What are the implications of adenocarcinoma of gastrointestinal (GI) origin metastasizing to the bladder?

From the Guidelines

Adenocarcinoma of gynecological origin metastatic to the bladder should be managed with a multidisciplinary approach, prioritizing systemic chemotherapy, local control, and symptom management to optimize quality of life and prolong survival. The clinical spectrum of bladder cancer, as outlined in the NCCN guidelines 1, can be divided into three categories, with metastatic lesions posing a critical concern for prolonging survival and maintaining quality of life.

When considering treatment options, it is essential to note that numerous agents with different mechanisms of action have antitumor effects on this disease 1. Systemic chemotherapy with platinum-based regimens, such as carboplatin/paclitaxel or cisplatin/gemcitabine, may be considered, depending on the primary tumor type.

Key considerations in managing adenocarcinoma of gynecological origin metastatic to the bladder include:

• Surgical intervention for isolated metastases, including partial cystectomy if technically feasible
• Radiation therapy for local control and symptom relief, particularly for bleeding or pain
• Immunotherapy with checkpoint inhibitors like pembrolizumab for certain molecular subtypes, especially those with high microsatellite instability
• Symptom management, including urinary catheterization for obstruction, pain control with opioid analgesics, and treatment of hematuria with tranexamic acid or bladder irrigation

Prognosis is generally poor with metastatic disease to the bladder, with median survival typically less than 12 months 1. Regular monitoring with cystoscopy, imaging studies, and tumor markers is essential to assess treatment response. Genetic testing for targetable mutations may identify additional treatment options in selected cases. Palliative care should be integrated early to optimize quality of life throughout the disease course, as the goal is to use available agents to increase survival and quality of life 1.

From the Research

Adenocarcinoma of Unknown Primary Origin

• Adenocarcinomas account for up to 60% of all metastatic neoplasms of unknown primary origin 2
• Metastatic adenocarcinomas are the most difficult metastatic tumor to accurately identify the primary site 2

Diagnosis of Metastatic Adenocarcinomas

• Electron microscopy and immunohistochemistry can be used to help identify the exact type (origin) of metastatic adenocarcinomas 2
• Relatively specific ultrastructural features and immunohistochemical tests can be used to diagnose metastatic adenocarcinomas of unknown primary origin 2
• Immunohistochemistry is a reliable, inexpensive, and widely available resource for diagnosing carcinoma of unknown primary origin (CUP) 3

Metastasis of Unknown Origin

• Metastasis of unknown origin (MUO) constitutes between 5% and 10% of all noncutaneous cancers 4
• The prognosis may be quite good for patients with MUO limited to lymph nodes in the mid to high cervical, axillary, and groin areas 4
• Patients with MUO to visceral sites have a poor prognosis 4

Treatment of Metastatic Adenocarcinomas

• The treatment of metastatic adenocarcinomas of unknown primary origin is often empiric chemotherapy 4
• Some metastatic adenocarcinomas may respond to chemotherapy, and a limited search for these tumors should be undertaken 4
• The FOLFIRINOX regimen has been shown to be effective as second-line therapy in metastatic pancreatic adenocarcinoma 5

Cancer of Unknown Primary

• Cancer of unknown primary (CUP) is an umbrella term used to classify a heterogeneous group of metastatic cancers based on the absence of an identifiable primary tumor 6
• CUPs are characterized by a set of distinct features comprising early metastatic dissemination in an atypical pattern, an aggressive clinical course, poor response to empiric chemotherapy, and a short life expectancy 6