Patients with invasive bladder cancer may benefit from getting chemotherapy before surgery or radiation therapy, according to a new review of previously published studies.

Researchers from the Advanced Bladder Cancer Meta-analysis Collaboration, based in London, looked at the combined results from 10 clinical trials to assess whether or not chemotherapy given before local treatment (known as neoadjuvant chemotherapy) had an effect on outcome.

Examining data from more than 2,600 patients, the researchers found that combination chemotherapy (using more than one drug) improved five-year survival by 5%. They reported their findings in The Lancet (Vol. 361, No. 9373: 1927-1934).

Treatment of bladder cancer that has invaded the bladder wall usually includes cystectomy (surgical removal of part or all of the bladder), radiation therapy, or a combination of the two. Chemotherapy is used in more advanced cases, but the best time to use it is still a matter of some debate.

One of the concerns with using treatments such as surgery or radiation by themselves is that about half the patients with invasive bladder cancer are likely to have small deposits of cancer metastases (cancer that has spread) elsewhere at the time they are diagnosed. These localized therapies, therefore, won’t treat the metastases.

Almost two decades ago, doctors reasoned they might be able to improve the effectiveness of treatment by giving chemotherapy before other treatments. Because chemotherapy can attack cancer cells anywhere in the body, it might wipe out the metastases while they were still small, allowing the surgery or radiation to take care of the rest of the disease.

Since that time, many clinical trials have looked at whether or not neoadjuvant chemotherapy benefits patients undergoing surgery, radiation therapy, or both. The results of these studies have been mixed, with some demonstrating an advantage and others finding none.

For the current study, researchers combined the results of 10 different clinical trials in which patients were randomized to get either neoadjuvant chemotherapy or just the standard therapy (surgery, radiation, or both) alone. Most of the studies used cisplatin in combination with other drugs for the chemotherapy regimen.

Patients were followed in the studies for an average of 6.2 years. During this time, the five-year survival rate for those receiving combination (more than one drug) neoadjuvant chemotherapy was 5% better than for patients who did not get neoadjuvant chemotherapy (50% vs. 45%). Neoadjuvant chemotherapy patients also had a longer average time until the cancer came back and a longer time until metastasis was noted. The results were not affected by the type of localized therapy used or by the stage (extent) of the disease.

"Our findings show a clear benefit associated with neoadjuvant combination chemotherapy for patients with invasive bladder cancer," the authors concluded.

However, they pointed out that the studies did not allow them to look at the side effects or quality of life associated with the additional treatment, although they noted that "clearly these are major issues for patients and clinicians when considering their treatment options."

An editorial accompanying the article acknowledges the importance of neoadjuvant chemotherapy as "a new standard of care," but points out the "benefit of potentially toxic chemotherapy is extremely modest."

More effective treatments are needed, the editorial authors conclude, noting that further work "will need to not only identify far more active regimens in this disease, but also more clearly identify patients who are most likely to benefit from available therapies."