Stage 3 Melanoma- surgery and adjuvant therapies

Practice-Changing Developments in Stage III Melanoma: Surgery, Adjuvant Targeted Therapy, and Immunotherapy

Sat, Jun 02 • 1:15 PM - 2:30 PM

 

Location: S406

work in progress please keep coming back

Alexander Van Akkooi- how much surgery in Stage 3?

A bit of history- Gould 1960 described the principle of the sentinel node that he saw when operating in the parotis (one of the glands producing saliva)- a lymph node draining lymph from a certain area. 

Now what is a Sentinel Node?

Definition

1st draining lymph node from the primary location (of the Melanoma for us)

Concept- a sentinel node as

A Incubator = assuming that progression follows a 'proper' order, going to the loco-regional lymph node first, then spreading further later

B Indicator = simultaneous hematogenic spread

prognostic information: node effected = worse prognosis

Read- Morton 2014

Lancet 2016- no benefit of complete lymph node dissection DECOG-SLT

MSLT-II: CLND vs observation and the Key result.....observation as good as surgery

picture

Grob et al 2018 on how staging shifts from AJCC version 7 to 8

https://www.skincancer.org/publications/the-melanoma-letter/2018-vol-36-no-1/ajcc-staging-system

Interesting to follow up on: neo-adjuvant immune therapy 

Summary

Sentinel node biopsy best diagnostic test

SN tumour burden is prognostic but has no certain therapeutical effect

CLND does not improve survival

For palpable nodes- neo-adjuvant therapy might reduce the extent of surgery necessary and help choose the right adjuvant treatment

Debate- targeted or immuno adjuvant for BRAF positive Stage 3 patients

Arguments for Adjuvant targeted therapy

Known facts

• Dab/ Tram improves OS in Patients with resected STage 3 patients
• improves RFS in same patients
• rare permanent toxicities

Targeted therapy adjuvant challenges known dogmas (only immuno provides long-term results)

Durability of response with targeted therapy in Stage 4, especially for patients with normal LDH and fewer than 3 organ sites involved

Overal argument to use targeted therapy adjuvant- Stage 3 patients have normal LDH and low volume micro metastatic disease

Read up

Long 2018

Schadendorf 2017 (CombiV-CombiD)

Overview

BUT

- higher rate of secondary skin cancers including secondary Melanomas- approx 2.3%

- testing BRAF in very low volume disease can be challenging

- 41% experience Grade 3 or 4 toxicity is high- but most all toxicity is fully reversible with drug discontinuation

Adjuvant immune therapy

Olivier Michielin

Immune therapy- metastatic vs adjuvant setting

Several options available, show DFS benefit but OS data still outstanding
Side effects are a challenge: toxicity on targeted is high but resolves when treatment stops while on immune therapy require experienced medical teams and might not resolve

Future- personalised adjuvant treatment

no treatment for those cured by surgery alone
e.g. stratification by whether patients are able to mount a diversity of T-cell clones against the tumour or not

Summary

- therapies in Stage 3 are rapidly evolving, we got first indications what works and what doesn't but we don't have the 'best way how to do it' yet

- Complete Lymph Node Dissection for all is no longer the way to go

- toxicity is a serious concern, especially as we are currently treating patients who might already be cured by surgery alone

- Stratification: who patient needs what will be the next challenge

RISK OF EQUIPOISE-VIOLATION
Placebos in Stage 3 trials are no longer ethical as we have data that shows that some therapies that delay progression and some data that shows improved overall survival