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Reply: Increased mortality for pregnancy‐associated melanoma: systematic review and meta‐analysis

Editor We read with interest the systematic review–meta-analysis by Byrom et al. in the early view section of the Journal. This is an interesting study with clinically relevant conclusions. However, in our opinion, there are several methodological issues in their study that should be underlined. Specifically, the authors report that pooled hazard ratios (HRs) from four studies showed an increased risk of melanoma death for pregnancy-associated melanoma compared with other melanomas, after adjustment for patient age and stage of the disease (pooled HR 1.56, 95% CI: 1.23–1.99). According to the authors, a number of studies not reporting HRs were excluded from their analysis, while the results of these non-quantified, and thus excluded, studies did not support their pooled finding. Of note, the excluded study by O’Meara includes the highest number of pregnant patients. However, the authors do not comment why they did not attempt to calculate missing HRs from other reported data in the studies, according to the methods proposed by Parmar et al. This would minimize the selection bias of convenient sampling, namely including only the four studies that reported HRs, while failing to quantify data from all the studies. In one of the studies pooled by Byrom et al., MacKie et al. report a HR (1.30; 95% CI: 0.54–3.15) for delivery during melanoma (reference: non-delivery). Byrom et al. in their metaanalysis, include this HR for delivery during melanoma in a forest plot including other three HRs for melanoma death during pregnancy, which is obviously not the same. It would be appropriate if the authors had either excluded the latter study, or calculated death HRs for the group who developed melanoma during pregnancy as opposed to the other three groups in the MacKie study, who developed melanomas before, after or between pregnancies. In addition pertaining to the pooling of potentially different outcomes is the fact that Byrom et al. combine the results of the Stensheim et al. study that reports on cause specific survival, with the studies by Moller et al. and Lens et al. that report on overall survival, without discussing this limitation. In conclusion, we believe that the study by Byrom et al. deals with a very relevant topic, but the reported pooled HRs are not sufficiently justified by the evidence and the limitations of the review are not sufficiently discussed.