Counterpoint: SENTINEL LYMPH NODE BIOPSY: Is it the new standard of care?
February 2002
T o label the use of a management tool as the “standard of care” for a particular disease is to make a bold statement indeed — both to the patients involved as well as to the medical and legal community. This label, in fact, means the net benefits to the patient that would come from using this management tool
are so tremendous it’s simply mandatory that it be provided. Recommending it should be reflexive at a level approaching that of the brainstem. “Should I recommend this course of action? Of course I should! It’s the standard of care!”
If you do not provide this service, realize then that your failure to do so is a negligent, substandard decision. Your patients have not received their most basic, baseline, minimum medical needs. And you are responsible for that.
For patients with primary cutaneous melanoma, excision of the tumor using the appropriate breadth and depth is the standard of care. Providing regular, frequent, total body skin examinations during the follow-up years is the standard of care. Recommending and reinforcing the use of regular sun protection habits is the standard of care.
Performing a sentinel lymph node biopsy is not the standard of care.
How Useful is SLNB as Prognostic Tool?
Let me start by saying that as a prognostic tool, it’s true that SLNBs provide accurate and useful information. In fact, data have shown that the status of the SLN trumps the importance of all characteristics of the primary tumor, including Breslow depth. That is to say, a patient with a 4.0 mm ulcerated primary melanoma that has a SLN that is negative by both conventional histopathology and RT-PCR will, most likely, fare better than a similar patient with a 1.0 mm non-ulcerated melanoma that has an SLN positive by both histopathology and RT-PCR.
Of course, the purpose of performing an SLN biopsy isn’t just to be able to tell patients how likely they are to succumb to the disease. It is to determine if they should be recommended to undergo treatment for it. One would assume that the treatment for high-risk melanoma should be pretty good, seeing as how many feel it’s mandatory for the patients to get screened with the SLN biopsies in the first place.
The trouble is, it’s not. Once you have picked up a positive SLN, you are then obliged to provide one or more of the following:
l An elective lymph node dissection (ELND) of the defined basin.
l High dose adjuvant interferon.
l One of a number of experimental protocols using vaccines, immunomodulators, etc.
Despite their frequent use following SLN biopsies, ELNDs have not been proven to improve overall survival in melanoma patients with stage IIb disease (which patients that undergo SLNBs fall into). And unlike SLN biopsies, ELNDs carry a significant risk of morbidity from the procedure (chronic lymphedema, etc).
Study Results on ELND
Four large prospective trials have addressed the issue of whether ELND affects the survival of patients with primary cutaneous melanoma. None of the studies have shown a difference in long-term survival between patients who did and did not receive ELND in addition to excision of the primary melanoma. Three of the four studies, however, do not adequately reflect the current method of performing an ELND because they did not utilize preoperative lymphoscintigraphy to accurately define the correct lymphatic basin to be removed. The fourth study, the Intergroup Melanoma Surgical Program study, did use preoperative lymphoscintigraphy and also showed no overall survival benefit. They did, however, go back and retrospectively review the data to find that there was a statistically significant survival benefit in some patients, provided that they were <60 years old with a melanoma 1mm to 2mm thick. Since the authors retrospectively reanalyzed data from subgroups of patients in a study that was prospective in design, other authors have correctly recommended interpreting the data with a “grain of salt.”
The bottom line is that despite presumed survival benefits from ELND based on indirect evidence of staging survival curves, the prospective study data so far have been shaky at best.
Efficacy of High Dose Interferon
High dose interferon recently has been shown to provide an increased overall survival — a modest one. Let’s be honest about this: It’s not a homerun — by any stretch. Until last year, there had not been a single published study to show that high dose interferon led to any statistically increased overall survival in patients with stage IIb melanoma.
In the 2001 Intergroup Trial E1694, Kirkwood and colleagues analyzed the benefit of receiving high dose IFN-alpha2b versus receiving the ganglioside GMK vaccine in stage IIb/III melanoma patients. The estimated 2-year overall survival rate for eligible patients receiving IFN-alpha2b was 78%. In the vaccine arm, it was 73%. There was no observation arm in the study. Based on the results of the control/observation arm in previous trials, it was unclear whether the vaccine provided any net overall survival benefits to the patients that received it. Bottom line: if you took 1 year’s worth of high dose interferon you had a maximum of a 5% higher chance of being alive in 2 years than if you took the vaccine. To some patients, that’s enough. To others it’s not worth it. Anyone that has cared for patients receiving high dose interferon knows the side effects can be severe. Unfortunately, in early 2002, it’s the best treatment we’ve got.
Is this why SLNBs need to be the standard of care? Is this why failure to recommend one should reflect negligence on the part of the physician, because they can determine if the patient should receive high-dose interferon, the only FDA-approved adjuvant treatment for advanced melanoma? That’s quite a leap if you ask me. Especially since a fair number of patients will refuse to take high-dose interferon in the first place.
Remaining Questions Regarding SLNBs
One last point. I don’t recall hearing of any formal recommendations or protocols from the AJCC, AAD, or other organizations on how to incorporate SLN biopsies into one’s practice. If SLN biopsies are to be the standard of care for the management of all high-risk melanoma patients, some guidelines for recommending them would be appreciated. It’s only fair. If I am going to be sued for malpractice for not referring a patient for one, at least let me know the grounds for the charges.
What are the required characteristics of the primary tumor? Many SLN biopsy advocates call for a Breslow depth of at least 1.00 mm. Wagner et al (2000) performed univariate and multivariate regression analysis on 275 melanoma patients and found 1.25 mm to be the optimal cut-off point. There is at least one melanoma information web site for patients that refers to patients having melanomas as thin as 0.1 mm sent for SLN biopsies.
Should the presence/absence of ulceration, regression, etc affect the cut-off threshold for Breslow depth?
Furthermore, should all SLNs that are negative by conventional histopathology/special stains be screened further with RT-PCR? If they should be found positive by RT-PCR, but negative by histopathology, what’s the standard of care then?
Clearly, there are a lot of questions that remain to be answered about SLN biopsies and the circumstances surrounding when/if to recommend them for our patients. Right now, I think most dermatologists view SLN biopsies as promising procedures that will likely become increasingly utilized as the treatment for advanced melanoma continues to improve, while associated side effects lessen. I also think that at the present time most of us find the whole topic of when, how, why, and if to refer patients for one very confusing and murky.
Having said that, it does nobody any good to call sentinel lymph node biopsies the standard of care for patients with high-risk melanomas. By doing so, you are labeling patients who are not referred for one as having received substandard care. The emotional, political and legal ramifications of this are considerable, particularly when there are no established guidelines for referral criteria. There are also no established protocols on how/if to interpret RT-PCR results of the lymph nodes should they differ from that of histopathologic examination — and not all institutions even use RT-PCR to assess the lymph nodes. Most importantly, there is no “standard of care” adjuvant therapy that is good enough and tolerable enough to be acceptable for all patients that are found to be SLN positive.
The standard of care is to sit down with the patient and have a forthright discussion over the pertinent issues as they pertain to him or her. In my own practice, I find that SLN biopsies provide useful prognostic information some patients will find helpful provided they are willing to consider undergoing an ELND with or without high dose interferon and/or enrollment into a therapeutic clinical trial. If patients seem eager to undergo an SLN biopsy, I encourage them to go to our tertiary care center that performs them as part of an ongoing clinical trial to help better define their management role. Some perfectly rational patients will be unwilling to undergo an ELND, high dose interferon and/or other adjuvant treatment for their disease. If that’s the case, I certainly don’t send them for an SLN biopsy. To do so simply because some wish to call it the “standard of care” isn’t just wrong, it’s irresponsible.
T o label the use of a management tool as the “standard of care” for a particular disease is to make a bold statement indeed — both to the patients involved as well as to the medical and legal community. This label, in fact, means the net benefits to the patient that would come from using this management tool
are so tremendous it’s simply mandatory that it be provided. Recommending it should be reflexive at a level approaching that of the brainstem. “Should I recommend this course of action? Of course I should! It’s the standard of care!”
If you do not provide this service, realize then that your failure to do so is a negligent, substandard decision. Your patients have not received their most basic, baseline, minimum medical needs. And you are responsible for that.
For patients with primary cutaneous melanoma, excision of the tumor using the appropriate breadth and depth is the standard of care. Providing regular, frequent, total body skin examinations during the follow-up years is the standard of care. Recommending and reinforcing the use of regular sun protection habits is the standard of care.
Performing a sentinel lymph node biopsy is not the standard of care.
How Useful is SLNB as Prognostic Tool?
Let me start by saying that as a prognostic tool, it’s true that SLNBs provide accurate and useful information. In fact, data have shown that the status of the SLN trumps the importance of all characteristics of the primary tumor, including Breslow depth. That is to say, a patient with a 4.0 mm ulcerated primary melanoma that has a SLN that is negative by both conventional histopathology and RT-PCR will, most likely, fare better than a similar patient with a 1.0 mm non-ulcerated melanoma that has an SLN positive by both histopathology and RT-PCR.
Of course, the purpose of performing an SLN biopsy isn’t just to be able to tell patients how likely they are to succumb to the disease. It is to determine if they should be recommended to undergo treatment for it. One would assume that the treatment for high-risk melanoma should be pretty good, seeing as how many feel it’s mandatory for the patients to get screened with the SLN biopsies in the first place.
The trouble is, it’s not. Once you have picked up a positive SLN, you are then obliged to provide one or more of the following:
l An elective lymph node dissection (ELND) of the defined basin.
l High dose adjuvant interferon.
l One of a number of experimental protocols using vaccines, immunomodulators, etc.
Despite their frequent use following SLN biopsies, ELNDs have not been proven to improve overall survival in melanoma patients with stage IIb disease (which patients that undergo SLNBs fall into). And unlike SLN biopsies, ELNDs carry a significant risk of morbidity from the procedure (chronic lymphedema, etc).
Study Results on ELND
Four large prospective trials have addressed the issue of whether ELND affects the survival of patients with primary cutaneous melanoma. None of the studies have shown a difference in long-term survival between patients who did and did not receive ELND in addition to excision of the primary melanoma. Three of the four studies, however, do not adequately reflect the current method of performing an ELND because they did not utilize preoperative lymphoscintigraphy to accurately define the correct lymphatic basin to be removed. The fourth study, the Intergroup Melanoma Surgical Program study, did use preoperative lymphoscintigraphy and also showed no overall survival benefit. They did, however, go back and retrospectively review the data to find that there was a statistically significant survival benefit in some patients, provided that they were <60 years old with a melanoma 1mm to 2mm thick. Since the authors retrospectively reanalyzed data from subgroups of patients in a study that was prospective in design, other authors have correctly recommended interpreting the data with a “grain of salt.”
The bottom line is that despite presumed survival benefits from ELND based on indirect evidence of staging survival curves, the prospective study data so far have been shaky at best.
Efficacy of High Dose Interferon
High dose interferon recently has been shown to provide an increased overall survival — a modest one. Let’s be honest about this: It’s not a homerun — by any stretch. Until last year, there had not been a single published study to show that high dose interferon led to any statistically increased overall survival in patients with stage IIb melanoma.
In the 2001 Intergroup Trial E1694, Kirkwood and colleagues analyzed the benefit of receiving high dose IFN-alpha2b versus receiving the ganglioside GMK vaccine in stage IIb/III melanoma patients. The estimated 2-year overall survival rate for eligible patients receiving IFN-alpha2b was 78%. In the vaccine arm, it was 73%. There was no observation arm in the study. Based on the results of the control/observation arm in previous trials, it was unclear whether the vaccine provided any net overall survival benefits to the patients that received it. Bottom line: if you took 1 year’s worth of high dose interferon you had a maximum of a 5% higher chance of being alive in 2 years than if you took the vaccine. To some patients, that’s enough. To others it’s not worth it. Anyone that has cared for patients receiving high dose interferon knows the side effects can be severe. Unfortunately, in early 2002, it’s the best treatment we’ve got.
Is this why SLNBs need to be the standard of care? Is this why failure to recommend one should reflect negligence on the part of the physician, because they can determine if the patient should receive high-dose interferon, the only FDA-approved adjuvant treatment for advanced melanoma? That’s quite a leap if you ask me. Especially since a fair number of patients will refuse to take high-dose interferon in the first place.
Remaining Questions Regarding SLNBs
One last point. I don’t recall hearing of any formal recommendations or protocols from the AJCC, AAD, or other organizations on how to incorporate SLN biopsies into one’s practice. If SLN biopsies are to be the standard of care for the management of all high-risk melanoma patients, some guidelines for recommending them would be appreciated. It’s only fair. If I am going to be sued for malpractice for not referring a patient for one, at least let me know the grounds for the charges.
What are the required characteristics of the primary tumor? Many SLN biopsy advocates call for a Breslow depth of at least 1.00 mm. Wagner et al (2000) performed univariate and multivariate regression analysis on 275 melanoma patients and found 1.25 mm to be the optimal cut-off point. There is at least one melanoma information web site for patients that refers to patients having melanomas as thin as 0.1 mm sent for SLN biopsies.
Should the presence/absence of ulceration, regression, etc affect the cut-off threshold for Breslow depth?
Furthermore, should all SLNs that are negative by conventional histopathology/special stains be screened further with RT-PCR? If they should be found positive by RT-PCR, but negative by histopathology, what’s the standard of care then?
Clearly, there are a lot of questions that remain to be answered about SLN biopsies and the circumstances surrounding when/if to recommend them for our patients. Right now, I think most dermatologists view SLN biopsies as promising procedures that will likely become increasingly utilized as the treatment for advanced melanoma continues to improve, while associated side effects lessen. I also think that at the present time most of us find the whole topic of when, how, why, and if to refer patients for one very confusing and murky.
Having said that, it does nobody any good to call sentinel lymph node biopsies the standard of care for patients with high-risk melanomas. By doing so, you are labeling patients who are not referred for one as having received substandard care. The emotional, political and legal ramifications of this are considerable, particularly when there are no established guidelines for referral criteria. There are also no established protocols on how/if to interpret RT-PCR results of the lymph nodes should they differ from that of histopathologic examination — and not all institutions even use RT-PCR to assess the lymph nodes. Most importantly, there is no “standard of care” adjuvant therapy that is good enough and tolerable enough to be acceptable for all patients that are found to be SLN positive.
The standard of care is to sit down with the patient and have a forthright discussion over the pertinent issues as they pertain to him or her. In my own practice, I find that SLN biopsies provide useful prognostic information some patients will find helpful provided they are willing to consider undergoing an ELND with or without high dose interferon and/or enrollment into a therapeutic clinical trial. If patients seem eager to undergo an SLN biopsy, I encourage them to go to our tertiary care center that performs them as part of an ongoing clinical trial to help better define their management role. Some perfectly rational patients will be unwilling to undergo an ELND, high dose interferon and/or other adjuvant treatment for their disease. If that’s the case, I certainly don’t send them for an SLN biopsy. To do so simply because some wish to call it the “standard of care” isn’t just wrong, it’s irresponsible.
T o label the use of a management tool as the “standard of care” for a particular disease is to make a bold statement indeed — both to the patients involved as well as to the medical and legal community. This label, in fact, means the net benefits to the patient that would come from using this management tool
are so tremendous it’s simply mandatory that it be provided. Recommending it should be reflexive at a level approaching that of the brainstem. “Should I recommend this course of action? Of course I should! It’s the standard of care!”
If you do not provide this service, realize then that your failure to do so is a negligent, substandard decision. Your patients have not received their most basic, baseline, minimum medical needs. And you are responsible for that.
For patients with primary cutaneous melanoma, excision of the tumor using the appropriate breadth and depth is the standard of care. Providing regular, frequent, total body skin examinations during the follow-up years is the standard of care. Recommending and reinforcing the use of regular sun protection habits is the standard of care.
Performing a sentinel lymph node biopsy is not the standard of care.
How Useful is SLNB as Prognostic Tool?
Let me start by saying that as a prognostic tool, it’s true that SLNBs provide accurate and useful information. In fact, data have shown that the status of the SLN trumps the importance of all characteristics of the primary tumor, including Breslow depth. That is to say, a patient with a 4.0 mm ulcerated primary melanoma that has a SLN that is negative by both conventional histopathology and RT-PCR will, most likely, fare better than a similar patient with a 1.0 mm non-ulcerated melanoma that has an SLN positive by both histopathology and RT-PCR.
Of course, the purpose of performing an SLN biopsy isn’t just to be able to tell patients how likely they are to succumb to the disease. It is to determine if they should be recommended to undergo treatment for it. One would assume that the treatment for high-risk melanoma should be pretty good, seeing as how many feel it’s mandatory for the patients to get screened with the SLN biopsies in the first place.
The trouble is, it’s not. Once you have picked up a positive SLN, you are then obliged to provide one or more of the following:
l An elective lymph node dissection (ELND) of the defined basin.
l High dose adjuvant interferon.
l One of a number of experimental protocols using vaccines, immunomodulators, etc.
Despite their frequent use following SLN biopsies, ELNDs have not been proven to improve overall survival in melanoma patients with stage IIb disease (which patients that undergo SLNBs fall into). And unlike SLN biopsies, ELNDs carry a significant risk of morbidity from the procedure (chronic lymphedema, etc).
Study Results on ELND
Four large prospective trials have addressed the issue of whether ELND affects the survival of patients with primary cutaneous melanoma. None of the studies have shown a difference in long-term survival between patients who did and did not receive ELND in addition to excision of the primary melanoma. Three of the four studies, however, do not adequately reflect the current method of performing an ELND because they did not utilize preoperative lymphoscintigraphy to accurately define the correct lymphatic basin to be removed. The fourth study, the Intergroup Melanoma Surgical Program study, did use preoperative lymphoscintigraphy and also showed no overall survival benefit. They did, however, go back and retrospectively review the data to find that there was a statistically significant survival benefit in some patients, provided that they were <60 years old with a melanoma 1mm to 2mm thick. Since the authors retrospectively reanalyzed data from subgroups of patients in a study that was prospective in design, other authors have correctly recommended interpreting the data with a “grain of salt.”
The bottom line is that despite presumed survival benefits from ELND based on indirect evidence of staging survival curves, the prospective study data so far have been shaky at best.
Efficacy of High Dose Interferon
High dose interferon recently has been shown to provide an increased overall survival — a modest one. Let’s be honest about this: It’s not a homerun — by any stretch. Until last year, there had not been a single published study to show that high dose interferon led to any statistically increased overall survival in patients with stage IIb melanoma.
In the 2001 Intergroup Trial E1694, Kirkwood and colleagues analyzed the benefit of receiving high dose IFN-alpha2b versus receiving the ganglioside GMK vaccine in stage IIb/III melanoma patients. The estimated 2-year overall survival rate for eligible patients receiving IFN-alpha2b was 78%. In the vaccine arm, it was 73%. There was no observation arm in the study. Based on the results of the control/observation arm in previous trials, it was unclear whether the vaccine provided any net overall survival benefits to the patients that received it. Bottom line: if you took 1 year’s worth of high dose interferon you had a maximum of a 5% higher chance of being alive in 2 years than if you took the vaccine. To some patients, that’s enough. To others it’s not worth it. Anyone that has cared for patients receiving high dose interferon knows the side effects can be severe. Unfortunately, in early 2002, it’s the best treatment we’ve got.
Is this why SLNBs need to be the standard of care? Is this why failure to recommend one should reflect negligence on the part of the physician, because they can determine if the patient should receive high-dose interferon, the only FDA-approved adjuvant treatment for advanced melanoma? That’s quite a leap if you ask me. Especially since a fair number of patients will refuse to take high-dose interferon in the first place.
Remaining Questions Regarding SLNBs
One last point. I don’t recall hearing of any formal recommendations or protocols from the AJCC, AAD, or other organizations on how to incorporate SLN biopsies into one’s practice. If SLN biopsies are to be the standard of care for the management of all high-risk melanoma patients, some guidelines for recommending them would be appreciated. It’s only fair. If I am going to be sued for malpractice for not referring a patient for one, at least let me know the grounds for the charges.
What are the required characteristics of the primary tumor? Many SLN biopsy advocates call for a Breslow depth of at least 1.00 mm. Wagner et al (2000) performed univariate and multivariate regression analysis on 275 melanoma patients and found 1.25 mm to be the optimal cut-off point. There is at least one melanoma information web site for patients that refers to patients having melanomas as thin as 0.1 mm sent for SLN biopsies.
Should the presence/absence of ulceration, regression, etc affect the cut-off threshold for Breslow depth?
Furthermore, should all SLNs that are negative by conventional histopathology/special stains be screened further with RT-PCR? If they should be found positive by RT-PCR, but negative by histopathology, what’s the standard of care then?
Clearly, there are a lot of questions that remain to be answered about SLN biopsies and the circumstances surrounding when/if to recommend them for our patients. Right now, I think most dermatologists view SLN biopsies as promising procedures that will likely become increasingly utilized as the treatment for advanced melanoma continues to improve, while associated side effects lessen. I also think that at the present time most of us find the whole topic of when, how, why, and if to refer patients for one very confusing and murky.
Having said that, it does nobody any good to call sentinel lymph node biopsies the standard of care for patients with high-risk melanomas. By doing so, you are labeling patients who are not referred for one as having received substandard care. The emotional, political and legal ramifications of this are considerable, particularly when there are no established guidelines for referral criteria. There are also no established protocols on how/if to interpret RT-PCR results of the lymph nodes should they differ from that of histopathologic examination — and not all institutions even use RT-PCR to assess the lymph nodes. Most importantly, there is no “standard of care” adjuvant therapy that is good enough and tolerable enough to be acceptable for all patients that are found to be SLN positive.
The standard of care is to sit down with the patient and have a forthright discussion over the pertinent issues as they pertain to him or her. In my own practice, I find that SLN biopsies provide useful prognostic information some patients will find helpful provided they are willing to consider undergoing an ELND with or without high dose interferon and/or enrollment into a therapeutic clinical trial. If patients seem eager to undergo an SLN biopsy, I encourage them to go to our tertiary care center that performs them as part of an ongoing clinical trial to help better define their management role. Some perfectly rational patients will be unwilling to undergo an ELND, high dose interferon and/or other adjuvant treatment for their disease. If that’s the case, I certainly don’t send them for an SLN biopsy. To do so simply because some wish to call it the “standard of care” isn’t just wrong, it’s irresponsible.
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