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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.

Background: There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node–positive (cN+) bladder cancer (BCa). Objective: To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. Design, setting, and participants: This was an observational study of 369 patients with cT2–4 N1–3 M0 BCa. Intervention: IC followed by consolidative radical cystectomy (RC). Outcome measurements and statistical analysis: The primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. Results and limitations: After PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9–69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26–57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. Conclusions: Cisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. Patient summary: In this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.

Context: Bladder recurrences have been reported in 22–47% of patients after surgery for upper urinary tract urothelial carcinoma (UTUC). This collaborative review focuses on risk factors for and treatment strategies to reduce bladder recurrences after upper tract surgery for UTUC. Objective: To review the current evidence on risk factors and treatment strategies for intravesical recurrence (IVR) after upper tract surgery for UTUC. Evidence acquisition: This collaborative review is based on a literature search of PubMed/Medline, Embase, Cochrane Library, and currently available guidelines on UTUC. Relevant papers on bladder recurrence (etiology, risk factors, and management) after upper tract surgery were selected. Special attention has been paid to (1) the genetic background of bladder recurrences, (2) bladder recurrences after ureterorenoscopy (URS) with or without a biopsy, and (3) postoperative or adjuvant intravesical instillations. The literature search was performed in September 2022. Evidence synthesis: Recent evidence supports the hypothesis that bladder recurrences after upper tract surgery for UTUC are often clonally related. Clinicopathologic risk factors (patient, tumor, and treatment related) have been identified for bladder recurrences after UTUC diagnosis. Specifically, the use of diagnostic ureteroscopy before radical nephroureterectomy (RNU) is associated with an increased risk of bladder recurrences. Further, a recent retrospective study suggests that performing a biopsy during ureteroscopy may further worsen IVR (no URS: 15.0%; URS without biopsy: 18.4%; URS with biopsy: 21.9%). Meanwhile, a single postoperative instillation of intravesical chemotherapy has been shown to be associated with a reduced bladder recurrence risk after RNU compared with no instillation (hazard ratio 0.51, 95% confidence interval 0.32–0.82). Currently, there are no data on the value of a single postoperative intravesical instillation after ureteroscopy. Conclusions: Although based on limited retrospective data, performing URS seems to be associated with a higher risk of bladder recurrences. Future studies are warranted to assess the influence of other surgical factors as well as the role of URS biopsy or immediate postoperative intravesical chemotherapy after URS for UTUC. Patient summary: In this paper, we review recent findings on bladder recurrences after upper tract surgery for upper urinary tract urothelial carcinoma.

Background: There might be differential sensitivity to neoadjuvant chemotherapy (NAC) in patients with primary muscle-invasive bladder cancer (MIBC) in comparison to patients with secondary MIBC after a history of non–muscle-invasive disease. Objective: To investigate pathologic response rates and survival associated with primary versus secondary MIBC among patients treated with cisplatin-based NAC for cT2–4N0M0 MIBC. Design, setting, and participants: Oncologic outcomes were compared for 350 patients with primary MIBC and 64 with secondary MIBC treated with NAC and radical cystectomy between 1992 and 2021 at 11 academic centers. Genomic analyses were performed for 476 patients from the Memorial Sloan Kettering/The Cancer Genome Atlas cohort. Outcome measurements and statistical analysis: The outcome measures were pathologic objective response (pOR; ≤ypT1 N0), pathologic complete response (pCR; ypT0 N0), overall mortality, and cancer-specific mortality. Results and limitations: The primary MIBC group had higher pOR (51% vs 34%; p = 0.02) and pCR (33% vs 17%; p = 0.01) rates in comparison to the secondary MIBC group. On multivariable logistic regression analysis, primary MIBC was independently associated with both pOR (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.26–0.87; p = 0.02) and pCR (OR 0.41, 95% CI 0.19–0.82; p = 0.02). However, on multivariable Cox regression analysis, primary MIBC was not associated with overall mortality (hazard ratio 1.70, 95% CI 0.84–3.44; p = 0.14) or cancer-specific mortality (hazard ratio 1.50, 95% CI 0.66–3.40; p = 0.3). Genomic analyses revealed a significantly higher ERCC2 mutation rate in primary MIBC than in secondary MIBC (12.4% vs 1.3%; p

Background: Radical cystectomy (RC) is indicated in primary or secondary muscle-invasive bladder cancer (primMIBC, secMIBC) and in primary or recurrent high- or very high-risk non–muscle-invasive bladder cancer (primHR-NMIBC, recHR-NMIBC). The optimal timing for RC along the disease spectrum of nonmetastatic urothelial carcinoma remains unclear. Objective: To compare outcomes after RC between patients with primHR-NMIBC, recHR-NMIBC, primMIBC, and secMIBC. Design, setting, and participants: This retrospective, multicenter study included patients with clinically nonmetastatic bladder cancer (BC) treated with RC. Outcome measurements and statistical analysis: We assessed oncological outcomes for patients who underwent RC according to the natural history of their BC. primHR-NMIBC and primMIBC were defined as no prior history of BC, and recHR-NMIBC and secMIBC as previously treated NMIBC that recurred or progressed to MIBC, respectively. Log-rank analysis was used to compare survival outcomes, and univariable and multivariable Cox and logistic regression analyses were used to identify predictors for survival. Results and limitations: Among the 908 patients included, 211 (23%) had primHR-NMIBC, 125 (14%) had recHR-NMIBC, 404 (44%) had primMIBC, and 168 (19%) had secMIBC. Lymph node involvement and pathological upstaging were more frequent in the secMIBC group than in the other groups (p

We report two cases with recurrences of urachal adenocarcinoma (UrAC) in the urethra. Both patients had mucinous UrAC without metastasis, for which they were treated with en-bloc partial cystectomy and umbilectomy. The first patient developed recurrence of UrAC in the distal urethra after 1 yr. Distal urethrectomy revealed multiple additional recurrences in the penile and prostatic urethra. The patient underwent radical cystoprostatectomy with en-bloc urethrectomy. At 5 mo after surgery, liver metastases were found. A search in our institutional database revealed a second patient who developed a solitary recurrence of UrAC in the prostatic urethra 8 yr after partial cystectomy. Radical cystoprostatectomy was performed. The patient subsequently experienced recurring UrAC in the urethra, which were treated with multiple surgeries and radiation. Unfortunately, local tumor control could not be achieved and the patient developed distant metastases 7 yr after cystoprostatectomy. Our two cases and four comparable cases reported in the literature indicate that urothelial spread of UrAC is rare but possible. It remains to be determined if UrAC spreads along the urothelium similar to urothelial cancer or if these multifocal urethral recurrences were the first sign of local metastasis.

Recent advances in semi-supervised learning algorithms (SSL) have made great strides in reducing the training dependency on labeled datasets and requiring that only a subset of the data be labeled. The presented work explores a class of semi-supervised learning algorithms that uses consistency regularization and self-ensembling to leverage the unlabeled portion of the dataset. Labeling medical image datasets are time-consuming and prohibitively expensive, requiring hundreds of hours of effort from expert diagnosticians. This research presents an approach for building and training a deep learning model to grade medical images while requiring only a minimal number of labels. Consistency regularization has been used in SSL to great success in datasets of natural images but not for more complex images such as pathology slides where the dataset consists of cell patterns. This research successfully proposes and applies an SSL algorithm based on the VGG-16 neural network, which combines techniques introduced by the Π model and FixMatch algorithms to a cell pattern-based pathology image dataset. The results presented in this research show that using the proposed approach, it is possible to label only 3% of the samples in a dataset, use the remaining 97% of samples as unlabeled data, and achieve a 19% increase over the baseline accuracy. The second contribution of this research shows a ratio of labeled vs. unlabeled images in a dataset beyond which continuing to label the data increases the cost but offers little performance gains.

Bladder cancer tissue grading, which assigns a numerical grade reflecting how aggressive a tumor looks under a microscope, is essential to determine the proper course of treatment, design a therapeutic plan and determine prognosis. The major problem is that there are considerable and clinically relevant variations in grading by pathologists – as they are humans with different opinions and experience – including in bladder cancer. This work presents a solution, i.e., Artificial Intelligence for Bladder Cancer grading (ABC) system, that is developed based on deep neural network architectures to provide a more reliable and accurate diagnosis for patients affected by this deadly disease and ultimately improve management and clinical outcomes. Whole Slide Images (WSI) are split up into equally-sized square tiles and annotated to build a training dataset. ABC introduces a new grading system concept that can provide a percentage distribution of each different grade in a specific tumor, unlike the current numerical grade value between 1 and 3 based on the general impression of the pathologist. This new approach aims to provide a more granular grading of bladder cancer tissues and better capture tumor grade heterogeneity. This new concept may offer a more precise prognosis and optimize management in the future. The ABC learning model is fully configurable, and any deep architecture model can be trained and used by ABC. Some trained models developed by ABC have shown high accuracy and consistency in grading and intra-observer variability. The combination of a loosely coupled architecture and fully integrated tiles’ utilization makes ABC a universal, scalable, and versatile system that could be configured and deployed worldwide.

Introduction: Currently, (multiple) biopsies are taken to obtain histopathological diagnosis of suspicious lesions of the penile skin. Optical coherence tomography (OCT) provides noninvasive in vivo images from which epidermal layer thickness and attenuation coefficient (μoct) can be quantified. We hypothesize that qualitative (image assessment) and quantitative (epidermal layer thickness and attenuation coefficient, μoct) analysis of penile skin with OCT is possible and may differentiate benign penile tissue from (pre) malignant penile tissue. Materials and Methods: Optical coherence tomography-imaging was performed prior to punch biopsy in 18 consecutive patients with a suspicious lesion at the outpatient clinic of the NKI-AVL. Qualitative analysis consisted of visual assessment of clear layers and a visible lower border of the lesions, quantitative analysis comprised of determination of the epidermal layer thickness and μoct. Results were grouped according to histopathology reports. Results: Qualitative analysis showed a statistically significant difference (P = 0.047) between benign and (pre) malignant lesions. Quantitative analysis showed that epidermal layer thickness and attenuation coefficient was significantly different between benign and (pre) malignant tissue, respectively, P = 0.001 and P < 0.001. Conclusion: In this preliminary study, qualitative and quantitative analysis of OCT-images of suspicious penile lesions shows differences between benign lesions and (pre) malignant lesions. These results encourage further research in a larger study population.