Metastatic Urachal Carcinoma Research Articles

Teaching NeuroImage: Metastatic Urachal Carcinoma in the Extraocular Muscles Mimicking Oculomotor Paralysis.

Teaching NeuroImage: Metastatic Urachal Carcinoma in the Extraocular Muscles Mimicking Oculomotor Paralysis.

FOLFIRI Chemotherapy for Patients With Metastatic Urachal Carcinoma.

Urachal carcinoma is a rare cancer, with limited evidence regarding systemic chemotherapy for metastatic urachal carcinoma. This study aimed to evaluate the efficacy and safety of a combination therapy of 5-fluorouracil and irinotecan (FOLFIRI) in patients with metastatic urachal carcinoma. Patients with metastatic urachal carcinoma treated with FOLFIRI between March 2008 and April 2023 at the Department of Medical Oncology, Tohoku University Hospital, were retrospectively analyzed using medical records. Six patients with urachal carcinoma received FOLFIRI. The histological type was adenocarcinoma in all patients. The metastatic or recurrent sites were the peritoneum, lungs, lymph nodes, and local relapse sites. Three patients received FOLFIRI as first-line chemotherapy, and the other three received FOLFIRI as second-line chemotherapy. Two patients had only non-measurable lesions as the targets of tumor response. The best response was the stable disease or non-complete response/non-progressive disease in four patients, with a disease control rate of 67%. The median progression-free survival was 7.5 months. In two patients with ascites only as the site of metastasis, the amount of ascites and serum tumor marker levels decreased after FOLFIRI was initiated. Grade 3/4 toxicities included grade 3 neutropenia in one patient and grade 3 diarrhea in one patient. FOLFIRI has modest efficacy and good tolerability for the treatment of metastatic urachal carcinoma.

Survival benefit of chemotherapy in a contemporary cohort of metastatic urachal carcinoma.

We relied on the most contemporary Surveillance, Epidemiology, and End Results (SEER) database and tested the hypothesis that chemotherapy may improve survival in metastatic urachal carcinoma (m-UraC). Within the SEER database (2004-2016), we identified m-UraC patients aged ≥ 18 years. Propensity score matching (PSM: cystectomy status, age and sex), Kaplan-Meier plots, cumulative incidence plots, Cox regression models and competing risks regression (CRR) models addressed overall mortality (OM) and cancer-specific mortality (CSM). Overall, 274 m-UraC patients were identified with a median age of 70 years. Most were male (66%) and Caucasian (72%). Overall, 32% received chemotherapy. Chemotherapy-exposed patients were younger (62 vs. 73 years, p<0.001) and more frequently underwent cystectomy (19 vs. 8%, P = 0.014). In 274 m-UraC patients, median OM and CSM were 6 (4 -10) months and 8 (6 -14) months, respectively. After 1:1 PSM, chemotherapy-exposed patients exhibited lower OM (median 16 vs. 3 months; multivariable HR 0.38, P <0.001) and lower CSM (median 17 vs. 4 months; multivariable CRR HR 0.52, P = 0.001). The association between chemotherapy and better survival was even stronger in younger (≤70 years) patients (OM HR: 0.23, P <0.001; CSM CRR HR: 0.42, P = 0.001), but not in older (≥71 years) patients (OM HR: 0.61, P = 0.2; CSM CRR HR: 1.02, P = 1), after PSM and multivariable adjustments. Overall, we validated the very aggressive nature of UraC, when distant metastases are present, and observed that m-UraC patients exposed to chemotherapy exhibited lower OM and CSM.

Treatment Outcome of Different Chemotherapy in Patients With Relapsed or Metastatic Malignant Urachal Tumor.

BackgroundMalignant urachal tumor is a rare subtype of genitourinary cancer. Our aim was to explore the optimal chemotherapy regimens for relapsed or metastatic urachal carcinoma.Materials and MethodsWe retrospectively enrolled 24 adult patients with relapsed or metastatic urachal carcinoma from January 2014 to September 2020 at Sun Yat-sen University Cancer Center. We summarized the chemotherapy regimens and classified them as fluorouracil based, platinum based, and paclitaxel based. Nine patients received XELOX (capecitabine and oxaliplatin) regimens, seven patients received TX (paclitaxel and capecitabine) regimens, and eight of them received chemotherapy including GP (gemcitabine and cisplatin), TP (paclitaxel and cisplatin), TN (paclitaxel and nedaplatin), and tislelizumab.ResultsThe disease control rate was 75%. Among all patients, one patient treated with XELOX achieved partial remission (PR), while 17 patients showed stable disease. The median progression-free survival (PFS) and overall survival (OS) in all treated patients was 7.43 and 29.7 months, respectively. The patients receiving first-line platinum-based chemotherapy presented better PFS than those without platinum (median PFS 8.23 vs. 3.80 months, p = 0.032), but not significant for OS between two groups. There is no significant difference in PFS and OS for fluorouracil-based and paclitaxel-based groups as first-line regimen. Next-generation gene sequencing revealed TP53 mutation and low tumor mutational burden in five out of seven cases.ConclusionThe platinum-based chemotherapy regimen is effective for relapsed or metastatic urachal carcinoma.

Ex vivo modelling of drug efficacy in a rare metastatic urachal carcinoma

BackgroundEx vivo drug screening refers to the out-of-body assessment of drug efficacy in patient derived vital tumor cells. The purpose of these methods is to enable functional testing of patient specific efficacy of anti-cancer therapeutics and personalized treatment strategies. Such approaches could prove powerful especially in context of rare cancers for which demonstration of novel therapies is difficult due to the low numbers of patients. Here, we report comparison of different ex vivo drug screening methods in a metastatic urachal adenocarcinoma, a rare and aggressive non-urothelial bladder malignancy that arises from the remnant embryologic urachus in adults.MethodsTo compare the feasibility and results obtained with alternative ex vivo drug screening techniques, we used three different approaches; enzymatic cell viability assay of 2D cell cultures and image-based cytometry of 2D and 3D cell cultures in parallel. Vital tumor cells isolated from a biopsy obtained in context of a surgical debulking procedure were used for screening of 1160 drugs with the aim to evaluate patterns of efficacy in the urachal cancer cells.ResultsDose response data from the enzymatic cell viability assay and the image-based assay of 2D cell cultures showed the best consistency. With 3D cell culture conditions, the proliferation rate of the tumor cells was slower and potency of several drugs was reduced even following growth rate normalization of the responses. MEK, mTOR, and MET inhibitors were identified as the most cytotoxic targeted drugs. Secondary validation analyses confirmed the efficacy of these drugs also with the new human urachal adenocarcinoma cell line (MISB18) established from the patient’s tumor.ConclusionsAll the tested ex vivo drug screening methods captured the patient’s tumor cells’ sensitivity to drugs that could be associated with the oncogenic KRASG12V mutation found in the patient’s tumor cells. Specific drug classes however resulted in differential dose response profiles dependent on the used cell culture method indicating that the choice of assay could bias results from ex vivo drug screening assays for selected drug classes.

Successful surgical management of recurrent urachal adenocarcinoma: A case report

Urachal carcinoma is a rare neoplasm for which there is a lack of a standard effective chemotherapeutic treatment. There is also no standard treatment available for recurrent metastatic urachal carcinoma and the prognosis is generally poor. We report a case of urachal carcinoma where the patient achieved long-term disease-free survival after repeated surgeries for recurrent lung metastases.

A Case of Metastatic Urachal Carcinoma Treated with Palliative Chemotherapy with Gemcitabine and Cisplatin

Urachal carcinoma is a rare, non-urothelial carcinoma that represents less than one percent of all bladder cancers. We present a case of a 48-year-old man who presented metastatic urachal carcinoma with intermittent abdominal pain and a poor Performance Status (PS). The patient initially underwent two cycles of XELOX-P (Oxaliplatin/Xeloda/Paclitaxel) chemotherapy after his initial salvage surgery. He came to our hospital for tumor progression and badly abdominal pain. He then received Gemcitabine and Cisplatin (GC) regimen at 80% of the dose with good tolerance and manageable toxicities. After six cycles of chemotherapy, he had a stable disease response, including impressive clinical response on medical symptoms and minor shrinkage of tumor mass on imaging. This case suggests the importance of palliative chemotherapy of GC regimen for the metastatic urachal cancer patients, and that performance status alone should not be limiting decision factors for cancer patients.

Urachal Carcinoma Shares Genomic Alterations with Colorectal Carcinoma and May Respond to Epidermal Growth Factor Inhibition

Metastatic urachal carcinoma is a rare, understudied, and aggressive malignancy with limited treatment options. Histologically, urachal carcinomas resemble enteric adenocarcinomas and anecdotally respond to systemic therapies utilized in colorectal cancer. Targeted exome sequencing of archival primary tumor tissue from a patient with metastatic urachal cancer revealed EGFR amplification and wild-type KRAS. The patient was treated with cetuximab, a monoclonal antibody directed against EGFR, as a single agent, and achieved a response lasting more than 8 mo. Subsequent whole-exome sequencing revealed no additional alterations likely to be associated with cetuximab sensitivity. Formalin-fixed, paraffin-embedded tumor specimens from nine additional urachal cancers were subjected to targeted exome sequencing. Mitogen-activated protein kinase (MAPK) pathway mutations were found in four of the nine samples, but no EGFR amplification was detected. Importantly, APC mutations were detected in two of the nine patients. To our knowledge, this is the first report of a response to single-agent cetuximab in a patient with metastatic urachal cancer and of molecular analysis to probe the basis for sensitivity. On the basis of these findings and the histologic, and now genomic, similarities with colorectal cancer, monoclonal antibodies directed at EGFR could be used in the treatment of metastatic urachal cancer. Patient summaryUrachal cancers are morphologically and genomically similar to colon adenocarcinomas and may respond to drugs targeting the epidermal growth factor receptor.

Report of Rare Urachal Carcinoma Presenting with Thrombocytopenia and Microangiopathic Hemolytic Anemia

Introduction:Thrombotic microangiopathy (TMA) is clinical syndrome characterized by microvascular thrombosis, consumptive thrombocytopenia and microangiopathic hemolytic anemia (MAHA). It is a feature of a number of clinical conditions, most prominently thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) and rarely an initial manifestation of systemic malignancy.Case:A previously healthy 31-year-old black woman presented to the emergency department with a 2 week history of lower back pain and hematuria and 1 week history of dyspnea on exertion and dizziness. She denied diarrhea, hematochezia, fever, or abdominal pain. Physical findings were unremarkable with normal blood pressure. Initial laboratory results revealed a white blood cell count of 4.4 x103/µL, hemoglobin of 4.4 g/dL, hematocrit 12.9%, platelets 43 x103/µL, absolute reticulocyte count 259.8 x103/µL, reticulocyte percentage 23.1%, haptoglobin <10 L mg/dL, LDH 1424 units/L, creatinine 0.7 mg/dL, total bilirubin 1.6 mg/dL, negative pregnancy test, and 10-15 white blood cells and >50 red blood cells per high powered field on microscopic urinalysis. Coombs test results were negative, the coagulation profile was normal, and peripheral blood smear revealed evidence of thrombocytopenia and MAHA (figure 1a). Diagnosis of TTP was made and treatment with daily therapeutic plasma exchange (TPE) was initiated. On hospital day 4, ADAMTS13 level drawn at diagnosis before initiation of plasma exchange returned at 94%, prompting further investigation as to the cause of her TMA. Serologic tests for hepatitis B & C virus, human immunodeficiency virus, antinuclear antibody (ANA), cardiolipin and beta-2 glycoprotein antibodies and computerized tomography (CT) scan of the abdomen and pelvis were all negative. Despite daily TPE for 6 days, she remained thrombocytopenic and continued to have ongoing hemolysis. Therefore, on hospital day 6, bone marrow aspiration and biopsy (figure 1b) was performed which showed a normocellular bone marrow for age (cellularity 70%) with full-spectrum trinlineage hematopoiesis, involved by metastatic signet-cell ring carcinoma. Immunostains were positive for CK7, CK20, CK 8/18, CDX2, pancytokeratin, and negative for PAX-8 and mammoglobin. TPE was discontinued and she was supported with packed red blood cell and platelet transfusions.Positron emission tomography–computed tomography (PET-CT) revealed a heterogeneously enhancing mass in the midline superior anterior wall of the bladder measuring 2.7 x 5.1 cm, but without abnormal uptake on PET. She underwent cystourethroscopy and a transurethral resection of bladder tumor which revealed a 6 cm solid sessile mass. Final pathology confirmed the diagnosis of moderate to poorly differentiated invasive urachal adenocarcinoma with mucinous and signet-ring cell features.Given the presence of metastatic disease, she was treated with a chemotherapy regimen consisting of cisplatin, fluorouracil, and leucovorin on days 1 through 5. Gemcitabine was held due to elevated liver transaminases. On day 1 of treatment, platelet count was 24 x103/µL and hemoglobin 8.1 g/dL. By treatment day 7, platelets had risen to 79 x103/µL. She last required a PRBC transfusion on treatment day 4.Discussion:TMA can occur in a variety of disorders, including TTP, HUS, malignant hypertension, scleroderma, antiphospholipid antibody syndrome, systemic lupus erythematosus, preeclampsia, HIV infection, and disseminated malignancy. Patients presenting with evidence of TMA and thrombocytopenia should elicit a high clinical suspicion for TTP and be urgently treated with plasma exchange. Deficiency of the von Willebrand factor-cleaving metalloproteinase ADAMTS13, or the presence of antibodies to ADAMTS13 plays a key role in the pathogenesis of primary TTP, although these findings are not necessary to make the diagnosis. However, patients with a high or normal ADAMTS13 level and without antibodies to ADAMTS13, especially those who do not improve with plasma exchange, should prompt an investigation for other causes of TMA. To our knowledge, we report the first case of metastatic urachal carcinoma presenting with features of MAHA and thrombocytopenia.Conclusion:TMA associated with malignancy is a rare, but potentially fatal condition. Recognition of this rare entity is critical to the initiation of appropriate treatment of underlying malignancy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Metastatic urachal carcinoma in bronchial brush cytology

Urachal carcinoma is rare comprising less than 1% of all bladder carcinomas. Metastases of urachal carcinoma have been reported to meninges, brain, ovary, lung, and maxilla. Cytologic features of metastatic urachal carcinoma have not been previously reported. We present a case of metastatic urachal adenocarcinoma in bronchial brushings and review the use of immunohistochemistry in its diagnosis. A 47-year-old female was seen initially in 2007 with adenocarcinoma of the bladder dome for which she underwent partial cystectomy. She presented in 2011 with a left lung mass and mediastinal adenopathy. Bronchoscopy showed an endobronchial lesion from which brushings were obtained. These showed numerous groups of columnar cells with medium sized nuclei and abundant cytoplasm. The cells were positive for CK20 and CDX2 and negative for CK7. The cytomorphological findings were similar to those in the previous resection specimen and concurrent biopsy. This is the first case report of bronchial brushings containing metastatic urachal carcinoma. No specific immunohistochemical profile is available for its diagnosis. The consideration of a second primary was a distinct possibility in this case due to the lapse of time from primary resection, absence of local disease, and lack of regional metastases.

Urachal Adenocarcinoma: A Clinician's Guide for Treatment

Urachal carcinoma is a rare non-urothelial malignancy frequently involving the midline or dome of the bladder due to direct extension from the urachal ligament, the structure from which this tumor arises. Nearly always an adenocarcinoma, it is important to recognize the diagnosis upfront due to the differences in surgery and chemotherapy as compared to traditional urothelial cancer. For patients with surgically resectable tumors, a partial cystectomy with en-bloc resection of the urachal ligament with the bladder dome and umbilicus is required to appropriately control the tumor. Leaving the umbilicus in place provides inadequate control and has been associated with a higher risk of relapse. A lymph node dissection also may help in the control of this cancer. While there is yet no proven role for neoadjuvant or adjuvant chemotherapy, combinations of 5-fluoruracil with cisplatin are active in those with metastases. Since the activity of this combination also has lead to surgical consolidation of node-positive disease, one might consider the potential for benefit from perioperative chemotherapy. A higher risk of relapse following surgery has been reported in those with positive margins, lymph node involvement, involvement of the peritoneal surface, or where the umbilicus was not resected en-bloc, and may predict a group of patients where the risk of relapse is sufficiently high enough to consider adjuvant chemotherapy. A recent clinical trial of 5-fluorouracil, leucovorin, gemcitabine, and cisplatin has recently completed accrual in metastatic urachal carcinoma, with patients now in long-term follow-up.

Urachal carcinoma with liver, lung, and brain metastases: benefit of a new combination chemotherapy (bevacizumab, 5-fluorouracil, irinotecan) &amp;ndash; case report

Urachal carcinoma with liver, lung, and brain metastases: benefit of a new combination chemotherapy (bevacizumab, 5-fluorouracil, irinotecan) &ndash; case report J Dekoninck1, P Demetter2, Filip Geurs1, R De Loecker31Department of Medical Oncology, Regional Hospital Sint Maria, Halle, Belgium; 2Department of Pathology, Hopital Erasme &ndash; Universit&eacute; Libre de Bruxelles (ULB), Anderlecht, Belgium; 3Department of Laboratory, Regional Hospital Sint Maria, Halle, BelgiumAbstract: After failure of cisplatin-based chemotherapy for metastatic urachal carcinoma, a 16-year-old patient presents with diffuse liver-, lung-, and brain metastases. The K-ras mutation is present in the liver as well as in the primary resected specimen. The regimen was therefore changed to bevacizumab, 5-fluorouracil, and irinotecan. This led to a partial response which lasted 7 months.Keywords: K-ras mutation, urachal cancer, adenocarcinoma

Treatment of metastatic urachal carcinoma in an elderly woman

A 67-year-old woman with a history of smoking presented with abdominal pain and hematuria. On physical examination, she had a palpable pelvic mass. Imaging revealed a large pelvic mass situated on the dome of the bladder, extending from the urachus, without evidence of other sites of metastases. After resection, urachal adenocarcinoma was histologically confirmed. No adjuvant therapy was administered. Repeat imaging obtained 3 months after resection revealed a large left pelvic mass consistent with recurrence. Physical examination, pelvic and complete lymph-node examination, laboratory tests, urine analysis, CT scan of the abdomen and pelvis, chest X-ray, bone scan, cystoscopy, histologic examination of tumor morphology, and MRI of the abdomen and pelvis. Metastatic urachal adenocarcinoma. Surgical excision combined with cystectomy and pelvic lympadenectomy, chemotherapy with 5-fluorouracil, leucovorin, and irinotecan.

Urachal carcinoma: Clinicopathologic features and long‐term outcomes of an aggressive malignancy

Urachal carcinoma (UrC) is a rare malignancy, and patients with this disease have a poor prognosis. In this article, the authors report 50 years of experience with this tumor at the Mayo Clinic. A urachal mass was described in 130 patients, and 66 of those masses were malignant. The authors identified multivariate predictors of malignancy in clinically diagnosed urachal masses and predictors of UrC-specific survival. This report presents a novel 4-category staging system for UrC along with the treatment history of this tumor and the results of salvage therapy. Twenty women and 46 men were identified with UrC. The strongest predictors of malignancy in a urachal mass were hematuria and age older than 55 years. The 5-year cancer-specific survival rate was 49%. The new Mayo staging system was less complicated than the Sheldon system, although both systems predicted cancer-specific mortality equally well. Positive surgical margins (hazard ratio [HR], 4.7), high tumor grade (HR, 3.6), positive local lymph nodes (HR, 5.1), metastases at diagnosis (HR, 3.3), advanced tumor stage (HR, 4.8), failure to perform umbilectomy (HR, 3.0), and primary radiation therapy (HR, 2.9) were all univariately associated with death (P <.05). Only grade and margins were significant in the multivariate analysis. No survival benefit was noted for lymphadenectomy or adjuvant therapy. Salvage surgery resulted in a long-term cure for 50% of patients who had local recurrences. No effective treatment was identified for patients with metastatic UrC. Early and complete extended partial cystectomy, including umbilectomy, is critical to the survival of patients with UrC. The authors recommend using the Mayo staging system in future studies because of its simplicity. The current results indicated that the most important predictors of prognosis were tumor grade and surgical margin status.

Carcinomatous Meningitis from Urachal Carcinoma: The First Reported Case

Carcinomatous meningitis (CM) occurs in less than 10% of cancer patients. Although patients frequently present with a focal complaint, multifocal signs are often found following careful neurological examination. The gold standard for diagnosis remains the demonstration of neoplastic cells in the cerebrospinal fluid. Despite the discouraging prognosis, palliative treatment may improve quality of life and lengthen lifespan. We report a patient with known primary carcinoma of the urachus who presented with headaches, nausea, vomiting and ataxia 1 week following resection of a nodular arachnoidal metastasis (indenting the cerebellum). Lumbar cerebrospinal fluid subsequently confirmed carcinomatous meningitis. This is the first reported case of carcinomatous meningitis resulting from metastatic urachal carcinoma.

Successful treatment of metastatic adenocarcinoma of the urachus: report of 2 cases with more than 10-year survival

Metastatic urachal cancer is often considered lethal. We report 2 cases of metastatic urachal carcinoma successfully treated with surgical excision followed by combinations of surgery, radiation, and chemotherapy against local recurrence and/or distant metastases, with a recurrence-free survival period of more than 10 years. These cases provide support for multimodal treatments of metastatic urachal cancer.