麻豆传媒

Bladder-preserving trimodality therapy may be a potential alternative to radical cystectomy in patients with high-grade T1 bladder cancer that has progressed despite intravesical bacillus Calmette-Guerin (BCG) therapy, researchers reported.

The single-arm, phase II cooperative group trial published in the , showed that at 3 years, 88% of 34 patients maintained their urinary bladder after receiving trimodality therapy. First-line intravesical BCG therapy had failed for all the patients, who were then recommended for radical cystectomy by their treating physicians.

Notably, said Douglas M. Dahl, MD, of Massachusetts General Hospital (MGH) and Harvard Medical School in Boston, and colleagues, recurrent disease and mortality rates from urothelial cancer remained high in patients treated with trimodality therapy, which consisted of radiation with radiosensitizing chemotherapy following repeated transurethral resection. With a median follow-up of 5.1 years, the cancer-specific mortality rate was 25%.

The team said the results mirror those previously reported in T1 patients treated with radical cystectomy. "We believe, however, that the high bladder salvage rate with survival rates comparable with cystectomy cohorts suggests that it is reasonable to consider in place of cystectomy," the researchers wrote.

Twelve patients developed local recurrence at 3 years, and the rates of distant metastases were 12% at 3 years and 19% at 5 years. The overall survival rate was 69% at 3 years and 56% at 5 years. A total of 18 patients had grade 3 adverse events, mostly hematological, and one developed grade 4 neutropenia.

In the following interview, Dahl, who is vice chairman of MGH's Department of Urology, discussed the findings in greater detail.

How does your study address the so-called gap in treatment options for patients with high-grade non-muscle invasive bladder cancer?

Dahl: In muscle-invasive disease, we have a to radical cystectomy for patients who are not good candidates for surgery. However, in spite of promising new treatment strategies for non-muscle invasive bladder cancer, many patients still face the prospect of radical cystectomy, particularly those with high-grade T1 disease that has failed to respond to intravesical therapy. Also, quite a few patients, particularly those who are elderly, are not good candidates for radical surgery, which can be highly morbid and have significant long-term adverse consequences.

We explored a reasonable alternative to standard radical cystectomy in patients with recurrent T1 bladder cancer using chemoradiation after thoroughly re-staging the transurethral resection. Previously, a trimodality option for patients who failed intravesical therapy had not been demonstrated. Our results showed good control of local disease with trimodality therapy. None of the patients developed muscle-invasive disease, and the rates of distant disease were comparable with those reported in patients treated with cystectomy.

What adverse events did you observe?

Dahl: We found that the chemotherapy used at radiosensitizing doses in trimodality strategies is generally well-tolerated, even in fairly frail patients. The most common toxicities seen with our treatment were transient hematologic effects associated with the systemic agents.

Also, we still saw patients, as we do in all T1 studies, who developed metastatic disease. We need a better combined local and systemic strategy to treat these patients.

How does trimodality therapy compare with other emerging bladder-sparing strategies?

Dahl: This is an important open question. The concern is that with T1 disease, approximately 30% of patients have occult higher-stage disease. When first-line intravesical therapy does not control the tumor, cystectomy should be considered and discussed with the patient. However, the arrival of exciting new intravesical strategies should decrease the number of patients who face possible cystectomy.

Immune checkpoint inhibition also shows promise, but thus far has not been specifically investigated in significant numbers in the same narrow patient population we studied.

What is your main take-home message for physicians?

Dahl: In select patients with T1 bladder cancer, particularly those who are not good candidates for surgery, trimodality therapy is effective and well-tolerated, and may be reasonably considered a standard alternative to radical cystectomy.

What's next for your research?

Dahl: The National Cancer Institute genitourinary cancers steering committee has approved a randomized phase II trial of pembrolizumab [Keytruda] plus radiotherapy versus radiotherapy with concurrent chemotherapy for high-grade T1 bladder cancer.

Read the study here and expert commentary about it here.