New Research Supports Trimodality Therapy for Bladder Cancer

Multicenter research co-led by a Massachusetts General Hospital radiation oncologist found that trimodality therapy has similar survival outcomes as radical cystectomy in select patients with muscle-invasive bladder cancer. The investigators say that bladder preservation should be offered to all eligible candidates, not just patients with significant comorbidities for whom surgery is not an option.

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"Even with recent improvements in surgical technique, cystectomy remains a major operation with significant morbidity and measurable perioperative mortality rates. Although many patients do well, it is a physiologically challenging major surgery that can be life-altering," says Jason Efstathiou, MD, DPhil, a radiation oncologist at Mass General, vice-chair of faculty & academic affairs and director of the Genitourinary Division in the Department of Radiation Oncology, and clinical co-director of the Claire and John Bertucci Center for Genitourinary Cancers. "Our study found that trimodality therapy—transurethral resection of the bladder tumor followed by concurrent chemoradiation—had similar oncologic outcomes as cystectomy in selected patients. It also avoids the potential complications of surgery and offers the hope of better quality of life."

Bladder Cancer Treatment Options

Many patients with bladder cancer are treated with radical cystectomy to remove the entire bladder. The procedure also usually removes the prostate and seminal vesicles in men and the uterus, ovaries, fallopian tubes, and part of the vagina in women.

"Cystectomy is still a very effective surgery, and many patients do well, but we can't ignore the well-documented potential downsides," says Dr. Efstathiou, citing high rates of complications and readmissions, as well as potential mortality. Patients require urinary diversion, such as the creation of a neobladder or ileal conduit, which can lead to significant effects on quality of life and sexual function, he adds.

Trimodality therapy, on the other hand, combines transurethral resection of the bladder tumor by a urologist—which Dr. Efstathiou calls "an elegant and careful operation done cystoscopically to remove as much of the tumor as possible"—followed by concurrent chemoradiation. A growing body of evidence supports this bladder-preserving approach as safe and effective. Several national and international guidelines, including the National Comprehensive Cancer Network Clinical Practice Guidelines, include trimodality therapy as a category 1 recommendation for stage II and stage IIIA bladder cancer.

Although many oncologists and urologists know of this treatment option, it's not commonly offered nationally.

"It's one thing to know about it—it's another thing to actually accept it as a valid alternative and therefore discuss it and offer it to patients," Dr. Efstathiou says. "It's almost like an afterthought. But our study argues against that thinking."

Trimodality Therapy for Bladder Cancer as Effective as Cystectomy

Dr. Efstathiou and colleagues at Mass General, Princess Margaret Cancer Centre in Toronto, Sinai Health System in Toronto, and the University of Southern California conducted a retrospective analysis of patients with clinical stage T2–T4aN0M0 muscle-invasive urothelial carcinoma of the bladder who were treated by high-volume urologists.

All patients would have been eligible for both types of treatment, but 440 had received radical cystectomy, and 282 had received trimodality therapy. The two groups were carefully matched for age, gender, stage of disease, presence of hydronephrosis, and receipt of neoadjuvant or adjuvant chemotherapy among other factors. The researchers then examined differences in survival.

The results were published in Lancet Oncology in May 2023. At a median follow-up of about four and a half years, the groups had similar metastasis-free survival, cancer-specific survival and disease-free survival. The findings were similar across centers, supporting the generalizability of the results.

The study also found that 29% of patients who had cystectomies at the contributing centers would have been eligible for trimodality therapy, refuting the commonly held belief that it's only appropriate for a small number of patients.

This therapeutic area has never had a completed randomized, controlled trial and likely never will, Dr. Efstathiou says. Patients typically do not choose cystectomy when given both options, so sufficient enrollment is likely not possible. Therefore, this comparative analysis is the best evidence to date comparing the treatment options.

"In the absence of completed randomized, controlled trials—with none in the foreseeable future—this study fills a need and provides important information," he says. "It exemplifies a wonderful close collaboration among urologic surgeons, radiation oncologists, and medical oncologists. And it ultimately demonstrates clinically relevant findings, with the potential to guide patients and health professionals during the decision-making process."

A History of Leadership in Bladder Preservation

Mass General was uniquely positioned to participate in this research, as a pioneer in bladder-preservation research. William Shipley, MD, launched clinical trials in the 1980s and 1990s with Radiation Therapy Oncology Group, or RTOG, which today is NRG Oncology. That research paved the way for four decades of treatment improvements.

Because trimodality therapy involves three specialties, it must be delivered at an institution where specialists can coordinate closely.

"Mass General has a uniquely rich experience by delivering highly coordinated treatment. Our patients come to a place where they can meet with all of these disciplines because they work hand in hand for the benefit of the patient. Mass General is world-renowned for excellent multidisciplinary care," Dr. Efstathiou says.

Today's patients are asking specifically about bladder-preservation options.

"Demand has increased. Patients want to hear about their options," he says. "And when patients are offered valid treatment options for their situation that are discussed objectively in a multidisciplinary environment, they feel a better sense of informed decision-making and less regret."

Future research in bladder cancer treatment includes investigations of adding immunotherapy and using hypofractionated radiation in far fewer doses. Dr. Efstathiou also believes eligibility criteria might someday expand beyond muscle-invasive disease, to recurrent bladder cancer that is not muscle-invasive, and oligometastatic bladder cancer.

Learn about the Center for Genitourinary Cancers

Refer a patient to the Department of Radiation Oncology