Genetic Differences Between Bladder and Upper Urinary Tract Carcinoma: Implications for Therapy

Sfakianos, John P.; Gul, Zeynep; Shariat, Shahrokh F.; Matin, Surena F.; Daneshmand, Siamak; Plimack, Elizabeth R.; Lerner, Seth P.; Rouprêt, Morgan; Pal, Sumanta K.

doi:10.1016/j.euo.2020.12.007

Cited by 29 publications

(27 citation statements)

References 62 publications

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“…Audenet et al showed that the majority of bladder tumours following RNU are clonally related, supporting the hypothesis that IVR occurs through neoplastic cell implantation, rather than representing a second primary tumour [ 31 ]. Recent molecular studies demonstrated that UTUC and bladder urothelial carcinoma share mutations in similar genes, but at varying frequencies, which recapitulate with their metachronous recurrences [ 32 ]. Such differences in quantitative gene alterations might contribute to the behaviour of these two cancers and imply that they and their metachronous recurrences should be treated as two related yet distinct entities [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent molecular studies demonstrated that UTUC and bladder urothelial carcinoma share mutations in similar genes, but at varying frequencies, which recapitulate with their metachronous recurrences [ 32 ]. Such differences in quantitative gene alterations might contribute to the behaviour of these two cancers and imply that they and their metachronous recurrences should be treated as two related yet distinct entities [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

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The Impact of Diagnostic Ureteroscopy Prior to Radical Nephroureterectomy on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma: A Comprehensive Systematic Review and Meta-Analysis

Nowak

Krajewski

Chorbińska

et al. 2021

JCM

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Background: The incidence of intravesical recurrence (IVR) following radical nephroureterectomy (RNU) is reported in up to 50% of patients with upper tract urothelial carcinoma (UTUC). It was suggested that preoperative diagnostic ureteroscopy (URS) could increase the IVR rate after RNU. However, the available data are often conflicting. Thus, in this systematic review and meta-analysis we sought to synthesize available data for the impact of pre-RNU URS for UTUC on IVR and other oncological outcomes. Materials and methods: A systematic literature search of the PubMed, Embase, and Cochrane Library databases was performed in June 2021. Cumulative analyses of hazard ratios (HRs) and their corresponding 95% confidence intervals (CI) were conducted. The primary endpoint was intravesical recurrence-free survival (IVRFS), with the secondary endpoints being cancer-specific survival (CSS), overall survival (OS), and metastasis-free survival (MFS). Results: Among a total of 5489 patients included in the sixteen selected papers, 2387 (43.4%) underwent diagnostic URS before RNU and 3102 (56.6%) did not. Pre-RNU diagnostic URS was significantly associated with worse IVRFS after RNU (HR = 1.44, 95% CI: 1.29–1.61, p < 0.001) than RNU alone. However, subgroup analysis including patients without biopsy during URS revealed no significant impact of diagnostic URS on IVRFS (HR = 1.28, 95% CI: 0.90–1.80, p = 0.16). The results of other analyses showed no significant differences in CSS (HR = 0.94, p = 0.63), OS (HR: 0.94, p = 0.56), and MFS (HR: 0.91, p = 0.37) between patients who underwent URS before RNU and those who did not. Conclusions: The results of this meta-analysis confirm that diagnostic URS prior to RNU is significantly associated with worse IVRFS, albeit with no concurrent impact on the other long-term survival outcomes. Our results indicate that URS has a negative impact on IVRFS only when combined with endoscopic biopsy. Future studies are warranted to assess the role of immediate postoperative intravesical chemotherapy in patients undergoing biopsy during URS for suspected UTUC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Impact of Diagnostic Ureteroscopy Prior to Radical Nephroureterectomy on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma: A Comprehensive Systematic Review and Meta-Analysis

Nowak

Krajewski

Chorbińska

et al. 2021

JCM

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“…UTUC is an uncommon disease, accounting for only 5%~10% of UC 17 18 . In our study, the sensitivity of the optimal panel reached 0.74 for UTUC, demonstrating the potential for UTUC screening purposes.…”

Section: Discussionmentioning

confidence: 99%

Urine Cellular DNA Point Mutation and Methylation as Potential Biomarkers for Early Detection of Urothelial Carcinoma

Zhang

et al. 2021

Preprint

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Background: Previously, our team identified a seven-gene mutation panel in urine sediment to discriminate UBC from benign urological diseases. In the present study, we aimed to validate the panel in an expanded and close to natural population cohort of hematuria. Also, we tried to optimize the panel by incorporating methylation biomarkers. We performed external validation to investigate the robustness and stability of the novel panel. Methods: Patients with urothelial carcinomas and controls were prospectively recruited in clinical trial ChiCTR2000029980. The mutation panel was validated in the expanded cohort(n=333) from Hunan multicenter. Several UBC-specific methylation biomarkers were identified by comprehensive analyses of a series of TCGA, GEO and an independent cohorts, and examined in the expanded cohort. Random Forest algorithm was used to construct an optimal panel. External validation of the optimal panel was carried out in Beijing single center cohort(n=89). NGS technique was used to analyze the DNA point mutations and MS-PCR for methylation.Results: The AUC, sensitivity and specificity of the mutation panel in expanded cohort were 0.81, 0.67 and 0.90, respectively. After screening, only cg16966315, cg17945976 and cg24720571 were left for further analysis. The optimal panel consisted of cg24720571 and 8 point mutations, including TERT 228(G_A), FGFR3 568(C_T), TERT 250(G_A), FGFR3 099(A_G), PIK3CA 091(G_A), PIK3CA 085(A_G), PIK3CA 082 (G_A) and HRAS 874(T_C). The AUC, sensitivity and specificity of the optimal panel in training group were 0.89, 0.84 and 0.79, respectively, and in test group were 0.95, 0.91 and 0.95, respectively. In the external validation, the AUC, sensitivity and specificity were 0.98, 0.93 and 0.93, respectively.Conclusions: The optimal panel was obviously superior to previous mutation panel and showed a highly specific and robust performance. The optimal panel may be used as a replaceable approach for early detection of UC.Trial registration: This research was registered in Chinese Clinical Trial Registry(ChiCTR2000029980).

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“…The most common VH of urothelial cancer is the squamous differentiation, that occurs in up to 20-40% of UTUCs [49]. In the squamous differentiation, high levels of PDL-1 expression have been found [50].…”

Section: Variant Histologymentioning

confidence: 99%

Current Knowledge on Genomic Profiling of Upper Tract Urothelial Carcinoma

Lorenzis

Albo

Longo

et al. 2021

Genes

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Recent research in next-generation sequencing characterized the genomic landscape of urothelial cancer. However, the majority of the studies focused on bladder cancer (BC). Upper urinary tract urothelial carcinomas (UTUC) and BC share some histological characteristics, but, considering the differences in terms of embryologic precursors, epidemiology, genetics, medical and surgical management and response to therapy, UTUC and BC should be considered as two distinct diseases. Our objective is to analyze through a literature search the latest updates and the current knowledge about the genomics of UTUC. We also evaluate genetic differences between BC and UTUC and the potential implications for systemic therapy. Molecular subtyping and variant histology and their correlation with response to chemotherapy were also explored. In summary, the most frequent genomic variations in UTUC included FGFR3, chromatin remodeling genes, TP53/MDM2 and other tumor suppressors/oncogenes. The genomics of UTUC, integrated with clinical data, could drive the selection of patients who could benefit from targeted therapy or off-label treatment. Routine implementation of tumor genomic characterization in UTUC patients should therefore be contemplated and evaluated prospectively.

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Genetic Differences Between Bladder and Upper Urinary Tract Carcinoma: Implications for Therapy

Cited by 29 publications

References 62 publications

The Impact of Diagnostic Ureteroscopy Prior to Radical Nephroureterectomy on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma: A Comprehensive Systematic Review and Meta-Analysis

The Impact of Diagnostic Ureteroscopy Prior to Radical Nephroureterectomy on Oncological Outcomes in Patients with Upper Tract Urothelial Carcinoma: A Comprehensive Systematic Review and Meta-Analysis

Urine Cellular DNA Point Mutation and Methylation as Potential Biomarkers for Early Detection of Urothelial Carcinoma

Current Knowledge on Genomic Profiling of Upper Tract Urothelial Carcinoma

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