Sam S. Chang, MD, MBA

Sam, make a couple of comments about nonmetastatic muscle invasive muscle cancer. As urologists, the go-to is radical cystectomy. We’ll do selective bladder preservation with radiation and chemotherapy traditionally, but what is the urologist view on the immuno-oncology [I/O] agents in bladder preservation?

 As with almost every disease process that we treat—prostate cancer, renal carcinoma, bladder cancer—we need to go beyond just resection and removal. It took us a long time to get on the neoadjuvant chemotherapy train, and we’ve improved with that. But with trials that have shown a benefit to adjuvant therapy, the nivolumab following cystectomy in patients with or without chemotherapy beforehand, clearly, we’ve involved our oncology colleagues in not only a neoadjuvant but also an adjuvant setting. Importantly, there are trials that are open, looking at I/O therapies either by themselves or in combination with chemotherapy, that perhaps would give us benefit in addition to therapy afterward.

There are also combinations of such things as enfortumab [vedotin] and pembrolizumab that are being looking at neoadjuvantly. Then cystectomy and therapy afterward. Unquestionably, radical cystectomy as the single modality and curative—for certain patients that’s still the truth, but the majority of patients will benefit from this combined therapy. This will give me a chance to give a shout out to you, Lenny, because the folks at Thomas Jefferson [University] have laid out an algorithm and a process in terms of setting up a multidisciplinary clinic, which you guys have done for prostate cancer and bladder cancer. It’s served as a model for a lot of academic institutions.

Sam, thank you. That makes my day, so thanks for that comment. That comes from a center of excellence for GU [genitourinary] oncology, so thanks.

Videos

The role of adjuvant therapy in nonmetastatic muscle invasive bladder cancer, and an overview of promising novel therapies in the treatment pipeline.

Emerging Novel Therapies for Nonmetastatic Muscle Invasive Bladder Cancer

With that broad introduction what we’d like to do in the next couple of minutes is now get into first-line treatment of non-muscle invasive bladder cancer and non-metastatic muscle-invasive bladder cancer. Sam, we’re going to have you comment at first about the interaction between urologists and oncologists, following guidelines. We have guidelines from NCCN [National Comprehensive Cancer Network], AUA [American Urological Association], ASCO [American Society of Clinical Oncology], other organizations. How do you think guidelines play into the daily care of patients with bladder cancer?

I think they are becoming increasingly used by the urologists in terms of non-muscle invasive disease. Honestly, for invasive disease and for metastatic disease I think the guidelines put out by the NCCN are widely used or at least referred to by our oncology colleagues. Urologists probably aren’t as familiar with the NCCN guidelines but all of them are honestly pretty similar in terms of what they’re outlining and what their strategies are. In fact, the AUA guidelines are actually AUA, ASTRO [American Society for Radiation Oncology], SUO [Society of Urologic Oncology], ASCO guidelines all combined for invasive disease and I think they provide a good framework for urologists and are becoming increasingly used because the landscape is really changing, and there are many more options than there used to be even just a decade ago.

Yes. I think in our training programs I think we’re increasingly trying to follow guidelines and not sort of shooting from the hip so I do think these guidelines are becoming very, very important. I know our oncology colleagues here at the Sidney Kimmel Cancer Center are very regimented on following NCCN guidelines as you pointed out.

An overview of treatment guidelines available to support urologists and medical oncologists who manage patients with bladder cancer.

Current Treatment Guidelines for Bladder Cancer

I think Karim you make a good point. Traditionally, the urologists are not comfortable with these infusions. Certainly, we’re very comfortable with intravesical therapies but one of the things I think we have to keep in mind is that with immuno-oncology there’s a whole new panel of potential side effect profiles—pneumonitis and GI [gastrointestinal] issues and pituitary issues and things like that. I do think that we’re going to have to be very mindful for this as we go forward. To follow up on that theme a lot of these immunotherapies that we now have in advanced bladder cancer are systemically administered. I’d like Petros to talk about in his clinic, in his medical oncology work, who really does the infusions? Are they always supervised by the medical oncologist and given by the advanced practice provider? How is your daily infusion of immunotherapy in your practice?

 Thanks so much Len and great discussion so far. I appreciate the comments by you, Sam, and Karim. When it comes to systemic therapy infusions, I think the medical oncologist has a major role and our colleagues in urological oncology refer to patients to medical oncologists for any systemic therapy including chemotherapy, immunotherapy, targeted therapy, so on and so forth. One of the main reasons is we have this academic context here and we have additional clinics but in terms of operationalizing and managing the administration of systemic therapies and with the side effects, I think the team here recognized that the medical oncologist has the resources and treatment to, and starts to deal with management of side effects that may happen from systemic therapies.

In terms of your great question about the logistics and the operations of administration, there are many medical oncologists, people who may see the patient, meet, evaluate, assess, discuss all the options, risks, benefits, alternative options, rationale, the data. A decision is made with the patient in an informed and fair decision manner and the patient embarks on systemic therapy, then infusions can take place. In those subsequent infusions an advanced practice provider and nurse practitioner or a physician assistant can see the patient before each administration and evaluate the patient in terms of symptoms, history, physical exam, and laboratory findings and if they feel the patient needs systemic therapy they can go ahead.

When it comes for a scan review, a restating CT of the chest, abdomen, and pelvis, I think with IV [intravenous] contrast, if that’s possible, then the attending medical oncologist sees the patient to do the scan review. In between, there is a continuous communication, I would say, between the practice provider and the medical oncologist and the nursing. It’s a team approach, we have team huddles, and we discuss every patient every week. We can anticipate, predict what might be needed, and also react to any types of side effects. Sometimes patients may come in on [INAUDIBLE] in order to be evaluated for a possible side effect. The last point I will make is we have a close communication with our infusion room and clinic. Like every other cancer center, we try to create space and time so we’re extending the hours in the weekdays including weekends to provide more capacity in the infusion room. And, of course, discussion with the infusion room nurses have a very important role in the administration of systemic therapy.

 Sam, certainly in the community setting there’s a lot more infusion being done. I think in most academic medical centers, I think most of us sort of have an agreement with medical oncology that they do most of the infusions and we handle some other aspects. What do you think the trend is going to be with urologists and infusions, particularly in the large urology groups out in the community?

I think that’s an excellent question, Lenny. I think the large group practices are clinicians; they’re not just urologic surgeons. They provide care for patients. In terms of who is going to be giving the medications, I think in those large group practices, as long as individuals understand, gain the knowledge, gain the importance of careful evaluation, follow up recognition of possible symptoms, therapies for possible side effects associated with immunotherapy, I think there’s going to be a continued trend to include immunotherapy in its IV formulation. Perhaps in the future there will be subcutaneous formulations to provide the medications and treatment alternatives for these patients.

I think the large group practices also understand the importance of a relationship ongoing with medical oncologists, and to be honest, some of those large group practices, as you know, have incorporated oncologists themselves within the group practice to help care for these patients. I think there’ll be a trend towards more large urology practices to do systemic therapy, but I think it will be very limited in scope in terms of who will be actually doing it. Those advanced practice providers would be an essential part of that team as well.

Administration of systemic therapy and management of side effects in patients with bladder cancer.

Treating Bladder Cancer in Community Settings

I want to turn it over to Dr Sam Chang to talk about some of the aspects of how we’re diagnosing bladder cancer, the initial process from making the diagnosis—testing, imaging, biopsy—and how we interact with primary care doctors, urologists, and oncologists in this process. Again, Dr Chang has been very involved with guidelines on bladder cancer so he’ll be the perfect one to give us that background, Dr Chang.

 Thanks very much, Dr Gomella. It’s a real honor to be with such a learned panel. I know I’ll gain much more from this than I’ll be able to contribute. This initial evaluation and process of diagnosing bladder cancer is one, we think, it starts from the urologist but actually many times it starts with the primary care physicians. The AUA [American Urological Association] has actually just come up with updated guidelines regarding microscopic hematuria and its proper evaluation and diagnostic approach because we still are finding, I think, bladder cancers at a much later stage than we would like. The next stage of evaluating a patient is diagnose, usually with cystoscopy and biopsy, endoscopic resection (we call it by different names), transurethral resection, but that will give us an idea of not only the histopathologic characteristics but the stage and grade of the tumors that may be present.

Importantly, that will be essential in terms of trying to remove as much tumor that’s actually there. I think understanding everything that is accounted for is essential and Dr Chamie is going to go over kind of what that bladder cancer patient journey is like. I think not only importantly are the AUA guidelines in terms of microscopic hematuria, but as we’ll go through non-muscle invasive and invasive bladder cancer components, the AUA has recently updated their guidelines just last year to help kind of formulate an algorithm that can kind of pattern for our clinicians to help diagnose, treat, and survey our patients with bladder cancer. Dr Chamie?

 Thank you, Dr Chang. Thank you, Dr Gomella. This is obviously an honor here. Obviously, patients with bladder cancer it’s a significant burden, not only from the perspective of mortality, but one that’s associated with significant recurrences, financial toxicities, pain. Oftentimes, patients succumb to other diseases but in the meantime go through multiple endoscopic resections and treatments. Patients are oftentimes diagnosed with bladder cancer after an episode of gross hematuria or after lower urinary tract symptoms they’re referred to a urologist. We’ve actually examined the role of high-grade bladder cancer, non-muscle invasive bladder cancer and 70% of patients are actually initially diagnosed by community physicians.

These physicians usually do less than 12 transurethral resections a year, which counts to maybe 1 bladder tumor diagnosis per month. They’re often referred to the urologist. The urologist does the resection, and the initial treatments often take place in the community. It’s not until the tumors become more problematic, meaning that they start to recur more frequently or if currently with community physicians having less access to BCG [Bacillus Calmette-Guerin] or other agents, are they actually referred to other academic medical centers. When patients are usually diagnosed with bladder cancer, they tend to refer to urologists and then the referral to medical oncology tends to occur later on as the stage progresses or if they become more advanced. With regard to when patients are referred to medical oncology, Dr Chang when do you see that in your practice?

 Increasingly early. Number 1, the indications for starting systemic therapy has moved sooner and sooner in the disease process. It started with metastatic and more advanced disease but increasingly for our basic cancer patients they’ve become essential in terms of our evaluation of patients, not only prior to cystectomy but in a trimodal or multi-modality factor when we try to spare the bladder with invasive disease. But importantly, with non-muscle invasive disease as we get options now for those patients who don’t respond to BCG we call on our medical oncologist quite a lot. Not only for therapy—using immunotherapy—but to consider for trials that include immunotherapy and other IO [immuno-oncology] type agents.

When we’re talking about patients and their bladder cancer journey there’s obviously multiple phases. I mean we have phases where they initially get diagnosed and they’re undergoing ongoing treatment. And most of the time when we’re talking about non-muscle invasive bladder cancer, that’s usually managed by urologists because they have access to the cystoscopes and intravesical agents. Once patients complete therapy, once they’ve completed their BCG, most of the time, if we’re talking about non-muscle invasive bladder cancer again they’re usually just followed by just a urologist. But when the disease is out of control, obviously they get referred to medical oncology. That’s something that is going to be a tug of war in the future as urologists become maybe increasingly more comfortable giving some of these newer novel agents. Will they be referring to medical oncologists? Will they be doing it themselves? And obviously you have radiation oncologists that do their own cystoscopy so obviously there are ongoing shifts there.

The types of healthcare professionals who may play a role in evaluating and diagnosing bladder cancer.

Sam S. Chang, MD, MBA

Articles

Emerging Novel Therapies for Nonmetastatic Muscle Invasive Bladder Cancer

Current Treatment Guidelines for Bladder Cancer

Treating Bladder Cancer in Community Settings

Treatment Journey for a Patient With Bladder Cancer