E302: International Survey on Evidence for Index Lymph Node (ILN) Surgery Following Neoadjuvant Systemic Therapy (NST) for Stage III Melanoma

: NST might soon become standard of care (SoC) for macroscopic stage III melanoma after the phase II SWOG-1801 study and ongoing phase 3 NADINA trial. However, a therapeutic lymph node dissection (TLND) was required in these trials and is considered SoC for these patients. The PRADO study examined the use of the ILN excision histopathology to tailor subsequent treatment(s); patients with a Major Pathologic Response (≤10% viable tumor cells) did not undergo TLND (or adjuvant therapy) and only 4/60 recurred after a median follow-up of 28.1 months. 3/4 recurrences were within the ILN basin and all were managed with a TLND. The INMC surgical consensus and international guidelines recognize the promise of the ILN approach but consider PRADO a proof-of-concept study that needs confirmation to alter practice. Since there is a lack of consensus on how to proceed, we designed this survey for melanoma investigators from around the world.

Methods: A survey was created in www.surveymonkey.com and reviewed by 6 local melanoma experts. After consensus on phrasing of questions and responses, the survey was formatted, and a new test version sent out to 3 international melanoma experts and 2 fellows. After subsequent final adjustments, the survey was sent on 25 May 2023 to 215 international melanoma experts and shared through other platforms. An additional 22 melanoma clinicians were contacted through a 2^nd round of invitations on 1 June 2023; automatic reminders were sent to those who did not reply to the initial invitation or if responses were incomplete.

Results:

As of 10 August 2023, 117 responses were recorded (54%), Table 1 summarizes the characteristics of the respondents. Nearly all respondents were familiar with the NST data (PRADO, SWOG1801) and agreed NST will soon become SoC. There was no consensus as to whether the current evidence was sufficient to implement ILN as SoC, 49% agreed, 31% disagreed and 20% were undecided. With regard to what further evidence would be required to change practice; 66% thought a phase 3 randomized controlled trial (RCT) is needed to change practice while 33% thought a single arm phase 2 would suffice (104 respondents). After receiving additional information on the study power of the PRADO vs. OpACIN-neo analysis (21% versus 80% minimal acceptable power for practice changing trial) and information regarding a study design, 71% preferred a phase 3 RCT (n=472 MPR patients, 236 in each arm).

Conclusions:

There is a need to confirm the ILN approach in further studies. A phase 3 RCT is the preferred option.