There is a lot of work that needs to be done to address gaps in the guidelines for managing muscle-invasive bladder cancer (MIBC), but at the same time there are new prospects in biological predictors that could transform the treatment landscape for MIBC, according to experts.
At the second plenary session, oncologists Joaquim Bellmunt (USA) and Andrea Necchi (IT) gave updates on managing MIBC with Bellmunt speaking on the EAU and ESMO Guidelines and Necchi addressing issues in new drugs and therapeutic sequences in locally-advanced stages.
Bellmunt gave a concise overview on neoadjuvant and adjuvant therapies, organ preservation goals, treatment of relapse, personalized medicine, and follow-up and long-term implications.
Bladder cancer is the fourth most common cancer in men, and the eleventh most common cancer in woman, with approximately 400,000 new patients diagnosed annually worldwide, according to recent figures. An estimated 75% of bladder cancers are non-muscle-invasive bladder cancer (NMIBC), and the remaining are either muscle-invasive or metastatic disease.
For MIBC, Bellmunt said neoadjuvant chemotherapy (NAC) is the current standard, but the guidelines of organisations such as the EAU and ESMO are still lacking when it comes to issues such as the management of variant histologies. “There is also the lack of predictive biological factors for NAC in both guidelines,” he added.
In the ESMO Guidelines there are suggested options after NAC failure, whereas in the EAU Guidelines these are missing. He also noted that there is a lack of integration on the management of upper urinary tract (UUT) tumours in the EAU Guidelines, while in the ESMO these are not addressed at all.
But despite these gaps, he noted the prospects in new biological markers. “We are moving forward. We now have a lot of new biological predictors that are not yet confirmed in prospective randomised trials, but probably are going to be implemented in the decision when giving new adjuvant or neoadjuvant in muscle invasive disease,” he said.
“Then, there is more data coming up about the benefits of giving, for example, adjuvant chemotherapy in patients who fail new adjuvant. This means we switch to another type of chemotherapy. Although everything is retrospective, not prospective. Perhaps in this way we can select specific patients just to give additional therapy, and maybe we can improve the outcomes,” he added.
He also expressed optimism that a breakthrough is possible if research needs are met. “Breakthroughs, yes, that’s for sure. All these new data on new mutations…that correlate with outcomes, these might help us to select patients in a more appropriate way,” Bellmunt said, noting that although these are exploratory there are emerging potentials.
Necchi, meanwhile, described the treatment landscape as “continually evolving” and said that in the next 18 months agents such as ramucirumab, durvalumab, pembrolizumab, atezolizumab, avelumab, and nivolumab are the drugs to watch. These agents are undergoing testing in various trials and results are to be expected in the following months, with nivolumab’s expected outcomes by the last quarter of 2019.
Among the key messages he mentioned included the role of PD-L1. “PD-L1 should be tested with clinical assessment as there is value for both mono and combo in PD-L1 high patients, determined by tolerability concerns, and value for combo in PD-L1 low patients,” he explained.
According to Necchi, adjuvant chemotherapy is the first option that should be offered to patients. “There are multiple clinical trials available in chemotherapy. Clinical trial should be the first to be offered after the first intervention instead of the usual chemotherapy which is biased by poor data quality and the low level of evidence in the guidelines,” he noted.
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