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Special Issue "Urothelial Carcinoma: Clinical Diagnosis and Treatment"

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: 25 April 2023 | Viewed by 7427

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Prof. Dr. Massimiliano Creta

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Guest Editor

Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Italy
Interests: bladder cancer; radical cystectomty; radical nephroureterectomy; transurethral resection of bladder tumor; upper urinary tract urothelian carcinoma

Special Issue Information

Dear Colleagues,

Urothelial carcinoma (UC) represents the most common type of epithelial tumor diagnosed in Europe, North America, South America, and Asia. Although around 70–75% of newly diagnosed UC manifests as the non-muscle invasive bladder cancer, it can also involve the renal pelvis, ureter, and urethra. UC is a multifocal process, with tobacco smoking being the most relevant risk factor in developed countries. Patients with UC of the upper urinary tract have a 30% to 50% chance of developing cancer of the bladder, while patients with bladder cancer have a 2% to 3% chance of developing cancer of the upper urinary tract. Currently, UC represents a clinical and social challenge because of its incidence, post-treatment recurrence rate, and prognosis. In recent years, the poor diagnostic accuracy of available diagnostic tools such as urine cytology, white cystoscopy, and conventional imaging modalities have emphasized the urgent need for advancement in clinical guidance for UC. Moreover, novel treatment approaches, both medical and surgical, have significantly impacted the management of these patients. At the same time, the quality of life of these patients has gained growing interest. This Special Issue presents the up-to-date summaries related to the pathogenesis, diagnosis, prognostic assessment, and management of UC.

Prof. Dr. Massimiliano Creta
Guest Editor

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Keywords

bladder cancer
radical cystectomty
radical nephroureterectomy
transurethral resection of bladder tumor
upper urinary tract urothelian carcinoma

Published Papers (10 papers)

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Editorial

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Open AccessEditorial

En-bloc Laser Resection of Bladder Tumors: Where Are We Now?

and

J. Clin. Med. 2022, 11(12), 3463; https://doi.org/10.3390/jcm11123463 - 16 Jun 2022

Cited by 1 | Viewed by 718

Abstract

Transurethral resection of bladder tumors (TURBT) is a crucial procedure in the management of bladder cancer [...] Full article

(This article belongs to the Special Issue Urothelial Carcinoma: Clinical Diagnosis and Treatment)

Research

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Open AccessArticle

The Effect of Sex on Disease Stage and Survival after Radical Cystectomy in Non-Urothelial Variant-Histology Bladder Cancer

J. Clin. Med. 2023, 12(5), 1776; https://doi.org/10.3390/jcm12051776 - 23 Feb 2023

Viewed by 548

Abstract

Background: Female sex in patients treated by radical cystectomy (RC) is associated with more advanced stage and worse survival. However, studies supporting these findings mostly or exclusively relied on urothelial carcinoma of the urinary bladder (UCUB) and did not address non-urothelial variant-histology bladder cancer (VH BCa). We hypothesized that female sex is associated with a more advanced stage and worse survival in VH BCa, similarly to that of UCUB. Materials and Methods: Within the SEER database (2004–2016), we identified patients aged ≥18 years, with histologically confirmed VH BCa, and treated with comprehensive RC. Logistic regression addressing the non-organ-confined (NOC) stage, as well as cumulative incidence plots and competing risks regression addressing CSM for females vs. males, were fitted. All analyses were repeated in stage-specific and VH-specific subgroups. Results: Overall, 1623 VH BCa patients treated with RC were identified. Of those, 38% were female. Adenocarcinoma (n = 331, 33%), neuroendocrine tumor (n = 304, 18%), and other VH (n = 317, 37%) were less frequent in females but not squamous cell carcinoma (n = 671, 51%). Across all VH subgroups, female patients had higher NOC rates than males did (68 vs. 58%, p < 0.001), and female sex was an independent predictor of NOC VH BCa (OR = 1.55, p = 0.0001). Overall, five-year cancer-specific mortality (CSM) were 43% for females vs. 34% for males (HR = 1.25, p = 0.02). Conclusion: In VH BC patients treated with comprehensive RC, female sex is associated with a more advanced stage. Independently of stage, female sex also predisposes to higher CSM. Full article

(This article belongs to the Special Issue Urothelial Carcinoma: Clinical Diagnosis and Treatment)

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Open AccessArticle

Diminishing the Gender-Related Disparity in Survival among Chemotherapy Pre-Treated Patients after Radical Cystectomy—A Multicenter Observational Study

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J. Clin. Med. 2023, 12(4), 1260; https://doi.org/10.3390/jcm12041260 - 05 Feb 2023

Viewed by 522

Abstract

There is a well-documented problem of inferior outcome of muscle-invasive bladder cancer (MIBC) after radical cystectomy (RC) in women. However, previous studies were conducted before neoadjuvant chemotherapy (NAC) was widely adopted to multidisciplinary management of MIBC. In our study, we assessed the gender-related difference in survival between patients who received NAC and those who underwent upfront RC, in two academic centers. This non-randomized, clinical follow-up study enrolled 1238 consecutive patients, out of whom 253 received NAC. We analyzed survival outcome of RC according to gender between NAC and non-NAC subgroups. We found that female gender was associated with inferior overall survival (OS), compared to males (HR, 1.234; 95%CI 1.046–1.447; p = 0.013) in the overall cohort and in non-NAC patients with ≥pT2 disease (HR, 1.220 95%CI 1.009–1.477; p = 0.041). However, no gender-specific difference was observed in patients exposed to NAC. The 5-year OS in NAC-exposed women in ≤pT1 and ≥pT2 disease, was 69.333% 95%CI (46.401–92.265) and 36.535% (13.134–59.936) respectively, compared to men 77.727% 95%CI (65.952–89.502) and 39.122% 95%CI (29.162–49.082), respectively. The receipt of NAC not only provides downstaging and prolongs patients’ survival after radical treatment of MIBC but may also help to diminish the gender specific disparity. Full article

(This article belongs to the Special Issue Urothelial Carcinoma: Clinical Diagnosis and Treatment)

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Open AccessArticle

Risk Factors Involved in the High Incidence of Bladder Cancer in an Industrialized Area in North-Eastern Spain: A Case–Control Study

and

Montserrat Martín-Baranera

J. Clin. Med. 2023, 12(2), 728; https://doi.org/10.3390/jcm12020728 - 16 Jan 2023

Cited by 1 | Viewed by 447

Abstract

Bladder cancer (BC) is the most common of the malignancies affecting the urinary tract. Smoking and exposure to occupational and environmental carcinogens are responsible for most cases. Vallès Occidental is a highly industrialized area in north-eastern Spain with one of the highest incidences of BC in men. We carried out a case–control study in order to identify the specific risk factors involved in this area. Three hundred and six participants were included (153 cases BC and 153 controls matched for age and sex): in each group, 89.5% (n = 137) were male and the mean age was 71 years (range 30–91; SD = 10.6). There were no differences between groups in family history, body mass index, or dietary habits. Independent risk factors for CV were smoking (OR 2.08; 95% CI 1.30–3.32; p = 0.002), the use of analgesics in nonsmokers (OR 10.00; 95% CI 1.28–78.12; p = 0.028), and profession (OR: 8.63; 95% CI 1.04–71.94; p = 0.046). The consumption of black and blond tobacco, the use of analgesics in nonsmokers, and occupational exposures are risk factors for the development of BC in this area, despite the reduction in smoking in the population and the extensive measures taken in the last few decades in major industries to prevent exposure to occupational carcinogens. Full article

(This article belongs to the Special Issue Urothelial Carcinoma: Clinical Diagnosis and Treatment)

Open AccessArticle

Immunohistochemical Algorithm for the Classification of Muscle-Invasive Urinary Bladder Carcinoma with Lymph Node Metastasis: An Institutional Study

Karla Beatríz Peña

Francesc Riu

Josep Gumà

Francisca Martínez-Madueño

Marta Rodriguez-Balada

and

David Parada

J. Clin. Med. 2022, 11(24), 7430; https://doi.org/10.3390/jcm11247430 - 15 Dec 2022

Viewed by 531

Abstract

Muscle-invasive urothelial carcinoma represents 20% of newly diagnosed cases of bladder cancer, and most cases show aggressive biological behavior with a poor prognosis. It is necessary to identify biomarkers that can be used as prognostic and predictive factors in daily clinical practice. In our study, we analyzed different antibodies in selected cases of muscle-invasive urinary bladder carcinoma and lymph node metastasis to identify immunohistochemical types and their value as possible prognostic factors. A total of 38 patients were included, 87% men and 13% women, with a mean age of 67.8 years. The most frequent histopathological type was urothelial carcinoma. In the primary lesion, the mixed type was the most common. In unilateral metastasis, the mixed type was the most frequently found. In cases of primary lesions and bilateral metastasis, the luminal and mixed types were observed. The luminal subtype was the most stable in immunohistochemical expression across primary tumors and metastases. The basal type showed a better prognosis in terms of disease-free survival. In conclusion, immunohistochemical studies are useful in assessing primary and metastatic lesions in patients with urothelial carcinoma. Immunohistochemical classification can typify muscle-invasive urothelial carcinoma, and the immunophenotype seems to have prognostic implications. Full article

(This article belongs to the Special Issue Urothelial Carcinoma: Clinical Diagnosis and Treatment)

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Open AccessArticle

Prognostic Utility of the Modified Glasgow Prognostic Score in Urothelial Carcinoma: Outcomes from a Pooled Analysis

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J. Clin. Med. 2022, 11(21), 6261; https://doi.org/10.3390/jcm11216261 - 24 Oct 2022

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Abstract

Background: Many studies explored the prognostic value of the modified Glasgow Prognostic Score (mGPS) in urothelial carcinoma (UC), but the results are controversial. This study aimed to quantify the relationship between pretreatment mGPS and survival in patients with UC. Methods: A systematic literature search was conducted using Embase, PubMed, and Web of Science to identify eligible studies published before August 2022. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to assess the association between pretreatment mGPS and the prognosis of UC. Results: Thirteen eligible studies involving 12,524 patients were included. A high mGPS was significantly associated with poor overall survival (mGPS 1/0: HR = 1.33, 95% CI 1.12–1.58, p = 0.001; mGPS 2/0: HR = 2.02, 95% CI 1.43–2.84, p < 0.0001), progression-free survival (mGPS 1/0: HR = 1.26, 95% CI 1.03–1.53, p = 0.021; mGPS 2/0: HR = 1.76, 95% CI 1.12–2.77, p = 0.013), recurrence-free survival (mGPS 1/0: HR = 1.36, 95% CI 1.18–1.56, p < 0.0001; mGPS 2/0: HR = 1.70, 95% CI 1.44–2.000, p < 0.0001), and cancer-specific survival (mGPS 2/0: HR = 1.81, 95% CI 1.30–2.52, p < 0.0001). A subgroup analysis of OS also yielded similar results. Conclusions: Evidence suggests that high pretreatment mGPS in UC is closely related to poor survival. Pre-treatment mGPS is a powerful independent prognostic factor in patients with UC. Full article

(This article belongs to the Special Issue Urothelial Carcinoma: Clinical Diagnosis and Treatment)

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Open AccessArticle

Prognostic Significance of Organ-Specific Metastases in Patients with Metastatic Upper Tract Urothelial Carcinoma

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J. Clin. Med. 2022, 11(18), 5310; https://doi.org/10.3390/jcm11185310 - 09 Sep 2022

Cited by 3 | Viewed by 834

Abstract

Background: Existing data on metastatic upper tract urothelial carcinoma (mUTUC) are limited. In this study, we investigated the prognostic value of site-specific metastases in patients with mUTUC and its association with survival outcomes. Methods: We retrospectively collected data from the Surveillance, Epidemiology and End Results (SEER) database between 2004 and 2016. Kaplan–Meier analysis with a log-rank test was used for survival comparisons. Multivariate Cox regression was employed to predict overall survival (OS) and cancer-specific survival (CSS). Results: 633 patients were selected in this study cohort. The median follow-up was 6 months (IQR 2–13) and a total of 584 (92.3%) deaths were recorded. Within the population presenting with a single metastatic organ site, the most common metastatic sites were distant lymph nodes, accounting for 36%, followed by lung, bone and liver metastases, accounting for 26%, 22.8% and 16.2%, respectively. In patients with a single metastatic organ site, the Kaplan–Meier curves showed significantly worse OS for patients with liver metastases vs. patients presenting with metastases in a distant lymph node (p < 0.001), bone (p = 0.023) or lung (p = 0.026). When analyzing CSS, statistically significant differences were detectable only between patients presenting with liver metastases vs. distant lymph node metastases (p < 0.001). Multivariate analyses showed that the presence of liver (OS: HR = 1.732, 95% CI = 1.234–2.430, p < 0.001; CSS: HR = 1.531, 95% CI = 1.062–2.207, p = 0.022) or multiple metastatic organ sites (OS: HR = 1.425, 95% CI = 1.159–1.753, p < 0.001; CSS: HR = 1.417, 95% CI = 1.141–1.760, p = 0.002) was an independent predictor of poor survival. Additionally, survival benefits were found in patients undergoing radical nephroureterectomy (RNU) (OS: HR = 0.675, 95% CI = 0.514–0.886, p = 0.005; CSS: HR = 0.671, 95% CI = 0.505–0.891, p = 0.006) and chemotherapy (CHT) (OS: HR = 0.405, 95% CI = 0.313–0.523, p < 0.001; CSS: HR = 0.435, 95% CI = 0.333–0.570, p < 0.001). Conclusions: A distant lymph node was the most common site of single-organ metastases for mUTUC. Patients with liver metastases and patients with multiple organ metastases exhibited worse survival outcomes. Lastly, CHT administration and RNU were revealed to be predictors of better survival outcomes in the mUTUC cohort. Full article

(This article belongs to the Special Issue Urothelial Carcinoma: Clinical Diagnosis and Treatment)

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Open AccessArticle

Usefulness of the Urine Methylation Test (Bladder EpiCheck^®) in Follow-Up Patients with Non-Muscle Invasive Bladder Cancer and Cytological Diagnosis of Atypical Urothelial Cells—An Institutional Study

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J. Clin. Med. 2022, 11(13), 3855; https://doi.org/10.3390/jcm11133855 - 03 Jul 2022

Cited by 1 | Viewed by 918

Abstract

Urothelial bladder cancer is a heterogeneous disease and one of the most common cancers worldwide. Bladder cancer ranges from low-grade tumors that recur and require long-term invasive surveillance to high-grade tumors with high mortality. After the initial contemporary treatment in non-muscle invasive bladder cancer, recurrence and progression rates remain high. Follow-up of these patients involves the use of cystoscopies, cytology, and imaging of the upper urinary tract in selected patients. However, in this context, both cystoscopy and cytology have limitations. In the follow-up of bladder cancer, the finding of urothelial cells with abnormal cytological characteristics is common. The main objective of our study was to evaluate the usefulness of a urine DNA methylation test in patients with urothelial bladder cancer under follow-up and a cytological finding of urothelial cell atypia. In addition, we analyzed the relationship between the urine DNA methylation test, urine cytology, and subsequent cystoscopy study. It was a prospective and descriptive cohort study conducted on patients presenting with non-muscle invasive urothelial carcinoma between 1 January 2018 and 31 May 2022. A voided urine sample and a DNA methylation test was extracted from each patient. A total of 70 patients, 58 male and 12 female, with a median age of 70.03 years were studied. High-grade urothelial carcinoma was the main histopathological diagnosis. Of the cytologies, 41.46% were cataloged as atypical urothelial cells. The DNA methylation test was positive in 17 urine samples, 51 were negative and 2 were invalid. We demonstrated the usefulness of a DNA methylation test in the follow-up of patients diagnosed with urothelial carcinoma. The methylation test also helps to diagnose urothelial cell atypia. Full article

(This article belongs to the Special Issue Urothelial Carcinoma: Clinical Diagnosis and Treatment)

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Review

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Open AccessReview

A Systematic Review on the Role of Repeat Transurethral Resection after Initial en Bloc Resection for Non-Muscle Invasive Bladder Cancer

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J. Clin. Med. 2022, 11(17), 5049; https://doi.org/10.3390/jcm11175049 - 28 Aug 2022

Cited by 1 | Viewed by 742

Abstract

International guidelines recommend repeat transurethral resection of bladder tumors (reTURB) for selected patients with high-risk non-muscle invasive bladder cancer to remove possible residual tumors, restage tumors and improve the therapeutic outcome. However, most evidence supporting the benefits of reTURB is from conventional TURB. The role of reTURB in patients receiving initial En bloc resection of bladder tumor (ERBT) is still unknown. PubMed, Embase, Web of Science, The Cochrane Library, and China National Knowledge Infrastructure (CNKI) were systematically searched. Finally, this systematic review and meta-analysis included twelve articles, including 539 patients. The rates of residual tumor and tumor upstaging detected by reTURB after ERBT were 5.9% (95%CI, 2.0%–11.1%) and 0.0% (95%CI, 0.0%–0.5%), respectively. Recurrence-free survival, tumor recurrence and progression were comparable between patients with and without reTURB after initial ERBT. The pooled hazard ratios of 1-year, 2-year, 3-year and 5-year recurrence-free survival were 0.74 (95%CI, 0.36–1.51; p = 0.40), 0.76 (95%CI, 0.45–1.26; p = 0.28), 0.83 (95%CI, 0.53–1.32; p = 0.43) and 0.83 (95%CI, 0.56–1.23; p = 0.36), respectively. The pooled relative risks of recurrence and progression were 0.87 (95%CI, 0.64–1.20; p = 0.40) and 1.11 (95%CI, 0.54–2.32; p = 0.77), respectively. Current evidence demonstrates that reTURB after ERBT for bladder cancer can detect relatively low rates of residual tumor and tumor upstaging and appears not to improve either recurrence or progression. Full article

(This article belongs to the Special Issue Urothelial Carcinoma: Clinical Diagnosis and Treatment)

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Other

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Open AccessSystematic Review

The Impact of Surgical Waiting Time on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy: A Systematic Review

Francesco Del Giudice

Keiichiro Mori

Marco Moschini

Krzysztof Kaliszewski

and on behalf of European Association of Urology EAU-Young Academic Urologists YAU Urothelial Cancer Working Party

J. Clin. Med. 2022, 11(14), 4007; https://doi.org/10.3390/jcm11144007 - 11 Jul 2022

Cited by 1 | Viewed by 897

Abstract

Radical nephroureterectomy (RNU) with bladder cuff excision is a standard of care in patients with high-risk upper tract urothelial carcinoma (UTUC). Although several recommendations and guidelines on the delayed treatment of urologic cancers exist, the evidence on UTUC is scarce and ambiguous. The present systematic review aimed to summarize the available evidence on the survival outcomes after deferred RNU in patients with UTUC. A systematic literature search of the three electronic databases (PubMed, Embase, and Cochrane Library) was conducted until 30 April 2022. Studies were found eligible if they reported the oncological outcomes of patients treated with deferred RNU compared to the control group, including those patients treated with RNU without delay. Primary endpoints were cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS). In total, we identified seven eligible studies enrolling 5639 patients. Significant heterogeneity in the definition of “deferred RNU” was found across the included studies. Three out of five studies reporting CSS showed that deferring RNU was associated with worse CSS. Furthermore, three out of four studies reporting OS found a negative impact of delay in RNU on OS. One out of three studies reporting RFS found a negative influence of delayed RNU on RFS. While most studies reported a 3 month interval as a significant threshold for RNU delay, some subgroup analyses showed that a safe delay for RNU was less than 1 month in patients with ureteral tumors (UT) or less than 2 months in patients with hydronephrosis. In conclusion, long surgical waiting time for RNU (especially more than 3 months after UTUC diagnosis) could be considered as an important risk factor having a negative impact on oncological outcomes in patients with UTUC; however, the results of the particular studies are still inconsistent. The safe delay for RNU might be shorter in specific subsets of high-risk patients, such as those with UT and/or hydronephrosis at the time of diagnosis. High-quality additional studies are required to establish evidence for valid recommendations. Full article

(This article belongs to the Special Issue Urothelial Carcinoma: Clinical Diagnosis and Treatment)

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