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Investigative and Clinical Urology Mar 2022To assess the safety and efficacy of gemcitabine and cisplatin as neoadjuvant chemotherapy followed by selective bladder preservation chemoradiotherapy in...
PURPOSE
To assess the safety and efficacy of gemcitabine and cisplatin as neoadjuvant chemotherapy followed by selective bladder preservation chemoradiotherapy in muscle-invasive bladder cancer (MIBC).
MATERIALS AND METHODS
Patients with clinical T2-T4aN0M0 MIBC eligible for radical cystectomy and cisplatin-based chemotherapy were treated with gemcitabine 1,000 mg/m² on days 1, 8 and 15, and cisplatin 70 mg/m² on day 1 every 28 days for 3 cycles. After clinical re-staging with computed tomography scans and cystoscopy, patients with clinical complete response (CR) were eligible to proceed without cystectomy and receive bladder preservation chemoradiotherapy involving weekly cisplatin 10 mg/m² and up to 70.2 Gy of radiation. The primary endpoint of the present prospective phase II study was metastasis-free survival (MFS).
RESULTS
Between Oct 2017 and Nov 2019, a total of 138 MIBC patients were enrolled and treated with neoadjuvant gemcitabine/cisplatin. Neoadjuvant chemotherapy was well-tolerated, with fatigue, nausea, and pruritus being the most commonly observed adverse events. After completion of planned neoadjuvant chemotherapy, 54 patients with a clinical CR and 10 patients who did not have CR but refused surgery received bladder preservation chemoradiotherapy. With a median follow-up duration of 34 months (95% confidence interval [CI], 32%-36%), the 3-year MFS rate in 64 chemoradiotherapy patients was calculated to be 70% (95% CI, 58%-82%).
CONCLUSIONS
Neoadjuvant chemotherapy followed by selective bladder preservation chemoradiotherapy based on the clinical CR was feasible and efficacious in the treatment of MIBC.
Topics: Carcinoma, Transitional Cell; Chemoradiotherapy; Cisplatin; Deoxycytidine; Female; Humans; Male; Muscles; Neoadjuvant Therapy; Prospective Studies; Urinary Bladder; Urinary Bladder Neoplasms; Gemcitabine
PubMed: 35244990
DOI: 10.4111/icu.20210407 -
Indian Journal of Pathology &... 2023The expression of programmed cell death ligand1 (PDL1) is a research hotspot of immunotherapy. The treatment targeted for its expression has shown effectiveness in many...
CONTEXT
The expression of programmed cell death ligand1 (PDL1) is a research hotspot of immunotherapy. The treatment targeted for its expression has shown effectiveness in many tumors.
OBJECTIVE
The aim of the study was to determine PD-L1 expression in urothelial carcinoma (UC) and to compare the PD-L1 expression in muscle invasive bladder carcinoma (MIBC) and upper urinary tract urothelial carcinoma (UTUC). The predictive value of CD8+ tumor-infiltrating lymphocyte (TIL) density for the diagnosis of PD-L1 positivity and the association between CD8+ TIL density and prognosis in MIBC were also explored.
MATERIALS AND METHODS
Immunohistochemistry (IHC) staining for PD-L1 (SP263), CK5/6, CK20, CD44, and p53 was carried out using a 3D Histech digital scanner to scan and determine CD8+ TIL density.
RESULTS
122 patients received radical cystectomy, and the overall PD-L1 positivity was 34.43% (42/122). PD-L1 positivity in whole sections was higher than in tissue micro-array (TMA) (all P < 0.05). If multiple lesions were detected simultaneously, the number of patients with positive results increased from 42 to 49. The areas under the curve (AUCs) of CD8+ TIL density for the diagnosis of PD-L1 positivity were 0.739, 0.713, and 0.826. Univariate cox regression analysis demonstrated that high CD8+ TIL density and CD8PDL1 were protective factors of overall survival (OS), and multivariate cox analyses showed that only CD8+ TIL density was an independent prognostic factor for OS. For UTUC, the overall PD-L1 expression was 40.0% (16/40).
CONCLUSIONS
Our study results emphasize the importance of detecting PD-L1 expression in multiple tumor lesions from the same patient. In MIBC, CD8+ TIL density could be used as a prognostic marker for predicting the status of PD-L1 expression.
Topics: Humans; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; B7-H1 Antigen; Urinary Bladder; Prognosis; Lymphocytes, Tumor-Infiltrating; Muscles; CD8-Positive T-Lymphocytes
PubMed: 38084519
DOI: 10.4103/ijpm.ijpm_142_22 -
Nature Communications Nov 2022Urothelial Cancer - Genomic Analysis to Improve Patient Outcomes and Research (NCT02643043), UC-GENOME, is a genomic analysis and biospecimen repository study in 218...
Urothelial Cancer - Genomic Analysis to Improve Patient Outcomes and Research (NCT02643043), UC-GENOME, is a genomic analysis and biospecimen repository study in 218 patients with metastatic urothelial carcinoma. Here we report on the primary outcome of the UC-GENOME-the proportion of subjects who received next generation sequencing (NGS) with treatment options-and present the initial genomic analyses and clinical correlates. 69.3% of subjects had potential treatment options, however only 5.0% received therapy based on NGS. We found an increased frequency of TP53 mutations as compared to non-metastatic cohorts and identified features associated with benefit to chemotherapy and immune checkpoint inhibition, including: Ba/Sq and Stroma-rich subtypes, APOBEC mutational signature (SBS13), and inflamed tumor immune phenotype. Finally, we derive a computational model incorporating both genomic and clinical features predictive of immune checkpoint inhibitor response. Future work will utilize the biospecimens alongside these foundational analyses toward a better understanding of urothelial carcinoma biology.
Topics: Humans; Carcinoma, Transitional Cell; Genomics; High-Throughput Nucleotide Sequencing; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 36333289
DOI: 10.1038/s41467-022-33980-9 -
Urologia Internationalis 2023Bladder cancer is a common type of malignancy. UBC®Rapid is a novel immunoassay detecting urine cytokeratin 8/18 protein. Studies have shown good accuracy of UBC®Rapid...
OBJECTIVES
Bladder cancer is a common type of malignancy. UBC®Rapid is a novel immunoassay detecting urine cytokeratin 8/18 protein. Studies have shown good accuracy of UBC®Rapid in detecting bladder cancer. UBC®Rapid has however to date not been evaluated in Asian patients. We evaluated UBC®Rapid in detecting Asian bladder cancer, together with urine cytology.
METHODS
In total, 112 patients were recruited from National University Hospital Singapore and 103 patients were included in this study, comprising 49 patients with bladder urothelial carcinoma (UC), 21 patients with bladder benign lesions, and 33 patients with normal bladder. All the bladder cancer and benign lesions were confirmed by histology. Voided urine was collected for UBC®Rapid test. The results were compared with urine cytology.
RESULTS
The bladder UC group had remarkably higher UBC®Rapid value than the control groups. The sensitivity, specificity, positive, and negative predictive value of UBC®Rapid in detecting bladder UC were 53%, 85.5%, 76.5%, and 66.8%, respectively. Those of urine cytology were 40.8%, 96.3%, 90.9%, and 64.2%, respectively. Adding UBC®Rapid to urine cytology increased sensitivity to 57.1% but decreased specificity to 81.8%. UBC®Rapid was sensitive in detecting high-grade bladder UC (61.1%) and carcinoma in situ (CIS) (72.7%), as compared to urine cytology for bladder UC (55.6%) and CIS (54.5%), respectively.
CONCLUSION
UBC®Rapid is sensitive in detecting high-grade bladder UC and CIS in Asian population. It may be useful as an adjunct test to achieve better detection of bladder cancer.
Topics: Humans; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Urinary Bladder; Predictive Value of Tests; Carcinoma in Situ; Sensitivity and Specificity; Biomarkers, Tumor
PubMed: 36273445
DOI: 10.1159/000526763 -
Experimental and Molecular Pathology Jun 2023Cytokeratin 20 (CK20) expression is limited to umbrella cells in the normal urothelium. Since CK20 is often upregulated in neoplastic urothelial cells including...
Cytokeratin 20 (CK20) expression is limited to umbrella cells in the normal urothelium. Since CK20 is often upregulated in neoplastic urothelial cells including dysplasia and carcinoma in situ, immunohistochemical CK20 analysis is often used for the assessment of bladder biopsies. CK20 expression is a feature of luminal bladder cancer subtype, but its prognostic relevance is disputed. In this study, we investigated CK20 on >2700 urothelial bladder carcinomas in a tissue microarray format by immunohistochemistry. Cytoplasmic and membranous CK20 staining was seen in 1319 (51.8%) cancers. The fraction of CK20 positive and especially strongly positive cases increased from pTaG2 low grade (44.5% strongly positive) and pTaG2 high grade (57.7%) to pTaG3 high grade (62.3%; p = 0.0006) but was lower in muscle-invasive (pT2-4) carcinomas (51.1% in all pTa vs. 29.6% in pT2-4; p < 0.0001). Within pT2-4 carcinomas, CK20 positivity was linked to nodal metastasis and lymphatic vessel invasion (p < 0.0001 each) and to venous invasion (p = 0.0177). CK20 staining was unrelated to overall patient survival if all 605 pT2-4 carcinomas were jointly analyzed but subgroup analyses revealed a significant association of CK20 positivity with favorable prognosis in 129 pT4 carcinomas (p = 0.0005). CK20 positivity was strongly linked to the expression of GATA3 (p < 0.0001), another feature of luminal bladder cancer. The combined analysis of both parameters showed best prognosis for luminal A (CK20+/GATA3+, CK20+/GATA3-) and worst outcome for luminal B (CK20-/GATA3+) and basal/squamous (CK20-/GATA3-) in pT4 urothelial carcinomas (p = 0.0005). In summary, the results of our study demonstrate a complex role of CK20 expression in urothelial neoplasms including neoexpression in pTa tumors, a subsequent loss of CK20 expression in a subset of tumors progressing to muscle-invasion, and a stage dependent prognostic role in muscle-invasive cancers.
Topics: Humans; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Keratin-20; Urinary Bladder; Biomarkers, Tumor; Urothelium
PubMed: 36997051
DOI: 10.1016/j.yexmp.2023.104860 -
Journal of Medical Case Reports Mar 2022Osteosarcoma arising from the bladder is extremely rare, with only 38 cases reported to our knowledge. It is often detected owing to hematuria, and is treated by surgery...
BACKGROUND
Osteosarcoma arising from the bladder is extremely rare, with only 38 cases reported to our knowledge. It is often detected owing to hematuria, and is treated by surgery (for example, total cystectomy), radiation therapy, and chemotherapy; however, the prognosis is extremely poor.
CASE PRESENTATION
An 83-year-old Japanese man underwent cystoscopy for postoperative follow-up of urothelial carcinoma of the bladder, which revealed a 2-cm nodular tumor on the right wall. He had a history of abdominal aortic aneurysm and hypertension, and had been smoking 15 cigarettes per day for 45 years. Seven years previously, the patient underwent transurethral resection of bladder tumor for a 5-cm tumor on the right wall of the bladder. The histopathological diagnosis was urothelial carcinoma. No recurrence had been detected since then. Transurethral resection of bladder tumor was performed, and the histopathological diagnosis was cystosarcoma. Because of his advanced age, we decided that it would be difficult to perform total cystectomy. We therefore performed a second transurethral resection of bladder tumor and found no residual tumor. At 29 months after surgery, the patient remains alive without recurrence.
CONCLUSION
Bladder osteosarcoma has a poor prognosis. However, our case was detected early, and treatment with transurethral resection of bladder tumor alone resulted in long-term survival without recurrence.
Topics: Aged, 80 and over; Bone Neoplasms; Carcinoma, Transitional Cell; Humans; Male; Osteosarcoma; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35331306
DOI: 10.1186/s13256-022-03346-2 -
International Braz J Urol : Official... 2022Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of all urothelial tumors (1). Radical nephroureterectomy (RNU) remains the standard treatment for high, and...
INTRODUCTION
Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of all urothelial tumors (1). Radical nephroureterectomy (RNU) remains the standard treatment for high, and low-grade UTUC (2). Although the open approach has been considered the gold standard, robotic techniques have shown comparable oncological outcomes with potential advantages in terms of peri-operative morbidity (3).
MATERIALS AND METHODS
We present a novel "Keyhole" technique for management of distal ureter and bladder cuff during robotic RNU. This technique allows the surgeon to directly visualize the ureteric orifices, delineate resection borders, and maintain oncologic principles of en-bloc excision without necessitating secondary cystotomy incision or concomitant endoscopic procedure. Descriptive demographic characteristics, surgical, pathological, and oncological outcomes were analyzed. Complications were reported using the Clavien-Dindo classification system.
RESULTS
Between 2015 and 2020, ten patients underwent robotic RNU with bladder cuff excision using the Keyhole technique (single-dock, single-position). Median age was 75 years. Eight patients underwent surgery for right-sided tumors. Median operative time, estimated blood loss, and length of hospital stay were 287 min, 100 mL, and 3 days, respectively. No intraoperative complications occurred, and one grade II complication occurred during the 90-day postoperative period. All patients had high-grade UTUC, being 90% pure urothelial. Bladder recurrences occurred in 30% of patients with an overall median follow-up of 11.2 months.
CONCLUSIONS
Keyhole technique for the management of distal ureter and bladder cuff during RNU represents a feasible approach with minimal 90-day complications and low bladder recurrence rate at centers of experience.
Topics: Aged; Carcinoma, Transitional Cell; Humans; Nephrectomy; Nephroureterectomy; Retrospective Studies; Robotic Surgical Procedures; Ureter; Ureteral Neoplasms; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35363457
DOI: 10.1590/S1677-5538.IBJU.2022.0147 -
The Oncologist Feb 2024To evaluate the presence and subtypes of tertiary lymphatic structures (TLSs) in urothelial carcinoma of the bladder (UCB) and to analyze their associated...
OBJECTIVE
To evaluate the presence and subtypes of tertiary lymphatic structures (TLSs) in urothelial carcinoma of the bladder (UCB) and to analyze their associated clinicopathological characteristics and prognostic significance.
METHODS
The study enrolled 580 patients with surgically treated UCB, including 313 non-muscle invasive bladder cancer (NMIBC) and 267 muscle-invasive bladder cancer (MIBC). The presence and subtypes of TLSs were identified by immunohistochemistry (CD20, CD3, Bcl-6, and CD21). TLSs were classified into non-GC (nGC) TLS and GC TLS subtypes based on germinal center (GC) formation. Disease-free survival (DFS) was used as an endpoint outcome to evaluate the prognostic significance of TLS and its subtypes in UCB.
RESULTS
TLSs were more common in MIBC than in NMIBC (67.8% vs 48.2%, P < .001), and the tumor-infiltrating lymphocyte (TIL) mean density was significantly higher in MIBC than in NMIBC (24.0% vs 17.5%, P < .001). Moreover, a positive correlation was found between TLS presence and GC structure formation and TIL infiltration in UCB. Endpoint events occurred in 191 patients. Compared to patients with endpoint events, patients without disease progression exhibited higher TIL density and more TLSs (P < .05). Kaplan-Meier curves showed that TLS was associated with better DFS in NMIBC (P = .041) and MIBC (P = .049). However, the Cox multivariate analysis did not demonstrate the prognostic significance of TLS.
CONCLUSIONS
TLS is heterogeneous in UCB, and that TLS and GC structures are related to TIL density and prognostic events. However, TLS as a prognostic indicator remains unclear, warranting further investigation.
Topics: Humans; Prognosis; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urinary Bladder; Tertiary Lymphoid Structures; Non-Muscle Invasive Bladder Neoplasms; Lymphocytes, Tumor-Infiltrating
PubMed: 37874923
DOI: 10.1093/oncolo/oyad283 -
Asian Pacific Journal of Cancer... Jun 2022Transitional cell carcinoma is considered the most predominant type of bladder cancer. Bladder can cer can also be found as squamous cell carcinoma that accounts for 5%...
UNLABELLED
Transitional cell carcinoma is considered the most predominant type of bladder cancer. Bladder can cer can also be found as squamous cell carcinoma that accounts for 5% of the total bladder cancer due to its etiology. The biomarkers associated with grade, prognosis, and stage of the disease are not well proved and known however, many studies have pointed to the association between SNAL/SLUG and Twist2 to the overall survival in patients with bladder cancer. These biomarkers were found to have a crucial role in inhibiting cadherin mediators specifically E-cadherin which are found normally in high level to integrate cell adhesion and normal function of the bladder. This research aims to detect SNAL/SLUG and Twist2 biomarkers in specimens of patients with bladder cancer and to detect their impact on E-cadherin, a tumor suppressor mediator responsible for improving survival and prevent metastasis.
MATERIALS AND METHODS
Using 150 archival tissue blocks from human bladder cancer cases to detect expression of SNAIL/SLUG and Twist2 in relation to loss of E-cadherin by immunohistochemical method.
RESULTS
Our results have revealed that in squamous cell carcinoma 40 specimens showed marked Twist 2 expression, and 30 specimens showed marked snail/slug biomarkers expression while poorly differentiated cancer cases showed marked expression of Twist 2 in 60 specimens and marked expression of Snail/slug marked expression in 50 specimens. Both were associated with E-cadherin loss. Among the 100 specimens with transitional cell carcinoma, 70 specimens showed divergent differentiation with 7 subtypes each showed different medium to high expression of Snail/Slug and Twist 2 biomarkers with the loss of E-cadherin. E-cadherin was strongly associated with the inverse increase in SNAL/SLUG and Twist2 biomarkers in urothelial carcinoma.
CONCLUSION
Detection of SNAIL/SLUG and Twist 2 biomarkers in urothelial cancer is an important predictor for the loss of E-cadherin, a cornerstone in urinary bladder cell adhesion and its loss in urothelial carcinoma may contribute to cancer invasion and poor prognosis.
.Topics: Biomarkers; Cadherins; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Epithelial-Mesenchymal Transition; Humans; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35763651
DOI: 10.31557/APJCP.2022.23.6.2079 -
Scientific Reports Apr 2022The main route of metastasis of bladder urothelial carcinoma is through lymph nodes; however, its exact mechanism remains unclear. In this study, we found an association...
The main route of metastasis of bladder urothelial carcinoma is through lymph nodes; however, its exact mechanism remains unclear. In this study, we found an association of nucleolar and spindle associated protein 1 (NUSAP1) expression with BUC tissues along with lymph node metastasis and the survival prognosis. A total of 178 pathological specimens following radical bladder cancer resection were obtained. NUSAP1 expression was analyzed by immunohistochemistry. We evaluated the correlation between clinicopathological characteristics and NUSAP1 expression. Logistic regression was used to determine the independent variables that influenced lymph node metastasis. Uni- and multi-factorial Cox regression methods were used to determine the prognostic value of NUSAP1 expression in urothelial carcinoma of the bladder. High expression of NUSAP1 in BUC was not significantly related to the patient's gender, age, or tumor number (p > 0.05), however was significantly associated with pathological grade, tumor diameter, pathological stage, and lymph node metastasis (p < 0.05). Lymph node metastasis was significantly correlated with pathological stage, pathological grade, tumor number, tumor diameter, and NUSAP1 expression (p < 0.05); only NUSAP1 expression was an independent predictor of lymph node metastasis in BUC (OR:1.786, 95% CI 1.229-2.596, p = 0.002). In addition, high NUSAP1 expression was an independent prognostic predictor for BUC. In BUC, NUSAP1 showed high expression and was significantly associated with lymph node metastasis, pathological stage, pathological grade, and tumor diameter. NUSAP1 was an independent predictor of lymph node metastasis and prognosis in BUC; higher expression indicated poorer prognosis of BUC patients.
Topics: Carcinoma, Transitional Cell; Female; Humans; Lymphatic Metastasis; Male; Microtubule-Associated Proteins; Prognosis; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 35487972
DOI: 10.1038/s41598-022-11137-4