BCa18: Road maps in personalising bladder cancer treatment

Bladder cancer, one of the most aggressive recurrent onco-urological malignancies, poses a special challenge to cancer experts due to the lack of response from many patients particularly those who are diagnosed at a late stage.

The EAU Update on Bladder Cancer (BCa18) is an interactive, expert-led meeting to be held in Munich from 8 to 9 June which aims to address the relative lack of a critical and focused meeting solely dedicated to bladder cancer management and its various malignant variants.

With case discussions preceded by update lectures, BCa18 participants can expect a to-the-point and critical examination of clinical dilemmas, insights on best practices, and the impact of emerging treatments and new therapies, among other key issues.

We spoke to Prof. Seth Lerner, professor of the Scott Department of Urology and the current Beth and Dave Swalm Chair in Urologic Oncology of the Baylor College of Medicine Medical Center in Houston, Texas (USA). He co-chaired the Analysis Working Group of The Cancer Genome Atlas (TCGA) project for muscle-invasive bladder cancer.

Lerner, one of the resource speakers and faculty member at BCa18, will speak on the shifting landscape of molecular classification and the impact of genomics in clinical practice.

“The convergence of clarifying the genomic landscape of bladder cancer (BCa) and drug development have ushered in a new exciting era for BCa management,” said Lerner, who also heads the Multidisciplinary Bladder Cancer Program and directs the Faculty Group Practice at Baylor College of Medicine.

He described BCa18 as a unique opportunity for specialists to carefully consider and assess the current treatment landscape with the view to identify the most optimal treatment for their patients.

Below is a Q&A where Lerner shared his thoughts on current challenges and promising options in managing bladder cancer:

Q: What are some of your key messages in your lecture on molecular classification and the use of new genomic markers in metastatic bladder cancer?

Lerner: Expression-based subtypes inform us about the wide spectrum and heterogeneity of urothelial cancer and provide a potential road map for personalizing treatment based on the specific subtype of an individual patient’s cancer. The next generation of clinical trials should be designed to validate these and other prognostic and predictive biomarkers and test treatment selection strategies based on molecular phenotypes.

Q: With recent insights from the genomic/molecular classification of bladder tumours, how would these developments impact current treatment strategies in your view?

Lerner: The Cancer Genome Atlas Project and research at several other institutions have defined the biological landscape of urothelial bladder cancer. Recent studies focusing on predictive biomarkers associated with response to cisplatin-based neoadjuvant chemotherapy have identified DNA damage repair gene alterations, as well as expression-based molecular subtypes that are associated with response, defined as no residual disease at the time of cystectomy.

Before these biomarkers can be incorporated into treatment selection for individual patients, a new generation of clinical trials testing the safety and efficacy of treatment selection based on these molecular alterations are being designed. If positive, these trials will usher in a new era of personalized medicine and we can look at the “one size fits all” approach in the rear-view mirror.

Q: Among the meeting’s educational goals is to provide a critical update on BCa management. In what areas in BCa management do you think are the biggest challenges for bladder cancer specialists? In what way can this meeting help specialists face these challenges?

Lerner: We now have well-defined strategies for accurate diagnosis and risk stratification with risk group- directed therapy for non-muscle invasive cancer (NMIBC). Significant challenges remain, however, with uptake of guidelines into clinical practice and we must find effective ways to educate urologists to implement these guidelines.

Drug development for NMIBC has dramatically accelerated and it is likely that one or more new drugs will be approved in the next five years after a ‘drug approval drought’ since the approval of Valrubicin in 1998.

In muscle invasive disease, Level 1 evidence supports integration of neoadjuvant chemotherapy and radical cystectomy, yet at best only 50% of patients are eligible to receive cisplatin-based chemotherapy. So we must validate predictive biomarkers of chemotherapy response and move toward a personalized medicine approach versus the current “one-size-fits-all” approach.

In locally advance and metastatic disease, we now have five new approved immune checkpoint blockade inhibitors which is a giant leap forward but only about 25% to 30% of patients will benefit and there are several predictive biomarkers that may help identify those patients most likely to benefit. But the remaining patients are in need of innovative targeted therapy approaches and combinations of immunotherapy and chemotherapy in order to improve overall survival.

We now understand the genomic landscape of the entire spectrum of the disease and translating these findings into clinical practice is the next frontier.

To learn more about BCa18, visit the meeting website.