麻豆传媒

Urothelial carcinoma (UC) is the most common cancer of the bladder and urinary tract, but little is known about the many rare subtypes of invasive UC and .

These aggressive histologies can make up all or part of a tumor and are often associated with , noted the authors of a review in the Jean Hoffman-Censits, MD, of Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, and colleagues focused on pure or predominant sarcomatoid urothelial cancer UC, squamous cell carcinoma (SCC), micropapillary UC, plasmacytoid UC, adenocarcinoma, and small cell carcinoma.

"Full understanding of the molecular characteristics, biology of these tumors, and response to modern UC therapies remain an unmet need," the team wrote. "The role of neoadjuvant and adjuvant chemotherapy has not been well characterized for most of these histologies, and prospective data are extremely limited. Participation in clinical trials is recommended in advanced disease."

In squamous cell carcinoma of the bladder, for instance, the second most common urinary tract tumor after UC, mortality is largely driven by local recurrence, and chemotherapy or surgery is recommended. On the other hand, small cell carcinoma of the bladder has histologic similarities with small cell lung cancer (SCLC). This has led to the extrapolation of treatment from those used in SCLC and UC, with neoadjuvant chemotherapy improving survival, the authors explained.

In the following interview, Hoffman-Censits, who is co-director of the Upper Tract Urothelial Cancer Multidisciplinary Clinic and co-leader of the Women's Bladder Cancer Program at the Greenberg Bladder Cancer Institute, discussed some of the management considerations in greater detail.

What do you consider the single most clinically challenging issue in patients with these nonconventional bladder cancer subtypes?

Hoffman-Censits: I think it's how to choose the right drug or drugs at the right time for each patient. Most modern studies allow some sub-majority percentage of differentiation, but most exclude pure subtypes and do not report on individual variant outcomes. This means that choosing the right treatment for those with subtypes is informed by little prospective data.

Furthermore, when trying to extrapolate from other, more common malignancies, it can be challenging to obtain insurance coverage for drugs expected to be effective. Though retrospective data and some small prospective studies have been published for each subtype, there tends to be even less guidance on second-line therapies and beyond for subtypes.

What is your main take-home message to physicians?

Hoffman-Censits: Whenever possible, these patients should be enrolled in clinical trials. With or without trial intent, early next-generation sequencing, IHC [immunohistochemistry], and other biomarker testing to identify druggable targets is vital, especially as new tumor-agnostic approvals have begun. For instance, 35-40% of micropapillary bladder cancers express HER2 and patients might be candidates for newly approved [HER2-directed antibody-drug conjugate] trastuzumab deruxtecan [Enhertu] or other HER2-targeted agents.

In your expert opinion, are these rare subtypes of invasive urothelial cancer generally underreported?

Hoffman-Censits: Yes, rare subtypes of bladder cancer are likely underreported. In an unrelated study, 2-3% of pathology reviews at a major cancer center led to a diagnostic change or alteration. While some patients might not be well enough or have resources to travel for an opinion, a can be a high-yield endeavor that might influence care for an individual patient and increase reporting of subtypes.

What can be done to increase clinical trial enrollment of patients with these nonconventional bladder cancer subtypes?

Hoffman-Censits: Patients with pure subtypes of bladder and upper tract cancers often have more aggressive presentation, worse outcomes, and different biology than those with conventional urothelial cancer. Thus, pure subtype tends to be an exclusion criteria for trials. Future trials should be designed with allowance for and reporting of individual subtypes in at least exploratory subgroups to generate data with novel therapies.

Read the review here.