66: Improved Survival with Sentinel Node Biopsy - An Emulated Randomized Controlled Trial

Thursday, March 21, 2024

2:57pm – 3:07pm ET

Location: C102

Abstract Presenter(s)

Alexander H R Varey, MBChB MRCS(Eng) FRACS FRCS(Plast) PhD (he/him/his)

A/Prof
Melanoma Institute Australia, University of Sydney, Westmead Hospital
Sydney, New South Wales, Australia

Submitter(s)

Alexander H R Varey, MBChB MRCS(Eng) FRACS FRCS(Plast) PhD (he/him/his)

A/Prof
Melanoma Institute Australia, University of Sydney, Westmead Hospital
Sydney, New South Wales, Australia

Author(s)

Alexander H R Varey, MBChB MRCS(Eng) FRACS FRCS(Plast) PhD (he/him/his)

A/Prof
Melanoma Institute Australia, University of Sydney, Westmead Hospital
Sydney, New South Wales, Australia
RF

Raphael P. Feser, n/a

Biostatistician
Melanoma Institute Australia, United States
NA

Nurudeen A. Adegoke, n/a

Biostatistician
Melanoma Institute Australia, United States
RS

Richard Scolyer, BMedSci MBBS MD FRCPA FRCPath(UK) FAHMS

Medical Director
Melanoma Institute Australia, Australia
John Thompson, MBBS, MD, DSc, FRACS, FACS (Hon), FAHMS

Surgeon
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia
North Sydney, New South Wales, Australia
SL

Serigne N. Lo, PhD

Biostatistician
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia, United States

Disclosure(s):

Alexander H R Varey, MBChB MRCS(Eng) FRACS FRCS(Plast) PhD: Novartis Pharmaceuticals Australia Pty Ltd: Speaker (Terminated, May 1, 2022)

Introduction: Sentinel node biopsy (SNB) in addition to wide excision (WE) was shown to increase recurrence free survival (RFS) on an intention-to-treat (ITT) analysis of the first Multicenter Selective Lymphadenectomy Trial (MSLT-1), compared to WE alone. However, melanoma-specific survival (MSS) was not significantly different between the two arms on ITT analysis, likely due to underpowering. In such situations, where a larger randomized controlled trial (RCT) with long-term follow-up is not feasible, a well-established causal inference method is to emulate a pragmatic RCT using observational data (Hernan and Robins 2016). Consequently, this study aimed to emulate a large RCT to determine the true effect of SNB on survival outcomes.

Methods:

A trial protocol was established as follows: adult patients diagnosed with a primary cutaneous melanoma between 01/01/2000 and 31/12/2016 with no clinical evidence of metastatic disease and a primary melanoma thickness 1.1-4.0mm were recruited from a prospectively-maintained single-institution database. Patients having SNB >90 days following diagnosis or receiving adjuvant immunotherapy were excluded. Absolute risks difference were estimated combining emulated pragmatic RCT and inverse probability weightings.

Results:

Of 5746 patients recruited, 3849 (67%) had a SNB. MSS was significantly improved in the SNB group at 5 years (85% v 76%) and 10 years (73% v 61%), a hazard ratio (HR) 0.71 [95%CI 0.52; 0.98], p-value: 0.03. Likewise, OS was improved in the SNB group at 5 years (79% v 66%) and 10 years (58% v 44), HR = 0.72 [95%CI 0.54; 0.96]. Similar improvements were seen for RFS at 5 years (64% v 43%) and 10 years (43% v 26). The number of patients needed to be biopsied (NNB) to save one person from dying from melanoma varied by melanoma thickness and age from 4 to 17 (Table 1).

Conclusions:

This emulated RCT demonstrated that SNB improved all survival outcomes in patients with melanomas 1.1-4.0mm thickness. These results are consistent with the subgroup analysis of MSLT-1. The MSS benefit was greatest in patients aged ≤40 years, in whom the NNB to save one death from melanoma was four for melanomas 1.1-2.0mm thick and six for melanomas 2.1-4.0mm thick.

Learning Objectives:

Upon completion, participant will be able to define the survival benefit afforded by performing a sentinel node biopsy for a patient with intermediate thickness melanoma.
Upon completion, participant will be able to define the number of patients that need to have a sentinel node biopsy to save one patient with intermediate thickness melanoma from recurrence.
Upon completion, participant will be able to define the number of patients that need to have a sentinel node biopsy to save one patient with intermediate thickness melanoma from dying.