- Email: [email protected]
Cost Effectiveness of Mohs Micrographic Surgery
See related article on pg 1188
Cost Effectiveness of Mohs Micrographic Surgery Robert S. Stern1 Chren’s study provides further evidence that for primary facial nonmelanoma skin cancers (NMSCs), recurrence rates with Mohs micrographic surgery (MMS) are modestly better than those for excision surgery. In 20 years, use of MMS has grown B10-fold and its cost now exceeds two billion dollars annually. Clinical experience and available data suggest that the skill of the treating physician is at least as important a determinant of outcome as the choice of MMS or excision. As patients and referring physicians increasingly share in the cost of more expensive procedures, evidence-based guidelines that establish the clinical circumstances in which the additional benefits of MMS outweigh its higher cost are needed, still lacking, and unlikely to become available. Journal of Investigative Dermatology (2013) 133, 1129–1131. doi:10.1038/jid.2012.473
Over the years, I have worked with a number of highly skilled Mohs surgeons who provide excellent care to our patients. Mohs units are one of the financial underpinnings of many departments of dermatology. The growth of Mohs micrographic surgery (MMS) over the past 35 years has been extraordinary. In 1976, I did not know anyone in the greater Boston area who was a fulltime Mohs surgeon. Now, the Mohs College lists more than two dozen to whom I could bicycle to in less than half an hour. This excludes an unknown, but not insubstantial, number of individuals who are not members of the Mohs College, but provide what they call MMS. MMS fellowships attracts many of our brightest residents. For recurrent nonmelanoma skin cancers (NMSCs) in the ‘‘H zone’’, MMS is clearly superior to excision, and in most cases is the treatment of choice (Smeets et al., 2004; Mosterd et al., 2008). However, recurrent tumors represent only a minority of all tumors treated with MMS in the United States. For primary NMSCs even in the H zone, the new study of Chren et al. (2013, this issue) as well as the Dutch study showed little difference between MMS
and excision (Smeets et al., 2004; Mosterd et al., 2008). The use of MMS may provide greater standardization and hence less variance in recurrence rates among providers than does excision. On the other hand, the study of Chren et al. (2012) suggests that the results among surgeons performing excisions may vary substantially. More predictability in the risk of recurrence may be beneficial to the individual patient with tumors at sites such as the ‘‘H zone’’ where recurrence is likely to result in substantial morbidity, but the data available argue more strongly for using a skilled physician than choosing an MMS over excision for primary NMSC. Medicare data document the exceptional growth in the utilization of MMS. From 1992 to 2002, the utilization of MMS increased 332% (Maxwell et al., 2007). By 2009, the rate of the use of MMS was 700% greater than in 1992 (Donaldson and Coldiron, 2012). Extrapolated to 2013, nearly 2% of all Medicare recipients will have MMS in that year. Is that too many or not enough? When more robust data are not available, one approach to assessing the appropriateness of the utilization of a procedure in various populations is
1
Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Correspondence: Robert S. Stern, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, GZ 522, Boston, Massachusetts 02215, USA. E-mail: [email protected]
& 2013 The Society for Investigative Dermatology
COMMENTARY
‘‘small area variation’’ (Wennberg and Gittelsohn, 1973). This technique assumes that if the rates of utilization vary greatly among areas, factors other than medical appropriateness are likely to be playing a role in the use of that treatment. The high variability in the utilization of MMS as measured by the percentage of all NMSC procedures by state provides evidence that the utilization of MMS is highly unlikely to reflect the application of uniform clinical criteria. Recent Medicare data emphasize differences in the utilization of MMS (Donaldson and Coldiron, 2012). In New Mexico, 12% of NMSCs of the face, scalp, neck, hands, feet, and genitalia are treated with MMS. In Minnesota, MMS is used in 53% of such tumors. It is hard to imagine the clinical differences in these populations that would explain this difference. For NMSCs located on the trunk, arms, and legs, the proportion of tumors treated with MMS varied among states by more than 15-fold (yes by 1,500%). Not surprisingly, states with a higher proportion of tumors on face, neck, hands, feet, and genitalia had a higher proportion of MMS-treated tumors at other sites (Po0.0001) Figure 1. In 2009, B1,800 providers billed Medicare for MMS (Donaldson and Coldiron, 2012). Nearly half of these providers did o200 cases for Medicare beneficiaries. More than half of the MMS patients are likely to be Medicare beneficiaries (Smeets et al., 2004; Stern, 2010; Chren et al., 2013). Low-volume providers are less likely to provide efficient and optimal service. By contrast, slightly more than 10% of providers of MMS to Medicare beneficiaries accounted for nearly 40% of all Mohs procedures. This year, MMS is likely to cost more than two billion dollars in the United States. In addition to recurrent tumors, on clinical grounds but without robust comparative clinical efficacy data to support these ‘‘impressions,’’ one expects Mohs to be superior to excision for large tumors, those with aggressive histology, or indistinct borders in critical www.jidonline.org 1129
COMMENTARY
Clinical Implications
The study of Chren et al. (2013) adds to data from a European comparative effectiveness study that indicates that the outcome of Mohs micrographic surgery (MMS) is at most slightly superior to that of the excision for primary facial nonmelanoma skin cancer.
A large multisurgeon randomized trial would provide a robust estimate of the relative effectiveness and variability among surgeons for MMS and excision for primary nonmelanoma skin cancers.
Although needed, such a study is unlikely to be done.
In the United States, the use of Mohs for Medicare beneficiaries increased 700% between 1992 and 2009.
areas. The best comparative clinical effectiveness data suggest that for many and probably most NMSCs treated with Mohs in the United States today, excision would be equally efficacious with results measured by recurrence rates (Smeets et al., 2004; Mosterd et al., 2008; Chren et al., 2013). A large multisurgeon randomized trial would definitely provide a more robust estimate of the relative effectiveness and variability among surgeons for MMS and excision and which primary NMSCs more likely benefit from Mohs. Although needed, I doubt that such a study is likely to be conducted. The earlier work of Chren et al. (2007) suggests that quality-of-life improvements following treatment of NMSC do not differ between MMS and excision. The Dutch group assessed preferences between excision and MMS in the
general public based on a discrete choice experiment using hypothetical scenarios (Essers et al., 2010). Their conclusion was that the general public preferred MMS. However, this result may have reflected a higher probability of the recurrence after excision than what the group of Chren or their group found in their studies (Mosterd, 2008; Chren et al., 2013). The Dutch group found that the cosmetic results of excision and MMS were similar (Essers et al., 2007). A number of publications claim that MMS is no more expensive than surgical excision of primary NMSCs, but these claims do not pass the test of face validity or a quick look at reimbursement schedules. The Dutch group studied the resource utilization that is required for MMS and surgical excision of basal cell carcinoma of the face. On the basis of
Percent MMS cases on trunk and extremities
0.18 0.16 0.14 0.12 0.1 0.08 0.06 0.04 0.02 0 0
0.1
0.2 0.3 0.4 Percent MMS cases on face and other sites
0.5
0.6
Figure 1. Percent of all nonmelanoma skin cancers treated with Mohs micrographic surgery (MMS) (2009) by state and body site. x Axis: face, scalp, hands, feet, and genitalia (face and other sites). y Axis: trunk, arms, and legs (trunk and extremities). Each data point represents results for a state. The line shows the relationship between the percentage of patients treated with MMS on face, scalp, hands, feet, and genitalia versus other body sites (least squares plot). Data points for selected states are identified by color. The number of Mohs College members per million white population is provided in parenthesis (utilization data from Donaldson and Coldiron (2012). Yellow: New Mexico (2.9); red: Arkansas (3.2); purple: New York (6.6); blue: Nevada (2.8).
1130 Journal of Investigative Dermatology (2013), Volume 133
resource utilization, MMS requires more resources than excision (Essers et al., 2006). On the basis of aggregate claims data, Mohs treatment is about twice as expensive as surgical excision of NMSC (Wilson et al., 2012). With the high proportion of all NMSCs treated with MMS, it is hard to argue that these cost differences are explained solely by greater complexity of Mohs-treated cases. Previously, for most patients, the outof-pocket costs of MMS and excision have been equal. Increasingly, however, patients are sharing in the cost of the medical care they receive and paying more for more expensive procedures. With changes in reimbursement that include global payment and capitation, primary-care providers and dermatologists who diagnose NMSCs, but do not provide MMS, may be at financial risk when they choose to refer a patient for a higher-cost procedure such as the MMS. At the same time, the number of persons offering MMS continues to expand. How these trends will impact the use of and reimbursement for MMS is uncertain. Both the MMS community and the American Academy of Dermatology have recently published ‘‘Appropriate Use Criteria’’ for MMS (Connolly et al., 2012). In only 17% of 270 scenarios evaluated was MMS considered inappropriate. These ‘‘inappropriate’’ scenarios for the use of MMS largely concerned small tumors of the trunk and extremities or ‘‘actinic keratosis, with focal SCC in situ.’’ Given the variabilities in the clinical presentation of NMSC and patients’ preferences, difficulties of physicians, insurers, and patients in setting clear criteria are not surprising. For recurrent and probably high-risk primary NMSCs (but what characterize high risk is still unclear), MMS is advantageous (Smeets et al., 2004; Mosterd, 2008). However, the available data suggest that many and perhaps most MMS-treated NMSCs in the United States are not high-risk tumors. For these tumors, the decision to utilize MMS is likely to reflect the economic advantage to the provider rather than a substantial clinical advantage for the patient. Unfortunately, reimbursement policies that remove the financial motivations to perform MMS but fail to provide adequate reimbursement for
COMMENTARY
MMS of recurrent and high-risk NMSCs are most likely to impact the Mohs units that provide services to those most in need of this valuable but overused procedure. CONFLICT OF INTEREST
See related article on pg 1311
‘‘Patch’’ing Up Our Tumor Signaling Knowledge
The author states no conflict of interest.
Scott X. Atwood1,2, Ramon J. Whitson1,2 and Anthony E. Oro1
REFERENCES
The tumor suppressor Patched1 (Ptch1) possesses well-described roles in regulating sonic hedgehog (SHH) signaling in the skin and preventing the formation of basal cell carcinomas (BCCs). In this issue, Kang et al. extend their previous work to show that a naturally occurring allele of Ptch1 found in FVB mice promotes early squamous cell carcinoma (SCC) growth without aberrant activation of the SHH pathway. The study reveals new roles for Ptch1 that lie at the nexus between BCC and SCC formation.
Chren MM, Linos E, Torres J et al. (2013) Tumor recurrence 5 years after treatment of cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol 133: 1188–96 Chren MM, Sahay AP, Bertenthal DS et al. (2007) Quality-of-life outcomes of treatments for cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol 127:1351–7 Connolly S, Baker D, Coldiron B et al. (2012) AAD/ ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. J Am Acad Dermatol 67:531–50 Donaldson M, Coldiron B (2012) Mohs micrographic surgery utilization in the medicare population, 2009. Dermatol Surg 38:1427–34 Essers B, Dirksen C, Nieman F et al. (2006) Cost-effectiveness of Mohs micrographic surgery vs surgical excision for basal cell carcinoma of the face. Arch Dermatol 142: 187–94 Essers B, Dirksen C, Prins M et al. (2010) Assessing the public’s preference for surgical treatment of primary basal cell carcinoma; a discretechoice experiment in the south of the Netherlands. Dermatol Surg 36:1950–5 Essers B, Nieman F, Prins M et al. (2007) Perceptions of facial aesthetics in surgical patients with basal cell carcinoma. J Eur Acad Dermatol Venereol 21:1209–14 Maxwell S, Zuckerman S, Berenson R (2007) Use of physicians’ services under Medicare’s resourcebased payments. N Engl J Med 356:1853–61 Mosterd K, Krekels G, Nieman F et al. (2008) Surgical excision versus Mohs’ micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomized controlled trial with 5-years’ follow-up. Lancet Oncol 9:1149–56 Smeets N, Krekels G, Ostertag J et al. (2004) Surgical excision vs Mohs’ micrographic surgery for basal-cell carcinoma of the face: randomized controlled trial. Lancet 364:1766–72 Stern RS (2010) Prevalence of a history of skin cancer in 2007: results of an incidence-based model. Arch Dermatol 146:279–82 Wennberg J, Gittelsohn A (1973) Small area variations in health care delivery. Science 182:1102–8 Wilson L, Pregenzer M, Basu R et al. (2012) Fee comparisons of treatments for nonmelanoma skin cancer in a private practice academic setting. Dermatol Surg 38:570–84
Journal of Investigative Dermatology (2013) 133, 1131–1133. doi:10.1038/jid.2012.506
The sonic hedgehog (SHH) signaling pathway has key roles during embryonic development, cell fate decisions, and tumor formation (Hui and Angers, 2011; Ingham et al., 2011). SHH binds to its receptor Patched1 (Ptch1), releasing Smoothened (Smo) inhibition that results in Gli-dependent transcription of SHH target genes. Inactivating mutations in Ptch1 in the skin promotes formation of basal cell carcinomas (BCCs) at high frequency and are the cause of Gorlin syndrome in the germline (Hahn et al., 1996). Although Gorlin patients have well-characterized susceptibility to other SHH-dependent tumors, Ptch1 loss in these patients does not appear to contribute to excessive SCC development. Moreover, sporadic BCCs also rely on high levels of SHH target gene induction for tumor growth, providing the rational for development of a targeted therapy. Indeed, inhibition of the SHH pathway with Smo antagonists recently received Food and Drug Administration approval for the treatment of late advanced or metastatic BCCs, and they have shown impressive efficacy in Gorlin patients (Atwood et al., 2012). Although the role for Ptch1 in BCC tumor suppression is clear, surprisingly little is known about how this enigmatic
protein functions at a mechanistic level. Ptch1 is a member of the sterol-sensing domain family and shares identity with the ABC transporter family (Ingham et al., 2011). Although this suggests it pumps key signaling molecules, none so far has been identified unequivocably. Moreover, Ptch1 function in suppressing Smo, arguably its most oft-written role, has not been delineated. Although it is clear that SHH binding to Ptch1 activates Smo, how the two proteins interact remains unknown. Initial studies suggested that the two proteins form a complex and argued for direct allosteric inhibition (Carpenter et al., 1998; Murone et al., 1999). However, later quantitative studies indicated that Ptch1 acts catalytically, suggesting it controls an enzymatic modifier of Smo function (Ingham et al., 2000; Taipale et al., 2002). Recently, entry into the primary cilium, a microtubule based organelle, has been shown to be important for Smo function, and Ptch1 appears to regulate ciliary entry in an as yet unknown manner (Rohatgi et al., 2007). Ptch1FVB promotes Ras-induced skin tumorigenesis
Distinct from its role in controlling the SHH pathway, recent studies indicate a
1
Department of Dermatology, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA
2
These authors contributed equally to this work.
Correspondence: Anthony E. Oro, Department of Dermatology, Program in Epithelial Biology, Stanford University School of Medicine, CCSR 2145, 269 Campus Drive, Stanford, California 94305, USA. E-mail: [email protected]
www.jidonline.org 1131
Cost Effectiveness of Mohs Micrographic Surgery Robert S. Stern1 Chren’s study provides further evidence that for primary facial nonmelanoma skin cancers (NMSCs), recurrence rates with Mohs micrographic surgery (MMS) are modestly better than those for excision surgery. In 20 years, use of MMS has grown B10-fold and its cost now exceeds two billion dollars annually. Clinical experience and available data suggest that the skill of the treating physician is at least as important a determinant of outcome as the choice of MMS or excision. As patients and referring physicians increasingly share in the cost of more expensive procedures, evidence-based guidelines that establish the clinical circumstances in which the additional benefits of MMS outweigh its higher cost are needed, still lacking, and unlikely to become available. Journal of Investigative Dermatology (2013) 133, 1129–1131. doi:10.1038/jid.2012.473
Over the years, I have worked with a number of highly skilled Mohs surgeons who provide excellent care to our patients. Mohs units are one of the financial underpinnings of many departments of dermatology. The growth of Mohs micrographic surgery (MMS) over the past 35 years has been extraordinary. In 1976, I did not know anyone in the greater Boston area who was a fulltime Mohs surgeon. Now, the Mohs College lists more than two dozen to whom I could bicycle to in less than half an hour. This excludes an unknown, but not insubstantial, number of individuals who are not members of the Mohs College, but provide what they call MMS. MMS fellowships attracts many of our brightest residents. For recurrent nonmelanoma skin cancers (NMSCs) in the ‘‘H zone’’, MMS is clearly superior to excision, and in most cases is the treatment of choice (Smeets et al., 2004; Mosterd et al., 2008). However, recurrent tumors represent only a minority of all tumors treated with MMS in the United States. For primary NMSCs even in the H zone, the new study of Chren et al. (2013, this issue) as well as the Dutch study showed little difference between MMS
and excision (Smeets et al., 2004; Mosterd et al., 2008). The use of MMS may provide greater standardization and hence less variance in recurrence rates among providers than does excision. On the other hand, the study of Chren et al. (2012) suggests that the results among surgeons performing excisions may vary substantially. More predictability in the risk of recurrence may be beneficial to the individual patient with tumors at sites such as the ‘‘H zone’’ where recurrence is likely to result in substantial morbidity, but the data available argue more strongly for using a skilled physician than choosing an MMS over excision for primary NMSC. Medicare data document the exceptional growth in the utilization of MMS. From 1992 to 2002, the utilization of MMS increased 332% (Maxwell et al., 2007). By 2009, the rate of the use of MMS was 700% greater than in 1992 (Donaldson and Coldiron, 2012). Extrapolated to 2013, nearly 2% of all Medicare recipients will have MMS in that year. Is that too many or not enough? When more robust data are not available, one approach to assessing the appropriateness of the utilization of a procedure in various populations is
1
Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Correspondence: Robert S. Stern, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, GZ 522, Boston, Massachusetts 02215, USA. E-mail: [email protected]
& 2013 The Society for Investigative Dermatology
COMMENTARY
‘‘small area variation’’ (Wennberg and Gittelsohn, 1973). This technique assumes that if the rates of utilization vary greatly among areas, factors other than medical appropriateness are likely to be playing a role in the use of that treatment. The high variability in the utilization of MMS as measured by the percentage of all NMSC procedures by state provides evidence that the utilization of MMS is highly unlikely to reflect the application of uniform clinical criteria. Recent Medicare data emphasize differences in the utilization of MMS (Donaldson and Coldiron, 2012). In New Mexico, 12% of NMSCs of the face, scalp, neck, hands, feet, and genitalia are treated with MMS. In Minnesota, MMS is used in 53% of such tumors. It is hard to imagine the clinical differences in these populations that would explain this difference. For NMSCs located on the trunk, arms, and legs, the proportion of tumors treated with MMS varied among states by more than 15-fold (yes by 1,500%). Not surprisingly, states with a higher proportion of tumors on face, neck, hands, feet, and genitalia had a higher proportion of MMS-treated tumors at other sites (Po0.0001) Figure 1. In 2009, B1,800 providers billed Medicare for MMS (Donaldson and Coldiron, 2012). Nearly half of these providers did o200 cases for Medicare beneficiaries. More than half of the MMS patients are likely to be Medicare beneficiaries (Smeets et al., 2004; Stern, 2010; Chren et al., 2013). Low-volume providers are less likely to provide efficient and optimal service. By contrast, slightly more than 10% of providers of MMS to Medicare beneficiaries accounted for nearly 40% of all Mohs procedures. This year, MMS is likely to cost more than two billion dollars in the United States. In addition to recurrent tumors, on clinical grounds but without robust comparative clinical efficacy data to support these ‘‘impressions,’’ one expects Mohs to be superior to excision for large tumors, those with aggressive histology, or indistinct borders in critical www.jidonline.org 1129
COMMENTARY
Clinical Implications
The study of Chren et al. (2013) adds to data from a European comparative effectiveness study that indicates that the outcome of Mohs micrographic surgery (MMS) is at most slightly superior to that of the excision for primary facial nonmelanoma skin cancer.
A large multisurgeon randomized trial would provide a robust estimate of the relative effectiveness and variability among surgeons for MMS and excision for primary nonmelanoma skin cancers.
Although needed, such a study is unlikely to be done.
In the United States, the use of Mohs for Medicare beneficiaries increased 700% between 1992 and 2009.
areas. The best comparative clinical effectiveness data suggest that for many and probably most NMSCs treated with Mohs in the United States today, excision would be equally efficacious with results measured by recurrence rates (Smeets et al., 2004; Mosterd et al., 2008; Chren et al., 2013). A large multisurgeon randomized trial would definitely provide a more robust estimate of the relative effectiveness and variability among surgeons for MMS and excision and which primary NMSCs more likely benefit from Mohs. Although needed, I doubt that such a study is likely to be conducted. The earlier work of Chren et al. (2007) suggests that quality-of-life improvements following treatment of NMSC do not differ between MMS and excision. The Dutch group assessed preferences between excision and MMS in the
general public based on a discrete choice experiment using hypothetical scenarios (Essers et al., 2010). Their conclusion was that the general public preferred MMS. However, this result may have reflected a higher probability of the recurrence after excision than what the group of Chren or their group found in their studies (Mosterd, 2008; Chren et al., 2013). The Dutch group found that the cosmetic results of excision and MMS were similar (Essers et al., 2007). A number of publications claim that MMS is no more expensive than surgical excision of primary NMSCs, but these claims do not pass the test of face validity or a quick look at reimbursement schedules. The Dutch group studied the resource utilization that is required for MMS and surgical excision of basal cell carcinoma of the face. On the basis of
Percent MMS cases on trunk and extremities
0.18 0.16 0.14 0.12 0.1 0.08 0.06 0.04 0.02 0 0
0.1
0.2 0.3 0.4 Percent MMS cases on face and other sites
0.5
0.6
Figure 1. Percent of all nonmelanoma skin cancers treated with Mohs micrographic surgery (MMS) (2009) by state and body site. x Axis: face, scalp, hands, feet, and genitalia (face and other sites). y Axis: trunk, arms, and legs (trunk and extremities). Each data point represents results for a state. The line shows the relationship between the percentage of patients treated with MMS on face, scalp, hands, feet, and genitalia versus other body sites (least squares plot). Data points for selected states are identified by color. The number of Mohs College members per million white population is provided in parenthesis (utilization data from Donaldson and Coldiron (2012). Yellow: New Mexico (2.9); red: Arkansas (3.2); purple: New York (6.6); blue: Nevada (2.8).
1130 Journal of Investigative Dermatology (2013), Volume 133
resource utilization, MMS requires more resources than excision (Essers et al., 2006). On the basis of aggregate claims data, Mohs treatment is about twice as expensive as surgical excision of NMSC (Wilson et al., 2012). With the high proportion of all NMSCs treated with MMS, it is hard to argue that these cost differences are explained solely by greater complexity of Mohs-treated cases. Previously, for most patients, the outof-pocket costs of MMS and excision have been equal. Increasingly, however, patients are sharing in the cost of the medical care they receive and paying more for more expensive procedures. With changes in reimbursement that include global payment and capitation, primary-care providers and dermatologists who diagnose NMSCs, but do not provide MMS, may be at financial risk when they choose to refer a patient for a higher-cost procedure such as the MMS. At the same time, the number of persons offering MMS continues to expand. How these trends will impact the use of and reimbursement for MMS is uncertain. Both the MMS community and the American Academy of Dermatology have recently published ‘‘Appropriate Use Criteria’’ for MMS (Connolly et al., 2012). In only 17% of 270 scenarios evaluated was MMS considered inappropriate. These ‘‘inappropriate’’ scenarios for the use of MMS largely concerned small tumors of the trunk and extremities or ‘‘actinic keratosis, with focal SCC in situ.’’ Given the variabilities in the clinical presentation of NMSC and patients’ preferences, difficulties of physicians, insurers, and patients in setting clear criteria are not surprising. For recurrent and probably high-risk primary NMSCs (but what characterize high risk is still unclear), MMS is advantageous (Smeets et al., 2004; Mosterd, 2008). However, the available data suggest that many and perhaps most MMS-treated NMSCs in the United States are not high-risk tumors. For these tumors, the decision to utilize MMS is likely to reflect the economic advantage to the provider rather than a substantial clinical advantage for the patient. Unfortunately, reimbursement policies that remove the financial motivations to perform MMS but fail to provide adequate reimbursement for
COMMENTARY
MMS of recurrent and high-risk NMSCs are most likely to impact the Mohs units that provide services to those most in need of this valuable but overused procedure. CONFLICT OF INTEREST
See related article on pg 1311
‘‘Patch’’ing Up Our Tumor Signaling Knowledge
The author states no conflict of interest.
Scott X. Atwood1,2, Ramon J. Whitson1,2 and Anthony E. Oro1
REFERENCES
The tumor suppressor Patched1 (Ptch1) possesses well-described roles in regulating sonic hedgehog (SHH) signaling in the skin and preventing the formation of basal cell carcinomas (BCCs). In this issue, Kang et al. extend their previous work to show that a naturally occurring allele of Ptch1 found in FVB mice promotes early squamous cell carcinoma (SCC) growth without aberrant activation of the SHH pathway. The study reveals new roles for Ptch1 that lie at the nexus between BCC and SCC formation.
Chren MM, Linos E, Torres J et al. (2013) Tumor recurrence 5 years after treatment of cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol 133: 1188–96 Chren MM, Sahay AP, Bertenthal DS et al. (2007) Quality-of-life outcomes of treatments for cutaneous basal cell carcinoma and squamous cell carcinoma. J Invest Dermatol 127:1351–7 Connolly S, Baker D, Coldiron B et al. (2012) AAD/ ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. J Am Acad Dermatol 67:531–50 Donaldson M, Coldiron B (2012) Mohs micrographic surgery utilization in the medicare population, 2009. Dermatol Surg 38:1427–34 Essers B, Dirksen C, Nieman F et al. (2006) Cost-effectiveness of Mohs micrographic surgery vs surgical excision for basal cell carcinoma of the face. Arch Dermatol 142: 187–94 Essers B, Dirksen C, Prins M et al. (2010) Assessing the public’s preference for surgical treatment of primary basal cell carcinoma; a discretechoice experiment in the south of the Netherlands. Dermatol Surg 36:1950–5 Essers B, Nieman F, Prins M et al. (2007) Perceptions of facial aesthetics in surgical patients with basal cell carcinoma. J Eur Acad Dermatol Venereol 21:1209–14 Maxwell S, Zuckerman S, Berenson R (2007) Use of physicians’ services under Medicare’s resourcebased payments. N Engl J Med 356:1853–61 Mosterd K, Krekels G, Nieman F et al. (2008) Surgical excision versus Mohs’ micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomized controlled trial with 5-years’ follow-up. Lancet Oncol 9:1149–56 Smeets N, Krekels G, Ostertag J et al. (2004) Surgical excision vs Mohs’ micrographic surgery for basal-cell carcinoma of the face: randomized controlled trial. Lancet 364:1766–72 Stern RS (2010) Prevalence of a history of skin cancer in 2007: results of an incidence-based model. Arch Dermatol 146:279–82 Wennberg J, Gittelsohn A (1973) Small area variations in health care delivery. Science 182:1102–8 Wilson L, Pregenzer M, Basu R et al. (2012) Fee comparisons of treatments for nonmelanoma skin cancer in a private practice academic setting. Dermatol Surg 38:570–84
Journal of Investigative Dermatology (2013) 133, 1131–1133. doi:10.1038/jid.2012.506
The sonic hedgehog (SHH) signaling pathway has key roles during embryonic development, cell fate decisions, and tumor formation (Hui and Angers, 2011; Ingham et al., 2011). SHH binds to its receptor Patched1 (Ptch1), releasing Smoothened (Smo) inhibition that results in Gli-dependent transcription of SHH target genes. Inactivating mutations in Ptch1 in the skin promotes formation of basal cell carcinomas (BCCs) at high frequency and are the cause of Gorlin syndrome in the germline (Hahn et al., 1996). Although Gorlin patients have well-characterized susceptibility to other SHH-dependent tumors, Ptch1 loss in these patients does not appear to contribute to excessive SCC development. Moreover, sporadic BCCs also rely on high levels of SHH target gene induction for tumor growth, providing the rational for development of a targeted therapy. Indeed, inhibition of the SHH pathway with Smo antagonists recently received Food and Drug Administration approval for the treatment of late advanced or metastatic BCCs, and they have shown impressive efficacy in Gorlin patients (Atwood et al., 2012). Although the role for Ptch1 in BCC tumor suppression is clear, surprisingly little is known about how this enigmatic
protein functions at a mechanistic level. Ptch1 is a member of the sterol-sensing domain family and shares identity with the ABC transporter family (Ingham et al., 2011). Although this suggests it pumps key signaling molecules, none so far has been identified unequivocably. Moreover, Ptch1 function in suppressing Smo, arguably its most oft-written role, has not been delineated. Although it is clear that SHH binding to Ptch1 activates Smo, how the two proteins interact remains unknown. Initial studies suggested that the two proteins form a complex and argued for direct allosteric inhibition (Carpenter et al., 1998; Murone et al., 1999). However, later quantitative studies indicated that Ptch1 acts catalytically, suggesting it controls an enzymatic modifier of Smo function (Ingham et al., 2000; Taipale et al., 2002). Recently, entry into the primary cilium, a microtubule based organelle, has been shown to be important for Smo function, and Ptch1 appears to regulate ciliary entry in an as yet unknown manner (Rohatgi et al., 2007). Ptch1FVB promotes Ras-induced skin tumorigenesis
Distinct from its role in controlling the SHH pathway, recent studies indicate a
1
Department of Dermatology, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA
2
These authors contributed equally to this work.
Correspondence: Anthony E. Oro, Department of Dermatology, Program in Epithelial Biology, Stanford University School of Medicine, CCSR 2145, 269 Campus Drive, Stanford, California 94305, USA. E-mail: [email protected]
www.jidonline.org 1131