This transcript has been edited for clarity.
This is Mark Kris again, continuing our discussion of the many faces of progression. What’s the most important consideration? More than anything else, it’s symptoms. If you have symptomatic progression, first and foremost you need to palliate that symptom. Whether it be pain, a pain medication, breathing difficulty — whatever interventions can happen to relieve that, you have to palliate the symptom.
The next issue comes that, if indeed it is successful in palliating the symptom and coming up with a therapy to do that, do you want to continue the systemic therapy? We have plenty of examples now of what I’ll call oligoprogression.
There’s growth of cancer in one site, and a good example of this would be the brain. The rest of the lesions in the body are under control, not symptomatic. It’s very reasonable to treat the problem in the brain and then continue the systemic therapy, of course, as long as it’s well tolerated and the disease is controlled in the rest of the body. If you have oligoprogression, a local therapy is effective, continue the current therapy.
The other thing that’s very, very important is what I would call equivocal findings on imaging. If something has grown by 2 mm in a 50-mm lesion, that is well within the variability of the measuring system. Make sure somebody has indeed progressed, particularly in those cases where there is a very small growth and one, frankly, that you can’t reliably measure. In general, continue therapy.
Asymptomatic progression is probably the toughest thing and the one that really takes a large amount of thought. I think, again, symptoms are really important. If you have a symptom, it’s a whole different ballgame. You have to palliate the symptom and then come up with an anticancer strategy to, in the long term, alleviate that symptom.
Also, the side effects of the treatment people are on are super critical. When a patient comes in and says, “Doc, I’ve had the best week in my life. I’ve had a life that’s just like it was before my cancer was diagnosed,” you have to think long and hard about changing that therapy. You need some very compelling reason to do that.
Even in the face of progression that you see with that scenario, you have to be really careful about changing. I think we see this even more now with the checkpoint inhibitors and with the targeted therapies.
Another important thing is the rate of growth. I remember many years ago, I went to a lecture by Tony Mok, and he showed a series of scans of a person with EGFR-mutant lung cancer. Over a period of 3 years, in the scans that he showed, the cancer had grown maybe on each scan by 10%.
The person was fine, tolerating therapy, and living the life they chose to live. The point there was that with indolent progression, there’s no reason to change. You really need to think about that. There’s something in many clinical trials now called “treatment beyond progression for patients” that fit that scenario: growth, but with excellent tolerance of the medicine and, even more important, lack of symptoms and the patient is living their life.
There is that condition that everybody wants to talk about that is rarely seen, called pseudoprogression. It happens occasionally; it’s pretty rare. The key there is symptoms. If you have, just like that last case we talked about, growth without symptoms and medicine being tolerated well, you have to be really careful if you’re going to make a change.
The bottom line is that progression is not one item. It is not RECIST progression. RECIST progression has to do with clinical trials. The fact that somebody’s cancer has grown by 21%, and it’s in the dominant lesion, does not mean you need to change therapies.
Our job is much harder here, actually. It involves talking to the patient, making sure that their symptoms are controlled, and making sure they’re living the life they choose to use. It’s the oncologist who assesses adverse effects to determine whether there are dangerous adverse effects or adverse effects that are going to ultimately impede their quality of life, such as neuropathy and hearing loss. Those are good reasons to stop, even if there’s slight progression.
It requires a large amount of thought. The good news is, oftentimes you don’t have to change systemic therapy. Either you just continue it and carefully follow the patient, or you palliate a single dominant lesion or a single symptomatic lesion effectively, and then we continue systemic therapy.
The thought as I leave today would be, please, resist RECIST when it comes to making decisions for clinical care of patients. You must follow it, of course, in clinical trials, and sadly you have to be very rigorous in that. However, when it comes to a patient, there’s much more to this decision than the RECIST criteria, which was never, ever created for clinical care.
COMMENTARY
Progression on Systemic Therapy: Assessment Considerations (Part 2)
Mark G. Kris, MD
DISCLOSURES
| December 26, 2024This transcript has been edited for clarity.
This is Mark Kris again, continuing our discussion of the many faces of progression. What’s the most important consideration? More than anything else, it’s symptoms. If you have symptomatic progression, first and foremost you need to palliate that symptom. Whether it be pain, a pain medication, breathing difficulty — whatever interventions can happen to relieve that, you have to palliate the symptom.
The next issue comes that, if indeed it is successful in palliating the symptom and coming up with a therapy to do that, do you want to continue the systemic therapy? We have plenty of examples now of what I’ll call oligoprogression.
There’s growth of cancer in one site, and a good example of this would be the brain. The rest of the lesions in the body are under control, not symptomatic. It’s very reasonable to treat the problem in the brain and then continue the systemic therapy, of course, as long as it’s well tolerated and the disease is controlled in the rest of the body. If you have oligoprogression, a local therapy is effective, continue the current therapy.
The other thing that’s very, very important is what I would call equivocal findings on imaging. If something has grown by 2 mm in a 50-mm lesion, that is well within the variability of the measuring system. Make sure somebody has indeed progressed, particularly in those cases where there is a very small growth and one, frankly, that you can’t reliably measure. In general, continue therapy.
Asymptomatic progression is probably the toughest thing and the one that really takes a large amount of thought. I think, again, symptoms are really important. If you have a symptom, it’s a whole different ballgame. You have to palliate the symptom and then come up with an anticancer strategy to, in the long term, alleviate that symptom.
Also, the side effects of the treatment people are on are super critical. When a patient comes in and says, “Doc, I’ve had the best week in my life. I’ve had a life that’s just like it was before my cancer was diagnosed,” you have to think long and hard about changing that therapy. You need some very compelling reason to do that.
Even in the face of progression that you see with that scenario, you have to be really careful about changing. I think we see this even more now with the checkpoint inhibitors and with the targeted therapies.
Another important thing is the rate of growth. I remember many years ago, I went to a lecture by Tony Mok, and he showed a series of scans of a person with EGFR-mutant lung cancer. Over a period of 3 years, in the scans that he showed, the cancer had grown maybe on each scan by 10%.
The person was fine, tolerating therapy, and living the life they chose to live. The point there was that with indolent progression, there’s no reason to change. You really need to think about that. There’s something in many clinical trials now called “treatment beyond progression for patients” that fit that scenario: growth, but with excellent tolerance of the medicine and, even more important, lack of symptoms and the patient is living their life.
There is that condition that everybody wants to talk about that is rarely seen, called pseudoprogression. It happens occasionally; it’s pretty rare. The key there is symptoms. If you have, just like that last case we talked about, growth without symptoms and medicine being tolerated well, you have to be really careful if you’re going to make a change.
The bottom line is that progression is not one item. It is not RECIST progression. RECIST progression has to do with clinical trials. The fact that somebody’s cancer has grown by 21%, and it’s in the dominant lesion, does not mean you need to change therapies.
Our job is much harder here, actually. It involves talking to the patient, making sure that their symptoms are controlled, and making sure they’re living the life they choose to use. It’s the oncologist who assesses adverse effects to determine whether there are dangerous adverse effects or adverse effects that are going to ultimately impede their quality of life, such as neuropathy and hearing loss. Those are good reasons to stop, even if there’s slight progression.
It requires a large amount of thought. The good news is, oftentimes you don’t have to change systemic therapy. Either you just continue it and carefully follow the patient, or you palliate a single dominant lesion or a single symptomatic lesion effectively, and then we continue systemic therapy.
The thought as I leave today would be, please, resist RECIST when it comes to making decisions for clinical care of patients. You must follow it, of course, in clinical trials, and sadly you have to be very rigorous in that. However, when it comes to a patient, there’s much more to this decision than the RECIST criteria, which was never, ever created for clinical care.
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
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