Ir J Med Sci DOI 10.1007/s11845-014-1157-5
ORIGINAL ARTICLE
Malignant melanoma: factors affecting the surgical interval from excision biopsy to definitive surgical management M. R. Boland • R. S. Prichard • G. A. Bass • Z. Al-Hilli • A. Levendale D. Gibbons • K. Sheahan • B. Kirby • E. W. McDermott • D. Evoy
•
Received: 21 January 2014 / Accepted: 3 June 2014 Ó Royal Academy of Medicine in Ireland 2014
Abstract Introduction Surgery remains the mainstay of treatment for malignant melanoma. Despite previous studies examining the surgical interval (SI) between the diagnostic excision biopsy (DEB) and definitive surgical management there remains few guidelines regarding an optimal time interval. The aim of this study was to determine the SI between DEB and definitive surgery and elucidate factors associated with delays in management of malignant melanoma. Methods A retrospective study of 107 consecutive patients who had a DEB and subsequent wide local excision between January 2011 and June 2012 was performed. Mode of referral and dates of diagnostic biopsy/definitive surgery were documented. Patient demographics and tumour characteristics were reviewed. Results The mean age was 59.6 years, and male:female ratio was 1:1.3. Median duration of the SI was 41 ± 27 days (range 6–137 days). The SI was increased when dermatologists performed the DEB as opposed to general surgeons (p = 0.035). The anatomic location of the lesion predicted the SI, with lesions of the head/neck undergoing definitive excision 48 ± 32.3 days after DEB M. R. Boland (&) R. S. Prichard G. A. Bass Z. Al-Hilli A. Levendale E. W. McDermott D. Evoy Departments of General Surgery, St Vincent’s Healthcare Group, Elm Park, Dublin 4, Ireland e-mail: [email protected] D. Gibbons K. Sheahan Departments of Pathology, St Vincent’s Healthcare Group, Elm Park, Dublin 4, Ireland B. Kirby Departments of Dermatology, St Vincent’s Healthcare Group, Elm Park, Dublin 4, Ireland
vs. 37.5 ± 22.6 days for all other sites (p = 0.001). Neither demographic factors nor histopathological prognostic features affected the SI. Reasons for a prolonged SI included referrals to different services and time for preoperative planning. Conclusions Significant variations were noted in the SI predominantly accounted for by mode of referral and location of the malignant melanoma. Further investigation is required to elucidate factors affecting the SI and its subsequent effect on patient outcomes. Keywords Melanoma Surgery Diagnosis Biopsy Excision Interval
Introduction Recent decades have seen an increase in the incidence of malignant melanoma and it remains the major cause of skin cancer deaths [1]. Outcome improvements will occur with a streamlined management plan to ensure timely diagnosis and definitive management. Despite advances in the molecular understanding of melanoma and improvements in adjuvant treatments, surgery remains the mainstay of treatment. Surgery is usually a two-stage approach, encompassing a diagnostic excision biopsy (DEB) followed by a definitive wide local excision (WLE) and sentinel node mapping when indicated. The aim of the second procedure is firstly to ensure that an adequate margin depending on Breslow depth has been excised, secondly to excise adjacent epidermal melanocytes that may have undergone a field change and have malignant potential and thirdly to stage the regional lymph node basin for metastatic disease [2, 3]. The surgical interval (SI) between these two stages has been
123
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examined by three previously published studies [4–6]. A study by McKenna et al. [4] examined the relationship between the SI and clinical outcomes including overall and disease-free survival and found no statistically significant correlation. The other two studies [5, 6], both from the United States, investigated the same relationship and whilst they found similar outcomes, they did notice a correlation between an increasing SI and reduced overall and disease-free survival. The changing surgical management of melanoma with the use of narrower surgical margins has seen an increase in the number of dermatologists performing at least the diagnostic excision. Therefore, management pathways will be dictated not only by local referral patterns but also by factors, such as individuals having a specialist interest in the management of melanoma. Interestingly only the European Dermatology Forum states that definitive surgical management should occur preferentially within 4–6 weeks of the initial diagnosis [7]. The aim of this paper was to assess the duration of SI between DEB and subsequent WLE and to assess the factors associated with a delay in the SI.
Table 1 Patient and tumour characteristics No of patients
107
Sex Male
44 (41 %)
Female
63 (59 %)
Age Mean
59.6 years
Tumour type Superficial spreading
43
Nodular
27
Lentigo maligna
13
Mixed
12
Naevoid/AL/other
12
Anatomical location Scalp/ear
4 (3.7 %)
Face Neck
22 (20.6 %) 2 (1.8 %)
Trunk
4 (3.7 %)
Back
15 (14 %)
Upper limbs
27 (25.2 %)
Lower limbs
32 (29.9 %)
Other
1 (0.9 %)
Clinicopathological features
Methods
Clark’s level Breslow depth
Median = 11 mm
A retrospective review of a prospectively maintained database including all adult patients diagnosed with primary invasive cutaneous malignant melanoma who underwent a DEB followed by a WLE between January 2010 and June 2011 within a tertiary referral centre was performed. Demographic data, clinicopathological characteristics of the tumours and staging investigations were recorded. The type of medical professional who carried out the DEB was recorded as follows: dermatologist, plastic surgeon, general surgeon or other. The surgical interval was defined as the time period in days between DEB and WLE and was calculated on an individual patient basis. Exclusion criteria included patients who had undergone either a DEB or an incisional biopsy only and those who underwent a more complex procedure than WLE alone as this may have affected the surgical interval. Cases in which the dates of procedures were unclear were also excluded. Analysis of surgical interval and associated factors was based on standard statistical methods. Data were analyzed using PASW version 18 (IBM Corp.). p values were all two-tailed and the alpha level of significance was set at 0.05. The prevalence is shown as a percentage. The Chi squared paired test was used for testing paired comparisons. ANOVA was used to test multi-variate analysis between and within groups. Post-hoc correlations were calculated with Dunett’s T3 test.
Ulceration
Present 17 (15.9 %)
123
Median = 3
Absent 69 (64.5 %) Not available 21 (19.6 %) Mitotic rate
Mean rate = 5.51/mm2
Table 2 Surgical interval and associated factors Median length of surgical interval (SI)
41 ± 27 days
SI based on specialty performing excision biopsy Dermatology
52.6 ± 31.2 days, p = 0.035
General surgery
35.4 ± 19 days
Plastic surgery
45 ± 25 days
SI based on anatomical location Head and neck
48 ± 32.3 days, p = 0.001
Other
37.5 ± 22.6 days
Results A total of 107 patients who underwent surgical intervention were identified. Patient demographic and tumour characteristics are detailed in Table 1. The mean age of patients was 59.6 years (range 17–93). Whilst age was not a statistically significant factor affecting the SI, the median SI for patients over the age of 70 was 48 days. The majority of patients were female (n = 63; 59 %). DEBs of
Ir J Med Sci
malignant melanoma were most commonly performed by a dermatologist (n = 47, 43.9 %) followed by the general surgeons (n = 31, 29 %) and plastic surgeons (n = 21, 19.6 %). The median duration of the surgical interval was 41 ± 27 days (range 6–137 days), as shown in Table 2 below. Seven patients (6.5 %) had a WLE performed within 14 days of the DEB. Eleven patients (10.3 %) had a WLE performed more than 90 days after the DEB was performed. The SI was longer if a dermatologist performed the DEB as opposed to a general surgeon (52.6 ± 31.2 vs. 35.4 ± 19 days, p = 0.035), as shown in Fig. 1. The two main histological subtypes of melanoma were superficial spreading and nodular at 40.2 % (n = 43) and 25.2 % (n = 27), respectively. Other less common histological subtypes included lentigo maligna at 12.1 % (n = 13) and mixed pathology at 11.2 % (n = 12). With regard to tumour subtypes, the SI was longer in cases of lentigo maligna lesions (median 54 days, range 33–137) compared with superficial spreading (median = 41 days, range 9–99) or nodular (median = 30 days, range 6–98) subtypes. This difference was not statistically significant (p = 0.122). The majority of melanomas were located on the limbs (lower [ upper limbs) followed by the face and the back (Table 1). Dermatologists performed the majority of DEBs involving the face (57.14 %) with plastic and general surgeons performing 42.85 and 4.76 %, respectively. General surgeons were more likely to excise more aggressive lesions on the trunk and limbs with the average rate of mitoses in this group being 8.66/mm2 compared with mitotic rates of 4.28 and 4.21/mm2 in the plastic surgery and dermatology groups, respectively. The anatomic location of the lesion predicted the SI, with lesions of
the head and neck undergoing WLE 48 ± 32.3 days after DEB compared with 37.5 ± 22.6 days for all other sites (p = 0.001). The median Breslow depth was 1.1 mm (mean 2.3 mm, range 0.1–40 mm) and the median Clark’s level was 3. The majority of patients did not have associated ulceration (n = 69; 64.5 %). The mean rate of mitoses was 5.51/ mm2; however, this was only recorded in 78 % of cases. Individual histopathological factors were not statistically significantly associated with a longer SI. Radiological investigations were performed in 22.2 % (n = 23) patients during the surgical interval and were carried out most commonly for staging purposes, particularly in the setting of aggressive disease. Ultrasound scans were commonly performed to assess nodal status, particularly in the axilla. Five patients (4.5 %) had multi-modal imaging performed. Ten patients (9 %) had plain X-rays performed; a chest X-ray in seven patients, a foot (n = 1), shoulder (n = 1) and pelvis (n = 1) X-rays were also taken. Eight patients (7 %) had an ultrasound performed, the most common of which was of the axilla (7/8) with the remaining one of the neck. Fourteen patients (13 %) underwent computed tomography (CT) scans, 11 of which had aggressive disease (T3b/T4b). Of these, 12 patients had CT scans of the thorax, abdomen and pelvis, one had a CT scan of the neck, and one had a CT scan of the brain. Two patients had tri-phasic liver CT scans performed as well as a CT scan of the thorax, abdomen and pelvis. The median SI amongst patients who had had any form of imaging performed during the SI was 36 days, the result of which was not statistically significant. Only 2/14 (14 %) CT scans performed found evidence of metastatic disease whilst 3/7 (43 %) ultrasound scans showed evidence of lymphadenopathy.
Discussion
Fig. 1 Surgical interval (days) from diagnostic excisional biopsy to wide local excision depending on the specialty who performed the initial biopsy. Mean, inter-quartile range, 95 % confidence intervals and outliers are depicted
The incidence of malignant melanoma has steadily risen in Ireland over the last decade with the number of reported cases increasing by almost 6 % annually [1]. Malignant melanoma is the fourth commonest malignancy in Ireland amongst females and the fifth commonest amongst males with over 720 new cases diagnosed on an annual basis across both sexes between 2007 and 2009 [1]. The incidence of melanoma in Ireland is amongst the highest in the European Union which is likely to be multi-factorial in nature, with Ireland having predominantly lighter skin types as well as relatively poor social awareness. Mortality has similarly risen from 16 deaths per year between 1950 and 1955 to 113 deaths per year between 2004 and 2007 [8]. The rise is particularly notable in men. Strikingly, mortality in Northern Ireland is much lower when compared with rates in the Republic of Ireland [9].
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The mainstay of treatment for melanoma is surgery and the National Cancer Registry estimates that greater than 90 % of patients undergo definitive excisional surgery [1, 10]. Whilst recent melanoma research has focused predominantly on advances in medical oncology, the most data would indicate that less than 10 % of patients actually receive adjuvant therapy [1]. As regards surgical management, the most recent guidelines published by the British Society of Dermatology [11] and the National Cancer Control Network [12] in the United States advise that a DEB should be performed and discussed in an MDT setting within 2 weeks of initial presentation. However, there remains a paucity of guidelines as to the optimal time interval between a DEB and WLE. The only current guidelines which mention the surgical interval are those produced by the European Dermatology Forum in 2012 and state that the definitive surgical management should occur preferentially within 4–6 weeks of the initial diagnosis [7]. The absence of guidelines with regard to the SI between DEB and WLE can be explained by the results of three previous studies addressing this issue. The study by McKenna et al. [4] demonstrated no correlation between the SI and clinical outcomes such as overall and disease-free survival. This study was however limited by the fact that more recent prognostic features, such as mitotic rate and ulceration, were not taken into account, as well as the low overall number of patients within the study which may limit the overall conclusions. However, these findings were echoed by two similar studies [5, 6]. The current study did not demonstrate a prolonged surgical interval in patients with adverse prognostic features; however, it does not specifically address disease outcomes. Whilst it does not appear imperative that definitive surgery is performed on an urgent basis a more streamlined process may help to ensure that WLE be performed within a set timeframe and should be considered when developing national guidelines. Within the same study by McKenna et al. [4] it was postulated that malignant melanoma may be a systemic pathological condition rather than a local one which may explain why the SI from DEB to WLE does not appear to have an effect on survival. However, the regional lymph node status remains an important prognostic indicator [13, 14] and so theoretically the SI between DEB and SLN biopsy may influence survival. The study by Carpenter et al. [5] which focused on this issue failed to demonstrate an independent association between survival and the SI but with delays greater than 56 days there was a trend toward significance. This study demonstrates a number of factors associated with a prolonged surgical interval. Firstly, this study found that as patient age increased so too did the SI. Many studies confirm age to be a negative prognostic indicator
123
for malignant melanoma [14, 15] and whilst previous studies have not shown a correlation between SI and survival it is notable that older patients appear to wait longer and have a poorer prognosis. Secondly, our study found that the SI was longer if a dermatologist performed the DEB compared to a general surgeon. Dermatologists performed 44.5 % of DEBs in the study cohort confirming the increasing role of the dermatologist in the treatment of malignant melanoma which has been previously well documented [16], especially as rapid access pigmented lesion clinics become more prominent. The longer SI is likely explained by the fact that many of these cases were subsequently referred to a plastic or general surgeon especially where there was a larger, more aggressive or cosmetically challenging lesion requiring a more invasive or complex WLE. Interestingly, general surgeons were more likely to be involved from an early stage in very aggressive lesions as shown by the fact that the average mitotic rate of lesions in cases where the general surgeon performed the DEB was 8.66/mm2 compared to 4.21/mm2 in cases where the DEB performed by a dermatologist. It is likely that referral patterns in aggressive cases are also influenced by the need for sentinel mapping and nodal dissection which usually require general surgical expertise. Finally, lesions of the head and neck were associated with a longer SI. This may be due to the fact that WLEs of these lesions require more extensive plastic surgical and aesthetic planning given nearby structures and associated cosmetic implications. This study has a number of weaknesses. The study cohort was small and therefore this may limit the conclusions that can be drawn regarding a prolonged surgical interval. Secondly, it was a descriptive study and no work has been performed looking at outcome data. However, work to identify the disease-free and overall survival is ongoing. Finally, this study was a single-institution retrospective review and may not reflect practices in other centres. The presence of a national melanoma database would enable a more detailed and complete analysis of the parameters investigated.
Conclusion This study has identified factors associated with the surgical interval between initial diagnostic excision biopsy of malignant melanoma and definitive wide local excision. The surgical interval depends on the age of the patient, the location of the lesion and the clinician who performed the initial excision biopsy. Further studies are required to assess effect on overall and disease-free survival. Acknowledgments
This article received no funding.
Ir J Med Sci
References 1. National Cancer Registry Ireland (2011) Cancer Trends No. 7— Melanoma of Skin. http://www.ncri.ie/pubs/pubfiles/melanoma% 20trends.pdf 2. Handley WS (1907) The pathology of melanotic growths in relation to their operative treatment. Lancet; i: 927–33, 996–1003 3. Kelly JW, Sagebiel RW, Calderon W et al (1984) The frequency of local recurrence and microsatellites as a guide to reexcision margins for cutaneous malignant melanoma. Ann Surg 200:759–763 4. MCKenna DB, Lee RJ, Prescott RJ, Doherty VR (2012) The time from diagnostic excision biopsy to wide local excision for primary cutaneous malignant melanoma may not affect patient survival. Br J Dermatol 147:48–54 5. Carpenter S, Pockaj B, Dueck A et al (2008) Factors influencing time between biopsy and definitive surgery for malignant melanoma: do they impact clinical outcome? Am J Surg 196:834–843 6. Parrett BM, Accortt NA, Li R et al (2012) The effect of delay time between primary melanoma biopsy and sentinel lymph node dissection on sentinel node status, recurrence, and survival. Melanoma Res 22(5):386–391 7. Garbe C, Peris K, Hauschild A et al; European Dermatology Forum; European Association of Dermato-Oncology; European Organization of Research and Treatment of Cancer (2012) Diagnosis and treatment of melanoma. European consensusbased interdisciplinary guideline—Update 2012. Eur J Cancer 48(15):2375–2390 8. World Health Organization Mortality Database. May 2013. http:// www.who.int/healthinfo/statistics/mortality_rawdata/en/index.html
9. Sant M, Allemani C, Santaquilani M, Knijn A, Marchesi F, Capocaccia R; EUROCARE Working Group (2009) EUROCARE4. Survival of cancer patients diagnosed in 1995–1999. Results and commentary. Eur J Cancer 45(6):931–991 10. Al-Hilli Z, Evoy D, Geraghty JG, McDermott EW, Prichard RS Surgery and the staging of Melanoma, Melanoma—from early detection to treatment. In: Dr. Duc Ht (Ed.), ISBN: 978-953-51-0961-7, InTech, doi:10.5772/53626. Available from: http://www.intechopen.com/books/melanoma-from-earlydetection-to-treatment/surgery-and-the-staging-of-melanoma 11. Marsden JR, Newton-Bishop JA, Burrows L et al (2010) Revised UK guidelines for the management of cutaneous melanoma. Br J Dermatol 163:238–256 12. Coit DG, Andtbacka R, Anker CJ et al; National Comprehensive Cancer Network (NCCN) (2013) Melanoma, version 2.2013: featured updates to the NCCN guidelines. J Natl Compr Cancer Netw 11(4):395–407 13. Balch CM, Buzaid AC, Atkins MB et al (2000) A new AJCC staging system for cutaneous melanoma. Cancer 88:1484–1491 14. Balch C, Soong S, Gershenwald J et al (2001) Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer Melanoma staging system. J Clin Oncol 19:3622–3634 15. Austin PF, Cruse CW, Lyman G et al (1994) Age as a prognostic factor in the malignant melanoma population. Ann Surg Oncol 1:487–494 16. McKenna DB, Marioni JC, Lee RJ, Prescott RJ, Doherty VR (2004) A comparison of dermatologists’, surgeons’ and general practitioners’ surgical management of cutaneous melanoma. Br J Dermatol 151:636–644
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ORIGINAL ARTICLE
Malignant melanoma: factors affecting the surgical interval from excision biopsy to definitive surgical management M. R. Boland • R. S. Prichard • G. A. Bass • Z. Al-Hilli • A. Levendale D. Gibbons • K. Sheahan • B. Kirby • E. W. McDermott • D. Evoy
•
Received: 21 January 2014 / Accepted: 3 June 2014 Ó Royal Academy of Medicine in Ireland 2014
Abstract Introduction Surgery remains the mainstay of treatment for malignant melanoma. Despite previous studies examining the surgical interval (SI) between the diagnostic excision biopsy (DEB) and definitive surgical management there remains few guidelines regarding an optimal time interval. The aim of this study was to determine the SI between DEB and definitive surgery and elucidate factors associated with delays in management of malignant melanoma. Methods A retrospective study of 107 consecutive patients who had a DEB and subsequent wide local excision between January 2011 and June 2012 was performed. Mode of referral and dates of diagnostic biopsy/definitive surgery were documented. Patient demographics and tumour characteristics were reviewed. Results The mean age was 59.6 years, and male:female ratio was 1:1.3. Median duration of the SI was 41 ± 27 days (range 6–137 days). The SI was increased when dermatologists performed the DEB as opposed to general surgeons (p = 0.035). The anatomic location of the lesion predicted the SI, with lesions of the head/neck undergoing definitive excision 48 ± 32.3 days after DEB M. R. Boland (&) R. S. Prichard G. A. Bass Z. Al-Hilli A. Levendale E. W. McDermott D. Evoy Departments of General Surgery, St Vincent’s Healthcare Group, Elm Park, Dublin 4, Ireland e-mail: [email protected] D. Gibbons K. Sheahan Departments of Pathology, St Vincent’s Healthcare Group, Elm Park, Dublin 4, Ireland B. Kirby Departments of Dermatology, St Vincent’s Healthcare Group, Elm Park, Dublin 4, Ireland
vs. 37.5 ± 22.6 days for all other sites (p = 0.001). Neither demographic factors nor histopathological prognostic features affected the SI. Reasons for a prolonged SI included referrals to different services and time for preoperative planning. Conclusions Significant variations were noted in the SI predominantly accounted for by mode of referral and location of the malignant melanoma. Further investigation is required to elucidate factors affecting the SI and its subsequent effect on patient outcomes. Keywords Melanoma Surgery Diagnosis Biopsy Excision Interval
Introduction Recent decades have seen an increase in the incidence of malignant melanoma and it remains the major cause of skin cancer deaths [1]. Outcome improvements will occur with a streamlined management plan to ensure timely diagnosis and definitive management. Despite advances in the molecular understanding of melanoma and improvements in adjuvant treatments, surgery remains the mainstay of treatment. Surgery is usually a two-stage approach, encompassing a diagnostic excision biopsy (DEB) followed by a definitive wide local excision (WLE) and sentinel node mapping when indicated. The aim of the second procedure is firstly to ensure that an adequate margin depending on Breslow depth has been excised, secondly to excise adjacent epidermal melanocytes that may have undergone a field change and have malignant potential and thirdly to stage the regional lymph node basin for metastatic disease [2, 3]. The surgical interval (SI) between these two stages has been
123
Ir J Med Sci
examined by three previously published studies [4–6]. A study by McKenna et al. [4] examined the relationship between the SI and clinical outcomes including overall and disease-free survival and found no statistically significant correlation. The other two studies [5, 6], both from the United States, investigated the same relationship and whilst they found similar outcomes, they did notice a correlation between an increasing SI and reduced overall and disease-free survival. The changing surgical management of melanoma with the use of narrower surgical margins has seen an increase in the number of dermatologists performing at least the diagnostic excision. Therefore, management pathways will be dictated not only by local referral patterns but also by factors, such as individuals having a specialist interest in the management of melanoma. Interestingly only the European Dermatology Forum states that definitive surgical management should occur preferentially within 4–6 weeks of the initial diagnosis [7]. The aim of this paper was to assess the duration of SI between DEB and subsequent WLE and to assess the factors associated with a delay in the SI.
Table 1 Patient and tumour characteristics No of patients
107
Sex Male
44 (41 %)
Female
63 (59 %)
Age Mean
59.6 years
Tumour type Superficial spreading
43
Nodular
27
Lentigo maligna
13
Mixed
12
Naevoid/AL/other
12
Anatomical location Scalp/ear
4 (3.7 %)
Face Neck
22 (20.6 %) 2 (1.8 %)
Trunk
4 (3.7 %)
Back
15 (14 %)
Upper limbs
27 (25.2 %)
Lower limbs
32 (29.9 %)
Other
1 (0.9 %)
Clinicopathological features
Methods
Clark’s level Breslow depth
Median = 11 mm
A retrospective review of a prospectively maintained database including all adult patients diagnosed with primary invasive cutaneous malignant melanoma who underwent a DEB followed by a WLE between January 2010 and June 2011 within a tertiary referral centre was performed. Demographic data, clinicopathological characteristics of the tumours and staging investigations were recorded. The type of medical professional who carried out the DEB was recorded as follows: dermatologist, plastic surgeon, general surgeon or other. The surgical interval was defined as the time period in days between DEB and WLE and was calculated on an individual patient basis. Exclusion criteria included patients who had undergone either a DEB or an incisional biopsy only and those who underwent a more complex procedure than WLE alone as this may have affected the surgical interval. Cases in which the dates of procedures were unclear were also excluded. Analysis of surgical interval and associated factors was based on standard statistical methods. Data were analyzed using PASW version 18 (IBM Corp.). p values were all two-tailed and the alpha level of significance was set at 0.05. The prevalence is shown as a percentage. The Chi squared paired test was used for testing paired comparisons. ANOVA was used to test multi-variate analysis between and within groups. Post-hoc correlations were calculated with Dunett’s T3 test.
Ulceration
Present 17 (15.9 %)
123
Median = 3
Absent 69 (64.5 %) Not available 21 (19.6 %) Mitotic rate
Mean rate = 5.51/mm2
Table 2 Surgical interval and associated factors Median length of surgical interval (SI)
41 ± 27 days
SI based on specialty performing excision biopsy Dermatology
52.6 ± 31.2 days, p = 0.035
General surgery
35.4 ± 19 days
Plastic surgery
45 ± 25 days
SI based on anatomical location Head and neck
48 ± 32.3 days, p = 0.001
Other
37.5 ± 22.6 days
Results A total of 107 patients who underwent surgical intervention were identified. Patient demographic and tumour characteristics are detailed in Table 1. The mean age of patients was 59.6 years (range 17–93). Whilst age was not a statistically significant factor affecting the SI, the median SI for patients over the age of 70 was 48 days. The majority of patients were female (n = 63; 59 %). DEBs of
Ir J Med Sci
malignant melanoma were most commonly performed by a dermatologist (n = 47, 43.9 %) followed by the general surgeons (n = 31, 29 %) and plastic surgeons (n = 21, 19.6 %). The median duration of the surgical interval was 41 ± 27 days (range 6–137 days), as shown in Table 2 below. Seven patients (6.5 %) had a WLE performed within 14 days of the DEB. Eleven patients (10.3 %) had a WLE performed more than 90 days after the DEB was performed. The SI was longer if a dermatologist performed the DEB as opposed to a general surgeon (52.6 ± 31.2 vs. 35.4 ± 19 days, p = 0.035), as shown in Fig. 1. The two main histological subtypes of melanoma were superficial spreading and nodular at 40.2 % (n = 43) and 25.2 % (n = 27), respectively. Other less common histological subtypes included lentigo maligna at 12.1 % (n = 13) and mixed pathology at 11.2 % (n = 12). With regard to tumour subtypes, the SI was longer in cases of lentigo maligna lesions (median 54 days, range 33–137) compared with superficial spreading (median = 41 days, range 9–99) or nodular (median = 30 days, range 6–98) subtypes. This difference was not statistically significant (p = 0.122). The majority of melanomas were located on the limbs (lower [ upper limbs) followed by the face and the back (Table 1). Dermatologists performed the majority of DEBs involving the face (57.14 %) with plastic and general surgeons performing 42.85 and 4.76 %, respectively. General surgeons were more likely to excise more aggressive lesions on the trunk and limbs with the average rate of mitoses in this group being 8.66/mm2 compared with mitotic rates of 4.28 and 4.21/mm2 in the plastic surgery and dermatology groups, respectively. The anatomic location of the lesion predicted the SI, with lesions of
the head and neck undergoing WLE 48 ± 32.3 days after DEB compared with 37.5 ± 22.6 days for all other sites (p = 0.001). The median Breslow depth was 1.1 mm (mean 2.3 mm, range 0.1–40 mm) and the median Clark’s level was 3. The majority of patients did not have associated ulceration (n = 69; 64.5 %). The mean rate of mitoses was 5.51/ mm2; however, this was only recorded in 78 % of cases. Individual histopathological factors were not statistically significantly associated with a longer SI. Radiological investigations were performed in 22.2 % (n = 23) patients during the surgical interval and were carried out most commonly for staging purposes, particularly in the setting of aggressive disease. Ultrasound scans were commonly performed to assess nodal status, particularly in the axilla. Five patients (4.5 %) had multi-modal imaging performed. Ten patients (9 %) had plain X-rays performed; a chest X-ray in seven patients, a foot (n = 1), shoulder (n = 1) and pelvis (n = 1) X-rays were also taken. Eight patients (7 %) had an ultrasound performed, the most common of which was of the axilla (7/8) with the remaining one of the neck. Fourteen patients (13 %) underwent computed tomography (CT) scans, 11 of which had aggressive disease (T3b/T4b). Of these, 12 patients had CT scans of the thorax, abdomen and pelvis, one had a CT scan of the neck, and one had a CT scan of the brain. Two patients had tri-phasic liver CT scans performed as well as a CT scan of the thorax, abdomen and pelvis. The median SI amongst patients who had had any form of imaging performed during the SI was 36 days, the result of which was not statistically significant. Only 2/14 (14 %) CT scans performed found evidence of metastatic disease whilst 3/7 (43 %) ultrasound scans showed evidence of lymphadenopathy.
Discussion
Fig. 1 Surgical interval (days) from diagnostic excisional biopsy to wide local excision depending on the specialty who performed the initial biopsy. Mean, inter-quartile range, 95 % confidence intervals and outliers are depicted
The incidence of malignant melanoma has steadily risen in Ireland over the last decade with the number of reported cases increasing by almost 6 % annually [1]. Malignant melanoma is the fourth commonest malignancy in Ireland amongst females and the fifth commonest amongst males with over 720 new cases diagnosed on an annual basis across both sexes between 2007 and 2009 [1]. The incidence of melanoma in Ireland is amongst the highest in the European Union which is likely to be multi-factorial in nature, with Ireland having predominantly lighter skin types as well as relatively poor social awareness. Mortality has similarly risen from 16 deaths per year between 1950 and 1955 to 113 deaths per year between 2004 and 2007 [8]. The rise is particularly notable in men. Strikingly, mortality in Northern Ireland is much lower when compared with rates in the Republic of Ireland [9].
123
Ir J Med Sci
The mainstay of treatment for melanoma is surgery and the National Cancer Registry estimates that greater than 90 % of patients undergo definitive excisional surgery [1, 10]. Whilst recent melanoma research has focused predominantly on advances in medical oncology, the most data would indicate that less than 10 % of patients actually receive adjuvant therapy [1]. As regards surgical management, the most recent guidelines published by the British Society of Dermatology [11] and the National Cancer Control Network [12] in the United States advise that a DEB should be performed and discussed in an MDT setting within 2 weeks of initial presentation. However, there remains a paucity of guidelines as to the optimal time interval between a DEB and WLE. The only current guidelines which mention the surgical interval are those produced by the European Dermatology Forum in 2012 and state that the definitive surgical management should occur preferentially within 4–6 weeks of the initial diagnosis [7]. The absence of guidelines with regard to the SI between DEB and WLE can be explained by the results of three previous studies addressing this issue. The study by McKenna et al. [4] demonstrated no correlation between the SI and clinical outcomes such as overall and disease-free survival. This study was however limited by the fact that more recent prognostic features, such as mitotic rate and ulceration, were not taken into account, as well as the low overall number of patients within the study which may limit the overall conclusions. However, these findings were echoed by two similar studies [5, 6]. The current study did not demonstrate a prolonged surgical interval in patients with adverse prognostic features; however, it does not specifically address disease outcomes. Whilst it does not appear imperative that definitive surgery is performed on an urgent basis a more streamlined process may help to ensure that WLE be performed within a set timeframe and should be considered when developing national guidelines. Within the same study by McKenna et al. [4] it was postulated that malignant melanoma may be a systemic pathological condition rather than a local one which may explain why the SI from DEB to WLE does not appear to have an effect on survival. However, the regional lymph node status remains an important prognostic indicator [13, 14] and so theoretically the SI between DEB and SLN biopsy may influence survival. The study by Carpenter et al. [5] which focused on this issue failed to demonstrate an independent association between survival and the SI but with delays greater than 56 days there was a trend toward significance. This study demonstrates a number of factors associated with a prolonged surgical interval. Firstly, this study found that as patient age increased so too did the SI. Many studies confirm age to be a negative prognostic indicator
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for malignant melanoma [14, 15] and whilst previous studies have not shown a correlation between SI and survival it is notable that older patients appear to wait longer and have a poorer prognosis. Secondly, our study found that the SI was longer if a dermatologist performed the DEB compared to a general surgeon. Dermatologists performed 44.5 % of DEBs in the study cohort confirming the increasing role of the dermatologist in the treatment of malignant melanoma which has been previously well documented [16], especially as rapid access pigmented lesion clinics become more prominent. The longer SI is likely explained by the fact that many of these cases were subsequently referred to a plastic or general surgeon especially where there was a larger, more aggressive or cosmetically challenging lesion requiring a more invasive or complex WLE. Interestingly, general surgeons were more likely to be involved from an early stage in very aggressive lesions as shown by the fact that the average mitotic rate of lesions in cases where the general surgeon performed the DEB was 8.66/mm2 compared to 4.21/mm2 in cases where the DEB performed by a dermatologist. It is likely that referral patterns in aggressive cases are also influenced by the need for sentinel mapping and nodal dissection which usually require general surgical expertise. Finally, lesions of the head and neck were associated with a longer SI. This may be due to the fact that WLEs of these lesions require more extensive plastic surgical and aesthetic planning given nearby structures and associated cosmetic implications. This study has a number of weaknesses. The study cohort was small and therefore this may limit the conclusions that can be drawn regarding a prolonged surgical interval. Secondly, it was a descriptive study and no work has been performed looking at outcome data. However, work to identify the disease-free and overall survival is ongoing. Finally, this study was a single-institution retrospective review and may not reflect practices in other centres. The presence of a national melanoma database would enable a more detailed and complete analysis of the parameters investigated.
Conclusion This study has identified factors associated with the surgical interval between initial diagnostic excision biopsy of malignant melanoma and definitive wide local excision. The surgical interval depends on the age of the patient, the location of the lesion and the clinician who performed the initial excision biopsy. Further studies are required to assess effect on overall and disease-free survival. Acknowledgments
This article received no funding.
Ir J Med Sci
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