Metastatic disease has progressed during or following platinum-containing chemotherapy urothelial carcinoma (UC)

Metastatic Urothelial Carcinoma: Progress During or Following Platinum-Containing Chemotherapy

Metastatic urothelial carcinoma (UC), the most common type of bladder cancer, is often treated with chemotherapy. When UC spreads, patients are usually treated with platinum-containing regimens, including cisplatin or carboplatin in combination with other agents. These therapies can improve outcomes, but metastatic disease can still progress, leading to the need for further treatment.

It is important to understand if and how UC progresses during or following platinum-containing chemotherapy. Recent research has shown that there are a number of factors associated with progression, including certain genetic mutations, the location of metastatic sites, and the type of disease. Research has also suggested that there are certain drugs that may be associated with improved outcomes in patients with UC.

Genetic Mutations

Research has suggested that particular genetic mutations may be associated with the progression of metastatic UC during or following platinum-containing chemotherapy. A specific mutation in the TP53 gene, known as R273H, was found to be significantly more frequent in a group of patients who experienced disease progression despite treatment with carboplatin plus gemcitabine or pemetrexed, compared to those who responded to the regimen. Additionally, research has found that other genetic mutations, including HRAS and ARID1A, may be associated with increased risk of progression of UC during or following platinum-containing chemotherapy.

Metastatic Sites

Research has also suggested that the locations of metastatic sites in relation to the bladder may predict progression of metastatic UC during or following platinum-containing chemotherapy. In a study of patients treated with cisplatin-based chemotherapy, those with metastases located between the bladder and midline of the torso had a significantly higher rate of progression or death following treatment compared to those with metastases in other locations.

Type of Disease

In addition to genetic mutations and metastatic sites, the type of UC may affect progression of the disease during or following platinum-containing chemotherapy. Patients with higher grade, higher stage, and larger tumors have all been shown to have a higher risk of progression of UC during or following platinum-containing chemotherapy. Additionally, research has shown that patients with poorly differentiated tumors may be at higher risk of progression of their disease.

Drugs Associated with Improved Outcomes

In addition to understanding which factors may be associated with progression of UC during or following platinum-containing chemotherapy, research has also identified certain drugs that may be associated with improved outcomes. For example, a combined regimen of carboplatin and paclitaxel was found to be associated with increased progression-free survival compared to cisplatin-based regimens in a study of patients with metastatic UC. Additionally, a study of patients with metastatic UC who were treated with gemcitabine and cisplatin found that those who received the combination of capecitabine and bevacizumab had significantly better outcomes than those who received gemcitabine and cisplatin alone.