Fed Ghali, MD, on clinical outcomes in plasmacytoid urothelial carcinoma

In this video, Fed Ghali, MD, highlights key findings from the study, “Evaluating Clinical Outcomes and the Role of Neoadjuvant Chemotherapy in Plasmacytoid Urothelial Carcinoma: Insights from a Combined National and Institutional Series,” which was presented at the Society of Urologic Oncology 25th Annual Meeting in Dallas, Texas. Ghali is an assistant professor of urology in the division of urologic oncology at the Yale School of Medicine and the Yale Cancer Center in New Haven, Connecticut.

Video Transcript:

We found a couple of key things that stand out. Most of these things add to what we anticipated ahead of time based on some of these other studies that I'd mentioned, the MD Anderson experience, which was recently reported, and other institutional series. The first thing to say is that this disease is very rare. In the National Cancer Database over the years that this has been collected, we found 123 individual cases reported across the country over several years. When we add our patients, that goes up to just under 150 patients. These are not large numbers, so we're still in the position of studying quite a rare disease.

Our data reiterated the fact that this is quite an aggressive disease. The median survival across the stages of bladder cancer, including both non-muscle invasive and more advanced disease, median survival was between 2 and 3 years, depending on the details of the cohort. In other words, these patients do face quite a challenge. It's an aggressive disease.

An additional thing that we identified—and this is has been reported, but we found this across a broad population—is that our staging of the disease, our understanding of the extent of disease, tends to underestimate the extent of disease quite a bit. One way you can look at this is by looking at the clinical T stage, for example, and the clinical nodal status. Meaning, how deep do we think the tumor goes in the bladder? Do we think that there's cancer in the lymph nodes? Then [you look at] how that changes after the patient undergoes a radical cystectomy, for example, where we maybe have the closest thing to a true standard when a pathologist gets to look at the tissue under the microscope. What you see is there's a large discrepancy. For example, around 8% or 9% of patients are thought to have cancer in their lymph nodes prior to surgery. When patients with plasmacytoid cancer undergo radical cystectomy and actually have their lymph nodes evaluated under the microscope, that number goes up to 25% to 30% depending on the cohort. What that suggests is that our clinical understanding of the extent of disease tends to underplay how extensive the disease actually is. Those of us who take care of patients with plasmacytoid urothelial cancer know this implicitly. I don't think anyone will be shocked by this, but I think it's helpful to have specific numbers to evaluate it. So, that was reiterated through the data was how aggressive this cancer is.

Another key finding from our study was that the role of neoadjuvant chemotherapy, giving chemotherapy prior to surgery, is not well established in variant histologies, variant subtype bladder cancer, and specifically plasmacytoid. All of the evidence that supports early neoadjuvant chemotherapy, the really high-quality evidence from clinical trials, is in classic urothelial carcinoma. What we found is that there's a large discrepancy between how frequently neoadjuvant chemotherapy is used. In the prior reports that I mentioned, and including our experience at Yale, somewhere between 65% and 75% of patients with plasmacytoid get chemotherapy prior to surgery. We are quite active about using chemotherapy in academic centers. If you compare that to the National Cancer Database, so looking at the experience from a broader collection of hospitals including community practice and other academic centers, the use of neoadjuvant chemotherapy drops to around 21%. So, the community is using chemotherapy prior to surgery much less frequently than we do at academic centers is what our data suggests.

Then finally, I think the ultimate question is do we think chemotherapy helps? In other words, is there evidence to suggest that chemotherapy is improving survival for patients? What we find is that if you compare the patients who have received chemotherapy and those who did not receive neoadjuvant chemotherapy, we can detect a difference in how long those patients live. In other words, neoadjuvant chemotherapy was associated with a longer survival.

But when we ran some statistical tests to account for differences in which types of patients get chemo and which don’t, so when we do an analysis that accounts for the patient's age, the clinical T stage—in other words, how advanced the tumor is locally in the bladder—and the primary treatment modality, what [we found] is that the benefit from neoadjuvant chemotherapy washes away. It’s not maintained. It's hard for us, based on our evidence here, to say that neoadjuvant chemotherapy is causal in any way or is resulting in prolonged survival. It's at least possible, if not likely, that there's a different type of patient—maybe a younger, healthier patient, for example—that receives chemotherapy, and that's really what's associated with survival.

This transcript was AI generated and edited by human editors for clarity.