Wait Times Beyond 68 Days for Sentinel Node Biopsy Linked to Worse Melanoma Survival in the Adjuvant Therapy Era
Key Insights
A UK retrospective study of 1,625 melanoma (search) patients found that delays beyond 68 days from diagnosis to sentinel node biopsy (SNB) were associated with significantly worse 5-year disease-specific survival (97.8% vs 91.2%; HR=3.17; p=0.021) in the post-2016 adjuvant therapy era.
Patients waiting more than 90 days for SNB had a significantly increased risk of clinical disease progression on the waiting list (1.5% vs 0.3%; OR=4.56; p=0.008) and larger micrometastatic deposits (median 2.95 mm vs 1.40 mm; p=0.003).
The current 90-day guideline threshold appears inadequate; the study identifies 68 days from diagnosis as a more appropriate cut-off, with late surgery independently predicting melanoma (search)-related death (aHR=4.52; p=0.004).
A large retrospective cohort study from a UK tertiary cancer centre has found that delays in sentinel node biopsy (SNB) for cutaneous melanoma (search) are associated with disease progression on the waiting list, increased micrometastatic tumour burden, and significantly worse disease-specific survival in the modern adjuvant systemic therapy era. The findings, published in Nature, challenge the current 90-day guideline threshold and propose a new 68-day target from diagnosis.
The study analysed data from 1,625 patients with pT1b-pT4b primary cutaneous melanomas listed for SNB alongside wide local excision between January 2010 and December 2023. Of these, 1,510 (92.9%) underwent the procedure, with 1,170 (72.0%) receiving early surgery (≤90 days) and 455 (28.0%) receiving late surgery (>90 days).
Disease progression on the waiting list
SNB was cancelled for 115 patients initially listed for the procedure, of which 11 (9.6%) were due to melanoma (search) progression. Patients who waited beyond 90 days had a significantly increased risk of clinical disease progression compared to those treated within 90 days (7 patients [1.5%] versus 4 patients [0.3%]; OR=4.56 [95% CI=1.33–15.6]; p=0.008). Time-to-treatment remained a significant independent predictor for melanoma progression before SNB after multivariable analysis adjusted for age, Breslow thickness, sex, and ulceration (aOR=4.31 [95% CI 1.27–16.77]; p=0.022).
Increased micrometastatic tumour burden with delay
The overall SNB positivity rate was 19.2% (290/1,510 patients). While rates of SNB positivity, extracapsular spread, and AJCC N-stage did not significantly vary between early and late subgroups, the median maximum micrometastatic deposit diameter was significantly greater in the late subgroup (2.95 mm versus 1.40 mm; p=0.003). Patients in the late group were also more likely to have high-risk deposits defined as >1 mm (OR=1.81 [95% CI=1.06–3.11]; p=0.030). These differences persisted after multivariable analysis for both median deposit size (aOR=1.10 [95% CI=1.04–1.16]; p<0.001) and high-risk deposits (aOR=2.04 [95% CI=1.16–3.66]; p=0.014).
Survival impact in the modern treatment era
With a median follow-up of 75 months for the full cohort, 309 recurrences and 159 melanoma (search)-related deaths were recorded. While the 90-day cut-point did not emerge as an independent predictor of survival, multivariable analysis using time-to-SNB as a continuous variable found that increasing time was significantly associated with poorer disease-specific survival (DSS) in the post-2016 cohort (aHR=1.01 [95% CI=1.00–1.02]; p=0.011).
A sensitivity analysis using maximally selected rank statistics identified a significant cut-off of 68 days from diagnosis to SNB. Kaplan-Meier curves stratified by this threshold showed a significantly worse 5-year disease-specific survival: 97.8% for patients treated within 68 days versus 91.2% for those treated later (HR=3.17 [95% CI=1.19–8.46]; p=0.021). Multivariable analysis confirmed that late SNB (>68 days) was independently associated with a greater risk of melanoma (search)-related death (aHR=4.52 [95% CI=1.61–12.70]; p=0.004).
Patients with positive sentinel nodes in the >68-day group were more likely to have larger micrometastatic deposits (median 2.30 mm versus 1.15 mm; p<0.009) and high-risk deposits >1 mm (OR=1.96 [95% CI=1.21–3.18]; p=0.006).
Implications for clinical guidelines
The proportion of patients receiving surgery beyond 90 days increased substantially from 2017 onwards, falling from 96% within target in 2010 to just 12% in 2023. The authors attribute this to increasing disease prevalence, service funding constraints, logistical issues with tracer agents, and the COVID-19 pandemic.
"Our data suggest that the current 90-day target should be shortened to 68 days from diagnosis or 82 days from excision biopsy, assuming similar median reporting intervals," the researchers note. They caution that the retrospective, single-centre design requires external validation and acknowledge the relatively short median follow-up of 39 months in the post-2016 cohort.
Better risk stratification may reduce unnecessary surgeries
In a separate development, the i31-SLNB gene expression test has demonstrated superior accuracy over the Melanoma (search) Institute Australia (MIA) nomogram in stratifying sentinel lymph node positivity risk. Published in Dermatology and Therapy, the study showed the i31-SLNB test could predict a <5% risk of SLN positivity more often than the MIA nomogram, with an observed SLN positivity rate of 2.6% compared to 5.8% for the nomogram. The MIA nomogram failed to identify any patients below the 5% risk threshold. Rohit Sharma of Marshfield Clinic Health System (search) explained that "incorporating tumor biology through DecisionDx-Melanoma (search)'s i31-SLNB test result can improve risk assessment, helping clinicians better distinguish which patients with melanoma may safely avoid SLNB."