medical, surgical & cosmetic dermatology · - avoid heat / exercise / subsequent sun for minimum 2...

Management of NMSCs Cancer Council WA General Practice Education Session Thursday 8th December 2016 The Bendat Parent & Community Centre

Dr Philip D.G. Singh MBBS(WA) FACD Dermatologist

Medical, Surgical & Cosmetic Dermatology

Declarations

No Conflicts of Interest

Perth Skin Specialists 2

NMSC Management

Not always straight-forward approach, as not all patients are straight-forward cases Essential to involve patient in owning their care, especially with home-based remedies


NMSC Management Get early start re: skin care recommendations; Some studies have shown 50% of children have

had significant sunburns before age 11 concern re: MM lifetime risk estimated that intensive photoprotection before age

18 can reduce NMSCs by 78% Adolescent behavioural patterns regarding sun

protection / skin care are not that different to scenarios of chronic disease diagnoses


Biopsies - Shave Biopsy

- Ideal for superficial or small lesions - Adequate for almost all lesions if good technique and confident with pathologist

(Dermatopathologist) caution with pigmented lesions

- Punch Biopsy Lesions suggesting invasion 2 or 3mm Bx sufficient in most cases can avoid need for sutures

Good vasculature areas (face/genitalia/mucosae) heal rapidly with minimal to nil scarring

- Incisional Biopsy or Wedge Biopsy Large exophytic lesions, Atypical lesions (DDx rare tumours such as DFSP) Pigmentation (DDx melanoma)

- Excisional Biopsy

Smaller, well-defined lesions

- Curettage often done with aim for definitive treatment of superficial lesions Debulking effect for those that may not tolerate surgery


Biopsies - Minimal handling of tissue material

especially punch biopsy (to avoid crush artefact)

- Anaesthesia technique - Slow injection - Small volumes - Small needles - Consider buffering with NaHCO3 (1:10 mix) - Distraction techniques - Ice/cooling


Dr Philip Singh MBBS(WA) FACD Perth Skin Specialists 7

Treatment

AKs

supBCC

supSCC

BCC

SCC

Appendigeal

Tumours

Merkel

DFSP

AFX

Cutaneous Lymphomas (B and T)

Cutaneous Mets

Solaraze

Efudix

Aldara

*

Picato

*

*

PDT

Kleresca

*

*

*

Cryotherapy

*

*

*

Shave Excision

*

*

*

*

C & C

*

*

*

Excision

RadioTherapy

*

*

*

PhotoTherapy

Laser

*

*

*

Solaraze (diclofenac)

- Not used much amongst Dermos - Option for those wanting to a routine really

gentle treatment for pre-malignant lesions - Issues;

Duration of use (3/12!) Weak activity

~50% cure rate of AKs

Side effect profile Irritation, itch, exfoliation, oedema, photosensitivity

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Dr Philip D.G. Singh MBBS FACD Perth Skin Specialists

Topical Retinoids

- e.g. Differin / Retin-A / Zorac - Long-term use required (usually >4-6/12) - No specific documented cure rates - Tolerability issues in the population of

concern Not the typically younger acne pts

9 Dr Philip D.G. Singh MBBS FACD Perth Skin Specialists

Efudix (5-FU) - Inhibits DNA synthesis - Ideal for AKs and supSCC, option for supBCC (~90%

clearance rate for these) - 2/52 BD face, 4-6/52 BD body sites - 7-10/7 for lips - Benefit is from duration of therapy AND extent of response - Beardmore grading of response - Option for occlusive therapy;

2 or 3x per week application, under glad wrap, left overnight, for up to 6 weeks

Scalp, Limbs - Tolerability;

Nausea, anorexia, lethargy Risk of allergy very low but possible


Aldara (Imiquimod) - Activates cytotoxic T-Cells against tumour

cells - Mon to Fri application for 6/52 for supBCC - 2 - 3x per week for up to 12/52 for AKs - Cure rate ~85% - Not for SCCs - Not an option for nodular lesions unless small

lesions on low-risk sites - Issue with tolerability - SFx include flu-like illness, or GI Sx

11


Picato (ingenol mebutate) - Developed from Radium weed / Milk weed - MOA via immune cellular cytotoxicity as well as rapid

induction of necrosis, targeting dysplastic cells - 0.05% for body sites, once daily, 2 days in a row - 0.015% for face and scalp, once daily, 3 days in a row - Each tube up to 25cm2 - Can be prominent reaction, but shorter-lived than

other field therapies - Negatives include potential severe reaction or even

allergic response, as well as cost compared with Efudix or Aldara


PDT - 2 types of cream

5-aminolevulinic acid (5-ALA) Methyl aminolevulinate (MAL) Metvix

- Product absorbed into cells, converted into Protoporophyrin IX which when exposed to either nm triggers cellular destruction

- Recommended for AKs, supBCC and supSCC - Lamp treatment for supBCC / supSCC - Current approach is to use Daylight PDT for AKs

Face and scalp AKs Quicker treatment Less painful

13


PDT - Cleanse area requiring treatment - Descale consider use of Salicylic Acid / Urea creams prior

Curettage Light cryo and abrasion (such as gauze)

- Apply chemical sunscreen to all exposed sites including treatment area - Apply Metvix cream - Within 30mins expose to outdoors (even in shaded areas on particularly

sunny days), maintain exposure for 2hrs - Gentle cleanser to remove cream - Apply bland moisturisers, continue with gentle cares ongoing - Avoid heat / exercise / subsequent sun for minimum 2 days - Avoid exposure to potential airborne allergens (fragrances / cleaning

products / etc) until settled - Peak reaction Day 2 / 3, resolving between 1 2 weeks - Can do repeat treatment after 3 months


Cryotherapy

- Great for supBCC / supSCC - Cure rates >92% (up to 99%) - 2x FTC - Ensure cover lesion and 2-3mm beyond - Gauge depth experience, palpation - Risk of hypopigmented scar


Shave / Punch Excision

- Technique-dependent - Great for superficial variants - Consider for small well-defined BCC

lesions (aim for at least 1mm margin around)


Curettage & Cautery - Relies on nature of tumours being friable tissue - Great for supBCC or supSCC - Great for nodBCC ** - Option for true SCC ** - Proper delineation of lesion margins - Adequate curettage

Ideally at least 2 passes with cautery following each pass

- Somewhat technique-dependent - Consider the resultant scarring


Excision

- Standard Excision - Wide Local Excision

- May involve large defects, therefore may

involve significant repairs (flaps/grafts) Potential future issue with residual tumour /

recurrence


Approach to Excision - Careful clinical delineation of lesion, use of dermoscopy to

assist - Apply marking for required surgical margin - Careful scalpel technique to help minimise step-deformities - Undermining as required

Near free-margin anatomy Flap repairs

- Haemostasis - Always consider internal closure - Ensure good approximation of wound edges - Skin closure of choice - Dressings and after-care

Dont under-estimate written advice


Surgical margins BCC = ~3mm

- Aggressive subtypes = 5 - 10mm (e.g. Invasive or Morphoeic)

SCC

- Tumour 10 - 20mm Merkel Cell Carcinoma = >10 - 20mm DFSP = 30mm AFX = >10 - 20mm


MOHS Surgery - Initially developed 1938 by Frederick E. Mohs, refined over the

years - Excision of visible tumour, precisely mapped out for immediate

processing and sectioning by pathologist - Pt in waiting room while the surgeon personally reviews the slide

sections - Pt brought back into theatre for sequential sectioning/removing of

affected tumour as required Allows specific tracking of involved margins Aim to ensure all cancer cells removed*

- Closure/wound repair determined once no residual tumour identified Repair may involve Oculoplastics / Plastics / other surgeons.

* Higher cure rate than other modes of treatment (at 98%)


MOHS Surgery - Difficult site - Critical need to conserve tissue - Recurrent lesions - Incompletely excised lesions - Aggressive subtypes

e.g. Morphoeic BCC - Rare Tumours

DFSP, AFX, MCC, Appendigeal Tumours


Radiotherapy Cure OR Control

Very large area of tumour Difficult location w.r.t. surgical approach Unable to proceed/tolerate surgery

Adjuvant treatment PNI involvement Involved margins, not willing/unable to proceed for re-

excision Palliative approach

Tumour bulk reduction Delay growth / proliferation Minimise risk of bleeding/infection Address pain/discomfort (relieve symptoms)

23


Radiotherapy

- Not recommended for pts with inherited cancer disorders

(e.g. Xeroderma Pigmentosa, Rothmund-Thompson, Blooms, Gorlins, Albinism, etc)

- Not recommended for pts with connective tissue disorders


Radiotherapy

- Traditionally radiation-sensitive tumours BCCs SCCs Cutaneous Lymphomas Kaposi Sarcoma Merkel Cell Carcinoma


Radiotherapy

- Acute vs Chronic side effects Radiation dermatitis Skin pigmentation changes Skin textural changes Hair loss in treated site Damage to underlying structures/organs

e.g. Glands, Cartilage Ulceration New skin cancer development


Phototherapy

- Indicated for Cutaneous T-Cell Lymphoma - Most units nowadays nbUVB (not PUVA) - Longer-term approach c.f. Psoriasis or

Eczema treatments - Risk of skin burns during treatment - Minor concern with long-term use as

potential increase risk of NMSCs


Laser

- CO2 or Erbium Ablative Laser supBCC / supSCC BCC Actinic Cheilitis spectrum


When to refer? Diagnostic uncertainty Treatment option uncertainty Beyond skill level / Beyond comfort zone

(technique/anatomy/other) Recurrent tumours Frequent Multiple Tumours

Tx pts Syndromic pts (e.g. Xeroderma Pigmentosa, Rothmund-Thompson,

Blooms, Gorlins, Albinism, etc)

Large tumours 30 Dr Philip D.G. Singh MBBS FACD Perth Skin Specialists

When to refer? Aggressive subtypes

e.g. Morphoeic BCC, desmoplastic SCC Recurrent tumours Incomplete excisions Concern about metastasis High risk sites

Lips, ears, nose, genitalia... Cosmetic risk sites often also Clinical

risk sites Head/Neck, functional sites/free margins Keloidal scar-prone sites

31


Approach to Management of BCCs

1) Lesion assessment - Is it superficial? - Is it invasive? Has it breached the DEJ?

- Nodular - Invasive - Micronodular - Morphoeic - Basisquamous (higher risk of mets)

- Is it Primary or Recurrent?



2) Lesion location - Risk of more aggressive involvement

- Is it high risk? - Head/Neck - Especially Eyes, Nose, Lips, Ears

- Is it low risk? - Distal peripheries

- Otherwise intermediate - Trunk / Proximal limbs

- Risk of healing issues - Distal lower limbs most concerning - Patient factors

- Age, Skin quality, Underlying diseases, Dermatoses

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3) Patient History - Tolerability of prior treatments

- Imiquimod Allergy? - Associated underlying disorder

- Transplant patient?



4) Follow-Up - Slow growing lesions, with less than 1/3rd of

recurrences present in 1st year - 44% risk of developing another BCC in the

first 3yrs. - Overall 10 times the risk of developing

another BCC compared to gen pop risk - Ongoing self-surveillance and clinical skin

checks



5) Prognosis - Excellent, 100% survival rate for cases

without spread to other sites - Incidence of metastatic BCC

Approach to Management of SCCs

1) Lesion assessment - Is it superficial? - Is it invasive? What category?

- Keratoacanthoma-type - Well Differentiated - Moderately-differentiated - Poorly differentiated

- Is it Primary or Recurrent?



2) Lesion location - Risk of more aggressive involvement

- Is it high risk? - Head/Neck - Especially Eyes, Nose, Lips, Ears

- Is it low risk? - Distal peripheries

- Otherwise intermediate - Trunk / Proximal limbs

- Risk of healing issues - Distal lower limbs most concerning - Patient factors

- Age, Skin quality, Underlying diseases, Dermatoses



3) Patient History - Tolerability of prior treatments

- Efudix Allergy? - Associated underlying disorder

- Transplant patient?



4) Follow-up - Pts who develop an SCC have 40% risk of

additional SCCs in the following 2yrs - 75% of local recurrences detected within

subsequent 2yrs, 95% detected within 5yrs - Ongoing self-surveillance and clinical skin

checks


Approach to Management of SCCs 5) Prognosis

- Absence of prognostic models taking all factors into account, thus estimating individual risk based on limited data and gestault

- Generally good for primary cutaneous SCC (cSCC) - Significant morbidity if lesions allowed to progress - Early-stage 5-yr survival rate >90% - Advanced-stage 5-yr survival rate 25 45% - Primary tumour risk of nodal or distant metastases 2 6% - One study showed incidence of metastatic cSCC 1.9

2.6%*


* The incidence of metastasis from cutaneous SCC and the impact of its risk factors. J Surg Oncol. 2012 Dec; 106(7):811-5.

Approach to Management of SCCs 5) Prognosis - Intrinsic Factors

- Location - Size - Invasion into subcutaneous fat or deeper - Poorly differentiated - Recurrent tumour - Peri-Neural Involvement

- Extrinsic Factors

- Haematological malignancy - HIV / AIDS - Immunobullous disorders - Organ Transplant - Long-term Immunosuppressive therapy



Sentinel Lymph Node Biopsy - Controversial especially amongst Dermatology field - No equivocal advantage in survival has been

demonstrated when c.f. delayed dissection for pts with metastases in the neck

- Used as a staging technique, allowing accurate planning of node dissection


Systemic Treatment Option - Oral Retinoids

- Acitretin

- Consideration for assisting in the reduction in number of proliferative lesions (Particularly SCCs)

Severe Actinopath population Transplant pts

- Should be viewed as lifelong treatment given potential risk of rebound flares

- Studies involving Renal Tx pts small number of trials

~15% relative decrease in number of keratotic lesions

- SFx; - Dry skin/mouth/eyes, GI, fragile skin/nail/hair, flushing, Renal or Liver derangement,

BIH, Pregnancy contraindication


Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study. J Clin Oncol. 1995 Aug; 13(8):1933-8.

Follow-up Skin Checks

Depending upon several factors, including; Patients PMHx Patients FHx Time since Dx of last skin cancer Patients SHx


Sunscreen - SPF 30+ or greater - Broad Spectrum, Photostability issue - Tolerable - Tailored to specific use

Sports? Water activities? - Physical blockers penetration limited to epidermis,

current evidence nil systemic absorption - Chemical & Physical Blocker Sunscreens

La Roche Posay Anthelios XL - Liposomal Sunscreens

Galderma Actinica Galderma Cetaphil Suntivity


Vit B3 (Nicotinamide) - MOA = Enhances DNA repair by boosting cellular ATP, and

minimises UV-induced suppression of cutaneous anti-tumour immunity

- 1 year study of 386 high risk pts, avg 66yo - 23% overall reduction of new BCC / SCCs

30% reduction SCCs 20% reduction BCCs

- 15% overall reduction of AKs - Effect NOT maintained after ceasing - Oral tablets, 500mg BD dosing - NOT niacin or nicotinic acid


Oral nicotinamide prevents common skin cancers in high-risk patients, Am Health Drug Benefits. 2015 Aug;8(Spec Issue):13-14.

A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention. N Engl J Med. 2015; 373:1618-1626.

Future Treatments

Radiotherapeutic bandages - Animal testing only so far SCCs

- Clinical trials using agents targeting EGFR proteins on tumour cells (e.g. Cetuximab)

BCCs - Clinical trials using agents targeting Hedgehog

signaling pathway (e.g. Vismodegib


Thank you

49

Suite 5, Level 2

7 Lyall St South Perth WA 6151

+61 8 9367 7546

www.perthskinspecialists.com.au

Medical, Surgical & Cosmetic Dermatology

Management of NMSCsDeclarationsNMSC ManagementNMSC ManagementBiopsiesBiopsiesSlide Number 7Solaraze (diclofenac)Topical RetinoidsEfudix (5-FU)Aldara (Imiquimod)Picato (ingenol mebutate)PDTPDTCryotherapyShave / Punch ExcisionCurettage & CauteryExcisionApproach to ExcisionSurgical marginsMOHS SurgeryMOHS SurgeryRadiotherapyRadiotherapyRadiotherapyRadiotherapyPhototherapyLaserSlide Number 29When to refer?When to refer?Approach to Management of BCCsApproach to Management of BCCsApproach to Management of BCCsApproach to Management of BCCsApproach to Management of BCCsApproach to Management of SCCs Approach to Management of SCCs Approach to Management of SCCs Approach to Management of SCCs Approach to Management of SCCs Approach to Management of SCCs Approach to Management of SCCs Systemic Treatment Option- Oral RetinoidsFollow-up Skin ChecksSunscreenVit B3 (Nicotinamide)Future TreatmentsThank you

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