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Ruchika Talwar: Hi, everyone. Welcome back to UroToday's Health Policy Center of Excellence. As you might know, we have been embarking on creating a resource for prostate cancer patients, caregivers, family members, and clinicians that focuses on helping prostate cancer patients navigate many of the complexities of the healthcare system, and that has spanned from the financial aspects of care to incorporating palliative care. And today we're going to talk a bit about the concept of time toxicity of prostate cancer treatment.

So I'm really excited to introduce our guest Dr. Daniel Sentana, who is a medical oncologist at Dana-Farber in Boston, affiliated with Harvard, who really is an expert in this space. And he's going to share his recent work to help us understand the idea of time toxicity, how we can support patients as clinicians through their prostate cancer treatments from this lens. So thank you, Dr. Sentana, for spending time chatting with us today. We really appreciate it.

Daniel Sentana Lledo: Absolutely. Well, thank you so much, Dr. Talwar, for having me here. This is a very exciting topic and very near and dear to my heart. This is some of the research I do to hopefully benefit patients with prostate cancer. So I would love to talk to you about what time toxicity is, why I think it's a very important and upcoming patient outcome that we're studying.

And so to start with, survivorship encompasses a long journey for patients, not just when they finish their treatment and are cancer-free, but really from the moment of diagnosis all the way to the end of life. And I think as clinicians and patients, many times they're accustomed to very common clinical outcomes or time-to-event endpoints in cancer. And these include things like disease-free survival, progression-free survival, overall survival, and they have different definitions, but they're essentially times since you either started treatment and the cancer came back, or you started treatment and you died from that cancer or something else. These are obviously very important endpoints and they're primarily used in clinical studies for determining the efficacy of our interventions and our treatments for patients.

However, at the same time, I think fortunately our patients with prostate cancer in particular nowadays get to live for a long time with their disease thanks to the excellent treatments and research that we're doing in this field. And so we have to shift outcomes a little bit into thinking what is the survivorship experience of our patients? And so in this regard, the idea of time toxicity has appeared to measure the amount of time that our patients spend in the healthcare system with physical contact and how this potentially is taking away the survival time that they're getting from their therapies. And so this is a wonderful graph from Arjun Gupta, who is one of the leaders in this movement. And essentially what he proposes is how can we best study this field?

I would say that this is relatively in its infancy, so there's only a few studies right now on this, but overall, the proposed metric that we have been using primarily is something called contact days or days with physical healthcare contact. And so what we're trying to determine is out of the time that a treatment may give you, so if this particular treatment buys you X amount of time, what amount of that time is truly time at home with your loved ones away from the healthcare setting, time that you are gaining from a cancer treatment in the whole sense?

And so in that sense here in this graph, for example, you have one option which would be to get chemotherapy versus another option would be to not get cancer treatment anymore. This is probably more applicable for people towards the end of life. And while getting chemotherapy in a study may have been shown to improve overall survival compared to not getting cancer treatment, if you get to the actual measuring of the days that patients are spending in each of these things, well actually you get much more time at home if you had not gotten any treatment than if you had gotten chemotherapy.

And obviously even patients that may not get cancer treatment can still require hospitalization and may require healthcare contact. It's not necessarily that those that do not get treatment, that's it. But obviously, once someone is receiving cancer treatment, then that involves clinic visits, assessing for lab work, imaging, other ancillary studies, and obviously dealing with the morbidity of our treatments.

And so the purpose of this research and the idea behind time toxicity is that we can better inform our patients and our clinicians about the expected course of our treatments. And that way when you're at a crossroads and trying to make a decision between different types of treatment, having this information is valuable for additionally considering, "Well, this treatment may prolong my life, but what is my life going to look like if I choose this path?"

As I said, the contact day is a very simplistic model where even if you just go for one hour for lab work, that's considered a whole day wasted. And that may not apply to everyone, but I think for many of our patients who come to tertiary care centers from outside the urban areas, that definitely is the case. But I foresee that we will be able to better measure the actual time spent with healthcare contact in the future. And some of the proposed ways that I have thought of, and others in this field have as well, are incorporating tracking technologies that are as simple as the ones that our patients have with their cell phones, with their wearable devices, but also sometimes in clinic, we have real-time technologies to do that.

And again, this graph just to show that even though a simple appointment may be considered, "Oh, you're just going to be coming once a week," that's most of the information our clinicians may be able to share with patients right now. The actual time burden can build up between waiting to see a provider, getting lab work, additional treatments, not to mention all the other things that can happen outside of that clinic visit.

We don't have a lot of data in this regard, but one of the more recent studies looking into the actual time measure that takes into these things shows us that really, even simple visits for lab work, for imaging, can take on average two hours, really. And if you add to that infusional treatments or even more increased healthcare utilization, then truly that takes up the whole time of your day. And really that whole day can be considered time toxic or wasted. And just to mention that in this study there were patients with GU malignancies, although it was not necessarily only focused on those patients, but you can tell on average, regardless of the malignancy that you have, this takes up time, and pursuing cancer therapy, as many of our patients know, is very time-consuming.

And this is further amplified by a recent, very interesting qualitative analysis where patients, without prompting them to bring up these topics, were asked between different treatments and what may make them choose one or the other and a good amount of patients—and these are just some examples from that paper—brought up the time burdens that play into their decision making. Not only how frequent visits are, but the length of the actual visits. And as our patients know, the amount of transportation parking that comes into it and how that really just ends up building up.

There's other impacts beyond just the time spent in the clinic. Other people feel that really receiving a particular treatment that really eats up into your life and it ties you down. You have a schedule you cannot get out of, and ultimately it has overall quality of life implications. And so some patients may choose different treatments based on other things outside from the survival time that that treatment may be able to confer. And so the focus of this research, and again, the focus of my work is to elucidate what is the quality of the time that we're gaining from a treatment rather than the quantity of the time.

And so if I had to summarize this, time toxicity is a growing field. I prefer to call it time spent with healthcare contact because truly time is not necessarily always toxic. It is important to come see your oncologist. It is important to get cancer care. And so in some situations, obviously in the curative intent setting that is worth the time commitment because you're aiming for a longer outcome. But I would say that for some patients, even receiving treatments down the line when they're near the end of life, despite the time commitment, it might still be important for them, "Well, if I can make it to this event or to spend more time with my family, then time spent with healthcare contact is not necessarily toxic." But this is what the field has been called.

As I said, I think tracking technology is going to make our measurements better, but for now we are mostly dealing with this contact day model. And I think our patients with prostate cancer and other genitourinary malignancies that fortunately now get to live longer, can really benefit from this knowledge. And so the purpose of my research and of my colleagues in looking at time toxicity is to give patients complementary information to make informed decisions about their care. I don't foresee that time toxicity will be the—and it would be naive to think that it would be the only decision point for patients between different treatments—but I think it's important to offer a realistic, objective measure of how much time they're going to be spending if they go on a particular treatment.

Unfortunately, there's not a lot of work in GU populations at this point. I am working on a couple of projects in this sense, and hopefully we would have some publications coming up that pertain to patients with advanced prostate cancer, but I would ask our patients, our clinicians, to just be on the lookout because this is a growing hot topic and it's going to come to you and it's going to be helpful for making decisions when you have to. And with that, I just want to thank UroToday for giving me the opportunity to talk about this very important topic. Thank you again.

Ruchika Talwar: Thank you so much. You covered so many important aspects of this concept. I loved the quotes that you showed because I think it really drives home the impact that time spent either getting to a clinician, waiting for a clinician, seeing a clinician, or other aspects of care delivery. It really underscores the impact that has on our patients that I think we don't always take into account. We're very focused on the time we have in the room with the patient.

And as time goes on, obviously we want to encourage any patients, caregivers who are listening to this to advocate for themselves when they are scheduling appointments or trying to undertake care coordination. But obviously the burden is not on the patient and it's something that the entire field needs to be more aware of.

So to that end, I'm curious, what advice do you have for clinicians who quite frankly are already incredibly busy and spending a lot of time ensuring that their patients get the best care possible? What are some simple tips that you have that we can coordinate into our workflows to try to take this into account and help minimize the burden that we may place regarding time toxicity?

Daniel Sentana Lledo: Absolutely. I think there are very simple things that are within our grasp as providers, and perhaps we just don't think about it. But as much as possible, especially for our patients that come from further away, to try to condense their care into the least amount of time that they have to come to our clinic. So many times, if you can schedule lab work that same day, if you can have the scans also earlier that day, as long as you tell your patients, "I may not have the results by the time of our visit, but this will save you in the long run, having to go a different day for our scans."

And I think as healthcare systems, just try to think of ways that we can minimize the time that our patients are spending in the clinic waiting for things. And unfortunately, many places have resources to do this, but I think those are some of the ways that the field is going to be moving forward in practical ways, let alone the clinical objective data of which treatment gives you more time at home than the other one. I think it'll be a matter of how we can decrease the burden of the time that patients are spending with healthcare contact in our day-to-day interactions in the clinic.

Ruchika Talwar: Yeah, I think those are all great tips. Shifting gears a little, now, thinking about incorporating time toxicity assessments in our investigations, I'm curious if you have any suggestions for researchers who are working on investigations in the prostate cancer space. How should we start incorporating this concept into our clinical trials, our clinical outcome studies, etc?

Daniel Sentana Lledo: Well, I think right now with this contact day model that I was mentioning, it is fairly straightforward to have a sense of what the time commitment is for our patients. And so as long as we have in our protocols and in our research data capturing and management, the ability to quantify the times that our patients are coming for certain lab work or infusion or receiving care within that study, then that will give you an objective measure of how much time they're spending with us. And if you subtract afterwards the survival time or the time until the cancer came back, that amount of time that they're spending in the study, then you get a very easy measure in that.

As I was saying, I think as this field gets more importance and more people start getting interested in it, we'll probably find better ways and more precise ways to derive these measurements. But that is definitely one of the easiest ones. And so far there's been a couple of papers looking retrospectively at clinical trials and obtaining that information, but I think we measure so much information in our clinical trials and so much data is collected, I foresee it would be so straightforward to just quantify the days that patients are coming in for something related to the study.

Ruchika Talwar: Yeah, yeah. Great suggestions there. Well, thank you so much again. This is such an important area of work and I really applaud you for leading the way looking at time toxicity of prostate cancer treatments. We really appreciate the time that you took to share your expertise.

Daniel Sentana Lledo: Absolutely. Well, thank you for having me again. And anyone that is interested is always welcome to contact me; I'm happy to provide more information and to help our patients out, which is ultimately the role of this research.

Ruchika Talwar: Couldn't agree more. And to our audience, thank you so much for joining us. We'll see you next time.