Colorectal-style drug sequence controlled rare metastatic urachal cancer for 27 months

A rare bladder cancer with no prospective treatment trials of its own has, for the first time in a published report, been treated in its third-line setting with a modern colorectal cancer regimen combining trifluridine/tipiracil with the anti-VEGF antibody bevacizumab. The single-patient case, published in Frontiers in Oncology, describes an 80-year-old woman with metastatic urachal adenocarcinoma who received five sequential lines of therapy modelled on metastatic colorectal cancer practice. The third-line combination kept her disease stable for roughly eleven months, the longest stretch of disease control in her course, and she survived 27 months from diagnosis.

Urachal adenocarcinoma is exceptionally rare, with an estimated incidence of about one case per five million people each year, accounting for fewer than one percent of bladder cancers. Most tumours arise from the urachal remnant at the bladder dome and show enteric differentiation, with immunohistochemical and molecular features, including CK20 and CDX2 positivity and recurrent alterations in KRAS, APC and TP53, that closely resemble colorectal adenocarcinoma. Because of this resemblance, treatment of metastatic disease is typically extrapolated from colorectal cancer on the basis of retrospective case series and consensus guidance. The only formally consensus-recommended regimen for advanced urachal carcinoma is FOLFOX, with FOLFIRI also reported in case series, and the role of bevacizumab is not addressed in existing guidelines.

The patient presented in May 2022 at age 80 with abdominal pain and haematuria. Biopsy of a bladder dome lesion extending into the urachus showed a moderately differentiated adenocarcinoma positive for CK20 and CDX2, with only scanty staining for markers of urothelial origin, and beta-catenin staining excluded a Wnt-pathway-driven mimicker. Colonoscopy ruled out a colorectal primary, and PET-CT revealed widespread peritoneal and omental metastases with likely pulmonary involvement, corresponding to Sheldon/Mayo clinical stage IVB disease. In retrospect, a lesion seen on imaging a year earlier during investigation of recurrent urinary tract infections and interpreted as a bladder hernia was considered likely to have been the primary tumour. Her performance status was 0 despite significant pre-existing PRPH2-associated retinopathy with severely reduced vision in both eyes.

Molecular profiling shaped the treatment strategy. The tumour carried a KRAS G12V mutation along with APC, FBXW7 and TP53 mutations, and was microsatellite stable with a low tumour mutational burden of 1 mutation per megabase and a PD-L1 combined positive score of 5. The microsatellite-stable profile and low mutational burden argued against benefit from immune checkpoint inhibition, while the KRAS G12V mutation precluded anti-EGFR therapy with cetuximab or panitumumab. Together these findings supported a colorectal cancer-based cytotoxic approach. Pre-treatment tumour markers in July 2022 were markedly elevated, with CEA at 49 ng/mL and CA19-9 at 123 kU/L.

First-line CAPOX chemotherapy began in mid-July 2022, consistent with standard first-line practice in metastatic colorectal cancer. After a single cycle, oxaliplatin was discontinued because of acute worsening of vision attributed to oxaliplatin neurotoxicity superimposed on her pre-existing retinal dystrophy; ophthalmological review found no new structural retinal changes, and visual field disturbance is a recognised rare adverse effect of the drug. Treatment continued as capecitabine alone for two cycles, then capecitabine plus bevacizumab at 7.5 mg/kg every three weeks for six further cycles. Tumour markers fell substantially to a nadir of CEA 26 ng/mL and CA19-9 61 kU/L, and a CT scan at three months showed stable disease by size criteria with cavitation of pulmonary metastases interpreted as a favourable response. By six months, markers had risen and CT confirmed progression of omental disease.

Second-line FOLFIRI plus bevacizumab started in February 2023, with irinotecan deliberately begun at a reduced 50% dose because of the uncertainty around its effects on her rare macular dystrophy, later escalated to 70%. Bevacizumab was continued given its established survival benefit beyond first progression in metastatic colorectal cancer. A CT scan at six weeks showed marginal improvement in the primary tumour and omental disease, but imaging at approximately five months confirmed radiological progression with increased pulmonary and peritoneal disease.

The third-line switch in July 2023 to trifluridine/tipiracil plus bevacizumab is the report’s principal novelty. Trifluridine/tipiracil has demonstrated survival benefit in refractory metastatic colorectal cancer, and the SUNLIGHT trial established improved outcomes when bevacizumab is added. The regimen was delivered at full standard dose throughout eleven cycles without any dose reductions, with pegfilgrastim added from cycle three as primary prophylaxis against cumulative myelosuppression. A restaging CT at six weeks showed stable disease; imaging at five months showed slight tumour increases, but because tumour markers were relatively stable and no formal RECIST-defined progression was recorded, treatment continued, and scans at eight and ten months confirmed ongoing stability. At eleven months, increasing ascites marked definitive progression. The authors emphasise that because no formal RECIST v1.1 assessment was performed, this interval is best characterised as time to progression under routine clinical evaluation rather than protocol-defined progression-free survival. Notably, a rise in tumour markers from about eight months preceded radiological progression by several months.

Fourth and fifth lines were brief and uninformative. Regorafenib, begun in July 2024 at a reduced starting dose of 80 mg/day, was discontinued after only one week because of significant fatigue and generalised myalgia. Fruquintinib, initiated at a reduced 3 mg/day, was held after thirteen days due to declining performance status. The authors state that the brevity of exposure makes it impossible to definitively assess the activity of either agent. In mid-August 2024 the patient was admitted with delirium, electrolyte derangement, ascites and a urinary tract infection; CT showed worsening peritoneal disease with small bowel obstruction, she underwent an emergency laparotomy with formation of a defunctioning ileostomy, and she died at the end of August 2024 from disease progression, 27 months after diagnosis.

The authors place the 27-month overall survival against a reported historical median of approximately 12 months for metastatic urachal carcinoma, while stressing that the comparison should be interpreted cautiously given differences in patient selection, baseline performance status, disease burden and treatment availability across cohorts. They note that her excellent baseline performance status despite her age may have contributed to her ability to tolerate sequential multi-line therapy. They also caution that because bevacizumab was co-administered with cytotoxic chemotherapy across all three effective lines, its independent contribution cannot be determined, and the findings should not be read as evidence of a survival benefit specifically attributable to VEGF inhibition in urachal carcinoma. As a single-patient case report, the observed benefit cannot be generalised, radiological responses reflected routine clinical interpretation rather than formal RECIST review, and tumour marker kinetics are not formally validated in urachal carcinoma, although in this patient they provided complementary information to imaging.

The report is hypothesis-generating rather than practice-changing. At the time trifluridine/tipiracil plus bevacizumab was initiated, no published data described its use in urachal carcinoma; only one other case has since appeared, in the second-line setting in a 53-year-old man after FOLFOX, achieving a progression-free survival of 17 months. The present case extends that observation to a more heavily pre-treated, older patient in whom activity appeared retained after two prior lines of colorectal-style therapy. The authors conclude that in the absence of prospective trials for this rare malignancy, carefully documented real-world experience remains essential to inform management, and that the observations warrant confirmation in larger series.

Subject of Research: A case report of metastatic urachal adenocarcinoma treated with sequential colorectal cancer-based therapy including trifluridine/tipiracil plus bevacizumab.

Article Title: Sequential colorectal cancer–based therapy including anti-angiogenics and 3rd-line trifluridine/tipiracil-bevacizumab for metastatic urachal adenocarcinoma: a case report

Article References: Abu Naib, S., & Gerlinger, M. (2026). Sequential colorectal cancer–based therapy including anti-angiogenics and 3rd-line trifluridine/tipiracil-bevacizumab for metastatic urachal adenocarcinoma: a case report. Frontiers in Oncology, 16, 1933091. https://doi.org/10.3389/fonc.2026.1933091

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1933091

Keywords: urachal adenocarcinoma, case report, bevacizumab, trifluridine/tipiracil, colorectal cancer therapy, anti-VEGF therapy, metastatic bladder cancer, KRAS G12V, rare malignancy, tumour markers, CAPOX, FOLFIRI