SLIDE 1
Management of Regional Lymphatic Metastases for Cutaneous Melanoma: Early Intervention is Best
John E Mullinax, MD, FACS Assistant Member, Surgical Oncology Moffitt Cancer Center FL Chapter, American College of Surgeons Annual Meeting, Orlando, FL March 23, 2019
SLIDE 2 Framing the Debate: Philosophical Considerations
- Cancer Surgeon vs. Surgical Oncologist
- Rather than extirpation as our only tool, we should be master the rationale for all
treatments of malignancy
- Timing and extent of resection should always be considered
- If we can resect, should we? And when?
- What effect will our resection have on the patient’s prognosis?
- Balance of morbidity with oncologic outcome
SLIDE 3 Framing the Debate: Terminology
- Elective lymph node dissection
- Complete removal of all lymph nodes within an anatomic boundary without a priori
evidence of regional metastatic disease
- Therapeutic lymph node dissection (TLND)
- Same, performed for “clinically evident” regional metastatic disease
- Completion lymph node dissection (CLND)
- Same, performed for “clinically occult” regional metastatic disease
SLIDE 4 Framing the Debate: Metastasectomy
- Ultimately the decision to perform therapeutic lymph node dissection
(TLND) for cutaneous melanoma is a decision to operate on metastatic disease
- Indicated for those with clinically evident disease limited to regional lymph node basin
(Stage IIIc)
- For those with SLN+ disease, completion lymph node dissection (CLND) is
undertaken based on the potential for clearance of metastatic disease
- When does the oncologic benefit of lymphadenectomy outweigh the
surgical risk for SLN+ disease?
SLIDE 5
- MSLT-1 (Melanoma SLN Trial-1)
- 2001 patients with >1.2mm thick melanoma randomized
to SLN vs. observation
- Improved
- 10-year relapse-free survival
- 10-year melanoma-specific survival for 1.2-3.4mm thick AND +LN
disease
SLIDE 6 MSLT-1 Final Analysis: SLN Biopsy is a Fundamental Staging Study for Cutaneous Melanoma
- Sentinel node biopsy reliably predicts melanoma-specific death at 5 and 10 years for
intermediate thickness primary melanomas
Melanoma-Specific Survival Melanoma-Specific Survival Years Years
SLIDE 7
MSLT-1 Final Analysis: SLN Biopsy is a Fundamental Staging Study for Cutaneous Melanoma
SLIDE 8
- Per-protocol analysis – 3 year melanoma-specific
survival 86% in each group
Trial 2)
with localized cutaneous melanoma and tumor positive sentinel lymph node
melanoma-specific survival
disease-free survival, rate
- f nonsentinel-node mets
- Median f/u 43 months
SLIDE 9
- 2006-2014
- 483 patients with +SLN
randomized
- Final analysis 233 observation vs
240 immediate TLND
distant-metastasis free survival
- 77% observation vs 75% TLND
(p=0.87)
planned accrual was not met
SLIDE 10 Surgical Approach for LN Disease: Summary
- MSLT-1 – patients with nodal disease and intermediate thickness
melanoma had improved DFS and MSS with early CLND than with delayed surgery
- MSLT-2 (& DeCOG) – lack of survival advantage with CLND suggests that
any increase in survival with early surgery occurred in patients with disease limited to SLN
- If no survival advantage then why perform early CLND at the time of SLN-
positive disease?
SLIDE 11
Rationale for Early Therapeutic Lymph Node Dissection
1. Surveillance is not possible for all patients on observation 2. Survival improved with early intervention of involved LN basin 3. Decreased morbidity of early vs. delayed CLND 4. Non-sentinel lymph node positive disease is strong predictor of prognosis
SLIDE 12 Rationale #1: Surveillance for LN Disease
- Patients observed in randomized trials
underwent close surveillance with ultrasound of LN basin
- Limitations exist in generalizing this
approach
- Cost
- Radiographic expertise
- Patient compliance
- In the absence of the ability to adequately
evaluate the LN basin, early CLND required
SLIDE 13 Rationale #2: Early intervention improves survival
- MSLT-1 demonstrated improved
survival of early vs delayed CLND
- Rate of LN Basin Failure:
Melanoma-Specific Survival Years
Observation Early CLND DeCOG 8% 15% MSLT-2 8% 23%
SLIDE 14 Rationale #3: Decreased morbidity of early intervention
- Length of stay overall
- USA: 2.8 days, Europe: 10.6 days, Australia: 9.5 days
- Length of stay by intervention (p=0.21)
- Early TLND: mean 8.3, median 7 days
- Delayed TLND: 9.9, median 9 days
SLIDE 15 Ghaferi et al. Ann Surg Oncol 2009
Overall Survival
Rationale #4: Non-sentinel lymph node disease impacts survival
- Rate of Non-SLN disease
- MSLT-2: 19.9% DeCOG: 25%
SLIDE 16
SLIDE 17 Selective Approach to Early Completion Lymph Node Dissection
- Ultimately, the decision should be
personalized to patient factors
- Ability to follow up
- Discussion of risks/benefits
- Identification of those at high risk for
Non-SLN positive disease
- Ability and willingness to have adjuvant
therapy
- Head and neck primary/regional LN
basins
SLIDE 18 Selective Approach to Early Completion Lymph Node Dissection
- Observation safe for those with “low-risk micrometastatic disease”
- CLND favored for those with “high-risk” features
- Extracapsular extension of disease within SLN
- Satellitosis of primary tumor
- >3 positive SLNs
- >2 involved nodal basins
- Immunosuppressed patient/auto immunity (unable to have adjuvant immunotherapy)
SLIDE 19 Conclusions: Early CLND for SLN+ melanoma
- Lymph node dissection at the time of diagnosis for nodal disease
addresses non-sentinel lymph node disease
- Up to 25% of patients in aggregate from large randomized trials
- Should consider
- Observation for low-risk patients where sonographic surveillance is possible
- Early CLND for high-risk patients
- Data from these RCTs generated in the pre-checkpoint inhibitor era
- Unknown outcomes regarding observation or early CLND in the era of modern
adjuvant treatment (immunotherapy)
SLIDE 20
Management of Regional Lymphatic Metastases for Cutaneous Melanoma: Early Intervention is Best
John E Mullinax, MD, FACS Assistant Member, Surgical Oncology Moffitt Cancer Center FL Chapter, American College of Surgeons Annual Meeting, Orlando, FL March 23, 2019
