Advancing Trimodality Therapy for Bladder Cancer

Massachusetts General Hospital urologists are expanding and improving treatment options for patients with muscle-invasive bladder cancer (MIBC) using a unique approach called trimodality therapy (TMT), a combination of transurethral resection, chemotherapy and radiation. The approach can help certain patients avoid radical cystectomy and still achieve good outcomes.

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"Mass General is well leveraged to treat this condition with a less radical treatment approach that has similar outcomes and success," says Matthew F. Wszolek, MD, chair of quality and safety in the Department of Urology and urological oncologist at the Mass General Cancer Center. "This a very good option for people who prefer to avoid major surgery and for people who are too sick for extensive surgery due to comorbidities."

Dr. Wszolek and colleagues published on the long-term effectiveness of TMT against muscle-invasive bladder cancer in European Urology. Now the team is examining outcomes and options in patients who have localized recurrence after TMT. A recent study found good outcomes among Mass General patients who had a complete response to TMT but went on to relapse and have surgery.

Trimodality Therapy for Muscle-Invasive Bladder Cancer

MIBC is a cancer that starts in the bladder and spreads into the detrusor muscle deep in the bladder wall. MIBC is more likely to metastasize to other parts of the body as well.

People with MIBC currently have two treatment options. The more traditional and widely used option is cystectomy, a surgery to remove the bladder and reconstruct the urinary tract. A newer, second alternative is TMT, which includes transurethral resection of as much of the bladder tumor as possible, followed by radiation and chemotherapy for about six weeks.

"TMT has been shown as a feasible alternative to radical cystectomy in select patients with MIBC, with fatigue and increased urinary and bowel frequency being the most common side effects," Dr. Wszolek says. "Chemotherapy and radiation to fight bladder cancer has been a major focus at Mass General but not necessarily elsewhere."

TMT is now part of the National Comprehensive Cancer Network to treat bladder cancer, although it is not offered everywhere.

Dr. Wszolek cautions that the TMT approach is not for everyone. Exclusion criteria can include:

• Hydronephrosis
• Poor bladder function
• Prior history of bladder cancer
• Tumor outside the bladder

Long-term Outcomes and Options After Chemoradiation for Bladder Cancer

In a long-term analysis of TMT outcomes published in European Urology, Dr. Wszolek and colleagues found that 66% of eligible patients achieved five-year disease-specific survival. Further, five-year disease-specific survival cancer can approach 80%-85% in patients who are optimal TMT candidates. However, 25% of patients who achieved a complete response to TMT later experienced nonmuscle-invasive (localized) bladder cancer recurrence, some as long as 10 years later. In contemporary series approximately 10%-15% of TMT patients develop bladder cancer recurrences that require radical cystectomy.

A recent publication analyzed the safety and outcomes of patients who required radical cystectomy after TMT.

The research team went on to compare outcomes among three groups:

1. Patients who received TMT, then later relapsed and required radical cystectomy (study group)
2. Patients who received initial cystectomy for muscle-invasive bladder cancer (no history of TMT or other radiation)
3. Patients who received cystectomy plus radiation for another condition (patient who did not receive TMT but, for example, had radiation for prostate cancer or rectal cancer)

Dr. Wszolek and colleagues found similar perioperative and early safety profiles between the groups. The post-TMT group had a higher risk of late surgical complications but there was no difference in overall or cancer-specific survival.

The research team also found that not all patients with recurrence needed immediate radical cystectomy. Tumor resection with adjuvant intravesical bacillus Calmette-Guérin (BCG, an intravesical immunotherapy commonly used to treat early bladder cancer) was effective in most patients: Three-year recurrence-free and progression-free survival after BCG were 59% and 63%, respectively. The results indicated that the approach also had a reasonable toxicity profile.

"TMT can help people avoid radical cystectomy, but there will always be a need for multiple approaches," Dr. Wszolek says. "Mass General continues to explore additional ways to expand options and improve outcomes in these patients. We have ongoing clinical trials adding immunotherapy to the treatment paradigm."

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