Response to Targeted Therapy in Urachal Adenocarcinoma

Abstract

We report the case of a young woman diagnosed with metastatic urachal carcinoma. A multimodal approach was used for the management of this patient. Due to disease progression despite surgery and two different chemotherapy regimens (neoadjuvant capecitabine + irinotecan + oxaliplatin and docetaxel + cisplatin after surgery), treatment with sunitinib was eventually started. Treatment with sunitinib resulted in stable disease and improvement of symptoms. Sunitinib was discontinued due to the occurrence of metrorrhagia, and restarted one week later. Disease eventually progressed and the patient died 18 months after the onset of symptoms. This is the first report on the use of sunitinib for the management of urachal carcinoma and provides initial evidence supporting the use of targeted therapy in this setting.

Biomarkers in Urachal Cancer and Adenocarcinomas in the Bladder: A Comprehensive Review Supplemented by Own Data

“…The immunohistochemical markers most often employed in the work up of adenocarcinomas of different sites usually include Cytokeratin 20 (CK20) and CK7. In our analysis of a total of 116 urachal adenocarcinomas, only 4 cases were negative for CK20—an overall positive rate of 97% [ 1 , 17 , 23 , 26 , 27 , 31 , 36 , 48 , 56 , 60 , 62 , 67 , 74 , 77 , 86 , 95 , 99 , 124 – 126 , 128 , 148 , 156 , 163 , 164 , 216 , 217 , 220 , 240 , 245 , 251 , 327 ]. Considering the robust CK20 expression in adenocarcinomas of sites of differential diagnostic interest, CK20 has no significant value in this setting.…”

“…In contrast, expression of CK7 in these tumors is widely variable. In urachal adenocarcinomas, CK7 exhibited a pooled reactivity rate of 51%, compared to considerable lower rates in colorectal cancer (0–38%, Table 2 , Supplementary Table 2 ) [ 1 , 17 , 23 , 26 , 27 , 31 , 36 , 48 , 56 , 60 , 67 , 74 , 77 , 86 , 99 , 124 , 125 , 156 , 163 , 164 , 216 , 217 , 220 , 240 , 251 , 255 , 292 , 327 , 328 ]. However, similar to urachal adenocarcinomas, primary bladder adenocarcinomas constantly exhibited relatively high CK7 reactivity rates (33%–70%), thus limiting the value of CK7 in the discrimination between these two entities [ 23 , 329 ].…”

“…As a rather specific nuclear marker for intestinal epithelia and corresponding adenocarcinomas, CDX2—a homeobox gene coding for a transcription factor with intestine specificity—has been proposed for differential diagnostic considerations. However, nuclear CDX2 reactivity was evident in the majority of urachal adenocarcinomas (90%) [ 1 , 17 , 23 , 26 , 31 , 60 , 99 , 125 , 126 , 128 , 216 , 217 , 240 , 245 , 251 , 327 , 330 ] and many primary bladder adenocarcinomas (13%–83%) [ 329 , 331 ]. In addition to its reactivity in almost all colorectal adenocarcinomas, CDX2 immunopositivity has been detected in considerable numbers in several adenocarcinomas from different sites such as the gastrointestinal tract, pancreas, and ovary [ 330 , 332 ].…”

Clinical, prognostic, and therapeutic aspects of urachal carcinoma—A comprehensive review with meta-analysis of 1,010 cases

“…To date, there are only few, however, promising data on the efficacy of targeted therapies in UrC. Testa et al [36] reported a necrotic involution of the tumor and a significant improvement of abdominal pain in a patient with metastatic UrC who was treated with secondline multikinase inhibitor (sunitinib) following failure of platinum-containing combination chemotherapy.…”

Mutations of KRAS, NRAS, BRAF, EGFR, and PIK3CA genes in urachal carcinoma: Occurence and prognostic significance

“…To date there are only few, however promising data on the efficacy of targeted therapies in UrC. Testa et al reported a necrotic involution of the tumor and a significant improvement of abdominal pain in a UrC patient who was treated with second-line multikinase inhibitor (Sunitinib) [6], while Goss et al observed a size regression of a UrC as a response to EGFR-inhibitor therapy with gefitinib (Iressa) [7]. Finally, a recent study reported a patient with lung metastatic UrC who was effectively treated with a monoclonal EGFR-inhibitor (cetuximab) for eight months [8].…”