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Conventional urothelial carcinoma seen at low (a) and high (b) power. Low- (c) and high-power (d) views of squamous differentiation. Glandular differentiation seen at low (e) and high power (f)
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The aim of the study was to stratify high-grade T1 (HGT1) bladder urothelial carcinoma into risk categories based on the presence of variant histology when compared to conventional urothelial carcinoma. The clinicopathological features of 104 HGT1 cases of urothelial carcinoma of the bladder with variant histology present in 34 (37%) were assessed....
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... Recent years have witnessed the rising clinical incidence of BC, making it one of the primary diseases that threaten the health and life safety of middle-aged and elderly men [12]. Finding a more effective treatment plan is of great significance to ensure the prognosis of patients. ...
... Recent studies have reported worse oncological outcomes among patients with histological subtypes compared to those with pure urothelial tumours, both in NMIBC and MIBC [21,22]. Additionally, the integration of molecular biomarkers and advanced diagnostic methodologies emerges as a promising avenue to refine clinical decision making. ...
... Recent studies have reported worse oncological outcomes among patients with histological subtypes as opposed to those with pure urothelial tumours both in NMIBC and MIBC [21,22]. ...
Objective
To evaluate the prognostic value of T1 substaging in patients treated with bacillus Calmette‐Guérin (BCG) or immediate radical cystectomy (iRC).
Materials and Methods
We performed an institutional review board‐approved retrospective study analysing non‐muscle‐invasive bladder cancer (NMIBC) patients with pT1 disease treated with either BCG or iRC between 2000 and 2020. Lamina propria (LP) invasion characteristics were extracted from the pathology report. The Kaplan–Meier method was used to calculate overall survival (OS), cancer‐specific survival (CSS) and metastasis‐free survival (MFS). Multivariable Cox models were used to determine the association between progression‐free survival (PFS) and characteristics in the BCG cohort. A logistic regression model explored the relationship between T1 substaging and upstaging to >pT2 at iRC.
Results
A total of 411 T1 high‐grade patients were identified. LP invasion characteristics were as follows: not specified: 115 (28%); focal/superficial (F/S): 147 (35.8%); and extensive/multifocal (E/M): 149 (36.2%). Overall, 303 patients (73.7%) received BCG, and 108 patients (26.3%) underwent iRC. The median (interquartile range) follow‐up was 53 (32–96) months. Patients with E/M LP invasion were significantly more likely to undergo iRC (34% vs. 19%; P = 0.003). Patients with E/M LP invasion showed poorer MFS and CSS compared to those with F/S LP invasion when treated with BCG but not when treated with iRC. Among BCG‐treated patients, progression occurred in 41 patients and E/M LP invasion was independently associated with progression after BCG (hazard ratio 5.3, 95% confidence interval [CI] 2.2–13.1; P < 0.001). T1 substaging was not associated with upstaging at RC (odds ratio 3.15, 95% CI 0.82–12.12; P = 0.095).
Conclusions
Extensive/multifocal LP invasion was associated with poor PFS, MFS and CSS in patients treated with BCG. T1 substaging provides valuable prognostic information and should be reported in pathology reports.
... More promising treatment strategies may involve improved classification schemes with adjunct molecular profiling and mutational signatures to optimize the timing and type of treatments, which may in turn suggest a role for systemic therapy. Molecular profiling has previously shown value in demonstrating which VH NMIBC patients respond to neoadjuvant chemotherapy [25,26], while altered classification schemes for histologic variants have attempted to provide clarity on treatment strategy [27,28]. In the muscle-invasive setting, previous work by Speir et al. [29] demonstrated that <50% involvement of squamous differentiation vs. >50% presence on TURBT impacted pathologic outcomes following neoadjuvant chemotherapy, suggesting percent presence may be useful for treatment decision-making in the NMIBC setting. ...
Introduction: Variant histology (VH) of urothelial carcinoma is uncommon and frequently presents at the muscle-invasive stage. VH is considering a significant risk factor for progression among patients with nonmuscle invasive bladder cancer (NMIBC). While there is some debate, expert opinion is generally that upfront radical cystectomy (RC) should be consider for these patients. Limited data exists to support this position. In this study, we sought to examine the rate of upstaging and overall survival for patients with VH NMIBC against patients with pure urothelial NMIBC who underwent RC, to help clarify the optimal treatment strategy for these patients. Methods: The institutional REDCap database was utilized to identify all patients with T1 and Ta bladder cancer that underwent RC over the study period (2004−2022). Matched-pair analysis was performed between patients with VH and pure urothelial NMIBC; 42 pairs were matched on prior intravesical therapy, presence of muscularis propria on transurethral resection of bladder tumor (TURBT), any carcinoma in situ presence on prior TURBTs, and final tumor staging on TURBT. The primary outcomes of interest were pathologic tumor upstaging rate at RC and overall survival. Secondary outcomes of interest included association of demographic or pretreatment variables with upstag-ing, and upstaging rates for specific variant histologies. Results: Patients with VH NMIBC undergoing RC were upstaged at a significantly higher rate than a matched cohort of patients with pure urothelial NMIBC (73.8% vs. 52.4%, P = 0.0244) and among those upstaged, had significantly higher rates of pT3 to pT4 (54.7% vs. 23.8%, P = 0.0088). Rate of node positivity at RC for VH NMIBC was also higher compared to pure urothelial NMIBC (40.5% vs. 21.4%, P = 0.0389). Among histologic variants, patients with plasmacytoid and sarcomatoid subtypes demonstrated the highest rates of upstaging; differences were not statistically significant. The overall median survival was 28.4 months for patients with VH after RC compared to 155.1 months for patients with pure urothelial NMIBC (P = 0.009). Conclusion: Patients with VH NMIBC undergoing RC are at significantly higher risk of upstaging at RC when compared to patients with pure urothelial NMIBC and have worse overall survival. While this study supports the concept of an aggressive treatment approach for patients with VH NMIBC, improvements in understanding of the disease are necessary to improve outcomes. Ó 2023 Elsevier Inc. All rights reserved.
... BC is a heterogeneous disease encompassing non-muscle-invasive (NMIBC) and muscle-invasive BC (MIBC) and entailing very heterogeneous managements and prognoses [17][18][19][20][21]. The results regarding CFM applications in BC detection are reported in Table 1. ...
Fluorescence confocal microscopy (FCM) represents a novel diagnostic technique able to provide real-time histological images from non-fixed specimens. As a consequence of its recent developments, FCM is gaining growing popularity in urological practice. Nevertheless, evidence is still sparse, and, at the moment, its applications are heterogeneous. We performed a narrative review of the current literature on this topic. Papers were selected from the Pubmed, Embase, and Medline archives. We focused on FCM applications in prostate cancer (PCa), urothelial carcinoma (UC), and renal cell carcinoma (RCC). Articles investigating both office and intraoperative settings were included. The review of the literature showed that FCM displays promising accuracy as compared to conventional histopathology. These results represent significant steps along the path of FCM’s formal validation as an innovative ready-to-use diagnostic support in urological practice. Instant access to a reliable histological evaluation may indeed significantly influence physicians’ decision-making process. In this regard, FCM addresses this still unmet clinical need and introduces intriguing perspectives into future diagnostic pathways. Further studies are required to thoroughly assess the whole potential of this technique.
... These variant histologies have different properties than classical urothelial cancer and are generally associated with more-advanced disease [15]. It is important to classify any presence of variant histology regardless of NMIBC or MIBC for prognostic and treatment evaluation purposes [15,16]. The malignant potential and clinical features of each subtype are still being investigated [17]. ...
Background:
In Sweden, all patients with urinary bladder cancer (UBC) are recorded in the Swedish National Register for Urinary Bladder Cancer (SNRUBC). The purpose of this study was to validate the registered clinical tumour categories (cT-categories) in the SNRUBC for Norrland University Hospital, Sweden, from 2009 to 2020, inclusive.
Methods:
The medical records of all 295 patients who underwent radical cystectomy for the treatment of UBC were reviewed retrospectively. Possible factors impacting the cT-categories were identified. To optimise cT-classification, computed tomography urography of all patients with suspected tumour-associated hydronephrosis (TAH) or suspected tumour in bladder diverticulum (TIBD) were retrospectively reviewed by a radiologist. Discrepancy was tested with a logistic regression model.
Results:
cT-categories differed in 87 cases (29.5%). Adjusted logistic regression analysis found TIBD and TAH as significant predictors for incorrect registration; OR = 7.71 (p < 0.001), and OR = 17.7, (p < 0.001), respectively. In total, 48 patients (68.6%) with TAH and 12 patients (52.2%) with TIBD showed discrepancy regarding the cT-category. Incorrect registration was mostly observed during the years 2009-2012.
Conclusion:
The study revealed substantial incorrect registration of cT-categories in SNRUBC. A major part of the misclassifications was related to TAH and TIBD. Registration of these variables in the SNRUBC might be considered to improve correct cT-classification.
... A study analyzed VHs of high-grade T1 (HGT1) bladder urothelial carcinoma and found that it was identified as a significant predictor of DFS. They considered patients with micropapillary, nested, or basaloid morphology or glandular divergent differentiation carcinoma as high-risk HGT1, while the presence of divergent squamous differentiation, inverted growth, microcystic, and villouslike or lymphoepithelioma-like carcinoma was considered as low-risk HGT1 (15). Francesco Claps' team evaluated VHs for disease-specific survival (DSS) in patients with invasive urothelial BC undergoing radical cystectomy (RC). ...
... Additionally, we did not collect some nutrition-related markers and biomarkers, and there are currently no standardized cutoff points for inflammatory markers. Despite our exclusion criteria for patients with VHs, the fact remains that some pathologists do not recognize or report about one-half of cases with variant histology in their practice (15). Therefore, the risk associated with variant histology in BC might indeed be underrecognized, which is one of our limitations. ...
Purpose
Patients with non-muscle invasive bladder cancer (NMIBC) have a high possibility of recurrence after surgery. We aimed to assess the factors associated with tumor recurrence and to construct a nomogram model that can contribute to personalized treatment plans of each patient.
Methods
496 patients with primary bladder cancer (BC) from 2 centers were retrospectively analyzed. Preoperative neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and traditional clinical parameters were collected, then using univariate and multivariate Cox regression analysis to find out the independent risk factors associated with tumor recurrence among them, and then these independent factors were incorporated into the nomogram model. The internal calibration curves and the external calibration curves were used to verify their usefulness.
Results
In the training cohort, 150 patients (43.1%) experienced recurrence. After Cox regression analysis, the independent risk factors affecting recurrence-free survival (RFS) were tumor grade, immediate postoperative instillation therapy (IPPIT), NLR, and SII. These factors were used to construct a model to predict RFS 1, 2, 3, and 5 years of NMIBC patients after surgery. And then, we found that the constructed model outperforms the conventional model in terms of accuracy and predictability, the results were verified by statistical tests.
Conclusion
Preoperative inflammatory response markers have a predictive value for postoperative recurrence in patients with NMIBC. The constructed nomogram model can be helpful in guiding personalized clinical evaluation and subsequent treatment.
... 93 A study on T1 tumors suggests differences in outcome among different morphologies, although the study is limited by the low number of cases. 103 In terms of treatment responses, Hajiran et al 104 showed that patients with muscle-invasive tumors with subtype histologies have worse survival outcomes compared to patients with divergent histologies after neoadjuvant chemotherapy. Chakiryan et al 105 showed that neoadjuvant chemotherapy improved the outcome of patients with conventional urothelial carcinoma, sarcomatoid urothelial carcinoma, and neuroendocrine carcinoma but not for patients with micropapillary urothelial carcinoma, squamous cell carcinoma, and adenocarcinoma. ...
The 2022 International Society of Urological Pathology (ISUP) Consensus Conference on Urinary Bladder Cancer Working Group 2 was tasked to provide evidence-based proposals on the applications of grading in noninvasive urothelial carcinoma with mixed grades, invasive urothelial carcinoma including subtypes (variants) and divergent differentiations, and in pure non-urothelial carcinomas. Studies suggested that predominantly low-grade noninvasive papillary urothelial carcinoma with focal high-grade component has intermediate outcome between low- and high-grade tumors. However, no consensus was reached on how to define a focal high-grade component. By 2004 WHO grading, the vast majority of lamina propria-invasive (T1) urothelial carcinomas are high-grade, and the rare invasive low-grade tumors show only limited superficial invasion. While by 1973 WHO grading, the vast majority of T1 urothelial carcinomas are G2 and G3 and show significant differences in outcome based on tumor grade. No consensus was reached if T1 tumors should be graded either by the 2004 WHO system or by the 1973 WHO system. Because of the concern for underdiagnosis and underreporting with potential undertreatment, participants unanimously recommended that the presence of urothelial carcinoma subtypes and divergent differentiations should be reported. There was consensus that the extent of these subtypes and divergent differentiations should also be documented in biopsy, transurethral resection, and cystectomy specimens. Any distinct subtype and divergent differentiation should be diagnosed without a threshold cutoff, and each type should be enumerated in tumors with combined morphologies. The participants agreed that all subtypes and divergent differentiations should be considered high-grade according to the 2004 WHO grading system. However, participants strongly acknowledged that subtypes and divergent differentiations should not be considered as a homogenous group in terms of behavior. Thus, future studies should focus on individual subtypes and divergent differentiations rather than lumping these different entities into a single clinicopathological group. Likewise, clinical recommendations should pay attention to the potential heterogeneity of subtypes and divergent differentiations in terms of behavior and response to therapy. There was consensus that invasive pure squamous cell carcinoma and pure adenocarcinoma of the bladder should be graded according to the degree of differentiation. In conclusion, this summary of the International Society of Urological Pathology Working Group 2 proceedings addresses some of the issues on grading beyond its traditional application, including for papillary urothelial carcinomas with mixed grades and with invasive components. Reporting of subtypes and divergent differentiation is also addressed in detail, acknowledging their role in risk stratification. This report could serve as a guide for best practices and may advise future research and proposals on the prognostication of these tumors.
... had significantly worse disease-free survival and cancerspecific survival (Lopez-Beltran et al. 2022). We explored the relationship between urothelial variants and LNM, and we discovered no statistically significant difference between patients with and without urothelial variants. ...
Purpose
Predicting lymph node metastasis (LNM) in patients with bladder urothelial carcinoma (BUC) before radical cystectomy aids clinical decision making. Here, we aimed to develop and validate a nomogram to preoperatively predict LNM in BUC patients.
Methods
Patients with histologically confirmed BUC, who underwent radical cystectomy and bilateral lymphadenectomy, were retrospectively recruited from two institutions. Patients from one institution were enrolled in the primary cohort, while those from the other were enrolled in the external validation cohort. Patient demographic, pathological (using transurethral resection of the bladder tumor specimens), imaging, and laboratory data were recorded. Univariate and multivariate logistic regression analyses were performed to explore the independent preoperative risk factors and develop the nomogram. Internal and external validation was conducted to assess nomogram performance.
Results
522 and 215 BUC patients were enrolled in the primary and external validation cohorts, respectively. We identified tumor grade, infiltration, extravesical invasion, LNM on imaging, tumor size, and serum creatinine levels as independent preoperative risk factors, which were subsequently used to develop the nomogram. The nomogram showed a good predictive accuracy, with area under the receiver operator characteristic curve values of 0.817 and 0.825 for the primary and external validation cohorts, respectively. The corrected C-indexes, calibration curves (after 1000 bootstrap resampling), decision curve analysis results, and clinical impact curves demonstrated that the nomogram performed well in both cohorts and was highly clinically applicable.
Conclusion
We developed a nomogram to preoperatively predict LNM in BUC, which was highly accurate, reliable, and clinically applicable.
... Looking five years into the future, the authors envision that the use of machine learning models in bladder cancer prognosis will significantly expand, specifically in terms of predicting survival outcomes. In addition, the adoption of ML could play a prime role in distinguishing between different histologic variants of bladder cancer, as specific variants are important factors in predicting prognostic outcomes and guiding subsequent cancer-related treatment in both NIMBC and MIBC [39][40][41]. An example of this is the use of noninvasive ML-based radiomics, which may effectively overcome the limitations of preoperative histopathological examination by accurately predicting histological variants of bladder cancer [42]. ...
Introduction:
The objective of this systematic review is to summarize the use of machine learning (ML) in predicting overall survival (OS) in patients with bladder cancer.
Methods:
Search terms for bladder cancer, ML algorithms, and mortality were used to identify studies in PubMed and Web of Science as of February 2022. Notable inclusion/exclusion criteria contained the inclusion of studies that utilized patient-level datasets and exclusion of primarily gene expression-related dataset studies. Study quality and bias were assessed using the International Journal of Medical Informatics (IJMEDI) checklist.
Results:
Of the 14 included studies, the most common algorithms were artificial neural networks (n = 8) and logistic regression (n = 4). Nine articles described missing data handling, with five articles removing patients with missing data entirely. With respect to feature selection, the most common sociodemographic variables were age (n = 9), gender (n = 9), and smoking status (n = 3), with clinical variables most commonly including tumor stage (n = 8), grade (n = 7), and lymph node involvement (n = 6). Most studies (n = 10) were of medium IJMEDI quality, with common areas of improvement being the descriptions of data preparation and deployment.
Conclusions:
ML holds promise for optimizing bladder cancer care through accurate OS predictions, but challenges related to data processing, feature selection, and data source quality must be resolved to develop robust models. While this review is limited by its inability to compare models across studies, this systematic review will inform decision making by various stakeholders to improve understanding of ML-based OS prediction in bladder cancer and foster interpretability of future models.
... Variant histologies (VHs) have been recognized as drivers of biological heterogeneity and increased aggressiveness in current clinical practice. In non-muscle-invasive bladder cancer (NIMBC), variant histologies (nested, glandular, micropapillary, squamous, inverted, basaloid, microcystic, villous-like, and lymphoepithelioma-like carcinoma) have been identified as risk factors for patient disease-free survival (DFS) [98]. Plasmacytoid, small-cell, and sarcomatoid VHs are linked to worse disease-specific survival (DSS) in muscle-invasive bladder cancer (MIBC), while lymphoepithelioma-like VH is associated with an improved DSS [99]. ...
Prostate cancer (PCa) is a critical global public health issue with its incidence on the rise. Radiation therapy holds a primary role in PCa treatment; however, radiation resistance has become increasingly challenging as we uncover more about PCa’s pathogenesis. Our review aims to investigate the multifaceted mechanisms underlying radiation therapy resistance in PCa. Specifically, we will examine how various factors, such as cell cycle regulation, DNA damage repair, hypoxic conditions, oxidative stress, testosterone levels, epithelial–mesenchymal transition, and tumor stem cells, contribute to radiation therapy resistance. By exploring these mechanisms, we hope to offer new insights and directions towards overcoming the challenges of radiation therapy resistance in PCa. This can also provide a theoretical basis for the clinical application of novel ultra-high-dose-rate (FLASH) radiotherapy in the era of PCa.
