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The University of Florida College of Medicine is accredited by the Accreditation Council for Continuing Medical Education, ACCME to provide continuing medical education for physicians. The University of Florida College of Medicine designates this enduring material for a maximum of .25 AMA PRA category 1 credit. Physicians should claim only the credit commensurate with the extent of their participation in this activity.

Melanie Cole (Host):  Welcome. I’m Melanie Cole. And today we’re discussing the multimodal approach for treating bladder cancer. We will recount the natural history of bladder cancer and the most common path experienced by patients. We’ll explain the treatment options available to patients with muscle invasive bladder cancer, when each are appropriate and what approaches clinicals are attempting to bring in and we’re going to describe the experience of patients after cystectomy or bladder preservation and the cancer-free and overall survival of patients in these populations.

In this panel discussion today we have Dr. Kathryn Hitchcock. She’s an Assistant Professor in the Department of Radiation Oncology at the University of Florida. And Dr. Brian Ramnaraign. He’s an Assistant Professor of Medicine in the Division of Hematology and Oncology at the University of Florida and Dr. Paul Crispen. He’s an Associate Professor of Urologic Surgical Oncology at the University of Florida and they all practice at UF Health Shands Hospital in Gainesville.

Dr.  Ramnaraign, I’d like to start with you. Please tell us about the natural history of bladder cancer. What’s the disease incidence and burden?

Brian Ramnaraign, MD (Guest):  So, thanks for the question Melanie. Bladder cancer is actually one of the more common cancers of the genitourinary tract. It’s commonly seen in older men with a history of smoking. But it can happen really, in anyone of any age. Usually the patients present with blood in the urine and it’s usually a painless hematuria as we call it. And when patients present with these symptoms; it can be really multiple causes including having a kidney stone or even having a urinary tract infection. But usually at this time they would come and present to their primary care doctor or urologist who would do further testing including maybe a CAT scan or cystoscopy which Dr. Crispen I am sure will go into a little more detail. And at that time, we may see a tumor in the bladder which we may biopsy and which should return back as positive for cancer. And then from there, of course, further workup.

Host:  Dr. Hitchcock, most people consider bladder cancer to be treated only by urologists but today, I’m joined by the three of you, different areas of providers. How important is this multidisciplinary care model for this type of cancer and specifically for patients with muscle invasive disease? How does the emphasis on a multidisciplinary approach change the patient’s treatment options and therapy received?

Kathryn Hitchcock, MD, PhD (Guest):  I’m so glad you asked about that. That is something that’s changing pretty rapidly and even during my career, looks completely different than it did at the beginning. As late at the 1990s, my specialty radiation oncology didn’t come into bladder cancer treatment very much except in very advanced stages where it was used for palliation. These days, there’s a much greater emphasis on the trimodal approach to bladder cancer and for many patients, we are able to spare their bladder, keep it as a functioning organ and the way to do that is by treating it with radiation therapy as well as chemotherapy in patients who in an earlier era would have had their bladder surgically removed.

Host:   Well Dr. Hitchcock, sticking with you, tell us about your role in bladder cancer care. As you are a radiation oncologist, tell us what you are doing specifically.

Dr. Hitchcock:  So, for patients who are appropriate to keep their bladders, who have muscle invasive bladder cancer; I work closely with a doctor like Dr. Ramnaraign in medical oncology to give concurrent chemotherapy and radiotherapy to the bladder and to the lymph nodes of the pelvis.

Host:  Dr. Crispen, let’s talk about clinical presentation and diagnostic criteria as well. What are some valuable prognostic tools to aid in early diagnosis? Tell us how important is accurate diagnosis, staging and grading.

Paul Crispen, MD (Guest):  It’s extremely important. That’s an excellent point to bring up. Without accurate staging and grading in these patients, we will not be able to offer them the appropriate therapy or even all of the therapies offered within the appropriate stage after it’s identified. As you also commented on the diagnosis, one important point that Dr. Ramnaraign brought up is when patients are evaluated for say blood in the urine or hematuria; unfortunately, we will see a lot of women presenting with more advanced stage because their hematuria is credited to a urinary tract infection as opposed to having a cystoscopy done to make the diagnosis of bladder cancer.

Once we have a patient where we highly suspect bladder cancer; we perform a cystoscopy, look in the bladder and if we see a tumor, we will then remove it with the scope. That scope procedure gives us very valuable information about a patient’s stage but also, they’re candidacy for treatment, more importantly as with this discussion, the potential treatment with radiation therapy and chemotherapy as Dr. Hitchcock and Dr. Ramnaraign are discussing. One important part about this resection, is it needs to be complete. We want to remove all the visible tumor within the bladder. We know that that will increase the chance of a patient having a successful radiation and chemotherapy treatment.

In fact, that’s so critical that once we identify these patients with Dr. Ramnaraign and Dr. Hitchcock at UF Health Shands Hospital; we always take these patients back for a repeat resection and resect more tissue to do everything we can to make sure the bladder is as clean as possible for the radiation therapy. In addition to that, we will often put markers in the bladder to help Dr. Hitchcock focus additional radiation to the spot where we removed the tumor. And so this initial diagnostic step gives us valuable information for patient treatment selection and as you alluded to, even prognosis. As we know that there’s patients that we’ll find specific pathologic features on their tumor that won’t make them good candidates for trimodal therapy.

Host:  Well along those lines then, as he’s talking about candidates for trimodal therapy, Dr. Ramnaraign, how does careful patient selection and extensive counseling, how are they paramount to successful intervention? Tell us a little bit about patient selection criteria.

Dr. Ramnaraign:  So, that’s a really great question Melanie. The most important thing is that whenever we have one of these new patients, we always have a multidisciplinary discussion with our colleagues in all these fields, Dr. Hitchcock in radiation oncology and Dr. Crispen in Urology to determine whether or not a patient is a good candidate for bladder preservation or whether or not they have to undergo a cystectomy and have the bladder removed. There are a lot of factors that might influence one decision over the other and that would include the size of the tumor, the location of their tumor, if there’s any obstruction and hydronephrosis which is a swelling of the kidney related to the tumor. So, there’s multiple reasons why a patient might chose – why we may choose one option over the other.

Dr. Crispen:  And I would just like to add another point here, is that despite with these known selection features as Dr. Ramnaraign is pointing out; unfortunately, very few patients nationally are offered this type of therapy. And if we look at large data series, less than five percent of patients are being offered this bladder preservation approach with the chemotherapy and the radiation therapy. And I think one of the reasons that is is patients are not being evaluated by doctors like Dr. Ramnaraign and Dr. Hitchcock upfront. They are only seeing those specialists following their bladder removal surgery which at that time, it’s too late.

Dr. Hitchcock:  I’d like to also add that part of the selection of patients is related to their age. Many patients who are diagnosed with bladder cancer are senior citizens. They may have some other health issues going on that may not make them the best candidates for one therapy versus another and although before I saw it myself, I might not have predicted it; radiation therapy even at the same time as chemotherapy is surprisingly gentle, even fairly elderly patients who maybe aren’t at their best performance still get through the treatment pretty well. They don’t have a lot of pain. It doesn’t really affect their quality of life very much and so it can be a really good treatment that keeps them from starting down a bad path health wise.

Host:  Well then Dr. Crispen, explain bladder preservation for nonmetastatic muscle invasive bladder cancer and tell us a little bit about some of the current population outcomes and ongoing studies for these patients.

Dr. Crispen:  So, when we look at all choices of bladder preservation therapy; we have multiple modalities to choose from. You could look at a partial cystectomy or partial bladder removal surgery, a maximal endoscopic resection, chemotherapy alone or radiation therapy alone. However, the one bladder preservation therapy that works the best, that has the best data and that is our modality of choice at UF Health Shands Hospital is trimodality therapy which includes maximal endoscopic resection by a urologist, and then combined chemotherapy and radiation therapy with doctors like Dr. Ramnaraign and Dr. Hitchcock. With a carefully selected patient, and appropriate treatment; we see excellent outcomes here at our center. As with and is also documented at other centers which – and these outcomes approach those seen with bladder removal surgery. And that’s again in appropriately selected patients.

So, when we have a combined approach, we have multiple specialist involved; we can get the same results and the same survival as we do with bladder removal surgery. And in terms of percentages; what we’re looking at percentages in the 60 to 80% overall and cancer-free survival at five years in these patients.

Host:  That’s fascinating. Dr. Ramnaraign, for patients that are undergoing cystectomy as Dr. Crispen was discussing, and you’re talking about preferred regimens for neoadjuvant or adjuvant chemotherapy in balder cancer; have there been trials demonstrating that neoadjuvant chemotherapy before removal of bladder does improve patient outcome? Is that something that’s going on right now?

Dr. Ramnaraign:  So, we’ve studied this question in the past and it has been shown that neoadjuvant chemotherapy before cystectomy does improve outcomes and does improve overall survival. So, it is the standard of care now for us to prescribe neoadjuvant chemotherapy before cystectomy. And with regards to neoadjuvant chemotherapy; there are two choices that we have. One is a combination called MVAC which is four treatments and then there is a treatment called gemcitabine with some cisplatin. And here at UF Health Cancer Center, we prefer to give gemcitabine and cisplatin because it’s better tolerated than the MVAC treatment.

Dr. Crispen:  I would also just like to add to Dr. Ramnaraign’s points that despite this overwhelming evidence that the neoadjuvant chemotherapy prior to bladder removal surgery is out there. It’s been out there for over 13 years now. Only about 30 to 40% of appropriate patients nationwide receive that type of therapy. And that can be for a number of reasons, but I suspect it may just be from patients not being offered their treatment and being evaluated in multidisciplinary care clinics as we have here. in fact, when we look at our rates of neoadjuvant chemotherapy use at UF Health Shands Hospital; our rates of neoadjuvant chemotherapy per use in select patients is 60 to 80% depending upon which year we look at.

Host:  That is so interesting. Dr. Hitchcock, give us an example as we’re talking about all of this and putting it together to this multimodal therapy; give us an example of work you’ve done together.

Dr. Hitchcock:  The most important work that we’ve done together is what Crispen described just a moment ago and that is working toward true trimodality therapy and even in cases where that’s not appropriate, true trimodality assessment of the patient before any major steps in their treatment are done, that’s an ongoing process. At UF Health Shands Hospital is a big medical center and it takes getting a lot of people on board into a system like that. But we’re meeting with a lot of success here and I think that other facilities, other practitioners could get in touch with us if they’d like to hear some tips about how to make that work.

Host:  Well I think that is one of the most important points of a podcast like this, is for other providers to be able to see this multimodal approach that you are doing there at UF Health Shands Hospital. Dr. Crispen, how do you envision your research translating to patient care? As we start to wrap this up, what would you like other providers to know about the exciting technology and changes and advances in bladder cancer and bladder preservation?

Dr. Crispen:  Well, we have a special interest in bladder preservation therapy at UF Health Shands Hospital. And that involves all of our cancer providers, chemotherapy, radiation therapy and surgical therapy. And with this, we are trying to have every possible clinical trial available to our patients to try to increase the number of patients who can undergo bladder preservation therapy and improve the success of patients who are undergoing select types of bladder preservation therapy.

I can give you two examples of this. We’ll start with the one with trying to improve on our success of trimodal therapy is one particular trial where patients will under go the standard trimodality therapy as we offer all patients who are appropriate but then offer them additional therapy after they’ve completed their radiation to further decrease the chance of the cancer coming back.

Another example is in patients who may be going down the path for bladder removal surgery is that we give them chemotherapy with Dr. Ramnaraign and his partners in medical oncology and then evaluate those patients for specific mutations within their tumor. And in patients with select tumors, we’ll then evaluate for a complete treatment response and if they would have a complete treatment response, based upon their chemotherapy alone; we would follow them closely and avoid bladder removal surgery all together in those patients.

And so, those are just two examples of our current trials and we’ll evaluate other trials in the future to make sure we’re doing everything we can to avoid the need to remove bladders in these patients.

Host:  Dr. Ramnaraign, do you have some final thoughts on bladder cancer and the multimodal approach that you are doing there at UF Health Shands Hospital and what you’d like other providers to know about referral.

Dr. Ramnaraign:  So, I think the most important part about bladder cancer care is that there really should be a multidisciplinary approach towards managing these patients. I think it’s really important for patients to see a urologist like Dr. Crispen, a radiation oncologist like Dr. Hitchcock and a medical oncologist such as myself in order to make sure that they are getting the appropriate care and that they are being evaluated by all the physicians who may or may not play a role in their care in the future. And here at UF Health Shands Hospital, we are planning to start a multidisciplinary clinic where patients can come in and in one day see all three of us as opposed to having three separate clinic appointments. So, the most important thing is that it’s a teamwork and it takes a team to manage a patient with bladder cancer or any kind of bladder cancer.

Host:  Well absolutely it does. And Dr. Hitchcock, last word to you. What would you like other providers to know about this multidisciplinary care and how important it is for their patients that they are referring that you have this ability to work together and that you are doing fascinating clinical trials and really advancing the field of bladder cancer.

Dr. Hitchcock:  Well I guess when I think about the big picture here, I think about my grandparents’ generation that included people who went from driving horse drawn carriages to seeing people in outer space. We are experiencing exactly that kind of surgeon technology in the medical world right now. And it would be a real shame for patients not to have access to the best that our modern technology can offer. The best way for that to happen as we’ve said, is for all of the different physicians on the team to be able to contribute and make their recommendations. And so, I would just encourage doctors in other places who are thinking about referring patients to really get in touch with the people they are referring to if they want to refer their patients for multimodality care, make sure that they are sending them to a facility that practices treatment in this way for bladder cancer.

Host:  Thank you so much doctors, for joining us today, sharing your incredible expertise and what an exciting time for you to be studying bladder cancer and bladder preservation in this multimodal approach. Thank you again for joining us. This concludes today’s episode of UF Health MedEd Cast with UF Health Shands Hospital. To learn more about cancer clinical trials available at the UF Health Cancer Center, please visit www.ufhealth.org/navigator and to learn more about this and other healthcare topics at UF Health Shands Hospital, please visit www.ufhealth.org/medmatters to get connected with one of our providers. Please remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. For more health tips and updates please follow us on your social channels. Until next time, I’m Melanie Cole.