Expert Discusses Sequential Therapy Benefits for Patients With Muscle-Invasive Bladder Cancer

Though the current standard of care when treating muscle-invasive bladder cancer calls for neoadjuvant chemotherapy followed by radical cystectomy, the procedure is associated with a fair amount of morbidity and is not suggested lightly, according to Stanley Yap, MD.

Stanley Yap, MD

Though the current standard of care when treating muscle-invasive bladder cancer calls for neoadjuvant chemotherapy followed by radical cystectomy, the procedure is associated with a fair amount of morbidity and is not suggested lightly, according to Stanley Yap, MD.

As a way to potentially avoid radical cystectomy, Yap and his team recently studied the idea of sequential therapy in patients who achieved a pathological response following chemotherapy.

In an interview withTargeted Oncology, Yap, assistant professor of urologic oncology, UC Davis Comprehensive Cancer Center, discussed the findings of the study, as well as other potential markers that could be used in the space, and what lies ahead in muscle-invasive bladder cancer research.

TARGETED ONCOLOGY:What was the idea behind your study of sequential therapy in patients with muscle-invasive bladder cancer and what did you find?

Yap:

When you treat muscle-invasive bladder cancer, the standard of care currently is to give neoadjuvant chemotherapy followed by radical cystectomy, however, we know a couple things: One, radical cystectomy is associated with a fair amount of morbidity and certainly not something that we take lightly. Secondly, one of the strongest markers of success of these patients is pathologic response to the chemotherapy. Patients who are PT0 following chemotherapy have an 85% 5-year survival rate.

Taking both of those data we approach this idea of sequential therapy—patients who pathologically responded following chemotherapy, we offered them surveillance and a potential radical cystectomy down the road if there was recurrence—and looked at this group of patients that we had over the past 10 years. What we found is that there was a group of patients that did extremely well, they had no recurrences, kept their bladders intact, and had a 100% cancer-specific survival rate.

What we also found was that there was another group of patients that recurred and did not fare as well, so our original hypothesis that pathologic response could be a marker for us to approach sequential therapy and potentially avoid a radical cystectomy in these patients demonstrated that there was a group that we can do this, but unfortunately, it’s not a strong enough or clear enough marker at this point and until we get there, the standard of care needs to be neoadjuvant chemotherapy with radical cystectomy.

TARGETED ONCOLOGY:Are there any theories at this point of other markers that could be utilized in this space besides pathological response?

Yap:

I think that’s the future of this and I think this is a glimpse into how we should treat this down the road. Pathologic response is a good marker, but it’s not good enough. But I think there’s a lot of potential for other biomarkers used in conjunction with clinical markers to identify this group of patients and that’s really what we need to move to in the future.

TARGETED ONCOLOGY:What are some of the challenges with radical cystectomy?

Yap:

I think it’s a large surgery that we know is associated with a fair amount of morbidity. In addition, a lot of these patients are older, more frail, and in a setting of the standard neoadjuvant chemotherapy, they’ve been through a fair amount of treatment and don’t necessarily recover from surgery as well, so it’s arguably one of the highest morbidity surgeries we perform as urologists.

TARGETED ONCOLOGY:Are there any next steps in this research?

Yap:

We are continuing to look for better biomarkers whether it’s tissue markers, serum markers, or urine markers, and get a better understanding of the clinical markers that will predict and identify this group of patients. That’s where we’re headed now with our group.

TARGETED ONCOLOGY:Within muscle-invasive bladder cancer, are there other studies you’re interested in that you think are going to be changing going forward for urologists and oncologists?

Yap:

Sure, I think there’s a lot of work to be done in this space. I think when you look at, related to this, the quality of care that we deliver, there’s lots of improvements that we can move towards in terms of reducing the morbidity of this surgery. I think there are a lot of practices in this field that have demonstrated reduced progression, reduced recurrence, improved patient survival, but are not necessarily implemented on a broader scale. One of our goals is to identify those practices and really work to translate that across the board so we can use the knowledge we’ve gained to improve care across the spectrum.

There’s also a large role of identifying the patients that do respond to neoadjuvant chemotherapy, probably only about 40% of patients will have a pathologic response and one of the key goals is to get patients into that group because we know they do so much better. But we are lacking biomarkers as well to identify who will respond to chemotherapy and who won’t, so there’s a large role for personalizing care based on the patient and their disease, but we’re falling a bit short and perhaps we’re treating all patients the same when, in the future, we shouldn’t be.

TARGETED ONCOLOGY:Is that because of a lack of understanding of the different subgroups, or because there are not targets for each subgroup?

Yap:

I think both, there are clearly many subgroups and all patients don’t behave the same and it’s been the trick identifying those individual subgroups and clearly identifying them beforehand so we can direct therapy appropriately, whether that’s getting individual targeted therapies or finding other therapies to approach those patients.

TARGETED ONCOLOGY:What advances have been successful in the space that you think have really made a difference recently?

Yap:

I think we’ve made a lot of progress understanding this disease and identifying practices that will improve survival for these patients. We’ve introduced neoadjuvant chemotherapy, for example, in muscle-invasive bladder cancer which is where the majority of mortalities come from. We have many practices that have come about as far as non-muscle invasive disease to reduce the progression to more advanced disease.

The big concern in all of this is that despite all these advances, they haven’t translated into real improvements in survival and that’s a real issue. We know the practices are there, they can be better, but yet we haven’t seen an overall change.

TARGETED ONCOLOGY:Do you have any idea of why that is?

Yap:

I think some of it is that we need to translate these into practice better and I think we certainly need to improve these practices. As a whole we know that they improve that population’s survival but we probably have to over treat some patients to benefit the overall cohort, so I think that’s where we fall short.