Systemic Glucocorticoid Use and Risk of Site-Specific Cancers: A Methodologic Systematic Review of Observational...

Area of Science:

• Pharmacology
• Oncology
• Epidemiology

Background:

• Systemic glucocorticoids are frequently prescribed for inflammatory and autoimmune conditions.
• Concerns exist regarding their potential to increase cancer risk due to immunosuppressive and metabolic effects.
• Observational studies are crucial for assessing this risk, but often suffer from methodological limitations.

Purpose of the Study:

• To systematically review observational studies on the association between systemic glucocorticoid use and site-specific cancer risks.
• To identify methodological issues in existing studies that may bias findings.
• To synthesize current evidence on glucocorticoid impact on cancer incidence.

Main Methods:

• Systematic literature review of cohort and case-control studies up to May 1, 2025.
• Searches conducted in PubMed, Embase, Web of Science, and Cochrane Library.
• Included 38 studies assessing systemic glucocorticoid use and various cancer sites.

Main Results:

• Significant methodological issues were prevalent: 34% had time-window bias, 50% lacked appropriate lag-time, and 74% did not restrict patient populations by indication.
• Some studies suggested positive associations for non-Hodgkin lymphoma, lung cancer, and non-melanoma skin cancer, but findings were inconsistent and potentially biased by inadequate latency consideration.
• Evidence for breast cancer was largely null; results for colorectal cancer and melanoma were inconsistent.

Conclusions:

• Existing observational studies on systemic glucocorticoids and cancer risk are limited by significant methodological flaws.
• Inconsistent findings for several cancers highlight the need for improved study designs and analytical methods.
• Further robust research is essential to generate unbiased estimates of the impact of systemic glucocorticoids on cancer incidence.