Melanoma Patients and the Sentinel Lymph Node (SLN) Procedure: An Oncologic Surgeon s Perspective

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Melanoma Patients and the Sentinel Lymph Node (SLN) Procedure: An Oncologic Surgeon s Perspective Giorgos C. Karakousis, M.D. Associate Professor of Surgery Hospital of the University of Pennsylvania

Disclosures Consultant Castle Biosciences No relevant financial disclosures for this presentation

Clinical Questions and Controversies Indications for SLN Biopsy 1. Who should get a SLN biopsy with thin ( 1.00 mm) melanoma? Are there lower risk groups among patients with intermediate depth melanoma? Outcomes after SLN Biopsy 2. What are the outcomes of patients who have a positive SLN biopsy with thin melanoma? How do they compare to those who develop clinical nodal disease? Completion Lymph Node Dissection after SLN Biopsy 3. Which patients with a positive SLN should go on to get a completion lymph node dissection?

Reasons for SLN biopsy Prognostication/Staging Regional Control of Disease Therapeutic Value? http://www.qualityoflife.org/memorialcms/images/cancer/

Morbidity of SLN biopsy Lymphedema rates <~5% Infection <5% Hematoma < 5% Seroma 5-10% Parasthesias 5-10% Anaphylaxis from dye injection <<1%

Predictors of SLN positivity in patients with Thin Melanoma Thin (T1) melanomas ( 1.00 mm) account for approximately 60-70% melanomas SLN positivity in this group is 5% Current NCCN guidelines recommend discussing and considering SLN biopsy in T1a melanomas 0.76 mm and offering SLN biopsy in T1b melanomas 0.76 mm Little consensus as to which factors should drive decision for SLN biopsy in T1 lesions <0.76 mm

Predictors of SLN positivity in patients with Thin Melanoma Bartlett, Karakousis et al Ann Surg Onc 2014

Predictors of LN positivity in patients with Thin Melanoma NCDB database T1 melanomas 0.5mm who had nodal evaluation 8,772 Thickness, gender, ulceration, mitoses, Clark level, LVI, age Sinnamon, Karakousis JAMA Derm 2017

Predictors of SLN positivity in patients with Thin Melanoma Sinnamon, Karakousis JAMA Derm 2017

Predictors of SLN positivity in patients with Thin Melanoma Systematic review and Meta-analysis of 60 studies Cordeiro et al, Ann Surg Onc 2016

Predictors of SLN positivity-intermediate Thickness Melanoma Bartlett, Karakousis et al ASO 2015

Low risk groups for SLN+: Intermediate-Thickness Melanoma 75% patients < 1.5 mm Bartlett, Karakousis et al ASO 2015

Outcomes of Thin Melanoma Patients undergoing SLN biopsy Penn-JWCI study N=586 Melanoma specific survival 5 yr 10 yr Clinical Nodal Recurrence N=466 SLN+ pts N=120 SLN + p<0.0001 SLN+ 88% 84% CNR 72% 49% CNR Karakousis, Faries et al Ann Surg Onc 2016

Controversies in Melanoma Surgery Regional Control with Less Morbidity No significant difference in acute morbidity between immediate and delayed lymphadenectomy group Mean Hospital stay longer in the delayed lymphadenectomy group (9.9 days) versus immediate group (8.3 days), although this could probably largely be accounted for by increased number of deep groin dissections Lymphedema rates higher in delayed versus early lymphadenectomy group Faries et al. Ann Surg Onc 2010; 17: 3324-3329

Completion lymphadenectomy or not for +SLN Incidence of finding additional non-sentinel nodes on completion lymphadenectomy for a + SLN is approximately 15-20% Various factors may help to predict which patients are at risk for harboring additional metastatic disease in the non-sentinel nodes Disease in the non-sentinel nodes may portend a worse prognosis Completion lymphadenectomy has been the standard approach for patients with + SLN, but there are two randomized trial results which have now been published which suggest close surveillance is also a safe approach

Predictors of non-sentinel LN positivity Van der Ploeg et al. JCO 2011; 29 (16): 2206-14

DECOG study Distant metastasis free survival Overall survival Leiter et al. Lancet Oncology 2016; 17 (6): 757-67

MSLT2 Study Faries et al NEJM 2017

MSLT2 Study Faries et al NEJM 2017

Conclusions SLN biopsy is routinely offered to patients with T2 or greater melanomas ( 1 mm) and in patients with T1b lesions 0.76 mm* SLN biopsy can be selectively considered in other T1 lesions (+ deep margin, LVI, Clark level IV/V, high mitotic count) Primary value of SLN biopsy is prognostic/staging and therefore risks of procedure must be weighed against potential benefits. There may be therapeutic value, and increasingly so as newer adjuvant regimens are developed that can be used earlier in stage III disease. Patients with +SLN may be considered for either close surveillance with nodal ultrasound versus CLND; for high risk patients, particular consideration should be given for completion LND for regional control and improved staging.