Prognosis of patients with T1 low-grade urothelial bladder cancer treated with bacillus Calmette-Guérin immunotherapy.

BACKGROUND: The existence and prognosis of T1LG (T1 low-grade) bladder cancer is controversial. Also, because of data paucity, it remains unclear what is the clinical history of bacillus Calmette-Guérin (BCG) treated T1LG tumors and if it differs from other NMIBC (non-muscle-invasive bladder cancer) representatives. The aim of this study was to analyse recurrence-free survival (RFS) and progression-free survival (PFS) in patients with T1LG bladder cancers treated with BCG immunotherapy. METHODS: A multi-institutional and retrospective study of 2510 patients with Ta/T1 NMIBC with or without carcinoma in situ (CIS) treated with BCG (205 T1LG patients) was performed. Kaplan-Meier estimates and log-rank test for RFS and PFS to compare the survival between TaLG, TaHG, T1LG, and T1HG NMIBC were used. Also, T1LG tumors were categorized into EAU2021 risk groups and PFS analysis was performed, and Cox multivariate model for both RFS and PFS were constructed. RESULTS: The median follow-up was 52 months. For the T1LG cohort, the estimated RFS and PFS rates at 5-year were 59.3% and 89.2%, respectively. While there were no differences in RFS between NMIBC subpopulations, a slightly better PFS was found in T1LG NMIBC compared to T1HG (5-year PFS; T1LG vs. T1HG: 82% vs. 89%; P<0.001). A heterogeneous classification of patients with T1LG NMIBC was observed when EAU 2021 prognostic model was applied, finding a statistically significant worse PFS in patients classified as high-risk T1LG (5-year PFS; 81.8%) compared to those in intermediate (5-year PFS; 93,4%), and low-risk T1LG tumors (5-year PFS; 98,1%). CONCLUSIONS: The RFS of T1LG was comparable to other NMIBC subpopulations. The PFS of T1LG tumors was significantly better than of T1HG NMIBC. The EAU2021 scoring model heterogeneously categorized the risk of progression in T1LG tumors and the high-risk T1LG had the worst PFS.

Safety, Tolerability, and Preliminary Efficacy of TAR-200 in Patients With Muscle-invasive Bladder Cancer Who Refused or Were Unfit for Curative-intent Therapy: A Phase 1 Study.

PURPOSE: Half of patients with muscle-invasive bladder cancer worldwide may not receive curative-intent therapy. Elderly or frail patients are most affected by this unmet need. TAR-200 is a novel, intravesical drug delivery system that provides sustained, local release of gemcitabine into the bladder over a 21-day dosing cycle. The phase 1 TAR-200-103 study evaluated the safety, tolerability, and preliminary efficacy of TAR-200 in patients with muscle-invasive bladder cancer who either refused or were unfit for curative-intent therapy. MATERIALS AND METHODS: Eligible patients had cT2-cT3bN0M0 urothelial carcinoma of the bladder. TAR-200 was inserted for 4 consecutive 21-day cycles over 84 days. The primary end points were safety and tolerability at 84 days. Secondary end points included rates of clinical complete response and partial response as determined by cystoscopy, biopsy, and imaging; duration of response; and overall survival. RESULTS: Median age of the 35 enrolled patients was 84 years, and most were male (24/35, 68.6%). Treatment-emergent adverse events related to TAR-200 occurred in 15 patients. Two patients experienced treatment-emergent adverse events leading to removal of TAR-200. At 3 months, complete response and partial response rates were 31.4% (11/35) and 8.6% (3/35), respectively, yielding an overall response rate of 40.0% (14/35; 95% CI 23.9-57.9). Median overall survival and duration of response were 27.3 months (95% CI 10.1-not estimable) and 14 months (95% CI 10.6-22.7), respectively. Progression-free rate at 12 months was 70.5%. CONCLUSIONS: TAR-200 was generally safe, well tolerated, and had beneficial preliminary efficacy in this elderly and frail cohort with limited treatment options.

Analysis of prognostic factors of failure in perineal urethrostomy.

PURPOSE: To identify prognostic factors of failure in patients undergoing perineal urethrostomy (PU) with Blandy technique, with inverted U-shaped perineal flap. METHODS: This is a retrospective study of PU of non-oncological causes (2001-2017). Data of age, BMI, history of diabetes mellitus, etiology of urethral stricture, type of stricture, previous surgeries, dilatation and suprapubic catheter were collected. Failure was defined as the need for any instrumentation after surgery. Variables were analyzed by Cox regression and Kaplan-Meier curves were used for survival analysis. RESULTS: A total of 115 PU were performed. Median age was 61 years (IQR 53-68) and BMI 27.9 (IQR 25-30.9). The most frequent etiologies were: lichen sclerosus (30.4%), iatrogenic (27%), and idiopathic (25.7%). 62.6% had panurethral stricture. There were no complications in 73%. Clavien I complications occurred in 25.2%, Clavien II in 0.9% and Clavien IVa in 0.9%. The overall success rate was 51.3% with a median follow-up of 71 months. In the last 8 years, it was 75%. In the multivariate analysis, we found that age (p = 0.01), BMI (p = 0.01), date of surgery (p = 0.01), and suprapubic catheter (p = 0.003) were predictive variables. The voiding satisfaction rate was 88.7%. CONCLUSIONS: PU with Blandy technique is a surgery with low morbidity. During the entire study period, it had a failure rate of 48.7% but the failure rate decreased to 25% over the last 8 years. Age, BMI, date of surgery and suprapubic catheter are the most important prognostic factor of failure.

Neisseria meningitidis y el aumento del sexo oral. A propósito de un caso / Neisseria meningitidis and the increase of oral sex. A case report

La uretritis es una entidad caracterizada por disuria y secreción uretral purulenta, generalmente adquirida por vía sexual. Neisseria gonorrhoeae es uno de los microorganismos más frecuentemente responsables. Neisseria meningitidis es un diplococo gramnegativo aislado habitualmente en la faringe, que causa en ocasiones meningitis meningocócica, siendo poco común aislarlo en el área anogenital, donde podría ser patógeno genitourinario. Presentamos el caso de un hombre heterosexual de 25 años que tras una relación heterosexual con una pareja ocasional no profesional que incluyó sexo oral y vaginal presenta clínica de uretritis, orientándose como infección de transmisión sexual. El cultivo bacteriológico convencional para N. gonorrhoeae fue negativo, siendo la PCR para Chlamydia trachomatis positiva. Posteriormente, el laboratorio informó de un cultivo bacteriológico positivo para N. meningitidis serogrupo C, sensible a ceftriaxona, y PCR negativa para N. gonorrhoeae. N. meningitidis es la principal causa de meningitis bacteriana, pero estudios genómicos evidencian que alelos de la nitrato reductasa, la proteína ligadora del factor-H y la cápsula están asociados con aislamientos de N. meningitidis en infecciones genitourinarias. La transmisión desde orofaringe a uretra a través del contacto orogenital en el sexo oral desprotegido ha sido ampliamente demostrada. La prevalencia de N. meningitidis como causante de uretritis es baja, siendo los portadores asintomáticos en uretra muy raros. La PCR es un método para el diagnóstico de N. gonorrhoeae y C.trachomatis, pero no detecta N. meningitidis. El diagnóstico de gonorrea se basa en un número aumentado de polimorfonucleares con diplococos gramnegativos intracelulares en tinción de Gram de secreción uretral. En nuestro caso, el diplococo gramnegativo visualizado en la tinción fue meningococo. (AU)

Urethritis is an entity characterized by dysuria and purulent urethral discharge, generally acquired sexually. Neisseria gonorrhoeae is one of the most frequently responsible microorganisms. Neisseria meningitidis is a gram-negative diplococcus usually isolated in the pharynx, that occasionally causes meningococcal meningitis, being unusual it's isolation in the anogenital area where it could be a genitourinary pathogen. We present the case of a 25-years-old heterosexual male who, after a heterosexual intercourse with an occasional non-professional partner, including oral and vaginal sex, presented with symptoms of urethritis, orienting to a sexually transmitted infection. The bacteriological culture for N. gonorrhoeae was negative and the PCR for Chlamydia trachomatis was positive. Subsequently, the lab reported a positive bacteriological culture for sero-group C N. meningitidis, sensitive to ceftriaxone and a negative PCR for N. gonorrhoeae. N. meningitidis is the main cause of bacterial meningitis, but genomic studies have suggested that alleles of nitrate reductase, factor-H biding protein and capsule are associated with N. meningitidis isolation in genitourinary infections. Transmission from the oropharynx to the urethra through orogenital contact in unprotected oral sex has been widely proven. N. meningitidis prevalence as the cause of the urethritis is low, and the asymptomatic carriers in the urethra are extremely rare. PCR is a method for the N. gonorrhoeae and C.trachomatis diagnoses, but it does not detect N. meningitidis. The gonorrhoea diagnosis is based on an increased number of polymorphonuclear cells, with intracellular gram-negative diplococci in Gram’ stain of urethral discharge. In our case, the gram-negative diplococcus seen in the stain was a meningococcus. (AU)

[Neisseria meningitidis and the increase of oral sex. A case report]. / Neisseria meningitidis y el aumento del sexo oral. A propósito de un caso.

Urethritis is an entity characterized by dysuria and purulent urethral discharge, generally acquired sexually. Neisseria gonorrhoeae is one of the most frequently responsible microorganisms. Neisseria meningitidis is a gram-negative diplococcus usually isolated in the pharynx, that occasionally causes meningococcal meningitis, being unusual it's isolation in the anogenital area where it could be a genitourinary pathogen. We present the case of a 25-years-old heterosexual male who, after a heterosexual intercourse with an occasional non-professional partner, including oral and vaginal sex, presented with symptoms of urethritis, orienting to a sexually transmitted infection. The bacteriological culture for N. gonorrhoeae was negative and the PCR for Chlamydia trachomatis was positive. Subsequently, the lab reported a positive bacteriological culture for sero-group C N. meningitidis, sensitive to ceftriaxone and a negative PCR for N. gonorrhoeae. N. meningitidis is the main cause of bacterial meningitis, but genomic studies have suggested that alleles of nitrate reductase, factor-H biding protein and capsule are associated with N. meningitidis isolation in genitourinary infections. Transmission from the oropharynx to the urethra through orogenital contact in unprotected oral sex has been widely proven. N. meningitidis prevalence as the cause of the urethritis is low, and the asymptomatic carriers in the urethra are extremely rare. PCR is a method for the N. gonorrhoeae and C.trachomatis diagnoses, but it does not detect N. meningitidis. The gonorrhoea diagnosis is based on an increased number of polymorphonuclear cells, with intracellular gram-negative diplococci in Gram' stain of urethral discharge. In our case, the gram-negative diplococcus seen in the stain was a meningococcus. Urethritis due to N. meningitidis is indistinguishable from the secondary to N. gonorrhoeae, mimicking it even microscopically, only the epidemiology varies. The conventional bacteriological culture continues to be essential for a correct diagnosis.

Accuracy of the CUETO, EORTC 2016 and EAU 2021 scoring models and risk stratification tables to predict outcomes in high-grade non-muscle-invasive urothelial bladder cancer.

PURPOSE: Non-muscle-invasive bladder cancers (NMIBC) constitute 3-quarters of all primary diagnosed bladder tumors. For risk-adapted management of patients with NMIBC, different risk group systems and predictive models have been developed. This study aimed to externally validate EORTC2016, CUETO and novel EAU2021 risk scoring models in a multi-institutional retrospective cohort of patients with high-grade NMIBC who were treated with an adequate BCG immunotherapy. METHODS: The Kaplan-Meier estimates for recurrence-free survival and progression-free survival were performed, predictive abilities were assessed using the concordance index (C-index) and area under the curve (AUC). RESULTS: A total of 1690 patients were included and the median follow-up was 51 months. For the overall cohort, the estimates recurrence-free survival and progression-free survival rates at 5-years were 57.1% and 82.3%, respectively. The CUETO scoring model had poor discrimination for disease recurrence (C-index/AUC for G2 and G3 grade tumors: 0.570/0.493 and 0.559/0.492) and both CUETO (C-index/AUC for G2 and G3 grade tumors: 0.634/0.521 and 0.622/0.525) EAU2021 (c-index/AUC: 0.644/0.522) had poor discrimination for disease progression. CONCLUSION: Both the CUETO and EAU2021 scoring systems were able to successfully stratify risks in our population, but presented poor discriminative value in predicting clinical events. Due to the lack of data, model validation was not possible for EORTC2016. The CUETO and EAU2021 systems overestimated the risk, especially in highest-risk patients. The risk of progression according to EORTC2016 was slightly lower when compared with our population analysis.

Intermediate-risk Non-muscle-invasive Bladder Cancer: Updated Consensus Definition and Management Recommendations from the International Bladder Cancer Group.

CONTEXT: Intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease. OBJECTIVE: To update the International Bladder Cancer Group (IBCG) guidance and provide practical recommendations on IR NMIBC management. EVIDENCE ACQUISITION: A collaborative review of published randomized clinical trials, meta-analyses, systematic reviews, and clinical practice guidance on IR NMIBC published before January 2022 was undertaken using PubMed/Medline. EVIDENCE SYNTHESIS: Variation exists between guidelines in defining IR NMIBC. The IBCG recommends defining IR NMIBC as any TaLG tumor that is either recurrent or multifocal or has size ≥3 cm, OR any T1LG tumor. If the 3 tier grading system is used, than any TaG2 tumor would also be considered IR diease regardless of whether new diagnosis or recurrent. Accurate grading and staging of tumor, particularly in ruling out HG/G3 disease and/or carcinoma in situ, are crucial. The IBCG recommends that management of IR NMIBC should be further based on the following risk factors: multifocal tumor (more than one), early recurrence (<1 yr), frequent recurrence (>1/yr), tumor size (≥3 cm), and failure of prior intravesical treatment. Patients with no risk factors are best managed by one dose of postoperative intravesical chemotherapy. Patients with one to two risk factors should be offered additional adjuvant induction intravesical chemotherapy (or bacillus Calmette-Guérin (BCG) if prior chemotherapy has been used). Patients with three or more risk factors should be offered induction plus 1-yr maintenance BCG. Where BCG is not available or recurrent disease following BCG is present, alternative intravesical treatments such as chemotherapy (single agent, combination, or chemohyperthermia) or a clinical trial are recommended. CONCLUSIONS: Standardizing the definition of IR NMIBC is critical for appropriate management of patients and for allowing a comparison of outcomes across clinical trials. The IBCG recommends defining IR NMIBC as any TaLG tumor that is either recurrent or multifocal or  ≥3 cm, OR any T1LG tumor. If the 3 tier grading system is used, than any TaG2 tumor would also be considered IR disease regardless of whether new diagnosis or recurrent.  Adjunctive management should then be based on established risk factors. PATIENT SUMMARY: Standardizing the definition of intermediate-risk (IR) non-muscle-invasive bladder cancer (NMIBC), which is a heterogeneous disease, is critical for appropriate management of patients. The International Bladder Cancer Group recommends classification of IR NMIBC tumors and personalized management based on the following risk factors: multifocal tumor (more than one), early recurrence (<1 yr), frequent recurrence (>1/yr), tumor size (≥3 cm), and previous intravesical treatment.

Diagnostic Accuracy of Novel Urinary Biomarker Tests in Non-muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis.

CONTEXT: During the past decade, several urinary biomarker tests (UBTs) for bladder cancer have been developed and made commercially available. However, none of these is recommended by international guidelines so far. OBJECTIVE: To assess the diagnostic estimates of novel commercially available UBTs for diagnosis and surveillance of non-muscle-invasive bladder cancer (NMIBC) using diagnostic test accuracy (DTA) and network meta-analysis (NMA). EVIDENCE ACQUISITION: PubMed, Web of Science, and Scopus were searched up to April 2021 to identify studies addressing the diagnostic values of UBTs: Xpert bladder cancer, Adxbladder, Bladder EpiCheck, Uromonitor and Cxbladder Monitor, and Triage and Detect. The primary endpoint was to assess the pooled diagnostic values for disease recurrence in NMIBC patients using a DTA meta-analysis and to compare them with cytology using an NMA. The secondary endpoints were the diagnostic values for high-grade (HG) recurrence as well as for the initial detection of bladder cancer. EVIDENCE SYNTHESIS: Twenty-one studies, comprising 7330 patients, were included in the quantitative synthesis. In most of the studies, there was an unclear risk of bias. For NMIBC surveillance, novel UBTs demonstrated promising pooled diagnostic values with sensitivities up to 93%, specificities up to 84%, positive predictive values up to 67%, and negative predictive value up to 99%. Pooled estimates for the diagnosis of HG recurrence were similar to those for the diagnosis of any-grade recurrence. The analysis of the number of cystoscopies potentially avoided during the follow-up of 1000 patients showed that UBTs might be efficient in reducing the number of avoidable interventions with up to 740 cystoscopies. The NMA revealed that diagnostic values (except specificity) of the novel UBTs were significantly higher than those of cytology for the detection of NMIBC recurrence. There were too little data on UBTs in the primary diagnosis setting to allow a statistical analysis. CONCLUSIONS: Our analyses support high diagnostic accuracy of the studied novel UBTs, supporting their utility in the NMIBC surveillance setting. All of these might potentially help prevent unnecessary cystoscopies safely. There are not enough data to reliably assess their use in the primary diagnostic setting. These results have to be confirmed in a larger cohort as well as in head-to-head comparative studies. Nevertheless, our study might help policymakers and stakeholders evaluate the clinical and social impact of the implementation of these tests into daily practice. PATIENT SUMMARY: Novel urinary biomarker tests outperform cytology with the potential of improving routine clinical practice by preventing unnecessary cystoscopic examinations during the surveillance of non-muscle-invasive bladder cancer.

Impact of Adjuvant Chemotherapy on Survival of Patients with Advanced Residual Disease at Radical Cystectomy following Neoadjuvant Chemotherapy: Systematic Review and Meta-Analysis.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3-T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3-T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. MATERIALS AND METHODS: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). RESULTS: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75-0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32-0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58-1.35; p = 0.58). CONCLUSIONS: The administration of AC in patients with MIBC and pT3-T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients.

Oncological outcomes of salvage radical prostatectomy for recurrent prostate cancer in the contemporary era: A multicenter retrospective study.

BACKGROUND: Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR). METHODS: We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed. RESULTS: We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; ≥pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up. CONCLUSIONS: In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings.

Comparison of the performances of the ADXBLADDER test and urinary cytology in the follow-up of non-muscle-invasive bladder cancer: a blinded prospective multicentric study.

OBJECTIVE: To compare directly the performance of the ADXBLADDER test with that of cytology in the detection of non-muscle-invasive bladder cancer (NMIBC) recurrences. BACKGROUND: ADXBLADDER is a urine test based on the detection of MCM5, a DNA licensing factor expressed in all cells capable of dividing. Expression is usually restricted to the basal stem cell compartment; however, in malignancy, MCM5-expressing cells can be found throughout the epithelium. Detection of MCM5 in urine sediment can be indicative of the presence of a bladder tumour. PATIENTS AND METHODS: A multicentre prospective, blinded study was carried out from August 2017 and July 2019 at 21 European Union centres, 14 of which collected matching cytology data. Urine was collected from patients prior to cystoscopy. Urine cytology and ADXBLADDER were performed and compared to the diagnosis obtained by cystoscopy. The performance of cytology and ADXBLADDER were then compared. RESULTS: The overall performance of ADXBLADDER demonstrated a sensitivity of 51.9%, a specificity of 66.4%, and a negative predictive value (NPV) of 92%. The sensitivity of ADXBLADDER for low- and high-grade recurrences was 44.1% and 58.8%, respectively. By contrast, cytology sensitivity was 16.7%, specificity was 98% and NPV was 90.7%. Cytology sensitivity for both low- and high-grade disease was 17.6%. CONCLUSIONS: ADXBLADDER detection of both low- and high-grade NMIBC recurrence is superior to that of cytology, with ADXBLADDER able to exclude the presence of high-grade recurrence in 97.8% of cases compared to 97.1% with cytology. These results show that ADXBLADDER has promise as a more reliable alternative to urine cytology in the follow-up of NMIBC.

Outcomes of Salvage Radical Prostatectomy for M0 Castration-resistant Recurrent Prostate Cancer: A Reasonable Option in the Era of New Antiandrogen Therapies?

There is little evidence regarding salvage radical prostatectomy (sRP) for M0 castration-resistant prostate cancer (CRPC). We reviewed oncological results and complications for 23 men with radiographically recurrent M0 CRPC undergoing sRP at six institutions. Sixteen and ten men experienced at least one and one major (Clavien >2) complication, respectively. After sRP, nine men became incontinent, including two with severe incontinence. The majority of men had aggressive extraprostatic disease (≥pT3b 56.5%; pN1 30.4%; Gleason ≥8 65.2%). Postoperatively 69.6% reached undetectable prostate-specific antigen (PSA) without androgen deprivation therapy (ADT). Seven men had postoperative PSA persistence and six had CRPC persistence. Among the others, biochemical recurrence (BCR) occurred in 68.7% and CRPC in 58.8% at a median of 11 and 31 mo from sRP, respectively. At median follow-up of 4 yr, 17.4% were disease-free, 34.4% had died from PC, and 4.3% had died from other causes. sRP for M0 CRPC is feasible although the risk of complications is significant. A minority of patients can be cured and a significant proportion experience prolonged BCR- and CRPC-free status, thus delaying the need for systemic treatments. Further studies are needed to clarify the role of sRP for M0 CRPC in the era of new antiandrogen therapies. PATIENT SUMMARY: Salvage radical prostatectomy for radiorecurrent M0 castration-resistant prostate cancer (CRPC) is feasible, although continence outcomes are suboptimal and the risk of complications is significant. Survival is promising: some men can be cured and others experience a period without evidence of PC or CRPC. More research is needed to confirm our findings and demonstrate survival benefits.

Analysis of age influence on oncological results and toxicity of BCG immunotherapy in non-muscle invasive bladder cancer.

PURPOSE: The aim of this study was to analyse the influence of age on the treatment outcome and toxicity in patients with T1HG non-muscle invasive bladder cancers treated with BCG immunotherapy. METHODS: Data from 637 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in two academic centres were retrospectively reviewed. Median follow-up was 57 months. Patients were divided into two groups: younger (< 70 years old) and older (≥ 70 years old). Additional analyses in subgroups of older (> 75 and > 80) patients were performed. Log-rank test, Cox regression analysis, and propensity score matching were performed to compare the groups. RESULTS: There were 389 patients below and 248 patients above or equal 70 years old. Recurrence-free, progression-free, and cancer-specific survival rates did not differ significantly between younger and older patients. Recurrence-free survival for younger and older patients were 55.4% vs 52.9%, progression-free survival 75.9% vs 76.6%, and cancer-specific survival were 87.5% vs 89.9% (all p > 0.05). Differences in the oldest subgroups also did not reach statistical significance. In both regression analysis and propensity score matching, no statistically significant associations of age with any of analysed end-points were found. Finally, there were no statistically significant differences between younger and older group in terms of moderate and severe complications occurrence (47.6% vs. 44.5%; p > 0.05) CONCLUSIONS: It was shown that increasing age was not associated with BCG immunotherapy oncological outcomes, or with BCG toxicity in T1HG non-muscle invasive bladder cancer.

EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort†: Under the Auspices of the EAU-ESMO Guidelines Committees.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach. PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

Neoadjuvant Chemotherapy is Not Associated with Adverse Perioperative Outcomes after Robot-Assisted Radical Cystectomy: A Case for Increased Use from the IRCC.

PURPOSE: We sought to determine the trend of neoadjuvant chemotherapy use for nonmetastatic muscle invasive urothelial bladder cancer and whether it is associated with adverse perioperative morbidity after robot-assisted radical cystectomy. MATERIALS AND METHODS: We retrospectively reviewed the IRCC (International Robotic Cystectomy Consortium) database between 2006 and 2017. After excluding patients with nonmuscle invasive bladder cancer the patients were divided into 2 groups, including those who did vs did not receive neoadjuvant chemotherapy. Data were reviewed for demographics, preoperative, operative and 90-day perioperative outcomes. We used the Cochran-Armitage trend test to assess trends of neoadjuvant chemotherapy associations with high grade and overall complications with time. Multivariate stepwise regression analyses were done to determine whether neoadjuvant chemotherapy was associated with prolonged operative time, 90-day postoperative complications, readmissions, reoperations and mortality after robot-assisted radical cystectomy. RESULTS: A total of 298 patients (26%) received neoadjuvant chemotherapy. These patients were younger (age 67 vs 69 years, p=0.01) and more frequently had an ASA™ (American Society of Anesthesiologists™) score of 3 or greater (62% vs 55%, p=0.02) and pathological T3 stage or greater disease (28% vs 22%, p=0.04). The use of neoadjuvant chemotherapy increased significantly from 10% in 2006 to 2007 to 42% in 2016 to 2017 (p <0.01). On multivariate analysis neoadjuvant chemotherapy was not significantly associated with prolonged operative time, hospital stay, 90-day postoperative complications, reoperation or mortality. Neoadjuvant chemotherapy was associated with 90-day readmissions after robot-assisted radical cystectomy (OR 5.90, 95% CI 3.30-10.90, p <0.01). CONCLUSIONS: Neoadjuvant chemotherapy utilization has significantly increased in the last decade. It was not associated with perioperative surgical morbidity after robot-assisted radical cystectomy.