Abstract
UrC is a rare malignancy with uncertain pathogenesis. The main symptoms include gross hematuria, abdominal pain, and an abdominal mass. The lack of comprehensive clinical analysis necessitates selecting an optimal therapeutic strategy for each patient. Here, we present a comprehensive review of the clinical manifestations, diagnosis, and treatment of UrC, illustrated with a case successfully managed through surgical intervention and adjuvant chemoradiotherapy. Meanwhile, the analysis of NGS detected two tumor-specific mutated genes: MYC (gene amplification, CN: 59.5) and FLT1 (missense mutation, c.1061G>A (p.R354Q), abundance: 2.1%). These findings may provide insights into tumor growth and guide therapeutic strategies.
1 Introduction
During intrauterine development, the bladder descends into the pelvis and the urachus connects the umbilical to the bladder. Gradually, the urachus degenerates and forms a fibromuscular canal referred to as the median urachal ligament (1). In about one-third of adults, urachus residues still can be found, which makes the occurrence of UrC possible (2). UrC is rare in adults, with a significantly higher incidence in males. The patients are almost over 50 years old, and the pathological types are mucoid adenocarcinoma (69%), non-mucoid adenocarcinoma (15%), sarcoma (8%), transitional cell carcinoma (3%), squamous cell carcinoma (3%) and others (2%) (3). The secluded location and lack of early symptoms make UrC difficult to be detected and prone to recurrence and distant metastasis. In previous case reports, surgery was the main treatment method, and chemotherapy, radiotherapy or targeted therapy could be given selectively (4, 5). With the development of NGS, more tumor-related genetic mutations have been found and provide a high-resolution and global view of the cancer genome. However, data on clinical outcomes and genomic profiles in UrC are scarce due to its low incidence. Consequently, an adequate sample size is required to establish patterns in disease pathogenesis and therapeutic outcomes for future studies.
Here, we report a case of young female patient diagnosed with urachal mucinous cystadenocarcinoma. Following multimodal therapy, the patient remained disease-free with no evidence of recurrence or metastasis during four years of scheduled follow-up. Moreover, NGS analysis identified multiple gene mutations. These findings suggest implications for the pathogenesis and treatment of urachal mucinous cystadenocarcinoma. In conjunction with the present case, a comprehensive review of the literature related to UrC is provided. This review summarizes the clinical features and therapeutic approaches for UrC, and further analyzes the genetic alterations identified via NGS, providing a reference framework for managing this disease.
2 Case presentation
A 45-year-old woman with no significant previous medical history was sent to Southwest Hospital Urology Department in July 2021 due to recurrent painless gross hematuria. Both ultrasound and MRI revealed the presence of tumor mass in the anterior wall of the bladder. Besides, CT ureteral imaging also suggested the presence of a mass on the anterior wall of the bladder extending toward the umbilical (Figures 1A–D). Three-dimensional CT imaging also showed a clear soft tissue density shadow in the anterior wall of the bladder (Figure 1E), which increased the likelihood of UrC. She underwent robotic-assisted partial bladder and umbilical resection and bilateral pelvic lymph node dissection in July 2021. The surgically removed parts include part of the bladder, urachal, tumor, and umbilicus, and the lump size is about 3*2.9*2cm (Figure 2A). Postoperative pathological examination revealed urachal mucinous cystadenocarcinoma with tumor involvement extending through the full thickness of the adjacent bladder wall. Meanwhile, lymph node metastases were found on each side of the pelvic cavity. Hematoxylin-eosin (HE) staining indicated malignancy, consistent with mucinous cystadenocarcinoma of urachal origin (Figure 2B). Immuno-histochemistry (IHC) staining detected the positive expression of CDX-2, CK20, and Ki-67 (Figures 2C–E).
Figure 1
Figure 2
The NGS (Burning Stone Biotechnology, Guangzhou, China) was performed and the sequencing results identified two tumor-specific mutation genes: MYC (gene amplification, CN:59.5) and FLT1 [missense mutation, c.1061G>A (p.R354Q), abundance: 2.1%], but microsatellite instability index and other immune-related factors were not detected. Other mutations related to drug metabolism are shown in Table 1. For further treatment, this patient underwent two cycles of oxaliplatin and capecitabine chemotherapy at the original hospital in August 2021. Next, this patient was transferred to Sichuan Cancer Hospital in September 2021 and underwent PET-CT which showed that there was no distant metastasis (Figures 3A–D). Due to the positive pathological margin, the patient is receiving concurrent chemoradiotherapy. The chemotherapy regimen was gemcitabine + capecitabine. And radiation therapy regimens are as follows: the prescribed doses were 62.5 Gy to the positive lymph nodes of the gross tumor volume (GTVn), 62.5 Gy to the tumor bed clinical target volume (CTVtb), and 55 Gy to the high-risk clinical target volume (CTV1), delivered in 25 fractions. The irradiation was administered once daily, 5 days a week. Subsequently, the patient underwent two cycles of oxaliplatin and capecitabine chemotherapy. This patient underwent rigorous postoperative monitoring, including physical examinations, laboratory tests, and enhanced CT scans of the abdominal and pelvic cavity every 3 to 6 months. At the latest follow-up of 48 months, the patient was alive, and no significant treatment-related delayed toxicities were observed. And CT scan result showed no recurrence or metastasis, and the bladder showed postoperative changes (Figure 3E).
Table 1
| Gene | Variation | Mutant | Prediction (chemotherapy effect) |
|---|---|---|---|
| GSTM1 | Homozygous deletion polymorphism | – | Better than wild type GSTM1 (Platinum) |
| GSTP1 | p.I105V (Heterozygous polymorphism) | c.313A>G (p.I105V) | Better than wild type GSTP1 (Platinum and Anthracycline) |
| MTHFR | p.A222V (Homozygous polymorphism) | c.665C>T (p.A222V) | Better than wild type MTHFR (5-Fu); Toxic effect (Methotrexate) |
| NQO1 | p.R139W (Heterozygous polymorphism) | c.415C>T (p.R139W) | Worse than wild type NQO1 (Mitomycin) |
| UGT1A1 | p.G71R (Heterozygous polymorphism) | c.211G>A (p.G71R) | Toxic effect (Irinotecan and Etoposide) |
| XRCC1 | p.Q399R (Homozygous polymorphism) | c.1196A>G (p.Q399R) | Better than wild type XRCC1 (Platinum) |
Polymorphism of enzymes associated with drug metabolism from NGS.
Figure 3
3 Minireview of literature
As a rare malignant tumor, comprehensive understanding of UrC remains limited. The clinical manifestations of UrC are relatively hidden, typically presenting with urinary system symptoms, and are difficult to distinguish from bladder urothelial malignancies. While surgery serves as the primary treatment option, the evidence supporting therapeutic interventions for metastatic or advanced-stage disease is limited and inconsistent. Therefore, tailored treatment plans must be implemented based on individual patient characteristics. In addition, with the widespread adoption of genomic sequencing technologies, an increasing number of UrC-associated therapeutic targets have been identified. Thus, targeted therapy, immunotherapy, and other approaches might be crucial in the future treatment of UrC.
3.1 Clinical manifestations and diagnosis
For UrC, male patients are more common than females, and the common clinical symptoms include gross hematuria, abdominal pain, abdominal mass, dysuria, and other systemic symptoms such as nausea, fever, weight loss, or diarrhea (4). Based on the existing case analysis, cystoscopy plays an important role in the diagnosis of disease, and imaging tests such as computer tomography (CT), 18F-FDG PET CT, magnetic resonance imaging (MRI), and ultrasound are also essential (6–8). It has been reported that most UrCs are adenocarcinomas and have the same embryonic origin as the colon. Therefore, some gastrointestinal tumor markers can also be used to monitor the disease progression of UrC such as CEA, CA125, CA19-9, CA15-3, and alpha-fetoprotein. The most sensitive of them are CA19–9 and CEA (9, 10).
3.2 Tumor staging and prognosis
Currently, Sheldon and Mayo are the most common UrC staging systems (11, 12). The TNM staging of bladder cancer is not suitable for UrC (13). Recently, some scholars proposed a new TNM staging system that has a more balanced sample distribution and accurate correlation between staging and survival (14). Detailed information on various staging systems is shown in Table 2. Some epidemiological studies show significantly different survival between stage IIIA (-) and stage IIIB (+) disease (according to the Sheldon staging system) (15). Meanwhile, a retrospective analysis indicated that patients with positive surgical margins have a 60% lower 5-year survival rate than those with negative margins (16), suggesting that margin status may be an independent prognostic factor. In addition, lymph node or distant metastasis also influences the treatment and prognosis of UrC (6).
Table 2
| Sheldon (11) | Mayo (12) | Ontario (42) | New TNM staging (14) |
|---|---|---|---|
| I: no invasion beyond urachal mucosa | I: confined to the urachus and/or bladder | I: confined to the submucosa | I: Limited to the urachal submucosa |
| II: invasion confined to urachus | II: extending beyond the muscularis of the urachal and/or bladder | II: confined to the muscular wall of the bladder | II: invasion of bladder muscularis propria or microscopic invasion of bladder perivesical tissue |
| III: extending to A: bladder B: abdominal wall C: peritoneum D: organs other than the bladder | III: infiltrating regional lymph nodes | III: extending into the peri-urachal or vesical soft tissue | III: macroscopic invasion of bladder perivesical tissue or invasion of adjacent tissues, including the uterus, vagina, and prostate |
| IV: metastasis to A: lymph nodes B: distant parts | IV: infiltrating of non-regional lymph nodes or distant metastasis | IV: invasion of adjacent organs including the abdominal wall | IV: invasion of any nodal or distant location, or of the pelvic, abdominal wall, or peritoneum |
Various staging systems for urachal carcinoma.
3.3 Surgery and chemoradiotherapy
According to the NCCN Guidelines (Bladder Cancer Version 1. 2025), the recommended treatment for UrC is surgery or radiotherapy to achieve local control, combined with best supportive care. Current surgical approaches encompass extended partial cystectomy with en-bloc resection of the urachal mass, urachal remnant, and umbilicus, combined with pelvic lymph node dissection. For larger masses, radical cystectomy is recommended (7, 12). In fact, the guidelines indicate no current evidence supports the use of neoadjuvant or adjuvant chemotherapy in patients with pure adenocarcinoma of the bladder, including UrC. However, the following suggestions are given for systemic treatment strategies. For patients with node-positive pure adenocarcinoma, guidelines have consistently recommended the FOLFOX regimen (oxaliplatin, leucovorin, and fluorouracil) and the GemFLP regimen (fluorouracil, leucovorin, gemcitabine, and cisplatin) (17). For the metastatic, and advanced disease, consider using the NCCN Guidelines for Colon Cancer (https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf). Analysis of colon cancer adjuvant therapy guidelines reveals that CAPEOX (oxaliplatin and capecitabine) or FOLFOX regimens demonstrate superior efficacy over 5-FU/leucovorin in stage III colon cancer patients (18). Furthermore, the 3-month CAPEOX regimen maintains comparable efficacy while significantly reducing toxicity (19, 20).
This patient is classified as either Sheldon stage IVA or Mayo stage III. According to the guidelines and clinical case discussion, firstly, we surgically resected part of the bladder, urachal, tumor, and umbilicus. Subsequently, we administered oxaliplatin and capecitabine (CAPEOX regimen) chemotherapy to the patient, which enhances therapeutic efficacy and reduces toxicity. The drug metabolism information in Table 1 also suggests that certain gene mutations (GSTM1, GSTP1, and XRCC1) are associated with better responses to platinum. To reduce the risk of recurrence and metastasis associated with positive surgical margins and lymph node positivity, the patient underwent radiotherapy with adjuvant treatment of gemcitabine and capecitabine. After a four-year follow-up, the patient has shown no recurrence or metastasis. Previously, a meta-analysis of 1010 cases showed that, in the absence of effective radiotherapy, chemotherapy is the only treatment option with the potential to prolong survival (4). However, our case provides a useful reference for the radiotherapy management of UrC. Furthermore, some previous case reports have shown that 5-FU regimens are more effective than cisplatin-based chemotherapy regimens, and that the combination of antimetabolites and platinum chemotherapy drugs can produce the strongest anti-tumor effects. However, in the absence of prospective clinical trial data, treatment decisions must be individualized. Based on a comprehensive analysis of this clinical case, the patient presented with advanced tumor stage and positive surgical margins. Consequently, concurrent chemoradiotherapy was considered likely to significantly reduce the risk of recurrence and metastasis. Furthermore, the follow-up data to date demonstrate the efficacy of this regimen, with no evidence of recurrence or metastasis observed.
3.4 Targeted therapy based on genomic sequencing
Given the limited efficacy of chemotherapy for UrC, recent research has yielded important breakthroughs in exploring targeted therapeutic approaches. Genomic profiling studies have identified high-frequency driver mutations in UrC, including TP53 (70%), KRAS (28.3%), MYC (20.3%), SMAD4 (18.2%), and GNAS (18%) (21). Furthermore, studies have found that mutations in targetable genes such as EGFR, HER2, and BRCA are also present in UrC (21, 22). Inhibitors of related targets (such as EGFR inhibitors, PARP inhibitors, and MEK inhibitors) and immune checkpoint inhibitors have demonstrated preliminary clinical efficacy in case reports. For instance, responses to anti-EGFR therapy have been observed in patients harboring EGFR amplifications (4, 23). And another UrC patient with MSH6 mutation achieved stable disease after anti-PD-L1 therapy (23, 24). Recent investigations have revealed a predominantly immunosuppressive tumor microenvironment (TME) in UrC, characterized by an abundance of immunosuppressive immune cells, which provides a compelling rationale for PD-1/PD-L1 checkpoint blockade (25, 26).
In this case, NGS revealed a high copy number amplification of MYC (CN: 59.5). Additionally, a missense mutation in FLT1 (p.R354Q) was detected, although at a low variant allele frequency (VAF) of 2.1%. In bladder cancer patients, alterations in the MYC gene were observed in 7.06% of cases, with amplification (6.33%) and mutation (0.73%) being the most prevalent subtypes. In addition, alterations in the FLT1 gene were identified in 3.16% of cases, predominantly consisting of mutation (1.95%) and amplification (1.22%) [the information was obtained from cBioPortal (www.cbioportal.org)]. With additional NGS results from more cases, the molecular landscape of UrC can be further enriched. Ultimately contributing to the elucidation of its etiology and guiding clinical medication (27). These two genes are summarized as follows.
3.4.1 MYC
For MYC, the gene was altered in 6.57% of 594 cases of colorectal adenocarcinoma and 7.06% of 411 cases of bladder urothelial carcinoma. More than 50% of human malignancies have dysregulated MYC family oncogenes, which are linked to a poor prognosis and a low survival rate (28). Myc is involved in multiple processes of tumor progression, such as proliferation, apoptosis, differentiation, and metabolism. Additionally, MYC can increase immunosuppressive cytokines like TGFβ and decrease the production of antigen-presenting proteins like MHC I, which prevents cytotoxic T cells from acting and encourages immune evasion (29–31). Therapeutic drugs directly targeting MYC are under development, and their clinical efficacy remains to be verified (29). Encouragingly, scientists from Spain have developed a new therapy (Omomyc) targeting MYC-MAX heterodimer to inhibit MYC gene, which is most promising for clinical application (29, 32). Other promising candidates include inhibitors of the PI3K–AKT–mTOR pathway, inhibitors of the translation initiator eIF4A (silvestrol), PIN1 inhibitors, antisense oligonucleotides, etc. (33, 34). In contrast to colorectal and bladder tumors, MYC is markedly elevated in UrC and might be a special indicator of UrC (35).
3.4.2 FLT1
For FLT1 (fms-like tyrosine kinase), the gene was altered in 9.26% of 594 cases of colorectal adenocarcinoma and 3.16% of 411 cases of bladder urothelial carcinoma. Although the FLT1 (p.R354Q) mutation was detected in this patient, the VAF was only 2.1%, suggesting that the FLT1 mutation is likely subclonal and present in only a minority of tumor cells. Nevertheless, this finding underscores the intratumoral heterogeneity characteristic of complex solid tumors.
This gene encodes tyrosine kinase receptors which have been identified as high-affinity VEGF receptors (36). The VEGFR family consists of three receptors, namely VEGFR1 (FLT1), VEGFR2 (KDR/FLK1), and VEGFR3 (FLT4) (37). The role of FLK1 and VEGFA in tumor angiogenesis has been fully confirmed, however, the signal transmission related to FLT1 is still controversial. Currently, research has revealed that FLT1 is highly associated with embryonic vasculogenesis, macrophage function, and the pre-metastatic niche. Meanwhile, FLT1 inhibits angiogenesis in endothelial cells due to inadequate tyrosine phosphorylation (38, 39). NGS identified a missense variant (p.R354Q) in the FLT1 gene, resulting in an amino acid substitution within the I-SET domain. The I-SET domain, an immunoglobulin-like structural motif, is conserved across diverse protein families, including receptor tyrosine kinases, hemolin, titin, telokin, twitchin, and axonin-1 (40). This domain plays crucial roles in mediating cellular recognition, receptor interactions, muscle architecture, and immune system function (41). A retrospective study suggests that targeting FLT1 and PlGF can inhibit tumor growth. Currently available drugs targeting FLT1 include cabozantinib, cediranib, midostaurin, etc., but their clinical effectiveness needs further confirmation (37). The missense variant of this gene may render FLT1-targeted drugs ineffective.
Although the current evidence for targeted and immunotherapeutic interventions in UrC remains limited to isolated cases, these collective findings herald the advent of the era of precision medicine in UrC management. Unfortunately, no suitable targeted drugs are currently available for this case.
4 Conclusions
UrC is a rare tumor with a poor prognosis. Currently, surgery is the preferred treatment method, and chemotherapy and radiotherapy can stabilize the condition to a certain extent. However, due to a lack of extensive clinical analysis, the treatment of this disease remains to be further explored. For different patients, reasonable chemoradiotherapy regimens may reduce the risk of postoperative recurrence and metastasis. This patient underwent a multimodal treatment approach involving surgery, adjuvant chemotherapy, and concurrent chemoradiotherapy, which resulted in a four-year disease-free survival. This favorable outcome suggests that this regimen may achieve durable disease control with manageable toxicity for this rare urachal malignancy. In addition, mutational analysis of individual targets and diverse pathways suggests the promising potential of targeted therapy as a future alternative. Therefore, future investigations should focus on characterizing the molecular features of UrC, investigating its oncogenic processes, and improving clinical decision-making.
Statements
Data availability statement
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.
Ethics statement
The studies involving humans were approved by Ethics Committee of Medical Research and New Medical Technology of Sichuan Cancer Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The human samples used in this study were acquired from primarily isolated as part of your previous study for which ethical approval was obtained. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Written informed consent was obtained from the participant/patient(s) for the publication of this case report.
Author contributions
TT: Writing – original draft, Writing – review & editing. XP: Writing – original draft. DS: Data curation, Writing – review & editing. LZ: Investigation, Writing – review & editing. JC: Investigation, Writing – review & editing. HW: Supervision, Writing – review & editing. CC: Supervision, Validation, Visualization, Writing – review & editing, Writing – original draft. SX: Investigation, Resources, Writing – review & editing. CX: Supervision, Writing – original draft, Writing – review & editing.
Funding
The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the National Key Research and Development Program of China Stem Cell and Translational Research (2023YFC3402100), the National Natural Science Foundation of China (nos. 82541044), the Sichuan Province Natural Science Foundation key project (2024NSFSC0057), and the Major project of Chongqing Natural Science Foundation (CSTB2024TIAD-KPX0029).
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Supplementary material
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Summary
Keywords
chemoradiotherapy, FLT1, MYC, next-generation sequencing, targeted therapy, Urachal carcinoma
Citation
Tan T, Peng X, Shang D, Zheng L, Chen J, Wu H, Cao C, Xu S and Xu C (2026) Treatment outcomes and next-generation sequencing of a rare malignancy - urachal carcinoma: case report and literature review. Front. Oncol. 16:1744925. doi: 10.3389/fonc.2026.1744925
Received
12 November 2025
Revised
27 February 2026
Accepted
09 March 2026
Published
21 April 2026
Volume
16 - 2026
Edited by
Dechao Feng, University College London, United Kingdom
Reviewed by
Rajesh Kumar, Kerala University of Health Sciences, India
Kaiwen Xiao, Second Affiliated Hospital of Nanchang University, China
Updates
Copyright
© 2026 Tan, Peng, Shang, Zheng, Chen, Wu, Cao, Xu and Xu.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Chenhui Cao, caochenhui@uestc.edu.cn; Senlin Xu, xusenlintmmu@163.com; Chuan Xu, xuchuan100@163.com
†These authors have contributed equally to this work
Disclaimer
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