Alicia Morgans: Hi, I'm so excited to be at AUA 2022, where I have the opportunity to speak with Dr. Dan Barocas from Vanderbilt University. Thank you so much for being here.

Daniel Barocas: Thanks for inviting me.

Alicia Morgans: Always happy to talk to you.

Daniel Barocas: Likewise.

Alicia Morgans: Really excited to talk about the CEASAR Study that you've been working on for quite some time. Can you tell us what the CEASAR Study is?

Daniel Barocas: Sure. The CEASAR Study was started, it's a prospective cohort study of men with localized prostate cancer that was started in 2009. We actually began accruing patients in 2010 and '11 and we've been following them longitudinally now for 10 years. They're accrued through the [inaudible 00:00:43] registry sites. We have a great sort of population based cohort of almost 3000 men that we've been following as I said for 10 years.

Initially within that first five years, our primary outcomes were the quality of life outcomes. Now as we're getting out to the 10 year mark, we're looking also at the oncologic outcomes, cancer recurrence, metastatic disease, death from prostate cancer and overall survival. We've had a very cohesive team and it's been a really good experience. It was started by Dave Penson and I came in a little bit later and have carried it forward from there.

Alicia Morgans: You've definitely put your mark on it.

Daniel Barocas: Thanks.

Alicia Morgans: Which I appreciate. I know this was a lot of work and funded by RO1 funding. I think that's really special and important to mention as well.

Daniel Barocas: Right. It's had continuous funding since 2009 and we're looking ahead to enhancing that also because we're planning to get further funding to investigate for other oncologic outcomes that we can do with administrative data linkage.

Alicia Morgans: Wonderful. Well, I think that some of the things that are so important that have been reported in CEASAR include outcomes and quality of life information related to treatment of localized prostate cancer. Other things have also been studied within this registry because you and the team put together really extensive surveys that are administered on a regular basis. Can you tell us a little bit about the types of outcomes and some of those less considered outcomes that you look into?

Daniel Barocas: Sure. The main outcomes were urinary, sexual, and bowel function. Comparing different treatments, surgery, radiation, surveillance. Those studies three year and five year have been published and show the differential side effect profiles of each of those management strategies. Our hope is that patients and physicians use that information in counseling to decide on a treatment or management strategy. Those are the primary outcomes. We also have quite a bit of additional information on topics such as social support, treatment regret and satisfaction, financial toxicity. As you know now, in the 10 year survey we also have information about long term geriatric oncology domains like fatigue and cognitive function and so forth.

One of the interesting lines of investigation that we've done outside of the main outcomes is treatment regret. Chris Wallace, who is our fellow and is now at University of Toronto published an article in JAMA Oncology last year evaluating treatment regret among the different treatment pathways.

It's interesting. He found that somewhere between 10 and 15% of men express regret over which treatment they chose. As we dug into that, we found that it was really driven by the functional outcomes so people who had lousy, functional outcomes experienced more regret which is expected. Actually since one of the main drivers was sexual function outcomes and the sexual function outcomes tend to be worse with surgery, there was an association between surgery and regret. That was a pretty interesting finding and it got a lot of attention as it came through.

One of our other trainees, Dan Joyce, who's fantastic. He was our chief resident last year, now at the Mayo Clinic for fellowship has been studying the association between financial toxicity and regret. He actually found that regret seemed to be associated not with the direct treatment costs, but actually the indirect costs. For people who have low resources and need to take off work for appointments, hand off their other duties to other people, if they're a caregiver for example, those are the people who experience more regret. Those are some of the side studies that we've done that I think are quite revealing.

Alicia Morgans: I think that in the case of the financial toxicity, it's so interesting because we as a field generally look into and quantify the things that we can quantify easily.

Daniel Barocas: Right.

Alicia Morgans: These are the costs of treatment, the cost of complications, hospitalizations, those kinds of things. We don't, I think in a routine and systematic way capture the other costs, these indirect costs. What are your thoughts?

Daniel Barocas: It's an important aspect that is understudied and underappreciated. Our first study on financial toxicity was done by Ben Stone, one of our trainees. Showed that there is quite a significant proportion of men who report financial toxicity and this is just from what we consider routine treatments, routine tests that our guidelines say we should do. It's very important to consider that some of your patients, particularly if you're a tertiary care center are coming from long distances, having to take off a day or even two of work, having to stay in a hotel, having to send their kids to another caregiver or their parents, those sorts of things. It creates a big burden for patients and that burden is felt and it's differential. It's different for different people. I think being attuned to that is really important.

Alicia Morgans: Do you have the ability within CEASAR to look at financial toxicity and the potential association with oncologic outcomes?

Daniel Barocas: We may. As we're now in our 10 year follow up period, we have collected the quality of life outcomes, the surveys, and those are being analyzed now. We expect to publish those in this year. We are in the process of collecting the 10 year oncologic outcomes, but that's a more challenging data collection effort. As you know, we go into the charts and have to collect data that's sometimes 8 or 10 years old and we have trained abstracters pulling data out of that so we will have those oncologic outcomes and we will be able to associate the financial toxicity from the questionnaires with those outcomes. In fact, we've enhanced our questions about financial toxicity for this 10 year time point.

Alicia Morgans: That'll be so interesting though. To look and even to see if financial toxicity at the time of diagnosis is associated with financial toxicity long term. If there are some changes over time. Whether it associates with quality of life or outcomes because the physiologic effects of financial toxicity or any stress could have effects on comorbidities on cancer outcomes. It's just a really interesting interplay.

Daniel Barocas: Right. It's widely known and Angie Smith and others at UNC have done some work in this demonstrating an association between financial toxicity and adverse patient reported outcome. It is an important factor that's again, not considered frequently enough.

Alicia Morgans: Yeah, absolutely, but in CEASAR, you have the opportunity to look into it. Beyond that, what are some of the other future directions that you and the team are looking into?

Daniel Barocas: There are a few things. One of the things we're finding is that collecting those 10 year oncologic outcomes is challenging. There are some patients who are lost to follow up. One of our plans for next steps is to link the CEASAR data with Medicare data and our current fellow Basir Al-Hussain is leading that effort.

We are acquiring the Medicare data for our population as well as the general prostate cancer population. That'll give us the opportunity not just to study the oncologic outcomes, but also to study, for example, utilization of different treatments and so forth.

For example, we may be able to study in patients on active surveillance the frequency of repeat biopsies and MRIs and things like that. We may be able to study inpatients with recurrence or advanced disease. What types of treatments they got and whether they availed themselves of things like genomic testing and some of the novel therapeutics. That will be interesting from a disparities lens who gets what sort of treatment. We have pretty robust baseline socioeconomic data that we can associate with some of these utilization outcomes so that should be really interesting. Maybe 15 year outcomes. If our science officer finds that compelling enough to give us the next grant.

Alicia Morgans: Well, I hope that they do because I think the power of a cohort that you've put together in this way and have annotated as closely as you've been able to, recognizing the limitations is really a rare thing and a unique opportunity. I wish you and the team luck and I sincerely thank you for going through all of this and look forward to future papers.

Daniel Barocas: My pleasure. Thank you so much.

Alicia Morgans: Thank you.