EMUC16: Refined patient selection is crucial to improve impact of chemotherapy for bladder cancer patients

19 July 2016

Colin Dinney

Bladder cancer, widely considered as an underfunded area in urological malignancies, requires a more refined clinical staging if patients are to optimally benefit from treatment such as neoadjuvant chemotherapy (NAC).

The first step in improving the impact of NAC is to refine clinical staging in order to accurately identify those patients likely to progress despite radical cystectomy alone. Citing current research, Colin Dinney, professor and chairman of the Department of Urology at the University of Texas MD Anderson Cancer Center in Houston, Texas (USA), said the problem is that current staging is inadequate and more than 50% of patients are under-staged and potentially undertreated. “Advances in imaging and genomics hold promise in this regard,” he said.

According to Dinney, what is also required is to reliably identify likely responders to neoadjuvant platinum based chemotherapy. “This should improve response rates for those predicted to respond favorably and stimulate the development of novel approaches for those unlikely to respond. Both strategies applied hand-in-hand should improve the impact of NAC,” he added.

Dinney is one of the speakers at the upcoming 8th European Multidisciplinary Meeting on Urological Cancers (EMUC16) to be held in Milan (IT) from 24 to 27 November. Now on its eight year, the EMUC is a much-awaited meeting for onco-urological experts that enable them to share perspectives and critically examine current treatment strategies in urological malignancies.

Dinney, who will lecture on optimising patient selection for neoadjuvant chemotherapy during a session on high-grade bladder cancer, said that although NAC is known to improve the survival of patients with muscle invasive bladder cancer (MIBC), NAC is under-utilised due to the modest number of patients who actually benefit and the inability to identify those likely to respond prior to treatment.

“Meta-analysis reveals only a modest 6% improvement in five-year survival and only approximately 20-25% of unselected patients benefit. Moreover, not all patients with MIBC seem to need NAC to potentiate survival as patients with organ-confined bladder cancer (≤ pT2) who make up about 50% of those in contemporary surgical series have an excellent survival following cystectomy, with over 80% cured by cystectomy alone,” he explained.

He underlined the need for physicians to actively enroll patients in clinical trials.

“Physicians should make every effort to enroll patients on clinical trials that address critical issues.   A community-wide effort to exploit the scientific opportunities afforded by the use of NAC has produced a high profile clinical trial (the Southwest Oncology Group’s “CoxEN trial) designed to prospectively evaluate multiple platforms to predict sensitivity and resistance to platinum-based NAC,” he noted.

Underfunded malignancy

Bladder cancer in the US, according to Dinney, is the fourth most commonly diagnosed solid tumor in American males. But funding for bladder cancer research trials are insufficient and drug development has not seen the dramatic gains made in other solid tumour malignancies.

“Integrated clinical and laboratory investigations of this disease have lagged behind those of other cancers. Advances in our understanding of the biology and molecular genetics of bladder cancer are only now being translated into new, biology-based diagnostic or therapeutic approaches,” Dinney said adding that by far the drug atezolizumab is the only new agent receiving FDA approval.

Re-stating the case for NAC as a potential weapon to boost current treatment options, Dinney said NAC is ideal for developing “precision” therapy for bladder cancer.

“This is unique in that the pT0 (or ≤ pT1) status serves as an immediate surrogate for survival. Tissue and urine is readily available both pre and post-therapy for correlative studies to link a “marker expression” with a favorable response (pT0 or ≤ pT1). As a first step, we need to take advantage of this paradigm to optimize the impact of NAC by identifying those individuals most likely to benefit from treatment,” he said.

Expanded MDTs

At a focused meeting such as the EMUC, Dinney said complex issues are best discussed since the presence and participation of various experts enable not only fresh insights but also an active and incisive discussion of potential dilemmas in a multidisciplinary setting.

“By sharing data and perspective on critical issues, these meetings provide an opportunity to broaden perspectives and establish consensus on a path forward to address difficult problems. It is essential to have the critical mass engaged because it is unlikely that one organization has the breadth and patient numbers to use the available genomic data to precisely address complex issues,” said Dinney.

He, however, pointed out that clear communication is vital to boost the efficiency of multidisciplinary teams (MDTs) while adding that an expanded multidisciplinary team may be necessary in the future to further improve the work of MDTs.

“Moving beyond conventional therapy, the multidisciplinary team should be expanded to include translational and laboratory-based scientists, epidemiologists, biostatisticians and bio-informaticians working together to make advancements in the field that go beyond conventional therapy,” he said. “And from my perspective, effective communication between all stakeholders is paramount to maximize impact.”

EMUC presents not only a comprehensive and compact Scientific Programme that aims to critically assessed current and prospective therapies in onco-urology but also provides a platform for clinicians and researchers to link up and collaborate in both ongoing and future studies. Last year the seventh edition gathered in Barcelona, Spain nearly 1,300 participants from around 60 countries.

This year the three-day EMUC will be preceded by the 5th annual meeting of the EAU Section of Urological Imaging (ESUI) whose programme will focus on new developments, challenges and prospects in imaging. Also on the same day, 24 November, the 2016 EMUC Symposium on Genitourinary Pathology (ESUP) will take place to highlight new and current diagnostic issues in genitourinary cancers.

The European School of Urology (ESU) will also offer two courses, one on managing advanced metastatic urological cancers and another on the multidisciplinary approach in managing genito-urinary cancers using a clinical scenario-based interactive session. Hands-on training courses on robotic surgery and MRI Fusion biopsy will also be presented on Days 1 and 2. Moreover, the third Falcon Workshop will be held and for the first time the Uropathology Training Workshop for Clinicians will be offered. Both workshops are scheduled on the second day, 26 November.

Photo via ASCO.