Alicia Morgans: Hi, I'm so excited to be here with Dr. Arya Roy, and we are talking about the work that you presented at GU ASCO 2023. It was awarded a GU ASCO 2023 Merit Award, so congratulations, a really big, big achievement. I'd love to hear a little bit about the work you did in the NCDB looking at sarcomatoid variant bladder cancer.

Arya Roy: Sure. Thank you so much for inviting me. So the main project that I did from the NCDB database, the one which actually granted me the ASCO Merit Award, is a study which analyzed the impact of neoadjuvant chemotherapy in sarcomatoid variant of bladder cancer. And I would like to point out why I did this study because when I practice in my clinic with my attendings, sarcomatoid variant of bladder cancer is actually very rare. I have seen maybe one or two cases in the last two years. And usually, as the cancer is actually very rare, as the variant is very rare, we do not have a consensus about the management of this sarcomatoid variant. And the disease itself is very aggressive, so the patients usually die before we can do some treatments. So I wanted to see what are the outcomes of the sarcomatoid variant bladder cancer with respect to different treatments, let's say like neoadjuvant chemotherapy or adjuvant chemotherapy.

And I tried to do a single institutional study, but at that time, as the disease is actually very rare, we did not get good sample size. And also for doing the multi-institutional study there also happens the same problem, we will not get enough sample size. So I decided to do the NCDB data. We decided to obtain the data from the National Cancer Database, which is a big database which actually captures almost 70 percent of the newly diagnosed invasive cancers in the United States. So that's the reason why we chose the NCDB database for our study. So from that database we actually got a good sample size, and the total sample size of the sarcomatoid variant of the bladder cancer that we obtained from the NCDB database was around 570 patients, which is a good number for this rare variant of bladder cancer. And then we decided to study the impact of the neoadjuvant chemotherapy among these variants.

We divided the total group into two cohorts. One cohort was actually the total number of patients who received the neoadjuvant chemotherapy, and the other cohort was those who did not receive the neoadjuvant chemotherapy. When we analyzed the data, we observed that the group which actually received the neoadjuvant chemotherapy, they had more pathological down-staging when compared to the other group which did not receive the neoadjuvant chemotherapy. And the percentage was actually around 40 percent versus 6 percent which is a huge difference. And the next thing we wanted to assess the clinical outcomes of these two groups with respect to the neoadjuvant chemotherapy, and we found out that the group which received the neoadjuvant chemotherapy, they had significantly longer overall survival when compared to the group which did not receive the neoadjuvant chemotherapy. In the group which did not receive the neoadjuvant chemotherapy the median OS was around 20 months.

And the other group which received the neoadjuvant chemotherapy, the OS was actually double, like 40 months, which was good to know because we don't know usually what's the impact of neoadjuvant chemotherapy. And we usually, in this variant, we usually tend to do a radical cystectomy first and then we will do adjuvant chemotherapy based on the risk stratification. We tend to give adjuvant chemo for the patients who have higher risk. So it was good to know that when we give the neoadjuvant chemotherapy it actually improves the survival. And when we did the multivariate analysis, we found out that the receipt of the neoadjuvant chemotherapy as well as the pathological down-staging, both of them were actually independent predictors for survival.

So these were the main findings that we actually found from our study. There was also another interesting finding that we found out which was actually the racial disparity, because when we did analyze the sample we found out that African Americans, or a Black race, they had significantly poor survival when compared to the Caucasians. But the only thing is we did not know why they have because we cannot actually find out the reasons why they have this poor survival when compared to the Caucasians. But these were our main findings from the study.

Alicia Morgans: So important, and I think to your point about the concern that sarcomatoid variant is not going to respond to neoadjuvant chemotherapy, this suggests that there is not just a survival benefit, but there's actually a down-staging, which is so critical because these patients must be more fit if they're able to get neoadjuvant chemotherapy than no chemotherapy. So there is that confounder coming into play. But if you give it and you see this down-staging, which you saw, it suggests that for fit patients, we shouldn't rush right to surgery. We should really try to get them their neoadjuvant chemotherapy. And we also talked, I think, before you started recording, about how this is really a sarcomatoid predominant histology, and so that's really important too. We can see so many different percentages of histology variation in a patient's sampling, but when it's predominant we would expect that these are patients who are not necessarily going to respond to chemotherapy. So tell me, is this work impacting your practice? Is this impacting what you do on a day-to-day basis when you do see one of these rare patients?

Arya Roy: That's a great question. I would definitely say that yes, actually it will impact our clinical practice, because when we see a patient, when we see a sarcomatoid variant bladder cancer patient, as we do not have a consensus about the management we usually will be doubtful whether should I give this patient neoadjuvant chemotherapy or should I just go directly to radical cystectomy? And especially if it's like muscle invasive bladder cancer. And actually, from this study we found out that actually for the muscle invasive bladder cancer variant it's better when you give neoadjuvant chemotherapy because it's actually going to improve their survival. So I would say that this would definitely impact our practice because now we have a point that we found out that neoadjuvant chemotherapy would be better so if you practice this we can definitely improve the survival of the patients.

Even if we have a good sample size like 570 patients, this is a retrospective study so I would say that for confirming the findings, and also if you want to make changes in the guidelines, we would need more clinical trials involving these patients, especially the sarcomatoid variant, because it's always very hard when you have a very aggressive variant or when you have a very rare cancer, we do not get that much sample size so we won't be able to enroll a lot of patients into the clinical trials. But if there is a way that we can actually enroll more patients with sarcomatoid bladder, or if we can do a clinical trial for those patients, then we will be able to see what is the actual benefit with neoadjuvant chemotherapy, and then we can maybe develop that into our clinical practice or into our clinical guidelines, which would actually help these patients with the rare variants.

Alicia Morgans: Well, that is certainly true. And that sort of gets to something else that I wanted to talk to you about, so there are certain limitations to this trial, to any trial, and you mentioned of course retrospective and there's some data that we don't have. Can you tell me what are the limitations from your perspective?

Arya Roy: Sure, so even the database has some limitations. Like we said, it has certain strengths as well because it's actually one of the largest databases in the United States which captures about 70 percent of the invasive cancer, so we will get a good sample size of the patients. But sometimes it's based on the coding from the hospital, so sometimes we will have some missing data. So we may have to exclude those patients because we do not want any bias in our study. And one of the main limitations is actually the treatment regimens in the neoadjuvant chemotherapy because in the muscle invasive bladder cancer, we give either gemcitabine and cisplatin or dose-dense MVAC.

But when it comes to the databases, especially when it comes to the NCDB, we won't be able to find out the exact regimen that the patients received. So we won't be able to find out what is the clinical outcome of the patient who received the gem-cis or what's the clinical outcome of the patient who received dose-dense MVAC. So that's one of the main limitations that I observed. But I was thinking if we can do a clinical trial then it would be more valuable so that we can actually control for the treatments that the patients are also receiving.

Alicia Morgans: Absolutely, and a clinical trial would allow for randomization of patients too. So how did you account for the potential different either comorbidities, performance status issues, that patients who received chemotherapy may have, that are very different than patients who were not able to receive chemotherapy?

Arya Roy: Okay, that's an interesting question because when we found out the baseline characteristics, we found out that the patients who received the neoadjuvant chemotherapy, they were younger than the other group which did not receive it. But the other characters like race or their social economic status, both of them were almost equal in both these cohorts. So when we did the analysis, we actually adjusted for all the confounders that we could find from this study. For example, comorbidities, because we wanted to make sure that we are adjusting for this so that we can actually use this data. So we adjusted for age, we adjusted for gender of the patients, and we adjusted for comorbidities, insurance status, then also for some of the values for their socioeconomic status like their education, and the centers from which they are getting these treatments.

I feel like the centers would matter because in some places they'll get the treatments from comprehensive cancer centers and in some places they'll get the treatments from a community center. So we wanted to make sure that we are adjusting for all these factors so that there won't be any bias in our study.

Alicia Morgans: Wonderful. So what would your summary be or your message to listeners if they're trying to think about your work and really what to make of it?

Arya Roy: So when it comes to the rare variant of bladder cancer, let's say, even if it's like sarcomatoid bladder cancer, or even if it's small cell variant or squamous cell carcinoma, these are actually very rare. So when it comes to the clinical practice as these variants are actually very rare we do not have a specific consensus about the management, or we do not know how to treat these patients, or we don't do not know what will happen if these patients receive neoadjuvant chemotherapy or adjuvant chemotherapy. So from our study, I would say that we found out that neoadjuvant chemotherapy is actually beneficial in patients who have this sarcomatoid variant and especially in the muscle invasive space, muscle invasive bladder cancer space. So I would say that neoadjuvant chemotherapy is actually underutilized in most of these patients with a rare variant of bladder cancer.

So that's one of the important things that we need to consider. And also, we should know that when we give the neoadjuvant chemotherapy it will actually help us to downsize the tumor during the time of the radical cystectomy, which is also found to be one of the factors, one of the important factors, which is predicting the survival of the patients. So definitely we should keep in mind that for most of these rare variants neoadjuvant chemotherapy would be a good option for these patients, especially in a space where we do not have much treatment options.

Alicia Morgans: Well, that is very helpful. So thank you. So really, really important information on sarcomatoid variant. Certainly, as you said, lots of gray data there. In fact, I would say there's a paucity of general data there, not just gray data, so lots of confusion. And I do hope that this helps to guide us in terms of thinking that neoadjuvant chemotherapy may actually be really beneficial. And certainly we must keep in mind issues of diversity, equity, and inclusion as we're really trying to ensure the best for all of our patients. So thank you so much for this work and for the time that you took to talk to me about it today.

Arya Roy: Thank you so much for inviting me. It was a pleasure to be here. Thank you.