Improving Care for Patients With Muscle-Invasive Bladder Cancer

The outlook is often grim for patients diagnosed with muscle-invasive bladder cancer due to the high mortality rates associated with radical cystectomies, the part of treatment following neoadjuvant chemotherapy.

Researchers speculated they would be able to detect who could forgo this portion of treatment by observing patients’ pathological responses to the chemotherapy. In keeping patients under surveillance, physicians would be able to order a radical cystectomy if necessary.

Stanley Yap, an assistant professor at the University of California at Sacramento, presented on this study at the 2016 meeting of the American Urological Association, a gathering of thousands of urologists, oncologists and other oncology professionals in San Diego. He revealed that while monitoring pathological responses worked for some patients and allowed them to lead healthier lives than if they were to receive a radical cystectomy, it was not successful for a majority of patients.

CURE recently spoke with Yap to discuss what the study contributed to the field and how physicians can improve care for patients with bladder cancer.

Can you give an overview of the study and its key points?

When you treat muscle-invasive bladder cancer, the standard of care currently is to give neoadjuvant chemotherapy followed by a radical cystectomy, a surgery that is associated with a fair amount of morbidity.

One of the strongest markers of treatment success for these patients is the pathological response to the chemotherapy. Patients who achieved a complete clinical response from chemotherapy have an 85 percent five-year survival rate. Using these data, we approached the idea of sequential therapy. In the study, patients who pathologically responded following their chemotherapy were offered surveillance. Rather than remove their bladder immediately following chemo, it was only removed if doctors detected recurrence.

Our study followed a group of patients over the span of 10 years. We found one portion of patients did extremely well. They had no recurrences, they kept their bladders intact and had 100 percent cancer-specific survival.

Are there any theories of other markers that could be utilized in this space besides pathological ones?

What problems are associated with radical cystecomies?

What are the next steps of this research?

What improvements can be made to the treatment of bladder cancer, in general?

However, there was another group of patients who recurred and did not fare as well. Our original hypothesis that pathological response could be a marker for us to approach sequential therapy and potentially avoid radial cystectomy in these patients demonstrated there was a group we could do this. Unfortunately, it’s not a strong enough or clear enough marker at this point. Until we get there, the standard of care needs to be neoadjuvant chemotherapy with radical cystectomy.This study is a glimpse to how we should treat muscle-invasive bladder cancer down the road. Pathologic response is a good marker but it’s not good enough. I think there’s a lot of potential for other biomarkers used in conjunction with clinical markers to identify this group of patients.It’s a large surgery that’s associated with a fair amount of morbidity. In addition, a lot of these patients are older and more frail. They’ve already been through a fair amount of treatment due to the neoadjuvant chemotherapy and don’t necessarily recover from surgery well. It’s arguably one of the highest morbidity surgeries we perform as urologists. We are continuing to look for better biomarkers — whether it’s tissue markers, urine markers or something else – and a better understanding of the clinical markers that will predict and identify this group of patients.I think there’s a lot of work to be done with regard to bladder cancer. When you look at the quality of care we deliver, there’s lots of improvements we can move towards in reducing the morbidity of radical cystectomy. A lot of practices in this field have been demonstrated to reduce progression, reduce recurrence and improve patient survival that have not been implemented on a broader scale. One of our goals is to identify those practices and work to translate them across the board so that we can use the knowledge we’ve gained to improve care.

What can be done to ensure patients receive individualized care?

What advances have been successful that you think made a difference for this research?

There’s also a need to identify the patients who respond to neoadjuvant chemotherapy. Probably only 40 percent of patients will have a pathologic response. One of the key goals is to get more patients into that group because we know they do so much better without the radical cystectomy. There’s a large role for individualizing care, personalizing the care based on the patient and their disease. We still have a tendency to treat all patients the same. In the future, we shouldn’t.There are clearly many subgroups and all patients don’t behave the same. We need to identify those individual subgroups and clearly identify them beforehand so we can direct therapy appropriately, whether that’s getting individual targeted therapy or finding other therapies.We’ve made a lot of progress in understanding this disease and identifying practices that will improve survival for these patients. We’ve introduced neoadjuvant chemotherapy in muscle-invasive bladder cancer, where a majority of the mortality is coming from. We have many practices that reduce the progression of a non-muscle-invasive disease to a more advanced disease. Despite all the advances in the practices, they haven’t translated to real improvements in survival. We know the practices are there, though they can be better, yet we haven’t seen an overall change.

We need to improve and translate these practices better into treatments. As a whole, we know they improve that population survival, but we probably have to overtreat some patients to benefit the overall cohort. I think that’s where we fall short.