MSLT-I
Sentinel-node biopsy or nodal observation in melanoma (Multicenter Selective Lymphadenectomy Trial)
Phase 3N = 2,001NCT00275496
- Population
- Patients with primary cutaneous melanoma; intermediate thickness defined as 1.20 to 3.50 mm and thick as more than 3.50 mm.
- Design
- Randomised phase 3 trial in primary cutaneous melanoma: wide excision with postoperative nodal observation (lymphadenectomy if nodal relapse occurred) versus wide excision with sentinel-node biopsy and immediate lymphadenectomy if nodal micrometastases were found (assignment about 60% biopsy, 40% observation). The primary endpoint was melanoma-specific survival (2014 full text). First report (2006): the 5-year results of the third interim analysis in 1269 patients with intermediate-thickness melanoma. Final report (2014): 2001 patients registered. The 2014 comparisons are per-protocol (patients who underwent assigned treatment); the authors state intention-to-treat analyses were consistent. ClinicalTrials.gov lists PHASE3 and enrolment of 2001. Nodal status was initially known only in the biopsy group.
- Primary endpoint
- MSS
- Arms
- Wide excision and nodal observation (control): Wide excision and postoperative observation of regional nodes; lymphadenectomy if nodal relapse occurred
- Wide excision and sentinel-node biopsy (experimental): Wide excision and sentinel-node biopsy, with immediate lymphadenectomy if nodal micrometastases were detected
- People
- Morton DL, senior author Wang HJ, MSLT Group
DFSHR 0.74 (95% CI 0.59–0.93)Δ 60-month DFS+5.2 pointsΔ 60-month MSS+0.5 pointsDFSHR 0.76 (95% CI 0.62–0.94)Δ 120-month DFS+6.6 pointsDFSHR 0.70 (95% CI 0.50–0.96)
Show the numbers
| Endpoint | Analysis | Wide excision and sentinel-node biopsy | Wide excision and nodal observation | Effect |
|---|---|---|---|---|
| DFSIntermediate-thickness melanoma (1269 patients) | interimMorton 2006 | 78.3% at 5 y | 73.1% at 5 y | HR 0.74 (95% CI 0.59–0.93)P=0.009Mean estimated 5-year rates with standard errors (plus or minus 1.6 and 2.1). The hazard ratio is for recurrence (biopsy vs observation). The 2014 report describes the 2006 publication as the 5-year results of the third interim analysis. |
| MSSIntermediate-thickness melanoma (1269 patients) | interimMorton 2006 | 87.1% at 5 y | 86.6% at 5 y | Mean 5-year rates with standard errors (plus or minus 1.3 and 1.6); the abstract describes them as similar and gives no p-value. The 2014 report describes the 2006 publication as the 5-year results of the third interim analysis. |
| DFSIntermediate-thickness melanoma (1.20 to 3.50 mm), per-protocol (770 biopsy, 500 observation) | finalMorton 2014 | 71.3% at 10 y | 64.7% at 10 y | HR 0.76 (95% CI 0.62–0.94)P=0.01Mean 10-year rates with standard errors (plus or minus 1.8 and 2.3). The hazard ratio is for recurrence or metastasis (biopsy vs observation); the interval is from the full text. Secondary endpoint. |
| DFSThick melanoma (more than 3.50 mm), per-protocol (173 biopsy, 117 observation) | finalMorton 2014 | 50.7% at 10 y | 40.5% at 10 y | HR 0.70 (95% CI 0.50–0.96)P=0.03Mean 10-year rates with standard errors (plus or minus 4.0 and 4.7). The hazard ratio is for recurrence or metastasis (biopsy vs observation); the interval is from the full text. Secondary endpoint. |
| MSSIntermediate-thickness melanoma (1.20 to 3.50 mm), per-protocol (770 biopsy, 500 observation), with or without nodal metastases | finalMorton 2014 | 81.4% at 10 y | 78.3% at 10 y | HR 0.84 (95% CI 0.64–1.09)P=0.18Mean 10-year rates with standard errors (plus or minus 1.5 and 2.0); hazard ratio for death from melanoma, biopsy vs observation. Melanoma-specific survival was the primary endpoint; the authors report no significant difference, and none in thick melanomas. The abstract states the null result without figures. |
| MSSIntermediate-thickness melanoma with nodal metastases (subgroup) | exploratoryMorton 2014 | — | — | HR 0.56 (95% CI 0.37–0.84)P=0.006Hazard ratio for death from melanoma, biopsy-based management vs observation, in a subgroup defined by nodal metastasis (10-year MSS 62.1+/-4.8% vs 41.5+/-5.6%); the interval is from the full text. Nodal status was initially known only in the biopsy group; the authors added an accelerated-failure-time latent-subgroup analysis to account for this (estimated treatment effect on MSS 0.68, P=0.05). The same comparison in thick melanomas with nodal metastases showed no difference (HR 0.92, 95% CI 0.53-1.60, P=0.78). |
| Endpoint | Analysis | Wide excision and sentinel-node biopsy | Wide excision and nodal observation | Effect |
|---|---|---|---|---|
| DFSIntermediate-thickness melanoma (1269 patients) | interimMorton 2006 | 78.3% at 5 y | 73.1% at 5 y | HR 0.74 (95% CI 0.59–0.93)P=0.009Mean estimated 5-year rates with standard errors (plus or minus 1.6 and 2.1). The hazard ratio is for recurrence (biopsy vs observation). The 2014 report describes the 2006 publication as the 5-year results of the third interim analysis. |
| MSSIntermediate-thickness melanoma (1269 patients) | interimMorton 2006 | 87.1% at 5 y | 86.6% at 5 y | Mean 5-year rates with standard errors (plus or minus 1.3 and 1.6); the abstract describes them as similar and gives no p-value. The 2014 report describes the 2006 publication as the 5-year results of the third interim analysis. |
| DFSIntermediate-thickness melanoma (1.20 to 3.50 mm), per-protocol (770 biopsy, 500 observation) | finalMorton 2014 | 71.3% at 10 y | 64.7% at 10 y | HR 0.76 (95% CI 0.62–0.94)P=0.01Mean 10-year rates with standard errors (plus or minus 1.8 and 2.3). The hazard ratio is for recurrence or metastasis (biopsy vs observation); the interval is from the full text. Secondary endpoint. |
| DFSThick melanoma (more than 3.50 mm), per-protocol (173 biopsy, 117 observation) | finalMorton 2014 | 50.7% at 10 y | 40.5% at 10 y | HR 0.70 (95% CI 0.50–0.96)P=0.03Mean 10-year rates with standard errors (plus or minus 4.0 and 4.7). The hazard ratio is for recurrence or metastasis (biopsy vs observation); the interval is from the full text. Secondary endpoint. |
| MSSIntermediate-thickness melanoma (1.20 to 3.50 mm), per-protocol (770 biopsy, 500 observation), with or without nodal metastases | finalMorton 2014 | 81.4% at 10 y | 78.3% at 10 y | HR 0.84 (95% CI 0.64–1.09)P=0.18Mean 10-year rates with standard errors (plus or minus 1.5 and 2.0); hazard ratio for death from melanoma, biopsy vs observation. Melanoma-specific survival was the primary endpoint; the authors report no significant difference, and none in thick melanomas. The abstract states the null result without figures. |
| MSSIntermediate-thickness melanoma with nodal metastases (subgroup) | exploratoryMorton 2014 | — | — | HR 0.56 (95% CI 0.37–0.84)P=0.006Hazard ratio for death from melanoma, biopsy-based management vs observation, in a subgroup defined by nodal metastasis (10-year MSS 62.1+/-4.8% vs 41.5+/-5.6%); the interval is from the full text. Nodal status was initially known only in the biopsy group; the authors added an accelerated-failure-time latent-subgroup analysis to account for this (estimated treatment effect on MSS 0.68, P=0.05). The same comparison in thick melanomas with nodal metastases showed no difference (HR 0.92, 95% CI 0.53-1.60, P=0.78). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 0.74 | 0.59–0.93 |
| DFS | 0.76 | 0.62–0.94 |
| DFS | 0.7 | 0.5–0.96 |
| MSS | 0.84 | 0.64–1.09 |
| MSS | 0.56 | 0.37–0.84 |
Appears in
Sources
Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355(13):1307-17.
Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Nieweg OE, Roses DF, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7):599-609.