Vedang Murthy: Absolute pleasure to be here, Neeraj. Thank you so much for doing this and I'm very happy to chat with you about my talk at the APCCC.
Neeraj Agarwal: Thank you. And first of all, congratulations. I've always enjoyed your talks and your wisdom, words of wisdom during the APCCC meeting. And again, it was not different this time. So, please tell us about the very interesting topic. Please tell us more about the very interesting topic about the societal factors, inequalities you are dealing with in your perspective, in your Indian perspective, and what we can learn from them.
Vedang Murthy: I was tasked with talking about the Indian perspectives for dealing with inequality due to societal reasons. And to start off and give you some context, my world, like many of you from around the world, has two realities. The proportions may vary. On one hand is the population who are urban or semi-urban, PSA tested, multiple options available, shared decision-making, like many of you see in the West, long-term follow-up is feasible. And this incidence in these patients is rapidly rising. On the other hand, we have this huge rural population who often present with symptoms. Their awareness is limited about the disease. In fact, most of the decisions are taken by the family and the physicians, and these different realities demand different decisions and different pathways.
And to answer some of these or quantify some of these issues, we conducted a APCCC South Asia late last year. We got together 51 experts very similar to the main meeting and asked the same questions and got some very interesting results that I'll put in perspective in the next few minutes.
How do we balance the evidence with the reality? We make four shifts in what we do. We get things right the first time, the first short strategy. We prefer simplicity over sophistication. We believe logistics is as important a variable as anything else as biology, and that shapes outcomes and prefer feasibility, what is doable over what is the most efficacious.
Let me show you some examples. We treat as if there is no second chance. And this may creep in, some overtreatment may creep in because of this. For example, our surgeons prefer to do extended pelvic lymph node dissection with prostatectomy more often than the main APCCC that is in the blue. And so as radiation, we treat the pelvic nodes much more in our part of the world.
We also act early. We don't wait because if we wait, we may never be able to treat these patients. As an example, you can see here, adjuvant radiotherapy is much more commonly used for all different risk factors, different lymph nodes. You can see here in the yellow, much more used in South Asia. So, is intensified salvage therapy. More ADT is used with salvage radiation because that is the only chance we get to treat.
I talked about simplicity. So, radiation can get very complicated with all the machines and the accessories that we use, and things can get sometimes overly complicated. And we propose a simple SBRT solution for prostate radiotherapy. And simplicity doesn't mean it is less effective. It can be safe, it can be effective, and very well scalable if we give attention detail to the things that are actually free and don't cost anything.
And how do we know it works? Well, this is a randomized trial that we have concluded, the five weeks of treatment versus five days of radiation called PRIME in high-risk prostate cancer. The details will be presented in a couple of weeks in Stockholm in ESTRO, but very happy to share that the one-year Grade 3 serious side effects are less than 1% using the simple SBRT and the GU and GI adverse events are quite comparable. So, it works if done properly. It doesn't have to get complicated.
We also prefer non-ambiguity. For example, we avoid strategies that depend on the perfect follow-up. Continuous ADT is much preferred over intermittent ADT. Patients and doctors prefer orchiectomy over lifelong injections.
Also, I told about logistics, which can be quite important. Now, when we ask the patients, what would they prefer? Would they prefer the five-week treatment or the five-day treatment? In our trial, although they don't have a choice because it is randomized, a whopping over 92% actually say they prefer the five-day treatment because simply the logistics is so much easier to finish their treatment, say in a large city like Mumbai.
Feasibility is an important thing for us over going for the best available treatment. You can see here, less abiraterone is used in patients with high-risk disease who are often PSMA-staged as compared to the global levels. We also adapt low-dose abiraterone to be used, more than half the people support it. Also being the diabetes capital of the world, we often substitute other ARPIs over abiraterone, and that comes quite easily to our oncologists. So, comorbidities also drive how we adapt treatment.
Finally, I think generating local evidence is probably the most important thing in terms of dealing with inequality, because I think the solutions have to come from here. They're not going to come from adopting the guidelines from the West. And I think that is how we can all address inequality, certainly in India. Thank you so much.
Neeraj Agarwal: That was a beautiful presentation. As you rightly said, we all have those patients. Proportions can be different in different countries. Within the country, different regions, within the same city, different zip codes can have those patients more or less. So, we all have to learn from each other. And what I saw in your presentation just now is I think what we all try to balance, we have different formulas, if you will, different approaches. But what I have really admired over the time, especially by what has been done by investigators in Tata Memorial, and many under your leadership, Vedang, is to come up with newer approaches to cater to underserved population. We saw the very nice paper on low-dose immunotherapy being as effective as normal dose or regular dose immunotherapy, cutting cost by thousands of dollars potentially. Imagine, we can apply that here, how much cost saving it will be, low-dose abiraterone versus regular dose abiraterone, low-dose radiation therapy versus regular dose radiation therapy.
What you saw was, what you showed was five days of radiation therapy, maybe we don't have the results yet, maybe as good as five weeks of radiation therapy. That can be maybe a game-changer down the line. So, taking a step back, in busy clinic, I know you all see hundreds of patients a week. Let me just talk about something personal. How do you find time to come up with this cutting-edge research?
Vedang Murthy: I used to wonder the same thing when I joined as faculty many years back. The ideas would not come, but once you are spending time in the clinic and thinking about how to solve problems, it takes some time, but the ideas start popping up. And once the ideas are there, I think one has to build an ecosystem slowly around yourself so that you can get those ideas into action and into a trial or into some analysis. So, it takes time. Many of my residents also wonder, how do you get so many ideas? I think it just comes with time.
Neeraj Agarwal: And the need for the patients. You see those patients, your patients, you are obviously very passionate about the needs of your patients. And I think when you see them with them, you realize you have to come up with this, as you said, a localized innovative solution to meet the demands of your patients. And I think that passion of yours may be the main driver. Am I correct?
Vedang Murthy: To some extent, yes.
Neeraj Agarwal: So, tell me, when you are talking about five weeks of radiation versus five days of radiation to your patients, there is no equipoise here. There's so much difference in the duration of therapy, how easy it is to randomize. And I think we can all learn from that.
Vedang Murthy: In fact, it has been surprisingly easy to randomize. In fact, it's been the opposite of what we thought will be there because we have specified in our informed consent form that the side effects may be higher because that is what we thought would be. Although that is not the case, we had put it in. And in spite of that, patients say, "Can I not have the five days? Do you really need to randomize me?" I said, "Look, yes, we have to do it. We cannot offer this outside the trial." And the difficulty has been they want the five-day treatment instead of the five weeks. Once they know that is on the table, they demand it, but unfortunately, they can't get it.
Neeraj Agarwal: So, the way I look at this, they may have a five-day option. If they go on the trial, there's a 50% chance of getting a five-day option. If they don't go on the trial, there is a 0% chance.
Vedang Murthy: Correct. So, that is what they take.
Neeraj Agarwal: Yeah.
Vedang Murthy: And in fact, we have not shown the data. We have still not analyzed it. We've also done a very interesting regret analysis that if you have chosen a certain treatment and if you've had the five-day treatment or the longer treatment, do you regret that you came into the trial? So, that is also going to be very interesting to see.
Neeraj Agarwal: Very interesting. The second question is the two worlds you deal with. As I said, we all deal with two worlds. Patients who are very well-served, very educated, have a lot of means available, no issues with reimbursement and I would say resources. And other world is patients who are not even ready to make decisions by themselves. Their families are making decisions and they don't have much resources and they may not be very aware of the cancers, the condition they are dealing with, their potential treatment options, and so on. In the same clinic, you are seeing these patients back to back. Any magic formula for your team, because all these patients are there everywhere, we just proportions vary, any magic formula you are using on how to deal with these two contrasting group of patients in a same clinic, back to back for your team, what is any tips for the team on how to manage these patients?
Vedang Murthy: Once we realize that a patient has limited means of making a decision, whatever that is, we don't push giving too many options. We say, "I would do this." And I really think, and this is what we discuss with my resident, what would you actually do if it was your uncle or your dad or your grandfather or whatever? What would you actually do? We recommend that and we don't give too many options once that happens. And patients are very happy. They know this doctor is talking straight. They're telling me exactly what to do rather than beating around the bush about 3% of that versus 7% of this and give this first or give that later. That's too confusing. So, we come to the point rather than beating around the bush.
Neeraj Agarwal: That's very interesting. And I fully agree with you. Patients who have limited knowledge, limited means, what is... The way you said it, I loved it. What you would do for your brother or your father or your uncle if they have cancer and offer the same. Keep it simple. Love it. Now, the last thing is regarding the clinical trials, and I'll keep it really short, it is amazing how many clinical trials you do, which are investigator-initiated clinical trials. Any lessons you have learned, we'd like to share with our colleagues across the world on how to conduct clinical trials in a resource-constrained setting and resource constraints are everywhere, but we want to learn from you in easier said than done, but just a quick answer for that.
Vedang Murthy: I don't think you should jump onto doing a trial first. My advice would be to start slow and develop a ecosystem, develop a database of all the patients that you treat, review that, audit that frequently, and know what the problems are. If you don't know what you're doing, you will not be able to do anything meaningful. So, if you treated 200 patients in the last two years, know that this is what you've done and these were the problems phased. And that auditing process brings up all the ideas and that can then go into becoming a small phase-two trial or a single-arm trial to get your hands dirty before you launch into a randomized trial. I think that would be the process in my view briefly.
Neeraj Agarwal: Thank you. Before you design a trial, before you even get into conducting a trial, do the groundwork, know how many patients you have, how they have been treated, what problems happen during those treatments. So, groundwork is such a key before you come up with a trial in any setting, but more so in a constrained setting. Well, thank you so much to Dr. Vedang Murthy for taking the time and to share his words of wisdom with us.
Vedang Murthy: Thank you so much, Dr. Agarwal. Absolute pleasure.