Goals of Therapy in Sarcoma

Transcript:William D. Tap, MD: I think one of the most challenging things that even plagues our community is, what are really the set paradigms in how to treat patients? And I don’t know if that’s something we could just write down and say, “This is the exact way to look at patients.” What’s wonderful about this panel is that we have some of the world’s experts here, and I’d love to get into your mind. When I see a patient, how do I approach them? What am I thinking? And Martee, maybe I’ll start with you, because you can approach it from a gynecological standpoint and with a little unique aspect. What are you thinking when you see patients?

Martee L. Hensley, MD: I first ask myself, does this patient have a curable disease or a controllable disease? Because if we think that patient can be cured, then our willingness to use very aggressive therapies and talk her into how to be supported through those aggressive therapies, we’re going to have a lower threshold to do that because we think there’s a chance for cure. If, instead, she has a controllable disease, then I ask myself, what will be the best recipe to lead to tolerable disease control for as long as possible, whether that’s multi-agent chemotherapy to start, with a hope for breakthrough treatment down the road, single-agent chemotherapy, or even hormone blockade in specially selected patients? And then I counsel them, “I can’t cure your disease, but I think we can keep you living with it for a pretty long time using treatments that won’t make you very sick,” and then we’ll talk about which specific agents fall in those categories.

William D. Tap, MD: And it’s always important to say that that becomes a journey, and a lot of things can happen, good and bad, on a journey and things are emerging every day. That’s a wonderful way to approach. So, when we talk about soft tissue sarcomas, is it the same approach? Is it different approaches? Mark?

Mark Agulnik, MD: I think it’s the same. And the word that you used is cure, so it’s very important to set the expectations for the patients very early on. I’m not a huge fan of prognosis on a first visit because I actually don’t think you could tell what the prognosis is going to be until you start the journey with them and see how they start to respond to some of the therapies. And often people are too quick to ask, “What’s the prognosis?” And none of us have the crystal ball as far as I know, but I really do think you need to set expectations. And for the ability to cure, if you think you can cure someone or render them cured, whether or not they have oligometastatic disease or just localized disease, I think you need to use the word. And if you can’t cure them, taking them to the paradigm, could you create this as a chronic disease? Certainly, we’ve all seen patients with metastatic disease who have lived for many years, but we’ve also seen patients who have lived 6 to 8 weeks.

And so, the volume of disease that they have, the aggressiveness of the histology, you have to be up front and forward with them. But I do think it is a journey with them, and there are a lot of options for them. It’s really disheartening when someone walks in and says, “My surgeon said there’s no options.” I feel terrible, because from the time period that they met with the surgeon until they met you in your office, they’ve been living with that. I feel terrible for them.

William D. Tap, MD: I agree. And that’s an important aspect, because we put so much weight on surgery, and we know that can be a curative option for patients with localized disease. How do people approach patients differently if they have localized disease that may be unresectable, but potentially we can convert them with cytotoxic therapy versus metastatic disease? Any thoughts, Shreyas?

Shreyaskumar Patel, MD: So, reiterating some of the things that have been said already, just rephrasing it from a philosophical standpoint: the intent is always cure. The probability of us being able to achieve it is going to be very variable, and it comes down to the curable versus controllable disease population. Another way to look at it is that a prerequisite for cure may well be, or is usually, rendering them completely, grossly free of disease. Can the disease be completely gotten rid of? Can the CT scans be cleared up? Coming back to your question, if the patient has an unresectable tumor at baseline, the goals clearly are, can we make it resectable and therefore use therapies that have a higher response rate and a probability of shrinkage to get it away from the neurovascular bundle or the surrounding visceral organs to enable the surgeon to completely carve it out?

William D. Tap, MD: I just want to make a point here because I hear definitively that you believe you can do that in patients, right? Because it’s often where patients come and they say, “We’ll never be able to convert this to surgery.” Right?

Shreyaskumar Patel, MD: Right. And so this gets back to Mark’s comment, that on day 1 when the patient is first coming to you, you really don’t know the answer. So, that’s where it becomes more about philosophy and giving it your best shot. Right now, we may try the best of treatments, the disease progresses, and that patient is never going to make it to surgery and will never be cured. Can that happen? It happens unfortunately far too often than we would all care to admit, right?

But I think we are oncologists, we are eternal optimists. So, even when the chance of benefit is 2 out of 10, we will take the risks and recommend treatment to the 10 patients, as long as they’re appropriately selected for organ function, toxicities, and so on and so forth. But you want to give them the best possible chance of getting to an NED, no evidence of disease status, and that becomes the driving force. And that’s not just for an unresectable, locally aggressive primary. They may have a primary with two lung metastases, for example. These are people who can be rendered free of disease, and those are the ones sent home. Aggressive therapy that is going to induce some cytoreduction and volumetric reduction might facilitate other options. We don’t have a surgeon on the panel, but the surgeons don’t like to hear that this is where we would do primary chemotherapy and adjuvant surgery. They don’t like to hear that; they always want adjuvant chemotherapy. But the roles can reverse in the patient population that we’re talking about.

Transcript Edited for Clarity