Bladder Preservation High With 'Trimodal' Cancer Therapy

Roxanne Nelson, BSN, RN

April 05, 2016

A trimodal therapeutic approach to localized bladder cancer that involves adaptive image-guided (IG) intensity-modulated radiation therapy (IMRT), surgery, and chemotherapy has shown promise for bladder preservation, according to results from a proof-of-concept prospective study.

The study was published in the International Journal of Radiation Oncology * Biology * Physics.

Patients treated with the trimodal approach, developed to preserve bladder function without compromising good oncologic outcomes, undergo transurethral resection of the bladder tumor, followed by IG-IMRT and chemotherapy.

Conventional radiotherapy for bladder cancer irradiates a large volume of the small bowel, resulting in both acute and late toxicities. IG-IMRT improves delivery of radiation directly to the tumor and reduces damage to normal tissues, the researchers explain.

The proof-of concept study involved 44 patients. The results suggest that outcomes are better and toxicity is lower with the trimodal approach than has with conventional radiotherapy.

"Adaptive IGRT with a plan-of-the-day approach for bladder preservation is clinically feasible, with good oncologic outcomes and low rates of acute and late toxicities," said lead researcher Vedang Murthy, MD, associate professor and consultant radiation oncologist at the Tata Memorial Centre in Mumbai, India.

The bladder preservation rate at 3 years was 83%, but this might "fall a bit with longer follow-up," he told Medscape Medical News.

Even though there have been no head-to-head randomized trials, the 3-year rates of locoregional control, disease-free survival, and overall survival are very much comparable to the rates seen in large surgical series, Dr Murthy explained.

The current standard of care for muscle-invasive bladder cancer is either radical cystectomy with ileal conduit or, for selected patients, bladder preservation, the researchers write.

However, urinary diversion and reconstruction surgery is associated with significant morbidity, and patients who have undergone such therapy perceive subsequent quality of life to be poor.

Although there is currently a lack of level I evidence, the researchers note that for some patients, the trimodal approach can deliver bladder preservation rates of approximately 50% to 60% at 10 years, with unchanged oncologic outcomes.

Good Outcomes, Acceptable Toxicity

All 44 study participants had localized bladder cancer. And all underwent maximal safe resection of the bladder tumor and received platinum-based chemotherapy. Those with large tumors were also offered induction chemotherapy.

Sixteen patients (36%) received neoadjuvant chemotherapy and 30 (68%) received concurrent chemotherapy; all completed it as planned.

Patients received 64 Gy delivered in 32 fractions to the whole bladder, 55 Gy to the pelvic nodes, and, if appropriate, a simultaneous integrated boost to the tumor bed of 68 Gy.

Most patients (88%) had T2 disease, 73% received prophylactic nodal irradiation, and 55% received an escalated dose to the tumor bed.

At 3 years, the rate of locoregional control was 78%, of disease-free survival was 66%, of overall survival was 67%, and of cause-specific survival was 73%.

Local control and overall survival were better in patients who received the higher dose of 68 Gy than in those who received 64 Gy, but the difference was not significant.

On multivariate analysis, locoregional control was significantly better in younger patients (P = .01).

Acute and late grade 3 genitourinary toxicity was seen in five (11%) and two (4%) patients, respectively. In patients who did not receive nodal radiotherapy, there was no acute or late grade 3 or higher gastrointestinal toxicity and no late small bowel toxicity of any grade.

The higher dose of radiotherapy did not have any impact on the occurrence of toxicity.

Moving Into Practice

Even though this was a small proof-of-concept study, Dr Murthy explained that they are already moving the approach into clinical practice.

"Advanced technology is no good if it is restricted to the confines of clinical trials," he said. "We have now refined and implemented this technique in our routine practice at the Tata Memorial Centre, which has one of the busiest radiotherapy departments."

IGRT is already available widely in many centers, Dr Murthy pointed out.

"The extra burden with the plan-of-the-day technique is related to physics time and the radiographer's training to pick the right plan each day," he said. But "both are a small cost to pay for the improvement in accuracy of treatment."

"I am hopeful that adaptive IG-IMRT will become the standard of care for bladder preservation in the near future," he added.

It is "always a challenge for us to compare surgical outcomes with bladder preservation approaches," said Jeff M. Michalski, MD, MBA, FASTRO, vice chair of radiation oncology and chief of the genitourinary service at the Washington University School of Medicine in St. Louis, Missouri, who is secretary/treasurer of the American Society for Radiation Oncology.

"Many patients that are referred for bladder preservation are not optimal surgical candidates, and they frequently have medical comorbidities that make surgery a risky endeavor," he told Medscape Medical News.

 
The data in the adaptive radiation therapy...show outstanding results when more accurate radiation therapy is practiced.
 

Furthermore, he noted, "surgical series often report outcomes by surgical and pathological staging, which has been shown to be far more accurate than clinical staging. In most cases, the clinical staging looks 'better' than the surgical disease extent."

Despite these shortcomings, survival outcomes with a bladder-preservation strategy of radiation therapy with concurrent chemotherapy have been shown to be comparable to surgery.

"The data in the adaptive radiation therapy study published by Murthy et al show outstanding results when more accurate radiation therapy is practiced," Dr Michalski said. "In their series, they customized the daily treatments using daily onboard imaging to determine the actual treatment volume."

"As onboard imaging with CT and even MR becomes available, this type of adaptive radiation therapy technique should be offered to a greater number of patients who are seeking to avoid losing their bladders to surgery," he added.

The authors have disclosed no relevant financial relationships.

Int J Radiat Oncol Biol Phys. 2016;94:60-66. Abstract

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