Letter: Are All Extra‐Digestive Cancer Signals in Inflammatory Bowel Disease Telling the Same Story?

We read with interest the recent population-based study 1 examining temporal trends in extra-digestive cancer incidence and mortality in inflammatory bowel disease (IBD). The authors address an important question using a large provincial cohort and long follow-up. Their key observation—that extra-digestive cancer incidence declined in the matched non-IBD population but remained relatively stable in IBD—deserves attention. Our concern lies less in the descriptive signal itself than in how it is interpreted. The study identifies a meaningful divergence over time, but several features of the analysis suggest that this pattern should be interpreted with greater caution and more clinical granularity. First, because the main conclusion depends on secular trend comparisons, it would be important to clarify whether the composition of the IBD cohort remained comparable across calendar periods. If earlier years included a higher proportion of long-standing IBD survivors, whereas later years included more newly diagnosed patients or patients entering care in different treatment eras, then part of the observed pattern may reflect a shift in cohort composition rather than a change in cancer risk alone. In a study spanning multiple decades, this distinction is directly relevant to the interpretation of temporal divergence 2. Second, the reported increases in lymphoma, melanoma, cervical, uterine and thyroid cancers are clearly important, but they may not support a single explanatory framework 3. Some signals may align more closely with immune dysregulation or immunomodulatory exposure, whereas others may be more sensitive to detection practices or preventive care. This distinction is especially relevant for thyroid cancer, given that the study also reports substantially greater imaging use in IBD. That finding raises the possibility that incidental detection may contribute to at least part of the observed increase. This need for separation also applies to the study's incidence and mortality analyses. These outcomes are complementary, but they should not be treated as interchangeable expressions of the same process. Higher incidence may reflect greater occurrence, greater detection, or both, whereas higher cancer-specific mortality raises different questions about prognosis after diagnosis 4. Viewed in this way, some of the female-specific findings appear particularly important. The increases in cervical and uterine cancers, together with the elevated cancer-related mortality reported in women with Crohn's disease, suggest a clinically distinct pattern that is not fully visible within the study's aggregate framing of extra-digestive cancer burden in IBD. We therefore summarised these underemphasised female-relevant findings in Figure 1. Overall, this study makes an important contribution to the discussion of long-term cancer burden in IBD. Its clinical and epidemiologic value would be strengthened by a more cautious reading of temporal trends, clearer separation of cancer-specific signals, and more explicit distinction between descriptive findings and explanatory inference. These steps would help guide future work towards more precise risk interpretation and more clinically actionable surveillance strategies. Liang Jiao: conceptualization, formal analysis, writing – original draft. Yang Cao: conceptualization, formal analysis, writing – original draft, writing – review and editing, supervision. This work was supported by the East Clinical Center of Oncology (Grant No. ECCO-KY-23003). The authors declare no conflicts of interest. This article is linked to Murthy et al. paper. To view this article, visit https://doi.org/10.1111/apt.70439. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.