Intravesical Gemcitabine Reduces the Risk of Cancer Recurrence

In early-stage bladder cancers with a high risk of recurrence, administering medicines into the bladder is known to reduce the risk of bladder cancer returning. According to research by Professor Messing and colleagues published in JAMA, washing the bladder with the chemotherapy medicine gemcitabine after surgery substantially reduces the likelihood of cancer relapse (recurrence).

• Bladder Cancer Treatment—Early Stage (Detailed)

Around 80% of bladder cancers have not reached the muscle layer at diagnosis. The main treatment at this stage is TUR-M (transurethral resection—bladder), in which a cystoscope with a camera at its tip is passed through the urinary tract and the bladder’s inner lining containing the tumor is scraped away. After TUR-M, it is important for the pathology report to specify whether the tumor is superficial or extends deeper (invades). However, disease recurs in 50-80% of patients undergoing TUR, and progresses to more invasive disease in 20-25%.

Treatment of Early-Stage Bladder Cancer

The frequent local recurrence of bladder cancer despite its early stage has created a need to classify the risk of disease recurrence:

• Low-Risk Bladder Cancer: refers to patients whose tumors do not involve muscle at diagnosis, do not recur within the first 1 year after TUR, are smaller than 3 cm, and consist of 3 or fewer low-grade tumors. Treatment for low-risk bladder cancer is TUR alone or TUR combined with a single dose of intravesical chemotherapy (usually the chemotherapy medicine mitomycin).
• High-Risk Bladder Cancer: refers to patients with numerous recurrences, more than 3 lesions or any intravesical tumor larger than 3 cm, incomplete tumor removal because of extensive bladder involvement, and poorly differentiated cancer cells under the microscope. Treatment for high-risk non-muscle-invasive bladder cancer is medicine administered into the bladder after TUR (BCG vaccine or mitomycin).

Thus, until now, the two accepted intravesical agents in early-stage bladder cancer were BCG vaccine and mitomycin-C. In this study, gemcitabine, a chemotherapy known to be effective in systemic bladder cancer treatment, was administered into the bladder.

Although intravesical gemcitabine is used in Europe and Canada, it had not been accepted in the United States. This research is the first phase-3 clinical trial conducted in the United States on this treatment strategy in the past 20 years.

Messing “The real importance of this study is to offer a new treatment strategy with a medicine already available to us that is quite inexpensive, well tolerated and effective,” said.

Study Findings

The study team conducted, at 23 cancer centers with 406 eligible patients, a randomized, double-blind clinical trial . All cancerous tissue in the bladder was surgically removed by TUR-M. Then 201 patients received intravesical gemcitabine with saline within 3 hours after surgery. A second group of 205 patients received saline (saltwater solution) alone.

The researchers followed all patients for 4 years—the period when most bladder cancers recur—to discover which treatment strategy worked better.

The most important study result was a 34% reduction in recurrence risk among patients receiving gemcitabine infusion. Recurrence occurred in 67 patients (35%) in the gemcitabine group and 91 patients (47%) in the control group.

The study results suggest that gemcitabine may become a new standard for treating early-stage bladder cancer at high risk of recurrence; however, research comparing the effectiveness of different chemotherapy agents is also needed.

Gemcitabine’s Mechanism of Action

Gemcitabine suppresses DNA synthesis and triggers cell death by blocking the enzyme thymidylate synthase. Gemcitabine is a prodrug: it acts after being converted inside the cell by deoxycytidine kinase into two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate.