BCa18: Gains and prospects in BCa classification and treatment

09 June 2018

There are increment developments in genomics research on bladder cancer (BCa) molecular classification, but drug development and their prospective benefits still remain unclear due to the complex types of aggressive disease and the lack of sufficient patient numbers in major research trials.

At the second-day full plenary session of the EAU Update on Bladder Cancer (BCa18) which ends today in Munich, urologist Seth Lerner (USA), oncologist Thomas Powles (UK) and urologist Maurizio Brausi (IT) examined the latest developments in bladder cancer classification and treatment. Lerner tackled genomics’ impact on clinical practice, Powles discussed immunotherapy’s role in metastatic BCa, and Brausi examined the issues in palliative management of unresectable muscle-invasive bladder cancer (MIBC) tumours.

“MIBC is associated with a very high mutation rate… and the mutation processes affect survival,” said Lerner in his lecture which comprehensively covered topics such expression-based molecular subtypes, upper urinary tract tumours, prognostic biomarkers and how it may inform clinical decision-making.

“mRNA expression-based subtypes define unique biology and treatments,” said Lerner as he noted that the high number of mutations are linked to survival rates in patients. “These fusions may render a patient sensitive to targeted therapy,” he added.

He also said that the TCGA Version 2 single patient classifier can be applied to diverse expression datasets and identifies Neuronal as exquisitely sensitive to immunotherapy (IO). This has significant implications for patients also selected for targeted therapies.

Among Lerner’s take-home messages are: upper tract tumours are genomically distinct and that genomics define a rich array of potential biomarkers and targeted treatments.
Powles discussed immune checkpoint inhibitors licensed in metastatic urothelial cancer such as IO, atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab- drugs with PD-1 and PD-L1 as targets for inhibition.

Some of the key points mentioned by Powles on the topic of single-agent immune therapy in platinum refractory disease are:

• Immune checkpoint inhibitors have superseded chemotherapy in platinum-refractory disease;
• All of the drugs are associated with long-term durable remission;
• Pembrolizumab is the only agent with a positive randomized phase 3 study; and
• The biomarkers are consistently inconsistent.

Powles also noted the following points in single agent immune therapy in chemo-naïve patients:

• Atezolizumab and pembrolizumab are associated with well-tolerated durable remissions which are attractive for patients;
• Identifying these patients is important but we don’t currently know how; and
• The PD-L1 biomarker is important

Brausi discussed unresectable BCa, its palliative management and the role of surgery in the post-chemotherapy setting. Among Brausi’s take-home messages are:

• A multidisciplinary approach to locally advanced, N+, M+ bladder cancer is a must, and this involves urologists, general and vascular surgeons and orthopaedics, and at times gynaecologists;
• An accurate diagnosis of the disease extension (LNs at CT) is difficult and sometimes misleading;
• Neoadjuvant chemotherapy (NAC) should be proposed as the first-line treatment in these patients;
• Post-chemo RC with E-LND is the treatment of choice for patients who achieved a CR or PR;
• The rationale for a palliative aggressive surgery (debulking, reducing RR and possible future complications) is strong; and
• Metastasectomy is an option and useful in patients with solitary metastases.

Article by Joel Vega