Contrast with Australian Guidelines A/Pr Pascale Guitera,

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1 Contrast with Australian Guidelines A/Pr Pascale Guitera, Dermatologist, Sydney University NO CONFLICT OF INTEREST Sydney Melanoma Diagnostic Centre, RPAH

2 pages 16 pages lpracticeguidelines-managementofmelanoma.pdf new!!- with NOW constant updates

3 Level of evidence Intervention Diagnosis Prognosis Aetiology Screening

4 Prevention (2008) Environmental mel. risk is most strongly associated with an intermittent pattern of sun exposure, as in recreational exposure, and may be more potent when received in childhood and adolescence than in later life While robust conclusions are difficult at this time, the use of sunbeds and tanning booths is associated with a small increase in mel. risk. This risk may be more significant when exposure occurs before age 35 New evidence:zhang M. et al. Journal of clinical oncology 2012; 30 : 1-6 Cust AE, et al. International Journal of Cancer 2011;128: III-3 II Australian ban on tanning booth

5 Prevention (2) Brief sun exposures (for fair skinned individuals 6 8min in summer but 6 50min in winter depending on latitude) to around 15 20% body surface, most days are needed to maintain vit D levels, so total sun avoidance should not be practised without vit D supplementation. III-3 New evidence: controversial! Although sunscreens can reduce the risk of some non-mel. skin cancers, they have not conclusively been shown to reduce the risk of mel. III-3 New evidence: A C. Green et al J Clin Oncol 2011;29: Reduced mel. after regular sunscreen use: Randomized Trial Follow-Up. SUN CREAM DOES PROTECT

6 Population-based whole-body skin screening for mel. (2008) In the absence of substantive evidence as to its effectiveness in reducing mortality from mel., population-based skin screening cannot be recommended New evidence: Review JAAD 2017; 76:129-39: large ecological studies, a case control study and survey indicate benefit of skin cancer screening but evidence are very low Identification and management of high-risk individual High-risk individuals may benefit from regular clinical surveillance for new mel. and education to self-screen, based on expert opinion. There is no evidence to compare the relative effectiveness of specific surveillance techniques III-2

7 CDKN2A mutations cause high mel. risk in the context of familial mel., though their prevalence is low, even in that setting It is unclear at present whether individual risk management should be influenced by the results of genetic testing for CDKN2A mutations I IV Classification and staging of mel. = and new:ajcc 8thEdition: (activities +++ on new pronostic markers and new threshold for Breslow)

8 Clinical diagnosis (1) (new) NM, ALM and desmoplastic subtypes more commonly present as thick lesions and improved diagnostic accuracy of these is therefore critical. Nodular melanomas are associated with more rapid vertical growth compared to superficial spreading melanomas. Up to 20% of all melanomas are amelanotic or only partially pigmented, with this being more common amongst NM, ALM and desmoplastic subtypes. III-2, III-3, IV III-3, IV IV Scalp F70 nodular mel. Breslow 12mm Amelanosis/hypomelanosis is significantly associated with poorer diagnostic accuracy. III-2, III-3

9 Clinical diagnosis (2)- new From a meta-analysis of 9 level II studies prospectively performed in a clinical setting, the diagnostic accuracy for mel., as expressed by the relative diagnostic OR, was 15.6 times higher for DS compared with naked eye examination. Sensitivity of DS was 18% (95% CI 9% 27%; P=0.002) higher, but there was no evidence of an effect on specificity. 2 more level II studies showed results consistent with the larger meta-analysis. Ds reduce the benign:malignant ratio of excised melanocytic lesions and reduce the number of patients referred for biopsy in both specialists and primary care. I, II II

10 Sequential digital dermoscopic imaging (SDDI)-new 4level II studies and recent cohort studies show that SDDI allows the detection of suspicious dermoscopic change in mel. that lack dermoscopic evidence of mel. at a particular time. The routine use of SDDI in both specialist and primary care allows the detection of a significant proportion of patients mel. Long-term SDDI of multiple naevi in lower risk patients, while allowing detection of mel., is less efficacious. SDDI reduce the benign:malignant ratio of excised melanocytic lesions and reduce the number of patients referred for biopsy in both specialist and primary care. II, III-2 II, III-2 II No change=nevus 3months Change= early mel. 3months

11 Total body photo (2008) 8 level IV studies and 1 level III-3 study examined surveillance of high-risk subjects with TBP but only 1 included a comparison arm (of lower-risk subjects). All studies on high-risk patients showed early mel. detection and/or high mel. incidence. All studies were designed to assess the outcomes of surveillance in high-risk groups rather than the value of TBP

12 (In both systems: high false positive rates with seb.k. may cause a significantly poorer specificity when used by non-experts) Automated instrument- new To date, only 2 studies have been reported comparing specialist clinician diagnosis with an automated machine diagnosis with an adequate sample size to assess both specificity and sensitivity for the diagnosis of mel. II MelaFind System (Electro-Optical Sciences, Inc., USA), multispectral. Sensitivity of 98.3%, but a poor specificity of 9.9%,(higher than the study dermatologists) SciBase (Medtech, Sweden) electro-impedance:2 400 skin lesions (260 mel.), Nevisense overall sensitivity of 98% with 100% sensitivity on all stages of invasive mel.; Specificity 33%.

13 Biopsy- new Complete excision with a 2mm margin is the most reliable diagnostic biopsy method for skin lesions suspected of being mel. Punch biopsy has been shown in one large study to be associated with high rates of false negative histopathological diagnosis of 23% and should be used with caution for melanocytic lesions. Deep shave excision (saucerisation) is more likely to accurately stage the mel. if it is in situ or superficially invasive than if it is more deeply invasive. Partial biopsy has been shown to underestimate T-stage in 7-34% of punch biopsies and 3-19% of shave biopsies and provides insufficient information for appropriate surgical planning in 18% of punch biopsies and 3-5% of shave biopsies. Survival and the performance of sentinel node biopsy show no differences according to partial versus complete excisional biopsy type. III-2 III-2 III-2, IV III-2, IV III-2, IV

14 Similar Histopathological reporting Appropriate investigations Similar: none for stage I and II Regional LN ultrasonography > to palpation for the detection of regional LN metastasis Both LN ultrasonography and PET scanning < to SNB for the detection of occult LN metastasis II 1 III-2 New evidence: to be built as new adjuvant therapy introduced!

15 Treatment of primary mel. After initial excision biopsy; the radial excision margins, measured clinically from the edge of the mel.: (ptis) mel. in situ: margin 5mm (pt1) mel. < 1.0mm: 1cm (pt2) mel mm: 1 2cm (pt3) mel mm: 1 2cm (pt4) mel. > 4.0mm: 2cm New : There is case series evidence suggesting that 5 mm margins are often adequate to treat mel. in situ. However, in some cases they are inadequate and may lead to significant rates of disease recurrence. IV

16 SNB- new The status of the SN is the most significant predictor of mel.-specific survival for patients with mel. >1 mm Breslow. Overall, for patients with mel. >1 mm thick, SNB followed by immediate completion lymph node dissection for a positive node does not prolong melanoma specific survival or overall survival compared with not performing SNB (nodal observation) and delayed lymph node dissection for clinically detected nodes. For patients with intermediate thickness mel. ( mm thick) who harbour metastatic disease within the SN, early intervention with SNB may be associated with an increased mel. specific survival compared with nodal observation. Complication rates for SNB are low. The procedure should be performed in a centre with appropriate expertise as complication rates are inversely related to procedure volume - this particularly applies to primaries arising in the head & neck. III-3, IV II III-2 III-3

17 Follow-up (2008) Intervals between visits are mostly arbitrary. IV However, all studies stress that the more advanced the disease, the more frequent the visits need to be. US, only if performed by experienced ultrasonographers, is a useful adjunct to clinical examination in the follow-up of more advanced primary disease. No other tests have significant value in patients with localised disease New evidence: to be built as new efficient therapy introduced!

18 Lentigo maligna (2008) There are no prospective studies or randomised controlled trials available to form the basis of any recommendations for the management of LM IV

19 In summary, grading of recommendations «In clinical practice» Grade description A - Body of evidence can be trusted to guide practice B - Body of evidence can be trusted to guide practice in most situations C- Body of evidence provides some support for recommendation(s) but care should be taken in its application D - Body of evidence is weak and recommendation must be applied with caution

20 In summary (1) Prevention of mel. 1. Sunburn be avoided + UV protection B 2. Sunscreens be used to complement but not to replace physical methods C B 3. Risks associated with exposure to sunbeds be explained C B 4. As brief sun exposures are needed to maintain vit D levels, total lack of sun exposure is not advised without vit D supplementation C Population screening for mel.xx cannot be recommended C? x Identification and management of high-risk individuals High risk patient and their partner or carer be educated to recognise lesions suspicious, and to be regularly checked by a clinician with six-monthly full body examination supported by total body photography and dermoscopy as required C Good practice point Prophylactic removal of non-suspicious lesions is not recommended A

21 In summary (2) Identification and management of high-risk individuals continued... Screening for a genetic mutation such as the CDKN2A gene be contemplated only after a thorough clinical risk assessment, confirmation of a strong family history of mel. and appropriate genetic counselling C Classification of melanoma NEW AJCC/UICC B x Clinical diagnosis NEW Mel. are generally distinguished from benign lesions by their history of change and thick mel. often do not conform to the ABCD rule, but are Elevated, Firm and Growing. Therefore, careful history taking is important and any lesion that continues to grow or change in size, shape, colour or elevation over a period of more than 1 month should be biopsied ( ) Suspicious raised lesions should be excised and not monitored. C

22 In summary (3) 1- Clinicians who are performing skin examinations for the purpose of detecting skin cancer should be trained in and use dermoscopy. ( most GP in Australia) A 2- To assess individual melanocytic lesions of concern, recommend the use of short-term SDDI ( 3months) to detect mel. that lack dermoscopic features of melanoma. B - To assess individual or multiple melanocytic lesions in routine surveillance of high risk patients, recommend the use of long-term SDDI to detect mel. that lack dermoscopic features of melanoma. ( most GP in Australia) B (3- Consider the use of baseline total body photography as a tool for the early detection of mel. in patients who are at high risk )-not review NEW- Only flat or slightly raised lesions should undergo SDDI. - The interval for short-term monitoring is 3 months where any change leads to excision unlike >6months where certain specific changes are required for excision to be indicated. Where lentigo maligna is in the differential diagnosis 6 months is recommended

23 Biopsy-new In summary (4) 1. The optimal biopsy approach for a suspicious pigmented lesion is complete excision with a 2 mm clinical margin and upper subcutis. C 2. Partial biopsies may not be fully representative of the lesion and need to be interpreted with caution and in light of the clinical findings to minimise incorrect false negative diagnoses and understaging. C 3. In carefully selected clinical circumstances (such as large in situ lesions, large facial or acral lesions or where the suspicion of melanoma is low) and in the hands of experienced clinicians, partial incisional, punch or shave biopsies may be appropriate. C (Where a punch biopsy has been used for the diagnosis of a suspected BCC or SCC, and the diagnosis has been found to be melanocytic, then consideration should be given to excision of the entire lesion)

24 In summary (5) Histopathology (2008) The essential components of a histopathological report: Breslow thickness margins of excision (microscopic) mitotic rate/mm2 level of invasion (Clark) ulceration A (new: It is advisable to discuss unexpected pathology results with the reporting pathologist. ) Appropriate investigations (2008) The 6 recommendations are level D not detailed here as obsolete NEW: SNB should be considered for all patients with mel. >1 mm in thickness and for patients with mel. >0.75 mm with other high risk pathological features to provide optimal staging and prognostic information and to maximise management options for patients who are node positive.!!trials

25 In summary (6) In situ melanoma MARGIN of excision NEW: After initial excision biopsy, the radial excision margins, measured clinically from the edge of the mel., should be 5-10 mm (measured with good lighting and magnification) with the aim of achieving complete histological clearance. Melanoma in situ of non-lentigo maligna type is likely to be completely excised with 5mm margins whereas lentigo maligna may require wider excision. Minimum clearances from all margins should be stated/assessed. Consideration should be given to further excision if necessary; positive histological margins are unacceptable.

26 In summary (7) Lentigo maligna- still Biopsy is indicated for changing pigmented lesions on the face C 2. Where LM is histologically confirmed, complete excision is the preferred management C 3. Radiotherapy is an alternative treatment option for patients where surgical excision is problematic or best avoided C x 4. Cryotherapy may occasionally be useful in patients with severe comorbidities or in those in whom surgery is not a possible option D x 5. Topical treatment modalities for LM cannot be recommended at this time C 2 New meta- analysis: RT around 12 % recurrence/ IQ around 25% x

27 Plenty of interesting topics! 9 Congenital melanocytic naevi 13 Management of locoregionally recurrent mel. 16 Psychosocial issues in mel. 18 Multidisciplinary care of mel. 21 Treatment of desmoplastic mel. 25 Mel. in children 26 Pregnancy and mel. (including hormone replacement therapy and oral contraceptives) 27 Prognostic factors and survival outcomes in cutaneous mel. -Managementofmelanoma.pdf