Multidisciplinary Approach Vital in Bladder Cancer

Quality of care for patients being treated for urothelial carcinoma could be improved by having a multidisciplinary team treat the patient, says Robert Jones, M.D.

“We need to build stronger, more comprehensive and more specialized multidisciplinary teams,” says Jones, a professor of Clinical Research at the University of Glasgow.

Can you provide an overview on your presentation about the future of urothelial carcinoma?

In an interview with CURE at the 2017 Global Congress on Bladder Cancer held in Edinburgh, United Kingdom, Jones discussed the future treatment landscape for patients with urothelial carcinoma in a more multidisciplinary setting.I discussed the future role of the medical oncologist is in the management of advanced urothelial cancer, highlighting four key things, which I think are clear in cancer.

Firstly, early detection brings about better outcomes. As a medical oncologist, we're not diagnosticians, but early detection results in better outcomes. Traditionally, medical oncologists have been involved later in the course of the disease. We've gradually brought that role further forward. Currently, the earliest moment that the medical oncologist is [involved] is in the management of muscle-invasive bladder cancer with neoadjuvant chemotherapy.

It's clear that there are also patients with non-muscle invasive bladder cancer who have a very high risk of dying. Therefore, in the future, the medical oncologists are going to be getting involved in this setting for two reasons: Firstly, the current treatments in that situation leave a great unmet need. The toxicity and efficacy of both Bacillus Calmette-Guérin (BCG) and cystectomy are questionable. We badly need new treatments for those very high-risk patients. It may be that drugs play a part in the role of systemic therapy. I think that medical oncologists are going to get involved in that stage of the disease.

Secondly, it's clear that we're not going to continue treating all patients in the same way. We've failed up until now in trying to subdivide patients. There has been a lot of work around how you select patients for immune checkpoint therapy and that's all failed in bladder cancer. There is a lot of data coming through, particularly from The Cancer Genome Atlas, where we can clearly subdivide patients—there are at least detectable trends in response to treatment.

There is a lot of work that still needs to be done both with making those biomarkers ready for clinical use and in understanding the actual productivity of those markers. I think it is inevitable in the next few years that we're going to have to better understand the molecular biology [of the disease] because it's going to dictate how we treat bladder cancer, as it already does in other common cancers, such as breast cancer, lung cancer, and colorectal cancer.

Thirdly, it's clear that bladder cancer at many stages of presentation benefits from multimodality therapy. I think the multidisciplinary team in bladder cancer is poorly developed at an organizational level. We need to build stronger, more comprehensive, and more specialized multidisciplinary teams. The idea that bladder cancer is managed by the urology multidisciplinary team where there are nine patients with prostate cancer for every one patient with bladder cancer, is going to disappear and a multidisciplinary team is going to be focused purely on urothelial cancers.

Is there any ongoing research that you're interested in?

Finally, the fourth observation is that the molecular biology of cancer, including bladder cancer, is incredibly complex. This will reflect what I've already said about stratification. Part of our take on data is to do big randomized phase 3 trials. In a disease like bladder cancer, which is relatively rare, we are beginning to understand that the molecular pathways are not entirely linear. We're going to need to find new ways of making progress as we increasingly subdivide cancer patients. In my opinion, the era of the big randomized phase 3 trials is something we're going to have to part with over the coming years. At a scientific level, I think there is a lot of interesting research around gene expression profiling, both at the genomic and transcriptomic levels, which is already beginning to give us a nearly tractable hypothesis. There is also ongoing research to translate those complex biomarkers into simpler biomarkers that are potentially amenable to every pathology laboratory, in every specialist hospital in the world.

If we look more broadly, the whole area of how we research the optimum way to deliver individualized care to the patient is interesting. There is interesting research being conducted at Memorial Sloan Kettering Cancer Center looking at the use of patient-recorded outcome tools and how we can improve care and quality of life for our patients. That research is not bladder cancer—specific but it will relate to patients with bladder cancer. As treatment options become more complex, we must not forget that sometimes there are simple tools that can help us better meet the needs of our patients and this translates to survival benefits for patients.

How do you sequence the different systemic therapies available to patients with metastatic disease? This is a new problem we have because up until recently, we only had one line of treatment. There wasn't much debate about that. We do have more than one line of treatment now, potentially three lines of treatment, which are proven to be effective.

How do we sequence them? First of all, we have to look at the evidence base. Right now, I would say the evidence base is still platinum-based chemotherapy first and then an immune checkpoint inhibitor. One might consider further chemotherapy after that. In my view, there is an argument for changing that sequence based on the evidence we have, bearing in mind the evidence for first-line checkpoint inhibition is in patients who are not suitable for platinum-based chemotherapy. We're going to get trials coming through which will change that to where we will have uncertainties.

I also treat prostate cancer where we've gone from having no treatments to five different treatments in a relatively short period of time and many are discussing sequencing. There is never going to be 100 percent evidence for optimal sequencing. It is difficult to do those trials because they are complex. The lesson I've learned from prostate cancer is that the sequence in which a patient takes up different treatments is going to be largely driven by the patient’s preferences at the time. We shouldn't worry too much about drug sequencing in advanced disease. It's a privileged position to be in where you have a choice at any time.

Do you see immunotherapy developing even further in the long-term?

We need to stay focused on which of these options is best for the patient, taking into consideration previous treatments.We're still in the early days with immunotherapy. What we've seen with immunotherapy is that it doesn’t work for everyone. It's clear that if you're one of the small proportion of patients who do benefit, the benefits can be profound and prolonged. We're not going to discard that quickly.

Can we build on that to find immunotherapies that work for a larger group of patients? There is already work ongoing looking at immune combinations or combinations with cytotoxics. Immunotherapy is probably here for the long term because it's been an enticing hypothesis for many years. Now, we're getting evidence that we can manipulate it and hopefully we can build on that to bring those benefits to more patients.