Abstract: We included 34 studies evaluating 1614 women and approximately 2396 groins. The overall methodological quality of included studies was moderate. The studies included in this review used the following traceable techniques to identify sentinel nodes in their participants: blue dye only (three studies), technetium only (eight studies), blue dye plus technetium combined (combined tests; 13 studies) and various inconsistent combinations of these three techniques (mixed tests; 10 studies). For studies of mixed tests, we obtained separate test data where possible. Most studies used haematoxylin and eosin (H&E) stains for the histological examination. Additionally an immunohistochemical (IHC) stain with and without ultrastaging was employed by 14 and eight studies, respectively. One study used reverse transcriptase polymerase chain reaction analysis (CA9 RT-PCR), whilst three studies did not describe the histological methods used. The pooled sensitivity estimate for studies using blue dye only was 0.94 (68 women; 95% confidence interval (CI) 0.69 to 0.99), for mixed tests was 0.91 (679 women; 95% CI 0.71 to 0.98), for technetium only was 0.93 (149 women; 95% CI 0.89 to 0.96) and for combined tests was 0.95 (390 women; 95% CI 0.89 to 0.97). Negative predictive values (NPVs) for all index tests were > 95%. Most studies also reported sentinel node detection rates (the ability of the test to identify a sentinel node) of the index test. The mean detection rate for blue dye alone was 82%, compared with 95%, 96% and 98% for mixed tests, technetium only and combined tests, respectively. We estimated the clinical consequences of the various tests for 100 women undergoing the sentinel node procedure, assuming the prevalence of groin metastases to be 30%. For the combined or technetium only tests, one and two women with groin metastases might be 'missed', respectively (95% CI 1 to 3); and for mixed tests, three women with groin metastases might be 'missed' (95% CI 1 to 9). The wide CIs associated with the pooled sensitivity estimates for blue dye and mixed tests increased the potential for these tests to 'miss' women with groin metastases. There is little difference in diagnostic test accuracy between the technetium and combined tests. The combined test may reduce the number of women with 'missed' groin node metastases compared with technetium only. Blue dye alone may be associated with more 'missed' cases compared with tests using technetium. Sentinel node assessment with technetium-based tests will reduce the need for IFL by 70% in women with early vulval cancer. It is not yet clear how the survival of women with negative sentinel nodes compares to those undergoing standard surgery (IFL). A randomised controlled trial of sentinel node dissection and IFL has methodological and ethical issues, therefore more observational data on the survival of women with early vulval cancer are needed.

Plain-language summary: We included 34 studies (1614 women) that evaluated three techniques: blue dye only, technetium (a radioactive substance) only, or blue dye and technetium combined. Ten studies used all three techniques during the course of the study (one technique per participant). There are two attributes to a test: the ability to identify or detect the sentinel node, and the ability to identify the cancer in the sentinel node. We found that all tests can identify cancer in the groin nodes with good accuracy (more than 90% of nodes with cancer will be accurately identified with any of the tests), although the combined test was the most accurate (95%). The ability of the tests to detect sentinel nodes varied, with the blue dye test only detecting sentinel nodes in 82% of women, compared with 98% for the combined test. If sentinel nodes are not detected, they cannot be examined for cancer cells; therefore, women in whom sentinel nodes are not detected will usually need to undergo IFL. The combined and technetium only tests are able to predict accurately which women have cancerous spread to the groin. For a group of 100 women undergoing assessment, the findings mean that approximately one or fewer women having the combined or technetium only tests will undergo an unnecessary IFL, compared with approximately 11 women having the blue dye only test. This is mainly because the blue dye only test is not as good as technetium in identifying sentinel nodes. Fewer women with spread to the groin will be missed with the combined or technetium only tests (1 to 3 out of 30) compared with the blue dye only test (1 to 8 out of 30). It is not clear whether women with negative sentinel nodes (i.e. no spread of cancer to the groin lymph nodes) who do not undergo IFL will live as long as those who undergo IFL. The current best data on survival come from a Dutch study that followed up 259 women with negative sentinel nodes and reported a three-year survival of 97%.