Oncologic surveillance intensity after endoscopic treatment of upper tract urothelial carcinoma.

BACKGROUND: The optimal oncologic surveillance in patients with upper tract urothelial carcinoma (UTUC) elected for conservative treatment is still a matter of debate. METHODS: Patients elected for endoscopic treatment of UTUC were followed up according to EAU guidelines recommendations after treatment. Bladder cancer recurrence-free survival (BCa-RFS), UTUC recurrence-free survival (UTUC-RFS), radical nephroureterectomy-free survival (RNU-FS), and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. The crude risks of BCa and UTUC recurrences over time were estimated with the Locally Weighted Scatterplot Smoothing method. RESULTS: Overall, 54 and 55 patients had low- and high-risk diseases, respectively. Median follow-up was 46.9 (IQR: 28.7-68.7) and 36.9 (IQR: 19.8-60.1) months in low and high-risk patients, respectively. In low-risk patients, BCa recurrence risk was more than 20% at 24 months follow-up. At 60 months, time point after which cystoscopy and imaging should be interrupted, the risk of BCa recurrence and UTUC recurrence were 14% and 7%, respectively. In high-risk patients, the risk of BCa and UTUC recurrence at 36 months was approximately 40% and 10%, respectively. Conversely, at 60 months, the risk of bladder recurrence and UTUC recurrence was 28% and 8%, respectively. CONCLUSIONS: For low-risk patients, cystoscopy should be performed semi-annually until 24 months, while upper tract assessment should be obtained up to 60 months, as per current EAU guidelines recommendations. For high-risk patients, upper tract assessment should be intensified to semi-annually up to 36 months, then obtained yearly. Conversely, cystoscopy should be ideally performed semi-annually until 60 months and yearly thereafter.

The Role of 99mTc-Sestamibi Single-photon Emission Computed Tomography/Computed Tomography in the Diagnostic Pathway for Renal Masses: A Systematic Review and Meta-analysis.

CONTEXT: The diagnostic accuracy of current imaging techniques in differentiating benign from malignant neoplasms in the case of indeterminate renal masses is still suboptimal. OBJECTIVE: To evaluate the diagnostic accuracy of 99mTc-sestamibi (SestaMIBI) single-photon emission tomography computed tomography (SPECT)/CT in characterizing indeterminate renal masses by differentiating renal oncocytoma and hybrid oncocytic/chromophobe tumor (HOCT) from (1) all other renal lesions and (2) all malignant renal lesions. Secondary outcomes were: (1) benign versus malignant; (2) renal oncocytoma and HOCT versus clear cell (ccRCC) and papillary (pRCC) renal cell carcinoma; and (3) renal oncocytoma and HOCT versus chromophobe renal cell carcinoma (chRCC). EVIDENCE ACQUISITION: A literature search was conducted up to November 2022 using the PubMed/MEDLINE, Embase, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to identify eligible studies. Studies included were prospective and retrospective cross-sectional studies in which SestaMIBI SPECT/CT findings were compared to histology after renal mass biopsy or surgery. EVIDENCE SYNTHESIS: Overall, eight studies involving 489 patients with 501 renal masses met our inclusion criteria. The sensitivity and specificity of SestaMIBI SPECT/CT for renal oncocytoma and HOCT versus all other renal lesions were 89% (95% confidence interval [CI] 70-97%) and 89% (95% CI 86-92%), respectively. Notably, for renal oncocytoma and HOCT versus ccRCC and pRCC, SestaMIBI SPECT/CT showed specificity of 98% (95% CI 91-100%) and similar sensitivity. Owing to the relatively high risk of bias and the presence of heterogeneity among the studies included, the level of evidence is still low. CONCLUSIONS: SestaMIBI SPECT/CT has good sensitivity and specificity in differentiating renal oncocytoma and HOCT from all other renal lesions, and in particular from those with more aggressive oncological behavior. Although these results are promising, further studies are needed to support the use of SestaMIBI SPECT/CT outside research trials. PATIENT SUMMARY: A scan method called SestaMIBI SPECT/CT has promise for diagnosing whether kidney tumors are malignant or not. However, it should still be limited to research trials because the level of evidence from our review is low.

Simultaneous Bilateral Video-Endoscopic Inguinal Lymphadenectomy for Penile Carcinoma: Surgical Setting, Feasibility, Safety, and Preliminary Oncological Outcomes.

INTRODUCTION: Inguinal lymph node dissection (ILND) plays an important role for both staging and treatment purposes in patients diagnosed with penile carcinoma (PeCa). Video-endoscopic inguinal lymphadenectomy (VEIL) has been introduced to reduce complications, and in those patients elected for bilateral ILND, a simultaneous bilateral VEIL (sB-VEIL) has also been proposed. This study aimed to investigate the feasibility, safety, and preliminary oncological outcomes of sB-VEIL compared to consecutive bilateral VEIL (cB-VEIL). MATERIAL AND METHODS: Clinical N0-2 patients diagnosed with PeCa and treated with cB-VEIL and sB-VEIL between 2015 and 2023 at our institution were included. Modified ILND was performed in cN0 patients, while cN+ patients underwent a radical approach. Intra- and postoperative complications, operative time, time of drainage maintenance, length of hospital stay and readmission within 90 days, as well as lymph node yield, were compared between the two groups. RESULTS: Overall, 30 patients were submitted to B-VEIL. Of these, 20 and 10 patients underwent cB-VEIL and sB-VEIL, respectively. Overall, 16 (80%) and 7 (70%) patients were submitted to radical ILND due to cN1-2 disease in the cB-VEIL and sB-VEIL groups, respectively. No statistically significant difference emerged in terms of median nodal yield (13.5 vs. 14, p = 0.7) and median positive LNs (p = 0.9). sD-VEIL was associated with a shorter operative time (170 vs. 240 min, p < 0.01). No statistically significant difference emerged in terms of intraoperative estimated blood loss, length of hospital stay, time to drainage tube removal, major complications, and hospital readmission in the cB-VEIL and sB-VEIL groups, respectively (all p > 0.05). CONCLUSIONS: Simultaneous bilateral VEIL is a feasible and safe technique in patients with PeCA, showing similar oncological results and shorter operative time compared to a consecutive bilateral approach. Patients with higher preoperative comorbidity burden or anesthesiological risk are those who may benefit the most from this technique.

Aspectos prácticos sobre la determinación de PD-L1 en el tratamiento de carcinoma urotelial. Consenso del grupo de uropatología de la SEAP / Practical aspects of PD-L1 assessment in the treatment of urothelial carcinoma: Consensus of the uropathology group of the SEAP

La reciente llegada de nuevos fármacos de inmunoterapia para el tratamiento del carcinoma urotelial hace necesario establecer criterios para armonizar la determinación de PD-L1 mediante inmunohistoquímica como factor pronóstico y para la selección de pacientes a tratar. En este escenario, un grupo de uropatólogos de la Sociedad Española de Anatomía Patológica, junto con un oncólogo médico como colaborador externo subespecializado en urooncología, ha elaborado este documento de recomendaciones basadas en la evidencia disponible. En la determinación de PD-L1 son especialmente relevantes la selección de la muestra analizada, su procesamiento, la plataforma de inmunohistoquímica y anticuerpo empleados, así como el algoritmo que se aplique para la lectura. Todos estos aspectos deben indicarse en el informe de resultados, que debería poder ser fácilmente interpretable en un contexto de rápida evolución de terapias inmunológicas.(AU)

The recent addition of novel immunotherapy drugs for the treatment of urothelial carcinoma makes it necessary the establishment of criteria to harmonize the immunohistochemical assessment of PD-L1, both as a prognostic factor and for the selection of patients to be treated. In this scenario, a group of uropathologists from the Spanish Society of Pathological Anatomy, together with a medical oncologist as an external collaborator subspecialized in uro-oncology, have prepared this document of recommendations based on the available evidence. During PD-L1 assessment it is especially relevant the selection of the sample, its processing, the immunohistochemical platform and antibody used, and the algorithm applied in the interpretation of results. All these aspects must be indicated in the results report, which should be easily interpretable in a context of rapid evolution of immunological therapies.(AU)

[Practical aspects of PD-L1 assessment in the treatment of urothelial carcinoma: Consensus of the uropathology group of the SEAP]. / Aspectos prácticos sobre la determinación de PD-L1 en el tratamiento de carcinoma urotelial. Consenso del grupo de uropatología de la SEAP.

The recent addition of novel immunotherapy drugs for the treatment of urothelial carcinoma makes it necessary the establishment of criteria to harmonize the immunohistochemical assessment of PD-L1, both as a prognostic factor and for the selection of patients to be treated. In this scenario, a group of uropathologists from the Spanish Society of Pathological Anatomy, together with a medical oncologist as an external collaborator subspecialized in uro-oncology, have prepared this document of recommendations based on the available evidence. During PD-L1 assessment it is especially relevant the selection of the sample, its processing, the immunohistochemical platform and antibody used, and the algorithm applied in the interpretation of results. All these aspects must be indicated in the results report, which should be easily interpretable in a context of rapid evolution of immunological therapies.

The importance of second-look ureteroscopy implementation in the conservative management of upper tract urothelial carcinoma.

PURPOSE: The purpose of the study was to evaluate the effect of second-look ureteroscopy (SU) in the endoscopic operative work-up of patients with upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Patients with UTUC who underwent SU between 2016 and 2021 were included. Cancer detection rate (CDR) at SU was defined as endoscopic visualization of tumor. The effect of SU on recurrence-free survival (RFS), radical nephroureterectomy-free survival (RNU-FS), bladder cancer-free survival (BC-FS), and cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. Multivariate logistic regression analysis (MLR) assessed predictors of negative SU. Finally, we evaluated the effect of SU timing on oncological outcomes, classifying SUs as "early" (≤ 8 weeks) and "late" (> 8 weeks). RESULTS: Overall, 85 patients underwent SU. The CDR at SU was 44.7%. After a median follow-up was 35 (IQR: 15-56) months, patients with positive SU had a higher rate of UTUC recurrence (47.4% vs 19.1%, p = 0.01) and were more frequently radically treated (34.2% vs 8.5%, p = 0.007). Patients with high-grade disease (hazard ratio [HR]: 3.14, 95% CI 1.18-8.31; p = 0.02) had a higher risk of UTUC recurrence, while high-grade tumor (HR: 3.87, 95%CI 1.08-13.77; p = 0.04) and positive SU (HR: 4.56, 95%CI 1.05-22.81; p = 0.04) were both predictors of RNU. Low-grade tumors [odds ratio (OR): 5.26, 95%CI 1.81-17.07, p = 0.003] and tumor dimension < 20 mm (OR: 5.69, 95%CI 1.48-28.31, p = 0.01) were predictors of negative SU. Finally, no significant difference emerged regarding UTUC recurrence, RNU, BC-FS, and CSM between early vs. late SUs (all p > 0.05). CONCLUSIONS: SU may help in identifying patients with UTUC experiencing an early recurrence after conservative treatment. Patients with low-grade and small tumors are those in which SU could be safely postponed after 8 weeks.

P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation.

p53 immunohistochemistry (IHC) has been proposed as a surrogate for TP53 mutations in penile squamous cell carcinomas (PSCC). We aimed to evaluate the performance of a pattern-based evaluation of p53 IHC in PSCC. Human papilloma virus (HPV) DNA testing, p16 and p53 IHC, and whole exome sequencing were performed in a series of 40 PSCC. p53 IHC was evaluated following a pattern-based framework and conventional p53 IHC evaluation. Out of 40 PSCC, 12 (30.0%) were HPV-associated, and 28 (70.0%) were HPV-independent. The agreement between the p53 IHC pattern-based evaluation and TP53 mutational status was almost perfect (k = 0.85). The sensitivity and accuracy of the pattern-based framework for identifying TP53 mutations were 95.5% and 92.5%, respectively, which were higher than the values of conventional p53 IHC interpretation (54.5% and 70.0%, respectively), whereas the specificity was the same (88.9%). In conclusions, the pattern-based framework improves the accuracy of detecting TP53 mutations in PSCC compared to the classical p53 IHC evaluation.

International Opinions on Grading of Urothelial Carcinoma: A Survey Among European Association of Urology and International Society of Urological Pathology Members.

Background: Grade of non-muscle-invasive bladder cancer (NMIBC) is an important prognostic factor for progression. Currently, two World Health Organization (WHO) classification systems (WHO1973, categories: grade 1-3, and WHO2004 categories: papillary urothelial neoplasm of low malignant potential [PUNLMP], low-grade [LG], high-grade [HG] carcinoma) are used. Objective: To ask the European Association of Urology (EAU) and International Society of Urological Pathology (ISUP) members regarding their current practice and preferences of grading systems. Design setting and participants: A web-based, anonymous questionnaire with ten questions on grading of NMIBC was created. The members of EAU and ISUP were invited to complete an online survey by the end of 2021. Thirteen experts had previously answered the same questions. Outcome measurements and statistical analysis: The submitted answers from 214 ISUP members, 191 EAU members, and 13 experts were analyzed. Results and limitations: Currently, 53% use only the WHO2004 system and 40% use both systems. According to most respondents, PUNLMP is a rare diagnosis with management similar to Ta-LG carcinoma. The majority (72%) would consider reverting back to WHO1973 if grading criteria were more detailed. Separate reporting of WHO1973-G3 within WHO2004-HG would influence clinical decisions for Ta and/or T1 tumors according the majority (55%). Most respondents preferred a two-tier (41%) or a three-tier (41%) grading system. The current WHO2004 grading system is supported by a minority (20%), whereas nearly half (48%) supported a hybrid three- or four-tier grading system composed of both WHO1973 and WHO2004. The survey results of the experts were comparable with ISUP and EAU respondents. Conclusions: Both the WHO1973 and the WHO2004 grading system are still widely used. Even though opinions on the future of bladder cancer grading were strongly divided, there was limited support for WHO1973 and WHO2004 in their current formats, while the hybrid (three-tier) grading system with LG, HG-G2, and HG-G3 as categories could be considered the most promising alternative. Patient summary: Grading of non-muscle-invasive bladder cancer (NMIBC) is a matter of ongoing debate and lacks international consensus. We surveyed urologists and pathologists of European Association of Urology and International Society of Urological Pathology on their preferences regarding NMIBC grading to generate a multidisciplinary dialogue. Both the "old" World Health Organization (WHO) 1973 and the "new" WHO2004 grading schemes are still used widely. However, continuation of both the WHO1973 and the WHO2004 system showed limited support, while a hybrid grading system composed of both the WHO1973 and the WHO2004 classification system may be considered a promising alternative.

Long-Term Oncologic Outcomes of Endoscopic Management of High-Risk Upper Tract Urothelial Carcinoma: The Fundació Puigvert's Experience.

Objectives: Many patients with upper tract urothelial carcinoma (UTUC) outside of the low-risk criteria may possess low absolute risks of distant progression. Herein, we hypothesized that careful selection of high-risk patients undergoing an endoscopic approach could result in acceptable oncologic outcomes. Materials and Methods: Patients with high-risk UTUC managed endoscopically between 2015 and 2021 were retrospectively identified from a prospectively maintained single academic institution database. Elective and imperative indications for endoscopic treatment were considered. Regarding elective indications, the decision to perform endoscopic treatment was systematically proposed to high-risk patients in whom macroscopically complete ablation was deemed feasible, excluding invasive appearance on CT scan, and without histologic variant. Results: A total of 60 patients with high-risk UTUC met our inclusion criteria (29 imperative and 31 elective indications). The median follow-up in patients without any event was 36 months. At 5 years, the estimated overall survival, cancer-specific survival, metastasis-free survival, UTUC recurrence-free survival, radical nephroureterectomy-free survival, and bladder recurrence-free survival were 57% (41-79), 75% (57-99), 86% (71-100), 56% (40-76), 81% (70-93), and 69% (54-88), respectively. All oncologic outcomes were similar between patients with elective and imperative indications (all log-rank p > 0.05). Conclusions: In conclusion, we report the first large series of endoscopic treatment in patients with high-risk UTUC, arguing that promising oncologic outcomes can be achieved in properly selected candidates. We encourage multi-institutional collaborative work as a large cohort of high-risk patients treated endoscopically may allow subgroup analyses to define the best candidates.

Initial experience of robot-assisted partial nephrectomy with Hugo™ RAS system: implications for surgical setting.

PURPOSE: Hugo™ RAS system is one of the most promising new robotic platforms introduced in the field of urology. To date, no data have been provided on robot-assisted partial nephrectomy (RAPN) performed with Hugo™ RAS system. The aim of the study is to describe the setting and report the performance of the first series of RAPN performed with Hugo™ RAS system. METHODS: Ten consecutive patients who underwent RAPN at our Institution between February and December 2022 were prospectively enrolled. All RAPN were performed transperitoneally with a modular four-arm configuration. The main outcome was to describe the operative room setting, trocar placement and the performance of this novel robotic platform. Pre, intra and post-operative, variables were recorded. A descriptive analysis was performed. RESULTS: Seven patients underwent RAPN for right-side and three for left-side masses. Median tumor size and PADUA score were 3 (2.2-3.7) cm and 9 (8-9), respectively. Median docking and console time were 9.5 (9-14) and 138 (124-162) minutes, respectively. Median warm ischemia time was 13 (10-14) minutes, and one case was performed clamp-less. Median estimated blood loss was 90 (75-100) mL. One major complication (Clavien-Dindo 3a) occurred. No case of positive surgical margin was recorded. CONCLUSION: This is the first series to prove the feasibility of Hugo™ RAS system in the setting of RAPN. These preliminary results may help new adopters of this surgical platform to identify critical steps of robotic surgery with this platform and explore solutions before in-vivo surgery.

Energy source comparison in en-bloc resection of bladder tumors: subanalysis of a single-center prospective randomized study.

PURPOSE: Different energy sources are employed to perform en-bloc transurethral resection of bladder tumor (ERBT). No study compared different energy sources in ERBT. The aim is to compare the different ERBT sources in terms of pathological, surgical and postoperative outcomes. METHODS: This is a sub-analysis of a prospective randomized trial enrolling patients submitted to ERBT vs conventional TURBT from 03/2018 to 06/2021 (NCT04712201). 180 patients enrolled in ERBT group were randomized 1:1:1 to receive monopolar (m-ERBT), bipolar (b-ERBT) or thulium laser (l-ERBT). Endpoints were the comparison between energies in term of pathological analysis, intra, and post-operative outcomes. RESULTS: 49 (35%) m-ERBT, 45 (32.1%) b-ERBT, and 46 (32.9%) l-ERBT were included in final analysis. The rate of detrusor muscle (DM) presence was comparable between the energies used (p = 0.796) or the location of the lesion (p = 0.662). Five (10.2%), 10 (22.2%) and 0 cases of obturator nerve reflex (ONR) were recorded in m-ERBT, b-ERBT and I-ERBT groups, respectively (p = 0.001). Conversion to conventional TURBT was higher for lesions located in the anterior wall/dome/neck (p < 0.001), irrespective from the energy used. The presence of artifact in the pathological specimen was higher for lesions at the posterior wall (p = 0.03) and trigone (p = 0.03). CONCLUSIONS: In our study, no difference in staging feasibility among energies was found. Laser energy might be beneficial in lateral wall lesions to avoid ONR. Since there is an increased risk of ERBT conversion to conventional TURBT for lesions of the anterior wall, electrocautery might be preferred over laser to avoid waste of material.

The DEpth of Endoscopic Perforation scale to assess intraoperative perforations during transurethral resection of bladder tumor: subgroup analysis of a randomized controlled trial.

PURPOSE: Bladder perforation (BP) is the most important intraoperative adverse event of transurethral resection of bladder tumor (TURBT). It is frequently underreported despite its impact on the postoperative course. There is no standardized classification of BP. The study aims to develop a classification of the depth of endoscopic bladder perforation during TURBT. METHODS: This is a sub-analysis of a prospective randomized trial enrolling 248 patients submitted to en-bloc vs conventional TURBT from 03/2018 to 06/2021. The DEpth of Endoscopic Perforation (DEEP) scale is as follows: "0" visible muscular layer with no perivesical fat; "1" visible muscle fibers with spotted perivesical fat; "2" exposition of perivesical fat; "3" intraperitoneal perforation. Logistic and linear regression models were used to investigate predictors of high-grade perforations (DEEP 2-3) and to assess whether the DEEP scale independently predicted patients' postoperative outcomes. RESULTS: A total of 146/248 (58.9%), 56/248 (22.6%), 41/248 (16.5%), 5/248 (2.0%) patients presented DEEP grade 0, 1, 2, and 3, respectively. Female gender [B coeff. 0.255 (95% CI 0.001-0.513); p = 0.05], tumor location [B coeff. 0.188 (0.026-0.339); p = 0.015], and obturator-nerve reflex [B coeff. 0.503 (0.148-0.857); p = 0.006] were independent predictors of DEEP. The scale predicted independently major complications [Odd Ratio (OR) 2.221 (1.098-4.495); p = 0.026], no post-operative chemotherapy intravesical instillation [OR 9.387 (2.434-36.200); p = 0.001], longer irrigation time [B coeff. 0.299 (0.166-0.441); p < 0.001] and hospital stay [B coeff. 0.315 (0.111-0.519); p = 0.003]. CONCLUSION: The DEEP scale provides a visual tool for grading bladder perforation during TURBT, which can help physicians standardize complication reporting and plan postoperative management accordingly.

Topical instillation of BCG immunotherapy for biopsy-proven primary upper urinary tract carcinoma in situ: A single institution series and systematic review.

Primary upper tract carcinoma in situ (UTcis) is a rare disease whose diagnosis and natural history are poorly understood. Radical nephroureterectomy is the standard of care but in imperatives or selected cases, topical instillations of Bacillus Calmette-Guérin (BCG) may represent a good alternative. The aim of this study was to report the histologic response to BCG instillations for the treatment of biopsy-proven UTcis and to systematically assess the current evidence on topical BCG instillation for the treatment of UTcis. This is a retrospective analysis of patients with biopsy-proven UTcis treated with BCG instillation between 1995 and 2020 in an expert center. The initial diagnosis was performed by a standardized random biopsy scheme during ureterorenoscopy (URS) in patients with positive cytology but negative CT and bladder biopsies. BCG course consisted of 6 weekly instillation of 81 mg Immucyst (Sanofi Pasteur MSD AG, Baar, Switzerland). Administration techniques were single-J, double-J and nephrostomy tube. The primary outcome was the rate of complete histological response at the 3-month 2nd-look-URS. Kaplan-Meier analysis curves assessed recurrence- and progression-free survival. A total of 22 patients (23 renal units) were included. Twenty-one (91.3%) patients completed the planned 6-week instillation cycle. Only one major complication was recorded (renal tuberculosis). Twenty patients had a 3-month 2nd-look-URS, with a complete histological response achieved in 17/20 cases (85%). After a median time of follow-up of 40 months (30-62), 8/20 patients harbored disease recurrence, including 5 cases of disease progression (≥pT2). The main limitations are the retrospective and non-comparative design of the study. Our systematic review (CRD42022324876) identified 15 studies (289 renal units). UTcis suffers from the lack of a standardized definition, and considerable heterogeneity has been found in making the diagnosis and assessing the response to treatment. Our study is the first to propose a histological diagnosis of UTcis as well as a histological re-evaluation of the response to treatment. Topical instillations of BCG appear to be a promising alternative, avoiding radical treatment in the majority of cases.

Long-term Recurrence and Progression Patterns in a Contemporary Series of Patients with Carcinoma In Situ of the Bladder With or Without Associated Ta/T1 Disease Treated with Bacillus Calmette-Guérin: Implications for Risk-adapted Follow-up.

BACKGROUND: Limited data are available on patients with carcinoma in situ (CIS) of the bladder managed according to current clinical practice guidelines. OBJECTIVE: To assess the patterns of recurrence, progression to muscle-invasive bladder cancer (MIBC), and upper tract urothelial carcinoma (UTUC) in patients with CIS, and to compare the effectiveness of adequate versus inadequate bacillus Calmette-Guérin (BCG) immunotherapy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 386 patients with CIS of the bladder with or without associated pTa/pT1 disease treated with BCG between 2008 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier estimations and an inverse probability of treatment weighting (IPTW)-Cox regression were performed to compare recurrence-free survival (RFS) and progression-free survival (PFS) and UTUC incidence over time for patients who received adequate versus inadequate BCG treatment. RESULTS AND LIMITATIONS: The median follow-up was 70.5 mo. At 5 and 10 yr, RFS was 82% and 52%, PFS was 93.6% and 75.8%, and UTUC incidence was 1.7% and 2.9%, respectively. Most recurrence (73.6%) and progression (69.1%) events occurred in the first 3 yr of follow-up, while 38.7% of UTUC incident events were recorded after 5 yr of follow-up. IPTW-Cox regression revealed that patients who received BCG treatment had a lower risk of recurrence (hazard ratio [HR] 0.21, 95% confidence interval [CI] 0.13-0.34), progression (HR 0.46, 95% CI 0.25-0.87), and UTUC incidence (HR 0.24, 95% CI 0.09-0.64). Limitations include the retrospective design and potential selection bias. CONCLUSIONS: Patients with CIS of the bladder show a high risk of recurrence, progression, and UTUC incidence. Most of these outcomes occur during the first 3 yr of follow-up, but a significant proportion of the events occur at long-term follow-up. Although receipt of adequate BCG treatment improves outcomes, intensive and long-term surveillance may be warranted. PATIENT SUMMARY: We investigated the long-term cancer control outcomes for patients with carcinoma in situ (CIS; cancerous cells that have not spread from where they first formed) of the bladder. Patients with CIS have a high risk of cancer recurrence and progression. Treatment with bacillus Calmette-Guérin (BCG) improves outcomes.

DNA Methylation Urine Biomarkers Test in the Diagnosis of Upper Tract Urothelial Carcinoma: Results from a Single-Center Prospective Clinical Trial.

PURPOSE: The correct risk categorization and staging of upper tract urothelial cancer (UTUC) is key for disease management. Computerized tomography urography and urinary cytology have limited accuracy for risk stratification of UTUC. Ureteroscopy may increase the risk of bladder cancer recurrence. Recently, Bladder EpiCheckTM (EpiCheck) showed a high accuracy in the detection of bladder cancer. The aim of the study is to investigate the diagnostic accuracy of EpiCheck in the clinical management of UTUC and to compare it with urinary cytology. MATERIALS AND METHODS: In this single-arm, blinded, prospective, single-center study (February 2019-December 2020), all patients who were candidates for ureteroscopy for suspicion of UTUC were included. Bladder and upper urinary tract (UUT) samples were collected before ureteroscopy to test for cytology and Epicheck. EpiCheck accuracy was calculated in bladder and UUT samples and compared to cytology. RESULTS: EpiCheck resulted diagnostic in 83/86 (97%) and 73/75 (97%) of UUT and bladder samples. Histology was positive in 47/83 (57%) and 42/73 (58%) cases, respectively. In UUT samples, EpiCheck yielded a sensitivity/specificity/ negative predictive value (NPV)/positive predictive value of 83%/79%/77%/84% vs 59%/88%/61%/87% of cytology. The sensitivity/NPV for high-grade tumors was 96%/97% for EpiCheck vs 71%/86% for cytology. EpiCheck indicated ureteroscopy in 45/80 (56%) patients, missing 17%/4% of all/high-grade UTUC with 9% of unnecessary ureteroscopy. In bladder samples, the sensitivity/NPV for high-grade tumors was 71%/88% for EpiCheck and 59%/87% for cytology. CONCLUSIONS: Epicheck may be an important tool to decrease the number of unnecessary ureteroscopy. The clinical implementation of EpiCheck in UTUC warrants further investigation in multicentric prospective randomized trials.

En Bloc Versus Conventional Transurethral Resection of Bladder Tumors: A Single-center Prospective Randomized Noninferiority Trial.

BACKGROUND: It has been proposed that en bloc resection of bladder tumor (ERBT) improves the quality of tumor resection. A recent international collaborative consensus statement on ERBT underlined the lack of high-quality prospective studies precluding the achievement of solid conclusion on ERBT. OBJECTIVE: To compare conventional transurethral resection of bladder tumor (cTURBT) and ERBT. DESIGN, SETTING, AND PARTICIPANTS: This study (NCT04712201) was a prospective, randomized, noninferiority trial enrolling patients diagnosed with bladder cancer (BC) undergoing endoscopic intervention. Inclusion criteria were: tumor size ≤3 cm, three or fewer lesions, and no sign of muscle invasion and/or ureteral involvement. For a noninferiority rate in BC staging of 5% (α risk 2.5%; ß risk 20%), a total of 300 subjects were randomized to ERBT treatment at a 1:1.5 allocation ratio. INTERVENTION: TURBT and ERBT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the presence of detrusor muscle at final histology. Secondary outcomes include BC staging, T1 substaging, artifacts, complications, the rate of adjuvant treatment, and oncological outcomes. RESULTS AND LIMITATIONS: From April 2018 to June 2021, 300 patients met the inclusion criteria. Of these, 248 (83%) underwent the assigned intervention: 108 patients (44%) underwent cTURBT and 140 (57%) underwent ERBT. The rate of detrusor muscle presence for ERBT was noninferior to that for TURBT (94% vs 95%; p = 0.8). T1 substaging was feasible in 80% of cTURBT cases versus 100% of ERBT cases (p = 0.02). Complication rates, rates of postoperative adjuvant treatment, catheterization time, and hospital stay were comparable between the two groups (p > 0.05). The recurrence rate at median follow-up of 15 mo (interquartile range 7-28) was 18% for cTURBT versus 13% for ERBT (p = 0.16). Limitations include the single high-volume institution and the short-term follow-up. CONCLUSIONS: Our study has the highest level of evidence for comparison of ERBT versus TURBT. ERBT was noninferior to TURBT for BC staging. The rate of T1 substaging feasibility was significantly higher with ERBT. PATIENT SUMMARY: We compared two techniques for removing tumors from the bladder. The en bloc technique removes the tumor in one piece and is not inferior to the conventional method in terms of the quality of the surgical resection and cancer staging assessment.

Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients.

Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19-80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDH mutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.

International Society of Urological Pathology Expert Opinion on Grading of Urothelial Carcinoma.

CONTEXT: Grading is the mainstay for treatment decisions for patients with non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To determine the requirements for an optimal grading system for NMIBC via expert opinion. EVIDENCE ACQUISITION: A multidisciplinary working group established by the International Society of Urological Pathology reviewed available clinical, histopathological, and molecular evidence for an optimal grading system for bladder cancer. EVIDENCE SYNTHESIS: Bladder cancer grading is a continuum and five different grading systems based on historical grounds could be envisaged. Splitting of the World Health Organization (WHO) 2004 low-grade class for NMIBC lacks diagnostic reproducibility and molecular-genetic support, while showing little difference in progression rate. Subdividing the clinically heterogeneous WHO 2004 high-grade class for NMIBC into intermediate and high risk categories using the WHO 1973 grading is supported by both clinical and molecular-genetic findings. Grading criteria for the WHO 1973 scheme were detailed on the basis of literature findings and expert opinion. CONCLUSIONS: Splitting of the WHO 2004 high-grade category into WHO 1973 grade 2 and 3 subsets is recommended. Provision of more detailed histological criteria for the WHO 1973 grading might facilitate the general acceptance of a hybrid four-tiered grading system or-as a preferred option-a more reproducible three-tiered system distinguishing low-, intermediate (high)-, and high-grade NMIBC. PATIENT SUMMARY: Improvement of the current systems for grading bladder cancer may result in better informed treatment decisions for patients with bladder cancer.