An Unusual Case of Urothelial Carcinoma

Follow Petros Grivas, MD, PhD, professor in the Clinical Research Division at the Fred Hutchinson Cancer Center and director of the Genitourinary Cancers Program at the University of Washington, as he conducts a Morning Rounds with his treating team: Emily S. Weg, MD; Lisa Adams, PA-C; and Nerina T. McDonald, PA-C.

Chart review

Petros Grivas, MD

The discussion centers on the case of an 80-year-old man with urothelial carcinoma, whose presentation is unusual for patients with this disease. The team also reviews how practices differ in community care settings and how critical shortages have impacted treatment.

Emily S. Weg, MD

Grivas: [Looking at the Chart Review], this is not the most common scenario of presentation with bladder cancer. Most patients [with bladder cancer] come to us through urology; hematuria and other urinary tract symptoms are the main entrance points for patients. How often do you get calls from the emergency department for newly diagnosed, newly presented patients?

Weg: It’s unusual that the emergency department would call the radiation oncologist, but a lot of this patient’s presentation is typical. About 75% of patients with bladder cancer present with hematuria, and about 25% present with lower urinary tract symptoms such as frequency, urgency, discomfort, and voiding. The suprapubic pain and the dramatic nature of this presentation are a little unusual. Radiation oncology is usually roped into the picture once there’s already a proven tissue diagnosis.

Lisa Adams, PA-C

Grivas: Many patients may start in a community practice that might be closer to home for them. [As such], the patients we see in the tertiary academic center may be a little filtered. How do patients typically present at your practice?

Adams: At UCHealth in southern Colorado, we serve a larger rural population [for whom] access to primary care screening and early referrals to specialists [are more limited]. We do see this [type of] presentation [more often]; we have more patients diagnosed in the advanced
setting and more patients coming from the emergency department [ED] rather than the traditional routes.

Grivas: What are some of the practices at your institution regarding
ancillary services?

Adams: It takes a village to take care of cancers of any tissue type, and bladder cancer in particular. We always try to connect patients with newly diagnosed advanced bladder cancer to our genitourinary nurse navigator. Some patients benefit from our financial counselor services because there’s a financial toxicity that can result from treatment. Then there’s the social work [department]. We have a great oncology rehabilitation program to help patients maintain strength and stamina, or improve from their starting point, during their cancer journey.

Grivas: How do you deal with the gray areas of cisplatin eligibility at
your practice?

Adams: There’s a discussion of the pros and cons [of the treatment] with the patient and maybe consideration of other factors. Sometimes, we have patients who are very active with their hands—musicians, for example. Neuropathy
might be a larger concern for certain subsets of patients, and they may not be as willing to accept that risk with cisplatin.
When thinking about disease biology, we ask, “Is it affecting their current kidney function? Do we have a chance to improve that and recover the kidney function?” That can be an opportunity, especially in curative-intent settings where we may prefer to use cisplatin a little more aggressively to recover kidney function. There are a lot of nuances in each patient scenario.

Grivas: Absolutely. It’s always important to take patient preferences into account. The other challenge that has emerged recently, which I never expected, is a cisplatin and carboplatin shortage. I was shocked to be called to a meeting a few weeks ago with a chief medical officer and other clinical directors, and we said, “We’re not getting enough carboplatin/cisplatin for our patients.” Did this shortage impact your practice?

Adams: We did experience a carboplatin shortage for several weeks in mid-May, which led to some difficult decisions. We decided to reserve our available carboplatin for patients being treated in curative-intent settings. For patients on palliative therapies, we either assessed whether cisplatin would be an appropriate short-term substitution, depending on the patient scenario, or whether we could change therapies or administer a deintensified therapy. The shortage led to some hard decisions. We had to work with our pharmacy staff and help decide how best to manage our resources.

Grivas: What would you say is your main take-home message?

Adams: We’re very fortunate to be plugged into our sister academic campus at University of Colorado Anschutz Medical Campus. When we have these complex cases of advanced bladder cancer, we can refer to our subspecialists in the academic setting and learn from their multidisciplinary review of the cases. They will often refer back to us for management of their care [practices] locally after they’ve given those opinions. A nice flow of communication is huge. Even when we see more rural patients, inviting patients’ local
physicians to join our tumor boards virtually can be a great [benefit].

Nerina T. McDonald, PA-C

Grivas: When meeting these patients at your practice, what are their most common symptoms?

McDonald: Patients often present with urinary obstruction, irritated voiding, and pain. If they’re in a metastatic setting, I’ve seen a handful with bone pain due to bone metastases. Sometimes we see constitutional symptoms, such as fatigue, weight loss, anorexia, failure to thrive, etc.

Grivas: What kind of testing might we do for patients such as this one, assuming a cystoscopy and transurethral resection of bladder tumor
were performed?

McDonald: The National Comprehensive Cancer Network guidelines recommend germline testing and referrals to a genetic counselor, especially if patients present at a younger age or have a family history of colon or endometrial malignancies. You’re assessing for Lynch syndrome, DNA mismatch repair–
deficiency mutations, and other hereditary conditions. In terms of imaging, if there’s evidence of muscle-invasive disease, we would get a complete staging, including CT scans of the chest, abdomen, and pelvis, to check for other [disease] sites.

Grivas: What kind of supportive care environment do we have at our institution?

McDonald: I work with our [supportive care teams] very frequently. I let patients know when they come in that everyone’s journey through treatment is going to look different, and some patients will encounter certain toxicities more than others. I typically use our integrative medicine service. If patients have issues with neuropathy, there’s the option for acupuncture through that service. We have a great palliative care team at Fred Hutchinson, so they help with symptom management, ranging from constipation management to [management of] diarrhea, nausea, and emesis. Those are some of the ancillary services that I’ve found are helpful for patients on active therapy. Even for patients on a treatment break, those are good services to have available.

Grivas:With any systemic therapy, we emphasize the importance of education about adverse effects [AEs]. How do we handle this education? How would you inform the patient about the logistics of systemic therapy?

McDonald: Typically, the medical oncologist or I will see the patient the day they’re initiating treatment, and we’ll lay out all the expected toxicities. I usually counsel patients that the most important thing is to be aware of their own body. If anything feels off, or if they experience something new, [I advise them to] call the clinical team, and we can triage it from there, optimizing management of whatever comes up. We’ll also go over the logistics of the schedule: [We tell patients] when they can expect to come in for their next dose, for labs and monitoring, and for restaging scans. They’ll also meet with a clinical nurse coordinator for formal chemotherapy education, in which they’re counseled on AEs and safety—how to manage bodily fluids while on chemotherapy. They’re also provided with all relevant contact information. Should they have an issue over the weekend or at night, [we tell them] who to call.

Grivas: Do you want to highlight any major take-home points?

McDonald: A lot of this is a credit to you because you’ve done so much outreach to the community setting. You’re educating other providers about the clinical trials available at our institution so that if a patient seems eligible, or experiences progression on standard-of-care regimens, their community oncologists know where to contact us and how to get patients enrolled in a trial that could work well for them.

Grivas: Thank you, that’s kind of you. It’s definitely [important to have] a dialogue back and forth with colleagues in the community. It’s fantastic to partner with them.

Grivas' Take on Treatment Options in Bladder Cancer

Q: Are there any treatment options on the horizon that may impact the standard of care in bladder cancer?

Grivas: There’s so much going on in the field of advanced urothelial cancer—so many interesting clinical trials with compounds, with different mechanisms of action, and potential combinations, as well as promising biomarkers. Recently, we’ve seen some data with anti–HER-2 antibody-drug conjugates [ADCs]. This is a very promising modality in this disease. There are data from a phase 1/2 trial [NCT04879329] with disitamab vedotin [RC48], an ADC targeting HER2, as well as fam-trastuzumab
deruxtecan-nxki [Enhertu]. We’re also awaiting results from the phase 3
TROPiCS-04 trial [NCT04527991], which is evaluating sacituzumab govitecan-hziy [Trodelvy] as a single agent in patients with prior platinum-based chemotherapy
and immunotherapy.

In the frontline setting, there are a bunch of trials. The phase 3 EV-302 trial [NCT04223856] is evaluating enfortumab vedotin [Padcev] plus pembrolizumab [Keytruda] vs platinum-based chemotherapy. Other trials in the frontline setting, such as the phase 3 CheckMate901 [NCT03036098] and NILE [NCT03682068] trials, have not reported results yet. There are also several trials in the maintenance setting. These may change the future of bladder cancer treatment.

Q: What are some of the biggest takeaways from your discussion with your colleagues today?

Grivas: [Optimal treatment] starts with optimal communication among providers, medical oncologists, radiation oncologists, urologists, pathology radiologists, and other team members, including advanced practice providers, nurses, and pharmacists. It takes a team to optimally care for a patient and to manage their expectations, education, needs, and try to prolong survival. Best supportive care is very important.
It’s also critical to facilitate equal access to care. It’s important to encourage optimal communication between academic and community practices. It’s important to have a reasonable load in terms of providers and in that way optimize efficiency in clinics. Of course, we [also] try to optimize capacity in the infusion space. It’s important to customize and tailor [treatment] approaches based on both patient- and cancer-related factors.

We covered a lot about patients with locally advanced bladder cancer. [We discussed] the role of induction chemotherapy and the potential of consolidative approaches in patients with great responses, including radical surgery, chemoradiation, or maintenance immunotherapy. All those would be optimally administered in the context of a multidisciplinary tumor board or
multidisciplinary clinic.

We have several options that have transformed the way we treat this disease over the past 7 years. We have traditional cytotoxic chemotherapy and platinum-based chemotherapy. We have checkpoint inhibitors, we have ADCs, and we have erdafitinib [Balversa] as a targeted therapy for select patients in clinical trials. It’ll be great if we can integrate those agents and learn the optimal way to sequence them. The present is bright and the future is brighter, but we need to work together to enroll patients in clinical trials [for progress to continue].