# Methods — Certainty of evidence (paragraph for insertion)

**Suggested placement:** Methods §2.4, immediately after the AMSTAR-2 paragraph and before the synthesis paragraph.

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> **Certainty of evidence per outcome.** The certainty of evidence for each prespecified outcome was assessed using the GRADE framework (Guyatt et al., *BMJ* 2008; doi:10.1136/bmj.39489.470347.AD; updated *GRADE Handbook* 2024). Given the umbrella-review design, the methodological quality of the underlying systematic reviews was first appraised with AMSTAR-2 (Shea et al., *BMJ* 2017) and reporting was structured according to PRISMA 2020 (Page et al., *BMJ* 2021); GRADE was then applied per outcome to the body of evidence as represented by the included systematic reviews and the most recent pivotal primary trials and registry cohorts. Initial certainty was anchored at **Moderate** for each outcome, reflecting the mixed nature of the underlying primary literature (prospective single-arm trials of TAD/SLNB performance, large retrospective registry cohorts, and a small number of randomized arms). Downgrading followed standard GRADE rationale: risk of bias was anchored on AMSTAR-2 ratings of the contributing SRs (acknowledging that conservative abstract-based scoring may overestimate critical-flaw counts; full-text rescoring was performed before submission); inconsistency was assessed from the I² statistic reported by SRs and from point-estimate variability across SRs; indirectness from PICO mismatch (population, intervention, comparator, era — particularly the chemo-immunotherapy transition); imprecision from confidence-interval width, total event count, and optimal information size; and publication bias from funnel plot or Egger's test where reported. Upgrading for very large effect was applied where the relative effect met the GRADE thresholds (RR <0.5 or >2 = +1 level; RR <0.2 or >5 = +2 levels). Two reviewers (S.C.B. and D.D.) independently rated each outcome; discrepancies were resolved by discussion. Final certainty was reported as High (⊕⊕⊕⊕), Moderate (⊕⊕⊕○), Low (⊕⊕○○), or Very Low (⊕○○○) per the GRADE Working Group's terminology, and outcomes were classified as Critical or Important per the GRADE handbook (chapter 5). A condensed Summary of Findings table is presented as Table 6 (Results §3.6); the full per-outcome justification — including domain-by-domain downgrade/upgrade rationale, contributing SRs, and pooled estimates with 95% confidence intervals — is provided in Supplementary File **S7**.

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**Word count:** 322 words.

**References to add to bibliography (if not already present):**

- Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. *BMJ* 2008;336:924–926.
- Schünemann HJ, Brożek J, Guyatt GH, Oxman AD, eds. *GRADE Handbook for Grading Quality of Evidence and Strength of Recommendations*. Updated October 2024. The GRADE Working Group, 2024. https://gdt.gradepro.org/app/handbook/handbook.html
- Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2. *BMJ* 2017;358:j4008.
- Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. *BMJ* 2021;372:n71.
- Pollock M, Fernandes RM, Becker LA, et al. Chapter V: Overviews of Reviews. *JBI Manual for Evidence Synthesis*. JBI 2024.
