Response to comment on ‘Adj‐ PD ‐1 antibody vs. observation for resected nail apparatus melanoma’

We thank Qi et al. for their interest in our Letter to the Editor, Efficacy of Adjuvant Anti-PD-1 Antibody Versus Observation for Resected Nail Apparatus Melanoma1 and for their thoughtful and constructive comments.2 We appreciate the opportunity to further clarify the context and intent of our study. As highlighted by Qi et al., we fully acknowledge that the retrospective design of our analysis is associated with inherent limitations, including potential selection bias and residual confounding. For this reason, the manuscript was intentionally revised and published in a concise letter format, with conclusions carefully framed to avoid causal interpretation. All unmatched analyses and exploratory subgroup comparisons were removed, and the final report focuses exclusively on survival outcomes in the propensity score–matched cohort, which we explicitly describe as exploratory. Qi et al. correctly note the imbalance in baseline characteristics between treatment groups in the original cohort, particularly with respect to age and disease stage. To address this, we applied 1:1 propensity score matching based on age, sex and stage and restricted our primary analyses accordingly. As stated in the Methods and Limitations, we recognize that propensity score matching can mitigate but not eliminate bias, and that unmeasured confounders may still influence outcomes. Regarding survival endpoints, we acknowledge that the modest size of the matched cohort and the relatively short follow-up limit statistical power, especially for detecting small differences. In accordance with the editorial comments, we therefore focused on 3-year survival estimates rather than longer-term outcomes. Importantly, the absence of a statistically significant benefit of adjuvant anti-PD-1 therapy (adj-PD-1) in our matched cohort should be interpreted with caution and not as definitive evidence of lack of efficacy. The primary objective of our study was to address a specific gap in the literature concerning nail apparatus melanoma (NAM), a rare and biologically distinct melanoma subtype for which data on adj-PD-1 are extremely limited.3 While previous studies have reported reduced responsiveness to adj-PD-1 in acral melanoma compared with non-acral cutaneous melanoma, direct evidence regarding adj-PD-1 in NAM has been lacking.4 Our findings provide descriptive data in this narrowly defined population and suggest that the expected benefit observed in other melanoma subtypes may not be readily extrapolated to NAM. In this context, we note that a prior Japanese retrospective study has reported no survival benefit of adj-PD-1 compared with observation in certain sole melanoma.5 In contrast, a Western cohort study by Jacques et al. demonstrated a significant improvement in recurrence-free survival with adj-PD-1 in patients with resected acral melanoma.6 Although these studies addressed different anatomical and ethnic subgroups, they collectively suggest that the efficacy of adj-PD-1 may vary within acral melanoma, underscoring the need for subtype-specific evaluation. Finally, we would like to clarify that our report does not assess outcomes after recurrence, nor does it imply that adj-PD-1 causally influences the efficacy of subsequent systemic treatments. Analyses of post-recurrence therapy which we prepared were intentionally excluded from the final manuscript in accordance with reviewer and editorial recommendations during the review process. Whether prior exposure to adj-PD-1 may affect treatment strategies or outcomes at recurrence remains an important clinical question that warrants dedicated prospective investigation. We are grateful to Qi et al. for their comments, which align with the cautious interpretation emphasized in our revised manuscript. We hope that our report contributes constructively to the ongoing discussion regarding optimal postoperative management of rare melanoma subtypes such as NAM and encourages further collaborative research in this area. None. Dr. Takaya Komori has no conflict of interest to disclose. Dr. Yasuhiro Nakamura has received research, speaking and/or consulting support from Alexion Pharma, Bristol Myers-Squibb, Dai-ichi Sankyo, HUYA Bioscience International, Kyowa Kirin, LEO Pharma, Maruho, MSD, Novartis, Ono Pharmaceutical, Pierre Fabre, Sanofi, Sun Pharma and Tanabe-Mitsubishi Pharma. Not applicable. Not applicable. Data sharing is not applicable to this response as no new data were created or analysed in this study.