4. Discussion
To the best of our knowledge, this is the largest meta-analysis (including subgroup analyses by follow-up period) to compare SNB with END for early stage OSCC patients with clinically N0 necks (no metastases). We found no significant difference in OS (HR = 1.1226), DFS (HR = 0.9263), or DSS (HR = 1.0797). Ding et al. reported similar 5-year DFSs and OSs in SNB and END groups in their review article (9). However, they included only six prospective studies and did not discuss DSS. Saleem et al. found no significant difference in DFS or OS between patients who underwent SNB and END (37). However, unlike our study, their DFS data were heterogeneous. Saleem et al. included 10 studies in a meta-analysis, but one of those studies (Hiraki et al.) compared SNB and no neck dissection groups (38). Recently, Gupta et al. found no significant difference in OS between SNB and END groups (39). Isolated neck nodal and locoregional recurrences were compared, and there was no significant difference; however, only three studies were included.
Five of the studies included in our meta-analysis had high weights because of their large sample sizes (20, 24, 27-29). However, subgroup analyses revealed minimal heterogeneity. Thus, although the studies varied somewhat in terms of design and quality, the variations did not affect the results, and the survival outcomes of SNB and END were similar. In contrast to Saleem et al., we found no significant difference in OS, DFS, or DSS between SNB and END in any study (Figure 2), possibly because our subgroups were defined by follow-up period (3, 5, and 10 years) (9, 37, 39, 40). Earlier meta-analyses did not perform subgroup analyses by follow-up period. In our analyses, the outcomes of SNB and END were similar. Also, we included three more papers than the largest previous meta-analysis (37).
SNB reveals if there is a need for neck dissection; patients without neck node metastases can thus avoid unnecessary dissection. END is associated with minimal complications (41). The sensitivity of SNB for head and neck cancer was reported as 92% (42); in another study, it was 82.7%, and the specificity was 98.1% (15, 16, 43). The European SENT trial recommended SNB for patients with clinical N0 OSCC (43). SNB is also recommended by the National Comprehensive Cancer Network (44). SNB is also effective in patients with other cancers, and is widely used to evaluate breast cancer patients without metastases (12). However, SNB has certain disadvantages. The node closest to the injection site may be too bright, which can lead to error (45). Also, radiotracers may reduce SNB effectiveness. In patients with other cancers, the use of methylene blue was associated with high false-negative rates. When methylene blue was combined with indocyanine green or a technetium-based radiotracer, sentinel nodes were effectively detected (46). SNB accuracy was enhanced by dynamic lymphoscintigraphy and the use of a same-day protocol (47, 48). SNB tracers require further study.
The main strength of our meta-analysis is that it included 12 studies with 10,583 patients and revealed publication bias in terms of OS or DSS (Figure 3). Some bias in terms of the DFS for SNB was initially suggested, but the Duval and Tweedie trim and fill method indicated otherwise. Therefore, we conclude that the studies were not biased and the data are thus clinically relevant.
Our meta-analysis had some limitations. First, most of the included studies were non-randomized, so patient characteristics and tumor subsites may have differed among the groups, which would have slightly affected the results. However, few survival studies are randomized(49). Garrel et al. included mainly early stage OSCC patients with no clinical lymph node metastases, but also a small number of oropharyngeal cancer patients (< 13%) (28). Patients with human papillomavirus-positive oropharyngeal cancer have good prognoses and should be analyzed separately (50). Sundaram et al. included mainly T1 and T2 patients, but also a small number of T3 patients (< 13%) (26). Second, the tracers differed among the included studies. Several studies used tracers detectable by SPECT/CT (22, 25, 27, 31), but Hasegawa et al. used a tracer evident on single-photon emission CT (29). Third, we lacked data on smoking history and comorbidities, which may affect survival.