Testicular cancer in intersex individuals: A systematic review for clinical practice

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: Not quantified - described as 'significant evidence' for some conditions

• Primary Outcome: Testicular cancer risk in intersex individuals with different conditions

• Nnt Or Sensitivity: Unable to calculate due to insufficient data quality and small sample sizes

• Confidence Interval: Not reported

Clinical Application

Limited by poor evidence quality - clinical application requires careful individualized risk-benefit assessment Relevant to Australian multidisciplinary teams managing disorders of sex development, aligns with NHMRC guidelines emphasizing shared decision-making and evidence-based care for rare conditions Individuals with intersex conditions requiring gonadal management decisions, particularly those with partial gonadal dysgenesis, Turner syndrome with Y-chromosome material, androgen insensitivity syndromes, and ovotestis

Abstract

The objective of this systematic review was to identify the evidence of testicular cancer risk for people with intersex conditions. This assessment is hoped to help refine risk stratification tools for assessing gonadal malignancy risk and guide the development of more robust evidence-based management strategies. The literature was searched in Ovid MEDLINE, Embase, and Cumulative Index of Nursing and Allied Health using a search string developed by a multidisciplinary team. The protocol was registered at Prospective Register of Systematic Reviews as CRD42021231313. A total of 3608 articles were found. After selection, 301 publications were included (1215 individuals). The results identified significant evidence that pre-pubertal gonadectomy may be linked to lower rates of malignant gonadal changes for patients with partial gonadal dysgenesis, Turner's syndrome with Y-chromosome material, complete androgen insensitivity, partial androgen insensitivity, and patients with ovotestis/es. The evidence was not significant for patients with complete gonadal dysgenesis, Klinefelter syndrome, nor WT1-related syndromes. Specific cancer outcomes were unable to be assessed due to small sample sizes and thus it is unknown if clinically significant cancer outcomes are meaningfully altered by pre-pubertal gonadectomy. Importantly, the quality of data on the topic of gonadal malignancy in intersex patients with testicular tissue was determined to be poor overall. The quality was relatively more robust regarding the conditions of Complete Androgen Insensitivity, Klinefelter syndrome, and patients with ovotestis/es. More high-quality research is needed to draw specific conclusions on the risks and benefits of performing pre-pubertal gonadectomy for intersex patients. When counseling these patients, clinicians should be transparent regarding the paucity of data supporting pre-pubertal gonadectomy.

References

1. 1.Jones, N. C., Madhavaram, A., Haver, M. K., & Quinn, G. P. (2024). Testicular cancer in intersex individuals: A systematic review for clinical practice. International Journal of Cancer. https://doi.org/10.1002/ijc.70302