EORTC classification. CONCLUSION: Chemohyperthermia using HIVEC achieved an RFS rate of 62.9% at 1 year and enabled a bladder preservation rate of 87.1%. However, the risk of progression to muscle-invasive disease is not negligible, particularly for patients with very high-risk tumors. In these patients who fail BCG, cystectomy should remain the standard of care and HIVEC may be discussed cautiously for patients who are not eligible for surgery and well informed of the risk of progression.

BCG-unresponsive high-grade non-muscle invasive bladder cancer: what does the practicing urologist need to know?

PURPOSE: Bacille Calmette-Guérin (BCG) is a well-established treatment for preventing or delaying tumour recurrence following high-grade nonmuscle invasive bladder cancer (NMIBC) resection. However, many patients will experience recurrence or progression during or following BCG. This scenario has been one of the most challenging in urologic oncology for several decades since BCG implementation. Finally, significant progress has occurred lately. The aim of this review was to summarize for the practising urologist the current treatment options available in 2020 or expected to be ready for routine use in the near future for patients with high-risk NMIBC who experience BCG failure. METHODS: Narrative review using data through the end of 2020. RESULTS: First, the definition of BCG unresponsive disease which is critical in counseling and managing patients has finally reached a consensus. Second, some promising options other than radical cystectomy are finally available and many other should be in a near future. The options can be categorized as chemotherapy, device-assisted therapy, check-point inhibitors, new intravesical and systemic agents and sequential combinations of these newer modalities with conventional therapy. CONCLUSIONS: Considering the options that are currently under scrutiny, many of which in phase III trials, clinicians should have at their disposal several new treatment options in the next five years.

Surgical complications risk in obese and overweight recipients for kidney transplantation: a predictive morphometric model based on sarcopenia and vessel-to-skin distance.

PURPOSE: Sarcopenia or adipose tissue distribution within obese and overweight renal transplanted have been poorly evaluated. Our objective was to evaluate morphometric markers to predict surgical complications in kidney transplantation. METHODS: We retrospectively included patients with a BMI > 25 kg/m2 undergoing kidney transplantation from 2012 to 2017. Following measurements were performed on CT-scan sections: Sub-cutaneous Adipose Tissue surface (SAT), Visceral Adipose Tissue surface (VAT), Vessel-to-Skin distance (VSK), Abdominal Perimeter (AP), and Psoas surface. A multivariable logistic regression model with BMI was compared to a model containing morphometric variables to determine the best predictive model for surgical complications. RESULTS: 248 patients were included, 15 (6%) experienced transplant nephrectomy, 18 (7.3%) urinary leakage, and 29 (11.7%) subcapsular renal hematoma. Multivariable logistic regression evidenced that sarcopenia and VSK were risk factors of surgical complication within a year post-transplantation (respectively, OR = 0.9, 95%CI (0.8-0.9), p = 0.04 and OR = 1.2, 95%CI (1.1-1.3), p = 0.002). Area under the curve for a predictive model including VSK, age and psoas surface was 0.69, whereas BMI model was 0.65. CONCLUSION: Combined morphometric parameters of obesity were associated with surgical complications in kidney transplantation. Morphometric threshold may provide a more accurate and objective criteria than BMI to evaluate kidney transplantation outcomes. External validation is needed.

Efficacy of HIVEC in patients with high-risk non-muscle invasive bladder cancer who are contraindicated to BCG and in patients who fail BCG therapy.

PURPOSE: To evaluate Hyperthermic-Intra-Vesical Chemotherapy (HIVEC) efficacy regarding 1-year disease-free survival (RFS) rate and bladder preservation rate in patients with High-risk Non-Muscle Invasive Bladder Cancer (NMIBC) who fail BCG therapy or are contraindicated to BCG. METHODS: Between June 2016 and October 2019, patients treated with HIVEC for mostly high-risk NMIBC who failed BCG or BCG-naive if BCG contraindicated have been included in our study. These patients had a theoretical indication for cystectomy but were ineligible for surgery or refused it. RESULTS: Fifty-three patients, median age 72 [39-93] years, were included in this study (n = 29 BCG-failure and n = 24 BCG-naive). The median follow-up was 18 months. The bladder preservation rate was 92.4%. The 12 months-RFS rate was 60.5%. The RFS rates for BCG-naive and BCG-failure groups were respectively 70% and 52.2% at 12 months. Three patients progressed to muscle infiltration, all in the BCG-failure group and all in the very high-risk EORTC group. Two of them developed metastatic disease and died from bladder cancer. CONCLUSION: Chemohyperthermia using HIVEC achieved a RFS rate of 60% at 1 year and enabled a bladder preservation rate of 92%. Given the low risk of progression in the BCG-naive group, HIVEC could be a good alternative. Conversely, for patients with very high-risk tumors that fail BCG, cystectomy should remain the standard of care and HIVEC may be discussed cautiously for patients who are not eligible for surgery and well informed of the risk of progression to muscle-invasive disease.

Clinical interest of PD-L1 immuno-histochemistry expression as a predictive factor of Bacillus Calmette Guerin (BCG) efficacy in refractory high-risk non-muscle-invasive bladder cancer (NMIBC).

OBJECTIVE: To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC. MATERIALS AND METHODS: Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant. RESULTS: A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly (p = 0.97) more frequent in the TC PD-L1 ≥ 1% group (n = 7, 20.0%) than in the TC PD-L1-negative group (n = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p < 0.05), with increased expression of PD-L1 by IC after BCG therapy (p = 0.006). CONCLUSION: No association was observed between immuno-histochemistry PD-L1 positivity and ER after BCG therapy. Nevertheless, the relationship between immune infiltrate and PD-L1 positivity confirmed the interest of assessing the immune infiltrate density to define tumor's profile.

Temporary contraindication of obese recipients in kidney transplantation: A new morphometric tool for decision support.

BACKGROUND: Morbid obesity, based on body mass index (BMI) and/or clinical examination, can be a temporary contraindication (TCI) of kidney transplantation. However, BMI alone does not evaluate the intra- or extra-peritoneal distribution of fatty tissue, and clinical examination alone is subjective. The objective was to evaluate the interest of morphometric criteria to ensure reproducible and consensual decision of TCI. METHODS: We retrospectively included patients with a BMI >30 transplanted or temporarily contraindicated because of their weight from 2012 to 2017. The following measurements were performed on CT scan sections using a semiautomatic Hounsfield density detection software: subcutaneous adipose tissue surface (SAT), visceral adipose tissue surface (VAT), vessel-to-skin distance (VSK), abdominal perimeter (AP), and psoas index. Performance of morphometric measures to predict TCI was assessed through ROC analysis. RESULTS: Ninety-seven patients were included: 76 kidney transplant recipients and 21 on the TCI list. The area under the curve (AUC, 95%CI) for the BMI model to predict TCI was 0.81 (0.72-0.90). A 5-variable model including BMI, VAT, VSK, AP, and age gave an AUC of 0.88 (0.78-0.98). CONCLUSIONS: Morphometric obesity parameters are associated with TCI decision-making for kidney transplantation: When combined with BMI in a "morphometric tool," they were predictive of a TCI decision.

Epidemiology, biology and treatment of sarcomatoid RCC: current state of the art.

Long recognized to confer an extremely poor prognosis, sarcomatoid dedifferentiation of renal cell carcinoma (sRCC) is a tumor phenotype that is finally beginning to be better understood on the molecular and genetic levels. With an overall incidence that ranges from 1 to 32% depending on associated RCC subtype, the survival of sarcomatoid RCC patients rarely exceeds 2 years. The main reasons for its poor outcome include its aggressive biology, its tendency to present at an advanced or metastatic stage at the time of diagnosis, its high rate of tumor recurrence after nephrectomy, and its limited response to systemic therapies. Molecular pathology studies suggest that sarcomatoid dedifferentiation originates from a focal epithelial-mesenchymal transition (EMT) arising in the carcinomatous component of the tumor. It is hoped that the growing understanding of the molecular biology of sRCC will soon make it possible to adapt treatments based on the identification of actionable tumor alterations. The deliberate inclusion of these patients in the multicenter clinical trials of immune, targeted and combination therapies is a necessary next step in pioneering future treatment strategies.

Final results of the phase III URO-BCG 4 multicenter study: efficacy and tolerance of one-third dose BCG maintenance in nonmuscle invasive bladder cancer.

The objective of this study was to assess at 3 years bacillus Calmette-Guerin (BCG) maintenance treatment for NMIBC using one-third dose schedule and fewer instillations every 3 or 6 months. This was a phase III randomized study including patients with intermediate-risk or high-risk NMIBC, who received, after a full-dose induction schedule, three-weekly instillations of one-third dose BCG every 6 months (group I) and two-weekly instillations every 3 months (group II) during 3 years. We assessed oncological efficacy, BCG side effects, leukocyturia, and prostate-specific antigen. No tumor recurrence was reported at 36 months for 55 (82.09%) patients in group I versus 64 (90.14%) patients in group II (P=0.241). Muscle invasion was observed in six patients at 36 months (P=0.942). In terms of BCG toxicity, grade II and III local or systemic side effects were, respectively, reported in 8.7 and 23.9% of patients during the first year. Nevertheless, the adverse events (AEs) score at 36 months underlined a lower median value of 0.8 in group I versus 1.1 in group II (P=0.037). Furthermore, 9.9% major AEs occurred in group II versus 3% in group I (P=0.031). Leukocyturia and prostate-specific antigen level were not associated significantly with either tumor recurrence or muscle progression. We observed a significant difference in the AEs score at 36 months, suggesting less toxicity in patients who were treated with one-third dose of BCG for 3 consecutive weeks every 6 months.

Observational Studies Requested by European Health Authorities: Governmental Interference or an Enhancement of Everyday Urological Practice? The Hexvix® Observational Patients Evaluation Study as an Example of What to Expect.

OBJECTIVE: The Hexvix® Observational Patients Evaluation (HOPE) study was designed to determine the extent of distribution of the use of hexaminolevulinate in the diagnosis of non-muscle invasive bladder cancer (NMIBC) and assess patient and treatment characteristics associated with different endoscopic modalities and to address the French authorities' request for information on routine practices for NMIBC diagnosis and surveillance. PATIENTS AND METHODS: A prospective, observational study in 30 centres in France with fluorescence endoscopy equipment available. All candidates for endoscopy with transurethral resection who gave their consent were eligible. The primary endpoint was the proportion of patients with an NMIBC diagnosis performed with hexaminolevulinate. RESULTS: 506 patients were included: 252 (49.8%) diagnosed with hexaminolevulinate and 254 (50.2%) with white-light endoscopy alone. There were more patients with tumour recurrence, multiple lesions, lesions with a diameter <3 cm, stage Ta disease, and grade 1 lesions in the hexaminolevulinate group. The first quartile median recurrence-free survival time was 310 days in the hexaminolevulinate group and 144 days in the standard-endoscopy group (p = 0.0015). CONCLUSION: Hexaminolevulinate was in frequent use in France with specific patient and disease characteristics associated with its use. HOPE illustrates the type of data that can be gained in post-authorisation studies to address requests from European health authorities.

The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guérin.

OBJECTIVES: To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS). PATIENTS AND METHODS: In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette-Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups. RESULTS: Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints. CONCLUSIONS: Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR.

Efficacy and tolerance of one-third full dose bacillus Calmette-Guérin maintenance therapy every 3 months or 6 months: two-year results of URO-BCG-4 multicenter study.

OBJECTIVES: To assess bacillus Calmette-Guérin maintenance treatment schedule for non-muscle invasive bladder cancer at 2 years, using one-third of the full dose and fewer instillations every 3 months or 6 months. METHODS: This was a prospective, randomized, multicenter study. All patients had an intermediate- or high-risk non-muscle invasive bladder cancer. They received three weekly instillations of one-third dose bacillus Calmette-Guérin every 6 months (group I) and two weekly instillations every 3 months (group II) during 3 years. In the two schedules we assessed efficacy, tolerance, leukocyturia and prostate-specific antigen. RESULTS: No significant difference was observed between the two groups for recurrence at 6, 12 or 18 months. At 2 years, tumor recurrence was observed in 10.9% and muscle invasion in 2.9% of cases. Bacillus Calmette-Guérin tolerance was comparable - the adverse events score was 0.8 in group I and 1 in group II (P = 0.242). No statistical correlation was observed between the adverse events score over 2 years, either for leukocyturia (P = 0.8891) or prostate-specific antigen level (P = 0.7155). Leukocyturia level was not significantly associated with tumor recurrence or progression. CONCLUSION: One-third dose maintenance bacillus Calmette-Guérin is effective with no impact on tumor recurrence or muscle invasion. Furthermore, there seems to be no difference in tumor response or side-effects between patients receiving two or three maintenance instillations every 3 months or 6 months. In clinical practice, the use of leukocyturia or total prostate-specific antigen levels do not appear to be useful in predicting bacillus Calmette-Guérin toxicity.

[Metastatic lymph node collision of a prostatic adenocarcinoma and an urothelial carcinoma and review of the literature]. / Double métastase ganglionnaire d'un adénocarcinome prostatique et d'un carcinome urothélial et revue de la littérature.

INTRODUCTION: Tumor collision is the encounter of two tumors from two different topographical sites. Cases of metastatic lymph node collision are exceptional. We report the case of a metastatic lymph node collision of an urothelial carcinoma and a prostatic adenocarcinoma. OBSERVATION: A 61-year-old man was hospitalized for a right nephroureterectomy with peri-ureteral lymph node dissection. He was followed since 2004 for prostatic adenocarcinoma and treated with radical prostatectomy then radiation therapy 4 years later due to a new increase of PSA. In the follow-up, an urothelial carcinoma of the lower right ureter was discovered in 2014. Histological analysis of a peri-ureteral lymph node showed a double metastasis of urothelial and prostatic origin. The prostatic adenocarcinoma was composed of acinar and ductal subtypes. Immunohistochemical study including CK7, CK20, PSA, GATA3, P63 antibodies confirmed the distinct phenotype of the 2 tumors. DISCUSSION: Metastatic collision of urothelial carcinoma and prostatic adenocarcinoma has been reported in 4 cases only. Our review of literature shows that prostatic adenocarcinoma always precedes the urothelial carcinoma. Immunohistochemical study, when carried out for distinguishing both tumors, should include CK7, CK20 and PSA. GATA3, androgen receptor and P63 could be added in a second time.

ERG expression in prostate cancer: the prognostic paradox.

BACKGROUND: TMPRSS2/ERG fusion resulting in ERG overexpression occurs in 30 to 50% of prostate cancer (PCa) in Caucasian patients, but its prognostic relevance remains controversial. In the present study, we investigated ERG expression in all stages of PCa progression, and evaluated the prognostic impact of ERG status in clinically localized PCa (CLC) and in castration resistant disease (CRPC). METHODS: ERG and AR expressions were evaluated by immunohistochemistry on tissue microarrays containing samples of high grade PIN (n = 57), CLC surgically treated (n = 299, including 185 Caucasians and 114 African-Caribbeans), metastases (n = 17), and CRPC (n = 41). RESULTS: In Caucasians, ERG expression significantly increased from high grade PIN (17.5%) to pT2 (27%) and pT3 CLC (43%), then to metastases (53%). In CLC, stainings for ERG and AR were correlated, and ERG expression was less frequent in African-Caribbeans compared to Caucasians (11.5% vs. 33%). In Caucasians CLC, ERG was associated with longer recurrence free survival, after adjusting for classical prognostic markers. In CRPC, ERG was expressed in 29% of cases, and was associated with a longer overall survival. CONCLUSIONS: Our results confirm that ERG expression is less frequent in PCa from patients of African descent. Although ERG expression increases during PCa natural history, positive ERG status is associated with better outcome in both CLC and CRPC. This paradox could be explained in part by the fact that ERG expression is AR dependant, then ERG positive cancers are likely to progress in a rich androgen environment, with a better response to androgen suppression.

Is intermittent androgen-deprivation therapy beneficial for patients with advanced prostate cancer?

Use of intermittent androgen-deprivation therapy (IADT) in patients with prostate cancer has been evaluated in several studies, in an attempt to delay the development of castration resistance and reduce side-effects associated with ADT. However it is still not clear whether survival is adversely affected in patients treated with IADT. In this review, we explore the available data in an attempt to identify the most suitable candidate patients for IADT, and discuss factors that may inform appropriate patient stratification. ADT is first-line treatment for advanced/metastatic prostate cancer and is also recommended for use with definitive radiotherapy for high-risk localised prostate cancer. The changes in hormone levels induced by ADT can lead to short- and long-term side-effects which, although treatable in most cases, can significantly reduce the tolerability of ADT treatment. IADT has been investigated in several phase II and phase III studies in patients with locally advanced or metastatic prostate cancer, in an attempt to delay time to tumour progression and reduce the side-effect burden of ADT. In selected patient groups IADT is no less effective than continuous ADT, ameliorating the impact of ADT-related side-effects, and, to a degree, their impact on patient health-related quality of life (HRQL). Further comparative study is required, particularly in relation to HRQL and long-term complications associated with ADT.

Can we improve the definition of high-risk, hormone naïve, non-metastatic prostate cancer?

To identify criteria beyond Tumour-Node-Metastasis (TMN)-, prostate-specific antigen (PSA)- and Gleason score-based standard classifications to enhance the stratification of non-metastatic high-risk prostate cancer. A detailed search of the literature was performed using PubMed. The authors reviewed the literature and used a modified Delphi approach to identify relevant approaches to enhance standard classifications. Specific criteria for high-risk prostate cancer vary across guidelines and clinical trials, reflecting the differing perspectives concerning the definition of 'risk' between different specialities within the urology/radiation oncology community. In addition to the present classifications, evidence exists that the measure of cancer volume can provide additional prognostic value. More accurate imaging, especially multiparametric magnetic resonance imaging can also provide information concerning staging and cancer volume, and thus may assist in the identification of patients with high-risk prostate cancer. A refined definition of non-metastatic high-risk prostate cancer is proposed. Within this high-risk cohort, patients with multiple high-risk criteria are especially at risk of prostate cancer-specific mortality.

Risk stratification of metastatic recurrence in invasive upper urinary tract carcinoma after radical nephroureterectomy without lymphadenectomy.

PURPOSE: To assess the risk factors of metastasis relapse in pT2-3 upper tract urothelial carcinomas (UTUCs) treated by radical nephroureterectomy (RNU) without lymphadenectomy (LN). METHODS: A multicentric retrospective study was performed for pT2-3 pNx UTUCs treated by RNU between 1995 and 2010. The following criteria were retrieved: age, gender, American Society of Anaesthesiologists physical status, surgical approach, preoperative hydronephrosis, stage, grade, tumor location, surgical margin, lymphovascular invasion (LVI) status and outcomes. Metastasis-free survival (MFS) was measured by Kaplan-Meier method with the log-rank test. RESULTS: Overall, 151 patients were included. The median follow-up was 18.5 months (IQR 9.5-37.9). The 2- and 5-year MFS were 69 % ± 4.5 and 54.1 % ± 5.8, respectively. In univariate analysis, ureteral location, pT3 stage, positive LVI status and positive surgical margin were significantly associated with worse MFS (p = 0.03; 0.02; 0.01 and 0.006, respectively). In the multivariate analysis of ureteral location and pT3 stage were independent prognostic factors (p = 0.03 and 0.03, respectively). Based on the results of the univariate analysis, we proposed a risk model predicting MFS, which classifies patients into 3 categories with different overall survival (p < 0.001). CONCLUSION: In view of our data, tumor location, T stage, LVI and surgical margin status are mandatory to predict survival in case of RN without LN. Contingent upon external validation, our risk model based on these variables could be useful to provide relevant information concerning metastasis relapse probability and necessity of close follow-up for these patients.

[Non-muscle invasive bladder cancer]. / Tumeurs de la vessie n'infiltrant pas le muscle.

Non-muscle invasive bladder cancers (NMIBC) represent a heterogeneous group as regards their biology and their seriousness. NMIBC management should be adapted to the acknowledged prognostic factors. First line treatment of NMIBC includes a transurethral resection of the bladder (TURB). Recurrence and progression risks following TURB are significantly high. Acknowledged factors are T stage, grade, number and size of tumors, recurrence modalities and associated carcinoma in situ. The benefit of adjuvant therapy using chemotherapy or BCG intravesical instillations has been demonstrated particularly on recurrence risk. Progression is very likely reduced by maintenance BCG. However, when high grade tumours do not respond to BCG, radical cystectomy is the mainstay treatment.

Is an extended 20-core prostate biopsy protocol more efficient than the standard 12-core? A randomized multicenter trial.

PURPOSE: We determined the impact of increasing the number of cores from 12 to 20 at initial prostate biopsy in men suspicious of prostate cancer. MATERIALS AND METHODS: From December 2009 to November 2011, patients in 7 centers scheduled for a first prostate biopsy, with a prostate specific antigen less than 20 ng/ml and no nodule on digital rectal examination, were invited to participate in this superiority trial. Patients were randomized to a 12-core (PB12 group) or a 20-core (PB20 group) protocol. The primary end point was cancer detection rate. Secondary end points were cancer characteristics, rate of complications and patient tolerance assessed by a self-completed booklet before prostate biopsy and at day 5 and day 15. RESULTS: A total of 339 patients were randomized. Preoperative variables were similar in both groups. Cancer was detected in 71 patients (42.0%) in PB12 group and in 81 patients (48.8%) in PB20 group, and the difference was not significant (p >0.2). Gleason score and cancer length measured on prostate biopsy cores were not significantly different between groups. Although the cancer detection rate was linked to prostate volume, this was not affected by the number of extracted cores (p >0.4). Complications number and seriousness were comparable in both arms. No significant difference was noted regarding side effects and tolerance as self-assessed by the patient at day 5 and day 15 after prostate biopsy. CONCLUSIONS: Our findings suggest that there is no significant advantage in using a 20-core biopsy protocol vs 12-core protocol during an initial prostate biopsy.

Prognostic interest in discriminating muscularis mucosa invasion (T1a vs T1b) in nonmuscle invasive bladder carcinoma: French national multicenter study with central pathology review.

PURPOSE: Predictive factors of T1 nonmuscle invasive bladder cancer evolution that could guide treatment decision making are lacking. We assessed the prognostic value of muscularis mucosa invasion in nonmuscle invasive bladder cancer. MATERIALS AND METHODS: In a national multicenter study patients with primary T1 nonmuscle invasive bladder cancer were recruited from 6 French hospitals. All patients had undergone transurethral resection of bladder tumor. All T1 tumors were substaged according to muscularis mucosa invasion as T1a-no invasion beyond the muscularis mucosa or T1b-invasion beyond the muscularis mucosa with muscle preservation. Subsequent central pathology review was then done by a single referent uropathologist. Muscularis mucosa invasion was tested as a prognostic factor for survival on univariate and multivariate analysis. RESULTS: A total of 587 patients were enrolled in the study, including 388 (66%) with T1a and 199 (34%) with T1b tumors. Median followup after transurethral resection of bladder tumor was 35 months (IQR 14-54). There was no significant difference between groups T1a and T1b except high tumor grade in T1b cases (p <0.0001). After central review, initial pathological substaging was confirmed in 84% of cases. On multivariate analysis muscularis mucosa invasion (T1b substage) was significantly associated with recurrence-free (p = 0.03), progression-free (p = 0.0002) and cancer specific (p = 0.02) survival. The main study limitation was absent systematic subsequent transurethral resection of bladder tumor. CONCLUSIONS: Muscularis mucosa invasion appears to be highly predictive of T1 nonmuscle invasive bladder cancer behavior. Consequently, systematic T1a vs T1b discrimination should be highly advocated by urologists and pathologists. We believe that it could aid in crucial decision making when choosing between conservative management and radical cystectomy remains a moot point.