The Melanoma Institute Australia is a non-profit organization based at the Poche Centre in North Sydney, Australia which focuses on prevention of and cure for melanoma through research, treatment and education programs. The institute is affiliated with The University of Sydney and St Vincent’s and Mater Health Sydney. It relies on funding from individuals, organisations and government grants..
Importance:The MEL-SELF randomized clinical trial (RCT) evaluated patient-led surveillance as an alternative model of follow-up. The baseline characteristics of participants provide insights into current unmet clinical needs of this population. Objective:To describe the baseline characteristics of people screened for and randomized to the MEL-SELF RCT, and those potentially eligible but not randomized. Design, Setting, and Participants:Baseline data from the RCT's recruitment processes, from December 2021 to June 2024, were analyzed. Data were collected from dermatologist- and general practitioner-led skin cancer clinics in Australia, and included adults previously treated for early-stage melanoma (by American Joint Committee on Cancer Staging Manual [AJCC, 0-II]) attending routinely scheduled clinics, with a skin self-examination (SSE) partner, and a smartphone. Analysis took place between August 2025 and December 2025. Interventions:Participants were invited to participate in the MEL-SELF trial with randomization (1:1) to patient-led surveillance (usual care plus reminders to perform SSE, mobile dermatoscope, teledermatologist assessment, fast-tracked unscheduled clinic visits) or clinician-led surveillance (usual care) for 12 months. Main Outcomes and Measures:The main outcomes were enrollment; active run-in and allocation results, sociodemographic and clinical characteristics; SSE knowledge, attitudes, and practice (frequency and thoroughness); and psychological measures including fear of cancer recurrence (FCR) at baseline. Results:Of 1226 patients screened and potentially eligible, 504 were randomized to patient-led (n = 251) or clinician-led (n = 253) surveillance. Overall, 295 were female individuals (59%) and 209 were male individuals (41%), most were aged 50 years and older (mean [SD] age, 56.0 [11.6] years) and had a highest substage of melanoma in situ (245 [49%]) or IA (217 [43%]). SSE practice varied substantially, ranging from no SSE in the previous 12 months (103 [20%]) to weekly or monthly SSE (160 [32%]). A high proportion (232 [46%]) reported clinically significant levels of FCR, which was associated with being female, younger age, and higher depression, anxiety, and stress scores. FCR was associated with a higher perceived lifetime risk of melanoma, but not with participants' actual calculated risk of a subsequent new primary melanoma (OR, 1.00; 95% CI, 0.99-1.01). Characteristics were similar between the trial population and potentially eligible patients who completed the baseline questionnaire but were not randomized (n = 225). Conclusions:This secondary analysis of baseline characteristics in the MEL-SELF trial indicates suboptimal SSE practice and clinically significant levels of FCR. Future reports will evaluate comparative effects of patient-led surveillance on health, psychological and health resource use outcomes. Trial Registration:anzctr.org.au Identifier: ACTRN12621000176864.
9502 Background: Patients (pts) with stage II melanoma account for ~50% of those who develop metastatic disease. Checkpoint inhibitor neoadjuvant therapy (NAT) is standard for resectable stage III melanoma (NADINA & SWOG 1801) and pathological response correlates with recurrence. Other NAT benefits include personalised prognosis, tailored subsequent management, and collection of translational specimens to explore response and resistance mechanisms. The NeoReNi II trial aimed to determine feasibility, response and safety of NAT nivo+rela in resectable stage II melanoma. Methods: Eligible pts had biopsy (partial) confirmed AJCC (v8) clinical stage IIA (T2b, T3a), IIB (T3b, T4a), or IIC (T4b) cutaneous melanoma with residual macroscopic primary disease at enrolment. IIA pts had ≥20% 5 yr recurrence risk according to Melanoma Institute Australia stage II risk calculator (melanomarisk.org.au). All pts underwent sentinel lymph node (SLN) mapping at baseline and peri-operatively, and resection (wide excision + SLN biopsy [RES]) at wk 6 following 2 doses of nivo (480 mg, IV) + rela (160 mg, IV). Pts without major pathological response (MPR) had 11 cycles (Q4W) of adjuvant nivo/rela. FDG PET/CT was performed at baseline; CT prior RES; dermoscopy and reflectance confocal microscopy (RCM) baseline, wk 3 and prior to RES. The primary endpoint was the path complete response (pCR) rate. Secondary endpoints included feasibility of NAT in stage II, RECIST response, RFS, OS, safety/tolerability, surgical outcomes, QOL. Exploratory; biomarker, dermoscopy and RCM analyses. Results: From 6 Oct 2023 to 21 Oct 2025, 20 pts were recruited and received NAT, demonstrating partial biopsy leaving residual macroscopic stage IIA-C primary melanoma was feasible. Median age 67 yrs (46-81yrs), 9 females, 8 IIA, 8 IIB and 4 IIC. 18 (90%) pts received both NAT doses. 12 (60%) pts had pCR in the primary melanoma, 1 near-pCR (MPR 65%), 1 pPR and 6 (30%) pNR. Drug treatment related adverse events (TRAE) gd ≤ 2 occurred in all 20 pts (100%); 11 (55%) with fatigue, 8 rash (40%) and 5 arthralgia (25%). 3 (15%) pts had gd 3 (secondary adrenal insufficiency, nephritis, pneumonitis). There were no gd 4 or 5 TRAEs. 1 (5%) pt had a gd 3 AE related to surgery (cellulitis). 19 (95%) pts had no change in SLN mapping from pre to RES. 2 pts with pNR in primary melanoma had postitive SLN and 1 pt with pCR had focal fibrosis within a negative SLN, suggestive of possible treatment effect. Dermoscopy showed regression in all 12 MPR (100%) pts; 11 also showed changes in RCM (collagen reorganization and imflammatory infiltrates) concordant with pathology. At datacut off (11 Dec 25) 2 pts recurred, 5 and 11 mo respectively (both pNR);1 died due to melanoma (15 mo after 1 st recurrence; 20 mo after enrolement. Positive SLNBx at pNR). Conclusions: NAT with nivo + rela in resectable stage II melanoma was feasible and induced a high rate of pCR and MPR in the primary melanoma. Clinical trial information: NCT05418972 .
TPS9609 Background: Neoadjuvant immunotherapy (NAT) with immune checkpoint inhibitors (ICI) is a standard therapy for resectable stage III melanoma, with randomized trials demonstrating superior outcomes compared to adjuvant therapy alone. The phase 2 SWOG-1801 trial showed 72% EFS at 2 yrs for NAT & 49% for adjuvant PEMBRO (P=0.004), while the phase 3 NADINA trial confirmed superiority of NAT IPI/NIVO over adjuvant NIVO (2-year RFS 83.7% vs 57.2%, HR 0.32). Pathological response, particularly major pathological response (MPR; ≤10% viable tumor), strongly correlates with improved outcomes, with the International Neoadjuvant Melanoma Consortium (INMC) pooled analysis (N=610 ICI patients) demonstrating 3-yr RFS of 93% for MPR patients (pts) vs 41% for those with no pathological response. The PRADO trial demonstrated that selective index lymph node (ILN) resection (RES) can safely de-escalate surgery in MPR pts, with only 4/60 (6.7%) MPR pts recurring after median follow-up of 28.1 months, all locoregionally. ILN RES significantly reduced surgical morbidity & improved quality of life compared to therapeutic lymph node dissection (TLND). However, PRADO was a single-arm proof-of-concept study. An international survey of 117 melanoma experts showed 71% believe a phase 3 randomized controlled trial is needed to change practice. The MSLT-3 trial will definitively establish whether ILN RES is non-inferior to standard TLND for MPR pts. Methods: This phase 3, international, multicenter, randomized, non-inferiority trial will enroll approximately 1,574 pts with resectable stage IIIB-D cutaneous melanoma to identify 496 with MPR following NAT. Eligible pts must have cytologically/histologically confirmed resectable stage IIIB-D melanoma with at least one macroscopic lymph node in groin, axilla or neck basins. All pts are randomized 1:1 to ILN RES or TLND, stratified by continent/region, AJCC stage, & NAT regimen. Prior to NAT, all pts undergo radiological placement of a marker in the largest metastatic lymph node. Pts receive NAT per institutional standard of care (minimum one PD-(L)-1 checkpoint inhibitor, maximum 6 weeks duration) followed by surgery at weeks 6-9 according to randomized arm. Pathological response is assessed per INMC criteria. Pts with MPR in the ILN arm undergo surveillance only; non-MPR pts in the ILN arm proceed to TLND within 3 weeks. Primary endpoint is 2-year recurrence-free survival in MPR pts (non-inferiority margin -5%). Secondary endpoints include escalation to TLND for isolated nodal recurrence, salvage therapy rates, distant metastasis-free survival, event-free survival, overall survival, surgery-related AEs, quality of life (QLQ-C30, EQ-5D-5L, FACT-M), concordance of imaging/ctDNA with pathology & health economics. Clinical trial information: NCT07049276 .
