This transcript has been edited for clarity.
Welcome back to the second episode of this discussion about biomarkers. The last time we were together, we discussed sensitivity and specificity and the importance of these two aspects in terms of biomarkers in melanoma. We also discussed what kind of characteristics an ideal biomarker would have [in order] for us to use it in a clinical practice.
Right now, for melanoma, the best biomarker that we have is the presence or absence of the BRAF mutation. For early-stage melanoma — which is the setting that we would like to discuss more in terms of biomarkers — there are a couple of biomarkers that are currently being investigated and have been tested, mostly in retrospective analyses, that are tissue biomarkers, mostly gene expression profiles.
These gene expression profile tests use primary tumors to test different genes and combine the expression of these genes with either clinical or pathological information for the majority of them. Then, we have a score that classifies patients into high or low risk, depending on the expression of these biomarkers and in combination with other factors.
Why is this important? And why is it important that we focus on the primary tumor tissue, rather than solely on the information of the sentinel lymph node biopsy, to classify these patients as high and low risk?
We have data from retrospective studies across different databases and as well as the AJCC [American Joint Committee on Cancer] classification showing that, even for patients that have negative sentinel lymph nodes, these patients still have a high risk of recurrence, which means that the patients having a negative sentinel is not equal to having no risk of recurrence.
It is important because, when we are discussing this with the patients and we give them the information on the sentinel lymph node, we need to understand that there might be more than the negativity of the sentinel lymph node that will guide or inform the prognosis of these patients.
These gene expression profiles or these biomarkers that we have now that have been tested retrospectively can indeed help us to define these patients and distinguish two groups of patients, high and low risk, and to have a more personalized approach for these patients.
There are other tools that can also be used, like the nomograms, where we enter information from the tumor and from the patient that can give us an idea of the risk of recurrence or even the risk of positivity of the sentinel lymph node. This can help us also to understand whether we should discuss or we should offer sentinel lymph node biopsy to these patients or if these patients have such a low risk that this is not necessary and would even be detrimental.
As I said before, there are several gene expression profiles and other assays that use immunohistochemistry that can help us to provide information on the patient's risk in terms of relapse, and also in terms of survival, just using the primary tumor. These assays have been tested mostly in patients for whom a sentinel lymph node biopsy was performed, but there is also information on these biomarkers, or at least biomarkers that have been tested retrospectively, in patients that do not receive the sentinel lymph node biopsy.
Why is this important? We have clearly a huge population of patients that are diagnosed with an early-stage melanoma, and for them, we need to provide not only potential systemic therapy but also follow-up.
This follow-up might, in some cases, not be necessary if the patients actually have a low risk. We need to prospectively determine the validity, the importance, and the usefulness of these biomarkers in a prospective way. Right now, the only data that we have are mostly retrospective.
These biomarkers could indeed help us select the patients that would really need sentinel lymph node biopsy on one side and would actually really need systemic therapy on the other side. Most important for me is the possibility that we can select the patients that have such a low risk that we can skip all these procedures safely.
This is very important because it is associated not only with the fact that we reduce the number of patients that we treat, but we would also dramatically reduce the patients that we need to follow. This is, for me, one of the most important aspects of using these biomarkers.
Of course, we know from works that have been published before, and also from other analyses that have been produced before, that most likely you will not have just one biomarker every time. We most likely need to have a combination of biomarkers to understand and to define the patient's risk.
I think this is a principle that we should try to select the patients for whom we would offer adjuvant therapy early on, not only based on the sentinel lymph node biopsy on one side, and because we clearly cannot continue doing trials that would, in principle, treat all-comers and patients without stratification or without previous selection based on the risk of the patients.
COMMENTARY
Refining Melanoma Treatment With Biomarker-Driven Insights
DISCLOSURES
| March 20, 2025This transcript has been edited for clarity.
Welcome back to the second episode of this discussion about biomarkers. The last time we were together, we discussed sensitivity and specificity and the importance of these two aspects in terms of biomarkers in melanoma. We also discussed what kind of characteristics an ideal biomarker would have [in order] for us to use it in a clinical practice.
Right now, for melanoma, the best biomarker that we have is the presence or absence of the BRAF mutation. For early-stage melanoma — which is the setting that we would like to discuss more in terms of biomarkers — there are a couple of biomarkers that are currently being investigated and have been tested, mostly in retrospective analyses, that are tissue biomarkers, mostly gene expression profiles.
These gene expression profile tests use primary tumors to test different genes and combine the expression of these genes with either clinical or pathological information for the majority of them. Then, we have a score that classifies patients into high or low risk, depending on the expression of these biomarkers and in combination with other factors.
Why is this important? And why is it important that we focus on the primary tumor tissue, rather than solely on the information of the sentinel lymph node biopsy, to classify these patients as high and low risk?
We have data from retrospective studies across different databases and as well as the AJCC [American Joint Committee on Cancer] classification showing that, even for patients that have negative sentinel lymph nodes, these patients still have a high risk of recurrence, which means that the patients having a negative sentinel is not equal to having no risk of recurrence.
It is important because, when we are discussing this with the patients and we give them the information on the sentinel lymph node, we need to understand that there might be more than the negativity of the sentinel lymph node that will guide or inform the prognosis of these patients.
These gene expression profiles or these biomarkers that we have now that have been tested retrospectively can indeed help us to define these patients and distinguish two groups of patients, high and low risk, and to have a more personalized approach for these patients.
There are other tools that can also be used, like the nomograms, where we enter information from the tumor and from the patient that can give us an idea of the risk of recurrence or even the risk of positivity of the sentinel lymph node. This can help us also to understand whether we should discuss or we should offer sentinel lymph node biopsy to these patients or if these patients have such a low risk that this is not necessary and would even be detrimental.
As I said before, there are several gene expression profiles and other assays that use immunohistochemistry that can help us to provide information on the patient's risk in terms of relapse, and also in terms of survival, just using the primary tumor. These assays have been tested mostly in patients for whom a sentinel lymph node biopsy was performed, but there is also information on these biomarkers, or at least biomarkers that have been tested retrospectively, in patients that do not receive the sentinel lymph node biopsy.
Why is this important? We have clearly a huge population of patients that are diagnosed with an early-stage melanoma, and for them, we need to provide not only potential systemic therapy but also follow-up.
This follow-up might, in some cases, not be necessary if the patients actually have a low risk. We need to prospectively determine the validity, the importance, and the usefulness of these biomarkers in a prospective way. Right now, the only data that we have are mostly retrospective.
These biomarkers could indeed help us select the patients that would really need sentinel lymph node biopsy on one side and would actually really need systemic therapy on the other side. Most important for me is the possibility that we can select the patients that have such a low risk that we can skip all these procedures safely.
This is very important because it is associated not only with the fact that we reduce the number of patients that we treat, but we would also dramatically reduce the patients that we need to follow. This is, for me, one of the most important aspects of using these biomarkers.
Of course, we know from works that have been published before, and also from other analyses that have been produced before, that most likely you will not have just one biomarker every time. We most likely need to have a combination of biomarkers to understand and to define the patient's risk.
I think this is a principle that we should try to select the patients for whom we would offer adjuvant therapy early on, not only based on the sentinel lymph node biopsy on one side, and because we clearly cannot continue doing trials that would, in principle, treat all-comers and patients without stratification or without previous selection based on the risk of the patients.
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
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