Collaborative and standardized efforts to develop and evaluate novel drugs are necessary to ultimately provide effective long-term treatment for nonmuscle-invasive bladder cancer.
James M. McKiernan, MD
Editor’s Note: This article was developed as a result of a collaboration between members of the Division of Urologic Oncology at Columbia University Medical Center, James F. McKiernan, MD, and Jennifer Ahn, MD, and our freelance writer, Barbara L. Jones.
Management of nonmuscle-invasive bladder cancer (NMIBC) remains difficult, with high rates of recurrence and disease progression despite strict surveillance, local resection, and intravesical therapy. About 50% of patients experience disease recurrence within 5 years even with the most effective current treatment—intravesical bacillus Calmette-Guérin (BCG).
In a featured presentation at the 2012 Society of Urologic Oncology annual meeting in Bethesda, Maryland, James M. McKiernan, MD, director of Urologic Oncology at Columbia University in New York City, reviewed treatment alternatives under study for NMIBC, but pointed to a context characterized by nonstandardized study frameworks and a lack of creative collaborations that could result in truly novel treatments capable of producing better outcomes for patients.
Also, the heterogeneous nature of BCG failure makes it difficult to assess efficacy of new drugs. Study populations are often mixed, consisting of patients differing by timing of the BCG failure, presence or absence of carcinoma in situ, lymphovascular invasion, micropapillary features, and tumor stage.
Definitions of failure have been proposed, depending on the initial response to BCG and timing of recurrence, McKiernan said. But these have yet to be uniformly adopted into practice.
At present, however, multiple intravesical agents are under investigation, primarily for patients who have failed BCG therapy.
One strategy to address recurrence after BCG is the intravesical use of chemotherapeutic agents, which are used systemically for urothelial cancer:
Jennifer Ahn, MD
An ongoing phase II study of nanoparticle albumin-bound paclitaxel (Abraxane) currently has a complete response rate of 27% (7/26) at 11 months follow-up, similar to gemcitabine. An alternative strategy is to employ a multidrug regimen, as is standard with systemic chemotherapy.
BCG is not a chemotherapeutic agent, but an immunotherapy. Therefore, multiple agents have been developed to adopt this mechanism.
As more is understood regarding pathogenetic changes of bladder cancer, McKiernan and Ahn predict that targeted therapies and multidrug regimens will likely be a robust area of research and development. Still, at this time no agent is reliably superior to the rest. And, McKiernan noted that small cohorts, heterogeneous study populations, and various response rates complicate the interpretation.
Collaborative and standardized efforts to develop and evaluate novel drugs are necessary to ultimately provide effective long-term treatment for this high-risk, complicated population.