Critical appraisal:Van der Ploeg AP, Haydu LE, Spillane AJ, Scolyer RA, Quinn MJ, Saw RP, et al 2014

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Critical Appraisal

Article being appraised

van der Ploeg AP, Haydu LE, Spillane AJ, Scolyer RA, Quinn MJ, Saw RP, et al. Melanoma patients with an unknown primary tumor site have a better outcome than those with a known primary following therapeutic lymph node dissection for macroscopic (clinically palpable) nodal disease. Ann Surg Oncol 2014 Sep;21(9):3108-16 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24802907.


Applicable clinical question

Key Facts

Study Design

cohort study

Study aims:

To compare the outcome for MUP patients undergoing therapeutic LN dissection (TLND) for macroscopic nodal disease (American Joint Committee on Cancer stage IIIB or IIIC) with that of MKP patients diagnosed and treated similarly. Another objective was to assess the prognostic significance of primary tumor regression in the MKP cohort

Number of Patients:

551

Unknown primary (MUP)= 287 (52.2%), Known primary (MKP)= 264 (47.8%)
Reported outcome(s):

Melanoma specific survival
Disease free survival

Results of outcome(s):

Univariate analyses, DFS: MKP, more positive LNs, higher positive LN ratio, extracapsular tumour extension (ECE), adjuvant postoperative radiotherapy (all p<0.05).
Multivariate analyses, DFS, adverse prognostic factors for survival were MKP (p<0.001), ECE (p = 0.010), adjuvant radiotherapy (p<0.001), presence of >3 positive nodes (p<0.001).
MKP= adverse prognostic factor for DMFS in univariate analysis (p<0.001). In univariate analyses, significant adverse prognostic factors for MSS were MKP, older age, increased number of positive LNs, increased positive LN ratio, ECE, and adjuvant radiotherapy. Multivariate analyses= MKP (p<0.001), older age (p = 0.023), ECE (p<0.001), adjuvant radiotherapy (p<0.001), >3 positive nodes (p<0.001). DFS and MSS, a positive LN ratio was not assessed in the multivariate model because of correlation with the number of positive nodes. When a positive LN ratio was included in the multivariate model (in place of the number of positive nodes), it was not a significant predictor of DFS (p = 0.920) or overall survival (p = 0.753).
5-year cumulative DFS in the absence and presence of ECE was 51.4 and 36.2 %, respectively (p = 0.015), 5 years cumulative MSS in the absence and presence of ECE was 62.4 % and 37.3 %, respectively (p<0.001). 5-year MSS according to the number of positive nodes was 64.8 % for 1 positive node, 54.9 % for 2 or 3 positive nodes, and 38.7 % for >3 positive nodes (p<0.001).
5 years cumulative DFS for MUP patients was 56.3 %, and for MKP patients it was 37.7 % (p<0.001). 5 years cumulative DMFS was 66.1 and 48.6 % for MUP and MKP patients, respectively (p<0.001). MSS, 5 years cumulative survival was 68.3 % for MUP patients and 44.7 % for MKP patients (p<0.001). MKP stratified for regression of the primary melanoma, 5 year MSS was 50.4 % for patients with regression and 35.9 % for patients with no regression of the primary (p = 0.083).

Includes an economic evaluation

no

Evidence ratings

Level of evidence

III-2

Risk of bias
Moderate risk of bias Comments: Please replace this text and include any additional comments in regards to your quality rating

Risk of bias assessment: cohort study

Subject selection
"New technology" group
Selected group
Comparison group
Selected group
Comparability of groups on demographic characteristics and clinical features
Not comparable but adjusted analysis used
Measurement of outcomes
Outcome measures blind to technology used
No, but objective measures used
Same method of measurement used across comparison groups
Yes
Completeness of follow-up
Was follow-up complete and were all patients included in the analysis?
Yes (follow-up >95%) or survival analysis using all patients


Relevance of evidence
1 Additional comments: Please replace this text and briefly describe the reasons for your rating
Result of appraisal

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Completed by

Jackie Buck


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Article
van der Ploeg AP, Haydu LE, Spillane AJ, Scolyer RA, Quinn MJ, Saw RP, et al. Melanoma patients with an unknown primary tumor site have a better outcome than those with a known primary following therapeutic lymph node dissection for macroscopic (clinically palpable) nodal disease. Ann Surg Oncol 2014 Sep;21(9):3108-16 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24802907.
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