Purpose
In this study, we aimed to determine the clinicopathologic, radiologic, and molecular significance of the tumor invasiveness to further stratify the patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) who can be treated less aggressively.
Materials and Methods
Clinicopathologic and radiologic characteristics of 166 surgically resected HG UTUC (48 noninvasive, and 118 invasive) cases were evaluated. Six noninvasive UTUC cases with intratumoral tumor grade heterogeneity were selected for whole-exome sequencing (WES) to understand the underlying molecular pathophysiology. Barcode-tagging sequencing was done for validation of the target genes from WES data.
Results
Patients with noninvasive UTUC showed no cancer-specific death with better cancer-specific survival (p < 0.001) and recurrence-free survival (p < 0.001) compared to the patients with invasive UTUC. Compared to the invasive UTUC, noninvasive UTUC was correlated to a low grade (LG) on the preoperative abdominal computed tomography (CT) grading system (p < 0.001), histologic intratumoral tumor grade heterogeneity (p=0.018), discrepancy in preoperative urine cytology diagnosis (p=0.018), and absence of urothelial carcinoma in situ (p < 0.001). WES of the heterogeneous components showed mutually shared HRAS and FGFR3 mutations shared between the HG and LG components. HRAS mutation was associated with the lower grade on preoperative abdominal CT and intratumoral tumor grade heterogeneity (p=0.045 and p < 0.001, respectively), whereas FGFR3 mutation was correlated to the absence of carcinoma in situ (p < 0.001).
Conclusion
According to our comprehensive analysis, HG noninvasive UTUC can be preoperatively suspected based on distinct preoperative radiologic, cytologic, histologic, and molecular features. Noninvasive HG UTUC shows excellent prognosis and thus should be treated less aggressively.
Citations
Citations to this article as recorded by
Diagnostic accuracy of upper tract urothelial carcinoma using biopsy, urinary cytology, and nephroureterectomy specimens: A tertiary cancer center experience Jianping Zhao, Yuan Shen, Ming Guo, Surena F Matin, Donna E Hansel, Charles C Guo American Journal of Clinical Pathology.2024;[Epub] CrossRef
Clinical significance of tumor location for ureteroscopic tumor grading in upper tract urothelial carcinoma Satoshi Katayama, benjamin pradere, Nico C. Grossmann, Aaron M. Potretzke, Stephen J Boorjian, Alireza Ghoreifi, Siamak Daneshmand, Hooman Djaladat, John Sfakianos, Andrea Mari, Zine-Eddine Khene, David D'Andrea, Nozomi Hayakawa, Kazutoshi Fujita, Axel He Journal of Endourology.2024;[Epub] CrossRef
Development and validation of a radiomics-based nomogram for predicting pathological grade of upper urinary tract urothelial carcinoma Yanghuang Zheng, Hongjin Shi, Shi Fu, Haifeng Wang, Xin Li, Zhi Li, Bing Hai, Jinsong Zhang BMC Cancer.2024;[Epub] CrossRef
Purpose This study aims to evaluate the prognosis of pathologically node-positive bladder cancer after neoadjuvant chemotherapy, the role of adjuvant chemotherapy in these patients, and the value of preoperative clinical evaluation for lymph node metastases.
Materials and Methods Patients who received neoadjuvant chemotherapy followed by partial/radical cystectomy and had pathologically confirmed lymph node metastases between January 2007 and December 2019 were identified and analyzed.
Results A total of 53 patients were included in the study. The median age was 61 years (range, 34 to 81 years) with males comprising 86.8%. Among the 52 patients with post-neoadjuvant/pre-operative computed tomography results, only 33 patients (63.5%) were considered positive for lymph node metastasis. Sixteen patients (30.2%) received adjuvant chemotherapy (AC group), and 37 patients did not (no AC group). With the median follow-up duration of 67.7 months, the median recurrence-free survival (RFS) and the median overall survival (OS) was 8.5 months and 16.2 months, respectively. The 2-year RFS and OS rates were 23.3% and 34.6%, respectively. RFS and OS did not differ between the AC group and no AC group (median RFS, 8.8 months vs. 6.8 months, p=0.772; median OS, 16.1 months vs. 16.3 months, p=0.479). Thirty-eight patients (71.7%) experienced recurrence. Distant metastases were the dominant pattern of failure in both the AC group (91.7%) and no AC group (76.9%).
Conclusion Patients with lymph node-positive disease after neoadjuvant chemotherapy followed by surgery showed high recurrence rates with limited survival outcomes. Little benefit was observed with the addition of adjuvant chemotherapy.
Citations
Citations to this article as recorded by
A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant Therapy Garrett K. Harada, Steven N. Seyedin, Olivia Heutlinger, Armon Azizi, Audree Hsu, Arash Rezazadeh, Michael Daneshvar, Greg E. Gin, Edward M. Uchio, Giovanna A. Giannico, Jeremy P. Harris, Aaron B. Simon, Jeffrey V. Kuo, Nataliya Mar Advances in Radiation Oncology.2025; 10(1): 101671. CrossRef
Influence of Neoadjuvant Chemotherapy on Survival Outcomes of Radical Cystectomy in Pathologically Proven Positive and Negative Lymph Nodes Krystian Kaczmarek, Bartosz Małkiewicz, Karolina Skonieczna-Żydecka, Artur Lemiński Cancers.2023; 15(19): 4901. CrossRef
Comparison of responses to neoadjuvant and adjuvant chemotherapies in muscle-invasive bladder cancer Serhat Sekmek, Gökhan Ucar, Irfan Karahan, Dogan Bayram, Selin Aktürk Esen, Ismet Seven, Mehmet Ali Nahit Sendur, Dogan Uncu African Journal of Urology.2023;[Epub] CrossRef