Schwannoma of the seminal vesicle: Case report and review of the literature

Seminal vesicles can be affected by tumours originating in other locations. However, primary tumours of the seminal vesicle are extremely rare, with less than 100 cases reported in literature. Seminal vesicle adenocarcinoma is the most common type, but there are also other malign lesions. Diagnosis is challenging due to the lack of early symptoms and well-defined criteria. These tumours are usually asymptomatic and discovered incidentally during imaging tests or pelvic surgery. Definitive diagnosis requires anatomopathological analysis. Case report of 58-years-old man with schwannoma of the seminal vesicle. We describe the main characteristics of these tumours as well as their therapeutic approach

Prognostic Value of the WHO1973 and WHO2004/2016 Classification Systems for Grade in Primary Ta/T1 Non–muscle-invasive Bladder Cancer: A Multicenter European Association of Urology Non–muscle-invasive Bladder Cancer Guidelines Panel Study

Background: In the current European Association of Urology (EAU) non-muscle invasive bladder cancer (NMIBC) guideline, two classification systems for grade are advocated: WHO1973 and WHO2004/2016. Objective: To compare the prognostic value of these WHO systems. Design, setting, and participants: Individual patient data for 5145 primary Ta/T1 NMIBC patients from 17 centers were collected between 1990 and 2019. The median follow-up was 3.9 yr. Outcome measurements and statistical analysis: Univariate and multivariable analyses of WHO1973 and WHO2004/2016 stratified by center were performed for time to recurrence, progression (primary endpoint), cystectomy, and duration of survival, taking into account age, concomitant carcinoma in situ, gender, multiplicity, tumor size, initial treatment, and tumor stage. Harrell's concordance (C-index) was used for prognostic accuracy of classification systems. Results and limitations: The median age was 68 yr; 3292 (64%) patients had Ta tumors. Neither classification system was prognostic for recurrence. For a four-tier combination of both WHO systems, progression at 5-yr follow-up was 1.4% in lowgrade (LG)/G1, 3.8% in LG/G2, 7.7% in high grade (HG)/G2, and 18.8% in HG/G3 (log rank, p < 0.001). In multivariable analyses with WHO1973 and WHO2004/2016 as independent variables, WHO1973 was a significant prognosticator of progression (p < 0.001), whereas WHO2004/2016 was not anymore (p = 0.067). C-indices for WHO1973, WHO2004, and the WHO systems combined for progression were 0.71, 0.67, and 0.73, respectively. Prognostic analyses for cystectomy and survival showed results similar to those for progression. Conclusions: In this large prognostic factor study, both classification systems were prognostic for progression but not for recurrence. For progression, the prognostic value of WHO1973 was higher than that of WHO 2004/2016. The four-tier combination (LG/G1, LG/G2, HG/G2, and HG/G3) of both WHO systems proved to be superior, as it divides G2 patients into two subgroups (LG and HG) with different prognoses. Hence, the current EAU-NMIBC guideline recommendation to use both WHO classification systems remains correct. Patient summary: At present, two classification systems are used in parallel to grade non-muscle-invasive bladder tumors. Our data on a large number of patients showed that the older classification system (WHO1973) performed better in terms of assessing progression than the more recent (WHO2004/2016) one. Nevertheless, we conclude that the current guideline recommendation for the use of both classification systems remains correct, since this has the advantage of dividing the large group of WHO1973 G2 patients into two subgroups (low and high grade) with different prognoses. (c) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved

Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019?

Background: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. Objectives: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. Materials and methods: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. Results: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990–2000) to 3.2% (2000–2010) and to 1.1% (2010–2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. Conclusions: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas

Erratum to “European Association of Urology (EAU) Prognostic Factor Risk Groups for Non–muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel” [Eur. Urol. 79(4) (2021) 480–488, (S0302283820310198), (10.1016/j.eururo.2020.12.033)]

The publisher regrets that, of the affiliations of the senior author Bas W.G. van Rhijn, only two of the four were shown in the published version of the article. The four correct affiliations, which were also already listed in the original submission to European Urology, now appear above in this erratum. The correct affiliations for author Bas W.G. van Rhijn is updated as above. The publisher would like to apologise for any inconvenience caused

European Association of Urology (EAU) Prognostic Factor Risk Groups for Non–muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel

Background: The European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s. Objective: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression. Design, setting, and participants: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel. Intervention: Patients underwent TURBT followed by intravesical instillations at the physician's discretion. Outcome measurements and statistical analysis: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves. Results and limitations: A total of 3401 patients treated with TURBT + intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004-2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from 40%. Limitations include the retrospective collection of data and the lack of central pathology review. Conclusions: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary. Patient summary: The newly updated European Association of Urology prognostic factor risk groups for non-muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved

European Association of Urology (EAU) Prognostic Factor Risk Groups for Non–muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel[Formula presented]

Background: The European Association of Urology (EAU) prognostic factor risk groups for non–muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s. Objective: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression. Design, setting, and participants: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel. Intervention: Patients underwent TURBT followed by intravesical instillations at the physician's discretion. Outcome measurements and statistical analysis: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves. Results and limitations: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004–2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from 40%. Limitations include the retrospective collection of data and the lack of central pathology review. Conclusions: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary. Patient summary: The newly updated European Association of Urology prognostic factor risk groups for non–muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule. The updated European Association of Urology prognostic factor risk groups for patients with non–muscle-invasive bladder cancer provide urologists with information that they should take into account when choosing a patient's treatment and scheduling follow-up

Prognosis of Primary Papillary Ta Grade 3 Bladder Cancer in the Non-muscle-invasive Spectrum

BACKGROUND: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive. OBJECTIVE: To evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta-T1 bladder tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and time to progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox-regression models with interaction terms stratified by institution. RESULTS AND LIMITATIONS: Ta G3 represented 7.5% (387/5170) of Ta-T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7-4.8%) of Ta G2, 13% (95% CI 9.3-17%) of Ta G3, and 20% (95% CI 17-23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p < 0.001) and longer than for T1 G3 (p = 0.002). Patients with Ta G3 NMIBC with concomitant carcinoma in situ (CIS) had worse prognosis and a similar time to progression as for patients with T1 G3 NMIBC with CIS (p = 0.5). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The prognosis of Ta G3 tumors in terms of progression appears to be in between that of Ta G2 and T1 G3. However, patients with Ta G3 NMIBC with concomitant CIS have worse prognosis that is comparable to that of T1 G3 with CIS. Our results support the recent EAU NMIBC guideline changes for more refined risk stratification of Ta G3 tumors because many of these patients have better prognosis than previously thought. PATIENT SUMMARY: We used data from 17 centers in Europe and Canada to assess the prognosis for patients with stage Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC). Time to cancer progression for Ta G3 cancer differed from both Ta G2 and T1 G3 tumors. Our results support the recent change in the European Association of Urology guidelines for more refined risk stratification of Ta G3 NMIBC because many patients with this tumor have better prognosis than previously thought

Second TURB, restaging TURB or repeat TURB in primary T1 non-muscle invasive bladder cancer: impact on prognosis?

Purpose: A re-transurethral resection of the bladder (re-TURB) is a well-established approach in managing non-muscle invasive bladder cancer (NMIBC) for various reasons: repeat-TURB is recommended for a macroscopically incomplete initial resection, restaging-TURB is required if the first resection was macroscopically complete but contained no detrusor muscle (DM) and second-TURB is advised for all completely resected T1-tumors with DM in the resection specimen. This study assessed the long-term outcomes after repeat-, second-, and restaging-TURB in T1-NMIBC patients. Methods: Individual patient data with tumor characteristics of 1660 primary T1-patients (muscle-invasion at re-TURB omitted) diagnosed from 1990 to 2018 in 17 hospitals were analyzed. Time to recurrence, progression, death due to bladder cancer (BC), and all causes (OS) were visualized with cumulative incidence functions and analyzed by log-rank tests and multivariable Cox-regression models stratified by institution. Results: Median follow-up was 45.3 (IQR 22.7-81.1) months. There were no differences in time to recurrence, progression, or OS between patients undergoing restaging (135 patients), second (644 patients), or repeat-TURB (84 patients), nor between patients who did or who did not undergo second or restaging-TURB. However, patients who underwent repeat-TURB had a shorter time to BC death compared to those who had second- or restaging-TURB (multivariable HR 3.58, P = 0.004). Conclusion: Prognosis did not significantly differ between patients who underwent restaging- or second-TURB. However, a worse prognosis in terms of death due to bladder cancer was found in patients who underwent repeat-TURB compared to second-TURB and restaging-TURB, highlighting the importance of separately evaluating different indications for re-TURB