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Risk of synchronous and metachronous second nonmelanoma skin cancer when referred for Mohs micrographic surgery
Risk of synchronous and metachronous second nonmelanoma skin cancer when referred for Mohs micrographic surgery Malcolm Schinstine, PhD, and Glenn D. Goldman, MD Burlington, Vermont Background: Patients with basal cell carcinoma and cutaneous squamous cell carcinoma are at substantial risk for the onset of a second nonmelanoma skin cancer (NMSC). Objective: Our purpose was to determine the incidence of multiple (synchronous) NMSC at presentation to an academic Mohs micrographic surgery referral center and to note the incidence of second lesions occurring in a metachronous fashion. Methods: A retrospective study was conducted of 456 consecutive patients who presented for Mohs surgery over a 2-year period. Patients were assessed at initial visits for the presence of multiple NMSCs and were subsequently examined over 2 years for the onset of new NMSCs. Results: More than 39% of patients initially referred for Mohs surgery with a basal cell or squamous cell carcinoma either presented with multiple primary lesions or experienced a subsequent NMSC within 2 years. These tumors were divided almost equally between multiple primary NMSC at presentation and subsequent (metachronous) tumors. Conclusion: Patients referred for Mohs surgery in an academic setting are a select group at extremely high risk of additional NMSCs at or shortly after presentation for the index lesion. (J Am Acad Dermatol 2001;44:497-9.)
B
asal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common cancers in the United States, with more than 750,000 new lesions per year. In addition, the incidence of nonmelanoma skin cancer (NMSC) is expected to double in the next 30 years. Studies have shown that people with a history of NMSC, followed up over a 5-year period, are at increased risk of experiencing a second skin cancer.1 Few authors have reported on the incidence of new NMSC 1 to 2 years after treatment for a primary BCC or SCC. It was our impression that in our practice the incidence of multiple tumors and second NMSC was already very high 1 to 2 years after Mohs microgaphic surgery (MMS). In the current study, we have used a retrospective analysis and careful follow-up to determine the inci-
From the University of Vermont College of Medicine and Fletcher Allen Health Care, UHC Campus. Reprint requests: Glenn Goldman, MD, University of Vermont College of Medicine and Fletcher Allen Health Care, UHC Campus, 1 S Prospect St, Burlington, VT 05401. Copyright © 2001 by the American Academy of Dermatology, Inc. 0190-9622/2001/$35.00 + 0 16/1/110646 doi:10.1067/mjd.2001.110646
Abbreviations used: BCC: MMS: NMSC: SCC:
basal cell carcinoma Mohs micrographic surgery nonmelanoma skin cancer squamous cell carcinoma
dence of multiple NMSC at presentation for MMS and the 1- to 2-year incidence of subsequent NMSC in the same group.
METHODS A total of 456 patients who underwent MMS between September 1996 and September 1998 were included in this study. All patients were white. Of original lesions, 96% were located on the head and neck. Fewer than 10 patients were immunosuppressed. Approximately half of patients were older than 65 years. All diagnoses were confirmed by histopathologic evaluation. The first biopsy-confirmed NMSC was considered the patient’s “first” cancer. Patients were examined at least once, but usually 2 to 3 times, in a 2-year period after MMS by one of us (G. G.) and/or the referring physician, more than 90% of 497
498 Schinstine and Goldman
J AM ACAD DERMATOL MARCH 2001
Table I. Occurrence of new and multiple NMSCs
Primary lesion, No. (%)
No. and rate (%) of subsequent (metachronous) NMSC
No. and rate (%) presenting with multiple (synchronous) NMSC
BCC 383 (87.0) SCC 57 (13.0) Total 440 (100)
72 (18.8) 14 (24.6) 86 (19.5)
74 (19.3) 13 (22.8) 87 (19.8)
whom were dermatologists. Patients who had not been seen in follow-up were contacted by telephone and examined. Patient records were reviewed retrospectively by both authors. Of the 456 charts reviewed, 13 patients were lost to follow-up (3%). Patients were grouped according to type of NMSC (ie, BCC vs SCC), location of the primary lesion, the presence of multiple NMSCs at initial evaluation, occurrence of a second NMSC after MMS, age younger or older than 65 years, and gender. Patients who presented with multiple tumors were counted only once. In other words, subsequent or metachronous lesions were only counted in patients who originally presented with only 1 tumor.
RESULTS A total of 440 charts that met study criteria were included; results are summarized in Table I. There were approximately an equal number of men (211, 48%) and women (229, 52.0%) in the study. Of these, 383 (87.0%) initially presented with BCC and 57 (12.9%) presented with SCC. In those patients presenting with BCC, 74 (19.3%) were noted to have synchronous second NMSCs, and 72 (18.8%) were diagnosed with a metachronous NMSC. In comparison, of the 57 patients presenting with SCC, 13 (22.8%) presented with multiple NMSC, and 14 (24.6%) had metachronous NMSC. Overall, 87 of 440 patients (19.8%) had multiple NMSC at the time of presentation, and an additional 19.5% experienced new NMSC within 2 years after MMS. In total, 173 of 440 patients (39.3%) either presented with a second primary NMSC or experienced an additional NMSC within the 2-year follow-up period. Forty-seven women (20.5%) and 40 men (19.0%) presented with multiple NMSCs. Thirty-six women (15.7%) and 51 men (24.2%) experienced a metachronous NMSC. Notably, of 35 men who presented with SCC, 19 (54.3%) either presented with a second NMSC or had a second lesion within 2 years.
DISCUSSION In our Mohs practice we have had the impression that our new and return patients seemed to have a
very high incidence of multiple tumors and subsequent NMSC. We therefore sought to determine the actual incidence of new NMSC after MMS. We have demonstrated that approximately 39% of patients treated for an NMSC in an academic setting by MMS either presented with multiple primary NMSC or experienced another NMSC within 1 to 2 years. Remarkably, 19.8% of patients presented with multiple lesions at their initial consultation. Earlier studies have concentrated on the occurrence of new NMSC 5 years after treatment, with few investigators looking at the onset of a new NMSC over a shorter time frame.2-6 In the few studies looking at a follow-up period of less than 5 years, the incidence of new NMSCs has ranged from 14.6% to 22%. For example, Marghoob et al4 reported that 14.6% of patients treated for BCC had another BCC within 1 year after removal of the initial cancer. Karagas et al3 reported similar results with 17% of patients having a new NMSC after excision. Robinson6 showed that 22% of patients treated for BCC by MMS had a subsequent BCC within 5 years. Our results demonstrate a very high incidence of multiple primary tumors at presentation and a similarly high level of subsequent tumor formation within a short 2-year follow-up period. We believe the main reason for this high incidence is the selection of patients referred to an academic center for MMS and an abundance of index tumors located on the head and neck. Other authors have reported that patients initially presenting with multiple lesions are more likely to have new primary NMSC,1,5 and this was confirmed in our study. Many of our patients with multiple tumors at presentation have had upwards of 10 to 20 tumors over the last 2 years. In our practice, 39.3% of patients treated with MMS for BCC either presented with multiple tumors or experienced another NMSC within 2 years of initial presentation. In comparison, 47.4% of patients diagnosed with SCC and referred for MMS either presented with multiple tumors or had a subsequent NMSC. It has been suggested that individuals with SCC may be more sensitive to the carcinogenic effects of solar radiation.7 More likely, patients with SCC may have a higher cumulative sun exposure history than patients presenting with BCC.8 Karagas et al3 previously noted that men have a 50% greater chance of experiencing another BCC and a 300% greater chance of having a second SCC within 5 years of a primary NMSC. In contrast, Marghoob et al4 estimated the 5-year occurrence rate of a new BCC to be nearly equal in men and women, 47.4% and 42.9%, respectively. In our study, a nearly equal percentage of men and women had a subsequent NMSC after removal of a BCC.
Schinstine and Goldman 499
J AM ACAD DERMATOL VOLUME 44, NUMBER 3
However, men treated for SCC in our study presented with or developed additional NMSC at an astoundingly high rate of 54.3%. These numbers are similar to those reported previously and are consistent with the clinical impression that men with high cumulative sun exposure and facial SCC are at very high risk of experiencing subsequent NMSC and its related consequences. Because of the high incidence of a second NMSC, it has been suggested that patients with NMSCs be checked for new tumors at 3-month intervals for at least 1 year.2 From a practical standpoint, this may be difficult in an active practice. In light of the fact that we noted no adverse sequelae within a 6-month follow-up period, this is our standard practice for patients with BCC. Patients with SCC are seen at 3 months, given the high likelihood of the onset of new lesions, and because of the risk of metastasis. All patients are counseled that there is approximately a 40% chance that they will be seen again within 2 years with another cutaneous carcinoma. Because patients are highly likely to have multiple tumors at presentation, either we or the referring dermatologist performs a full skin check before the surgery. Mohs surgeons should be aware that they deal with
a skewed population in whom the incidence of second carcinoma is exceptionally high. REFERENCES 1. Karagas MR. Occurrence of cutaneous basal cell and squamous cell malignancies among those with a prior history of skin cancer. J Invest Dermatol 1994;102:10S-13S. 2. Frankel DH, Hanusa BH, Zitelli JA. New primary nonmelanoma skin cancer in patients with a history of squamous cell carcinoma of the skin. J Am Acad Dermatol 1992;26:720-6. 3. Karagas MR, Stukel TA, Greenberg ER, Baron JA, Mott LA, Stern RS, et al. Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer. JAMA 1992;267:3305-10. 4. Marghoob A, Kopf AW, Bart RS, Sanfilippo L, Silverman MK, Lee P, et al. Risk of another basal cell carcinoma developing after treatment of a basal cell carcinoma. J Am Acad Dermatol 1993; 28:22-8. 5. Schreiber MM, Moon TE, Fox SH, Davidson J. The risk of developing subsequent nonmelanoma skin cancers. J Am Acad Dermatol 1990;23:1114-8. 6. Robinson JK. Risk of developing another basal cell carcinoma: a 5-year prospective study. Cancer 1987;60:118-20. 7. Vitaliano PP, Urbach F. The relative importance of risk factors in nonmelanoma carcinoma. Arch Dermatol 1980;116:454-6. 8. Urbach F. Ultraviolet radiation: Interaction with biological molecules. In: Becker FF, editor. Cancer. Plenum Press; 1969. p. 44151.
RECEIVE TABLES OF CONTENTS BY E-MAIL To receive the tables of contents by e-mail, sign up through our Web site at: http://www.mosby.com/jaad Choose E-mail Notification. Simply type your e-mail address in the box and click the Subscribe button. Alternatively, you may send an e-mail message to [email protected]. Leave the subject line blank and type the following as the body of your message: subscribe jaad_toc You will receive an e-mail message to confirm that you have been added to the mailing list. Note that table of contents e-mails will be sent out when a new issue is posted to the Web site.
B
asal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common cancers in the United States, with more than 750,000 new lesions per year. In addition, the incidence of nonmelanoma skin cancer (NMSC) is expected to double in the next 30 years. Studies have shown that people with a history of NMSC, followed up over a 5-year period, are at increased risk of experiencing a second skin cancer.1 Few authors have reported on the incidence of new NMSC 1 to 2 years after treatment for a primary BCC or SCC. It was our impression that in our practice the incidence of multiple tumors and second NMSC was already very high 1 to 2 years after Mohs microgaphic surgery (MMS). In the current study, we have used a retrospective analysis and careful follow-up to determine the inci-
From the University of Vermont College of Medicine and Fletcher Allen Health Care, UHC Campus. Reprint requests: Glenn Goldman, MD, University of Vermont College of Medicine and Fletcher Allen Health Care, UHC Campus, 1 S Prospect St, Burlington, VT 05401. Copyright © 2001 by the American Academy of Dermatology, Inc. 0190-9622/2001/$35.00 + 0 16/1/110646 doi:10.1067/mjd.2001.110646
Abbreviations used: BCC: MMS: NMSC: SCC:
basal cell carcinoma Mohs micrographic surgery nonmelanoma skin cancer squamous cell carcinoma
dence of multiple NMSC at presentation for MMS and the 1- to 2-year incidence of subsequent NMSC in the same group.
METHODS A total of 456 patients who underwent MMS between September 1996 and September 1998 were included in this study. All patients were white. Of original lesions, 96% were located on the head and neck. Fewer than 10 patients were immunosuppressed. Approximately half of patients were older than 65 years. All diagnoses were confirmed by histopathologic evaluation. The first biopsy-confirmed NMSC was considered the patient’s “first” cancer. Patients were examined at least once, but usually 2 to 3 times, in a 2-year period after MMS by one of us (G. G.) and/or the referring physician, more than 90% of 497
498 Schinstine and Goldman
J AM ACAD DERMATOL MARCH 2001
Table I. Occurrence of new and multiple NMSCs
Primary lesion, No. (%)
No. and rate (%) of subsequent (metachronous) NMSC
No. and rate (%) presenting with multiple (synchronous) NMSC
BCC 383 (87.0) SCC 57 (13.0) Total 440 (100)
72 (18.8) 14 (24.6) 86 (19.5)
74 (19.3) 13 (22.8) 87 (19.8)
whom were dermatologists. Patients who had not been seen in follow-up were contacted by telephone and examined. Patient records were reviewed retrospectively by both authors. Of the 456 charts reviewed, 13 patients were lost to follow-up (3%). Patients were grouped according to type of NMSC (ie, BCC vs SCC), location of the primary lesion, the presence of multiple NMSCs at initial evaluation, occurrence of a second NMSC after MMS, age younger or older than 65 years, and gender. Patients who presented with multiple tumors were counted only once. In other words, subsequent or metachronous lesions were only counted in patients who originally presented with only 1 tumor.
RESULTS A total of 440 charts that met study criteria were included; results are summarized in Table I. There were approximately an equal number of men (211, 48%) and women (229, 52.0%) in the study. Of these, 383 (87.0%) initially presented with BCC and 57 (12.9%) presented with SCC. In those patients presenting with BCC, 74 (19.3%) were noted to have synchronous second NMSCs, and 72 (18.8%) were diagnosed with a metachronous NMSC. In comparison, of the 57 patients presenting with SCC, 13 (22.8%) presented with multiple NMSC, and 14 (24.6%) had metachronous NMSC. Overall, 87 of 440 patients (19.8%) had multiple NMSC at the time of presentation, and an additional 19.5% experienced new NMSC within 2 years after MMS. In total, 173 of 440 patients (39.3%) either presented with a second primary NMSC or experienced an additional NMSC within the 2-year follow-up period. Forty-seven women (20.5%) and 40 men (19.0%) presented with multiple NMSCs. Thirty-six women (15.7%) and 51 men (24.2%) experienced a metachronous NMSC. Notably, of 35 men who presented with SCC, 19 (54.3%) either presented with a second NMSC or had a second lesion within 2 years.
DISCUSSION In our Mohs practice we have had the impression that our new and return patients seemed to have a
very high incidence of multiple tumors and subsequent NMSC. We therefore sought to determine the actual incidence of new NMSC after MMS. We have demonstrated that approximately 39% of patients treated for an NMSC in an academic setting by MMS either presented with multiple primary NMSC or experienced another NMSC within 1 to 2 years. Remarkably, 19.8% of patients presented with multiple lesions at their initial consultation. Earlier studies have concentrated on the occurrence of new NMSC 5 years after treatment, with few investigators looking at the onset of a new NMSC over a shorter time frame.2-6 In the few studies looking at a follow-up period of less than 5 years, the incidence of new NMSCs has ranged from 14.6% to 22%. For example, Marghoob et al4 reported that 14.6% of patients treated for BCC had another BCC within 1 year after removal of the initial cancer. Karagas et al3 reported similar results with 17% of patients having a new NMSC after excision. Robinson6 showed that 22% of patients treated for BCC by MMS had a subsequent BCC within 5 years. Our results demonstrate a very high incidence of multiple primary tumors at presentation and a similarly high level of subsequent tumor formation within a short 2-year follow-up period. We believe the main reason for this high incidence is the selection of patients referred to an academic center for MMS and an abundance of index tumors located on the head and neck. Other authors have reported that patients initially presenting with multiple lesions are more likely to have new primary NMSC,1,5 and this was confirmed in our study. Many of our patients with multiple tumors at presentation have had upwards of 10 to 20 tumors over the last 2 years. In our practice, 39.3% of patients treated with MMS for BCC either presented with multiple tumors or experienced another NMSC within 2 years of initial presentation. In comparison, 47.4% of patients diagnosed with SCC and referred for MMS either presented with multiple tumors or had a subsequent NMSC. It has been suggested that individuals with SCC may be more sensitive to the carcinogenic effects of solar radiation.7 More likely, patients with SCC may have a higher cumulative sun exposure history than patients presenting with BCC.8 Karagas et al3 previously noted that men have a 50% greater chance of experiencing another BCC and a 300% greater chance of having a second SCC within 5 years of a primary NMSC. In contrast, Marghoob et al4 estimated the 5-year occurrence rate of a new BCC to be nearly equal in men and women, 47.4% and 42.9%, respectively. In our study, a nearly equal percentage of men and women had a subsequent NMSC after removal of a BCC.
Schinstine and Goldman 499
J AM ACAD DERMATOL VOLUME 44, NUMBER 3
However, men treated for SCC in our study presented with or developed additional NMSC at an astoundingly high rate of 54.3%. These numbers are similar to those reported previously and are consistent with the clinical impression that men with high cumulative sun exposure and facial SCC are at very high risk of experiencing subsequent NMSC and its related consequences. Because of the high incidence of a second NMSC, it has been suggested that patients with NMSCs be checked for new tumors at 3-month intervals for at least 1 year.2 From a practical standpoint, this may be difficult in an active practice. In light of the fact that we noted no adverse sequelae within a 6-month follow-up period, this is our standard practice for patients with BCC. Patients with SCC are seen at 3 months, given the high likelihood of the onset of new lesions, and because of the risk of metastasis. All patients are counseled that there is approximately a 40% chance that they will be seen again within 2 years with another cutaneous carcinoma. Because patients are highly likely to have multiple tumors at presentation, either we or the referring dermatologist performs a full skin check before the surgery. Mohs surgeons should be aware that they deal with
a skewed population in whom the incidence of second carcinoma is exceptionally high. REFERENCES 1. Karagas MR. Occurrence of cutaneous basal cell and squamous cell malignancies among those with a prior history of skin cancer. J Invest Dermatol 1994;102:10S-13S. 2. Frankel DH, Hanusa BH, Zitelli JA. New primary nonmelanoma skin cancer in patients with a history of squamous cell carcinoma of the skin. J Am Acad Dermatol 1992;26:720-6. 3. Karagas MR, Stukel TA, Greenberg ER, Baron JA, Mott LA, Stern RS, et al. Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer. JAMA 1992;267:3305-10. 4. Marghoob A, Kopf AW, Bart RS, Sanfilippo L, Silverman MK, Lee P, et al. Risk of another basal cell carcinoma developing after treatment of a basal cell carcinoma. J Am Acad Dermatol 1993; 28:22-8. 5. Schreiber MM, Moon TE, Fox SH, Davidson J. The risk of developing subsequent nonmelanoma skin cancers. J Am Acad Dermatol 1990;23:1114-8. 6. Robinson JK. Risk of developing another basal cell carcinoma: a 5-year prospective study. Cancer 1987;60:118-20. 7. Vitaliano PP, Urbach F. The relative importance of risk factors in nonmelanoma carcinoma. Arch Dermatol 1980;116:454-6. 8. Urbach F. Ultraviolet radiation: Interaction with biological molecules. In: Becker FF, editor. Cancer. Plenum Press; 1969. p. 44151.
RECEIVE TABLES OF CONTENTS BY E-MAIL To receive the tables of contents by e-mail, sign up through our Web site at: http://www.mosby.com/jaad Choose E-mail Notification. Simply type your e-mail address in the box and click the Subscribe button. Alternatively, you may send an e-mail message to [email protected]. Leave the subject line blank and type the following as the body of your message: subscribe jaad_toc You will receive an e-mail message to confirm that you have been added to the mailing list. Note that table of contents e-mails will be sent out when a new issue is posted to the Web site.