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
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
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
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?
• 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
MSLT-1 Final Analysis: SLN Biopsy is a Fundamental Staging Study for Cutaneous Melanoma Melanoma-Specific Survival Melanoma-Specific Survival Years Years • Sentinel node biopsy reliably predicts melanoma-specific death at 5 and 10 years for intermediate thickness primary melanomas
MSLT-1 Final Analysis: SLN Biopsy is a Fundamental Staging Study for Cutaneous Melanoma
• MSLT-2 (Melanoma SLN Trial 2) • 1934 patients 18-75yo with localized cutaneous melanoma and tumor positive sentinel lymph node • Primary endpoint – melanoma-specific survival • Secondary endpoints – disease-free survival, rate of nonsentinel-node mets • Median f/u 43 months • Per-protocol analysis – 3 year melanoma-specific survival 86% in each group
• 2006-2014 • 483 patients with +SLN randomized • Final analysis 233 observation vs 240 immediate TLND • Primary endpoint: 3-year distant-metastasis free survival • 77% observation vs 75% TLND (p=0.87) • Underpowered study as planned accrual was not met
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?
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
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
Rationale #2: Early intervention improves survival • MSLT-1 demonstrated improved survival of early vs delayed CLND Melanoma-Specific Survival • Rate of LN Basin Failure: Observation Early CLND DeCOG 8% 15% Years MSLT-2 8% 23%
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
Rationale #4: Non-sentinel lymph node disease impacts survival Overall Survival Ghaferi et al. Ann Surg Oncol 2009 • Rate of Non-SLN disease • MSLT-2: 19.9% DeCOG: 25%
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
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)
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)
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
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