Levenback 2012.

Study characteristics
Patient sampling	Prospective study; 551 enrolled; 56 were excluded following GOG centralised reviews and 7 women did not undergo the SN procedure
Patient characteristics and setting	452 women with vulval SCC at least 1 mm deep, and with tumour size 2 to 6 cm (772 groins); 132 lateralised, 320 midline/near midline lesions 11% had undergone prior wide local excision of the primary tumour Women were excluded if groin involvement was suspected, or if they had undergone prior groin surgery or irradiation, had multifocal disease or a grossly inflamed tumour Median age: NR Setting: 47 centres in the USA
Index tests	SN detection by blue dye with or without Tc‐99m Histological methods: ultrastaging with H&E staining were performed on all SNs. If these were negative, IHC staining with cytokeratin was performed H&E stains were used for all other nodes in the reference standard
Target condition and reference standard(s)	TC: groin lymph node involvement RS: complete IFL
Flow and timing	Intradermal injection of blue dye was given 5 minutes before groin incision. If a blue channel led to a lymph node, it was considered sentinel, whether or not the node was blue. If Tc‐99m was used, the node was considered 'hot' if the radioactivity was 10 x greater than background activity SND and RS were performed during the same operation Withdrawals described
Comparative
Notes	Registered ID: NCT00003325 We were unable to extract separate 2 x 2 data for the combined and single techniques. Additional data were requested 28 May 2013 The type of procedure (bilateral versus unilateral) was determined by the proximity of the lesion to the midline: if ≤ 2 cm of midline, bilateral IFL was performed Investigators analysed data by tumour size (< 4 cm and ≥ 4 cm): NPV was lower for the larger tumour size subgroup (98% versus 93%)
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
		Unclear	Low
DOMAIN 2: Index Test Test group
Had the test operator performed 10 or more procedures?	Unclear
		Unclear	Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
		Unclear	Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Were other imaging tests performed prior to the index test to rule out groin lymph node metastases?	Unclear
		Unclear