1. EPIDEMIOLOGY AND TREATMENT Hazard ARH Regional Medical Center
Melanoma
EPIDEMIOLOGY AND TREATMENT
DANIEL KENADY, M.D.
Hazard ARH Regional Medical Center

2. No disclosures

3. Epidemiology of Melanoma
IN1968B

4. Estimated New Melanoma Cases & Deaths: US, 2016
70000
60000
50000
40000
Cases
76380
30000
Deaths
20000
46870
29900
29510
10000
6750
10130
3380
Total
Male
Female
American Cancer Society. Cancer Facts & Figures 2004.

5. Lifetime Risk of Developing Cutaneous Melanoma in the US
1:74
1:100
1:150
1:250
1:600
1:1500
1935
1960
1980
1985
1993
2000
Rigel DS, Carucci JA. CA Cancer J Clin. 2000;50:215–236.

6. Melanoma Mortality Rates: US, 1975-2000
White Men
All Men
Overall
Women
Ries LAG, et al, eds. SEER Cancer Statistics Review, 1975–2000. Bethesda, MD: National Cancer Institute; 2003: Tables XVI-1–9.

7. Melanoma Diagnosis: Identifying Populations at High Risk
Factors known to increase risk
Familial
History of malignant melanoma
Skin type and color
Environmental
3 blistering sunburns before age 20
Outdoor summer jobs for 3 years in adolescent years
Use of sunlamps, tanning beds
Other
Actinic keratosis, elastosis
Marked freckling on upper back
Large number of normal nevi
Atypical nevi, congenital giant nevi
Each risk factor increases risk additively
CA Cancer J Clin. 2000;50:215–236.

8. NEJM 355:51,2006

10. Cutaneous Melanoma: Early Recognition and Diagnosis

11. The ABCDEs of Melanoma Diagnosis
Asymmetry
One half of the lesion is shaped differently than the other
The border of the lesion is irregular, blurred, or ragged
Border
Color
Inconsistent pigmentation, with varying shades of brown and black
>6 mm, or a progressive change in size
Diameter
Evolution
History of change in the lesion
Photos courtesy of the American Cancer Society.

12. Morphologic Types of Melanoma
Superficial 60%-70% Flat during early phase; notching, spreading scalloping, areas of regression
Nodular 15%-30% Darker and thicker than superficial spreading, rapid onset; commonly blue-black or blue-red (5% amelanotic)
Lentigo ~5% Enlarge slowly; usually large, flat, tan maligna or brown
Acral Uncommon On soles, palms, beneath nail beds;
lentiginous Asians (46%), usually large, tan or brown; irregular Blacks (70%) border; subungual melanoma more common in older, dark-skinned people
Desmoplastic 1.7% Rare, locally aggressive, occur primarily on head and neck in elderly
Data from Lotze MT, et al. Cutaneous Melanoma. In: DeVita VT Jr,. et al, eds. Cancer: Principles & Practice of Oncology. 6th ed. Philadelphia, PA: Lippincott-Raven; 2001.

13. Seborrheic Keratosis

14. Basal Cell Carcinoma

15. Hemangioma

16. Melanoma

18. Images courtesy of Kenneth Tanabe, MD

26. 2010 AJCC Melanoma Staging System: T Classification
Depth
Ulceration*
Stage T1 T2 T3 T4
1.0 mm mm mm
4.0 mm a† b‡ a b IA IB
IIA
IIB
IIC
*a, no ulceration; b, ulceration †Clark’s level II/III
‡ulceration or Clark’s level IV/V J Clin Oncol. 2001;19:

27. 2010 AJCC Melanoma Staging System: N Classification
Number
Type
Stage* N1 N2 N3 1
2-3 4+
and/or
matted,
in-transit,
satellite or
ulceration
a micro
b macro
c in-transit or
satellite, no
+ nodes
IIIA/B
IIIB/C
IIIB
IIIC
*reflects effects of ulceration J Clin Oncol. 2001;19:

28. 2010 AJCC Melanoma Staging System: M Classification
Location
Stage Mx M0 M1
Unassessable
No distant metastases
Distant metastases IV
a: Skin, subcutaneous tissues,
distant lymph nodes
b: Lung
c: All other distant sites or at
any site with  LDH*
*LDH = lactate dehydrogenase J Clin Oncol. 2001;19:

29. AJCC Staging Criteria: T Stage 5-Year Survival*
Ulceration
Depth – +
<1.0 mm mm mm
>4.0 mm
95%
89%
78%
67%
91%
77%
63%
45%
*10-year survival was 10-15% less in each category J Clin Oncol. 2001;19:

30. 5-Year Survival by Node Class
+ Nodes Microscopic Macroscopic
1 61% 46%
2 56% 37%
3 56% 27%
4 36% 24%
>4 35% 24%
J Clin Oncol. 2001;19:

31. 5-Year Survival in Stage III Melanoma
Microscopic
Macroscopic
J Clin Oncol. 2001;19:

33. Surgical Management and Sentinel Lymph Node Biopsy in Cutaneous Melanoma

34. Diagnostic Biopsy in Primary Melanoma
Narrow excisional biopsy (2-3 mm)
Goals
Rule out lesions with potentially similar features
seborrheic keratosis
pigmented basal cell cancer
solar lentigines
atypical nevi
Determine depth and level of invasion
Identify other prognostic features of the 1º lesion
Am J Clin Dermatol. 2002;3: Cancer Principles & Practice of Oncology, 6th ed. 2001: Guidelines of Care for Primary Cutaneous Melanoma. American Academy of Dermatology. 2001:1-11.

35. Diagnostic Biopsy in Primary Melanoma
Lesion Too Large for Excision/Closure
Incisional biopsy or punch biopsy
Must be full thickness through thickest part of lesion clinically
No shave biopsy

36. Wide Excision: Prospective Randomized Trials
Surgical Trial n
Tumor Thickness
Arms

37. Intergroup Trial Results: Surgical Margins
Local Recurrence
Survival
Skin Graft
2 cm
4 cm
2.1%
2.6%
70%
77%
11%
46%
These data are not reflected in the Balch Intergroup Trial reference (2001, Ann Surg Oncol), which also does not include skin graft data. The data for a smaller group of patients, however (reported in Balch, et al. Ann Surg 1993), are reflected here. Should this slide and its data be changed to reflect the 2001 report, or should the previous slide (#3) be changed to correlate with the data reported here?
Ann Surg. 1993;218:262–267.
Ann Surg Oncol. 2001;8:101–108.

38. Surgical Excision for Localized Cutaneous Melanoma: Recommended Margins
Melanoma Thickness
Margin*
1 mm
1.01–2.00 mm
2.01–4.00 mm
>4 mm
1 cm
1–2 cm†
2 cm
Margins may be modified to accommodate individual anatomic or cosmetic considerations
For clinically ill-defined lentigo maligna pattern lesions of the head and neck, pathological confirmation of negative peripheral margin is important
*Maximal achievable with 1 closure †Where anatomically feasible NCCN Practice Guidelines: Melanoma.

39. Rationale for Lymphadenectomy
Improve regional disease control
Enhance accuracy of staging
Improve odds of survival

40. Intergroup Melanoma Surgical Program: All Patients
100
Overall Survival (%)
Regional Node Dissection (n = 379) 90 80 70
Observation (n = 361) 60
Arm
ELND*
Obs
5-yr Survival
86%
82% 50
P = 0.25 40 1 2 3 4 5 6 7 8 9 10 11 12
Years
*Elective regional lymph node dissection
Ann Surg. 1996;224:255–66.

43. Techniques in SLN Mapping and Biopsy
Preoperative injection of radiocolloid + intraoperative blue dye improves accuracy of lymphatic mapping
Identification of SLN occurs both by sight and with a handheld gamma probe
Lymphatic drainage does not always match classic anatomical patterns
Excision of primary lesion
Should be performed at the time of SLN biopsy or thereafter
Recent studies have shown no significant decrement in ability to identify SLN when mapping and biopsy are performed after wide excision
Am J Clin Dermatol. 2002;3:401–426.
Ann Surg. 1999;230:453–465.
Ann Surg Oncol. 2003;10:196–200.
Ann Surg Oncol. 2003;10:416–425.

44. Sentinel Lymph Node (SLN) Mapping and Biopsy
Lymphatic metastases from tumor spread first through afferent channels
SLN is first node along those channels
SLNs are immuno- suppressed and proven to be sites of early metastases
SCOTT/AU: The photograph of the lymph node on the slide does not appear in the Morton reference.
Ann Surg. 1999;230:453–465.

47. Surgical Management of Clinical Stage I and II Melanoma
SLN identified
Evaluate by hematoxylin/eosin & immunohistochemistry, stepped sections
Node negative
Node positive
Observation
En bloc dissection
Adjuvant therapy
Arch Surg. 1992;127:392–399.

57. …or is it?

60. Potential Candidates for SLN Biopsy
Risk of nodal metastasis varies with tumor thickness
<5% for tumors 1 mm w/o ulceration, other adverse factors
20% for tumors 1–4 mm
35% for tumors 4 mm
SLN biopsy should be discussed with all patients with invasive melanoma
Patients with primary melanomas 1 mm are appropriate candidates for SLN biopsy
Some patients with thinner primary melanomas may also be appropriate candidates for SLN biopsy
Ulceration, Clark level IV invasion, truncal location, and mitoses should be considered
Patients with nevomelanocytic lesions assessed by biopsy in which biology is uncertain (eg, atypical Spitz nevus)
Evaluate each patient individually
Arch Dermatol. 2001;137: J Surg Oncol. 2003;82: NCCN Practice Guidelines: Melanoma.

68. Surgery >4 mm or node + (ELND) followed by randomization (n = 287)
E1684: Study Design
Observation
Arm A
52 Weeks
Surgery >4 mm or node +
(ELND) followed by randomization (n = 287)
IFN-a2b
Induction
Maintenance
Arm B
4 Weeks
48 Weeks
Induction: 20 MIU/m2 IV 5x weekly x 4 weeks
Maintenance: 10 MIU/m2 SC TIW x 48 weeks
J Clin Oncol. 1996;14:7-17.

69. E1684: Estimated Relapse-Free Survival
1.0
Arm
IFNa2b
Obs
Median RFS
1.72 yr
0.98 yr
0.9
0.8
0.7
0.6
Probability of relapse-free survival
0.5
0.4
IFN-a2b (n=143)
0.3
Observation (n=137)
0.2
0.1 1 2 3 4 5 6 7 8
Years
P=0.0023
J Clin Oncol. 1996;14:7-17.

70. E1684: Estimated Overall Survival
1.0
Arm
IFNa2b
Obs
Median OS
3.82 yr
2.78 yr
0.9
0.8
0.7
0.6
Probability of survival
0.5
IFN-a2b (n=143)
0.4
Observation (n=137)
0.3
0.2
0.1 1 2 3 4 5 6 7 8
P=0.0237
J Clin Oncol. 1996;14:7-17.

71. Recommendations for Adjuvant Therapy
For patients with IIB, IIC or III: 2B recommendations-clinical trial vs observation vs HD IFN (4 weeks) followed by 48 weeks of LD IFN.
Many caveats and contra-indications to HD IFN.
Careful adherence to standards of supportive care nearly always prevent serious complications of the therapy.

72. FUTURE ADJUVANT THERAPIES
* VEMURAFENIB –BRAF-mutant cases
* IPILIMUMAB ( anti-CTLA-4 ANTIBODY)
* NIVOLUMAB ( anti-PD-1 antibody)

74. ANIMAL SLIDE