Screening for gonadal malignancy in androgen insensitivity syndrome: A systematic review

Historically, gonadectomy was uniformly recommended for patients with Androgen Insensitivity Syndrome (AIS) due to the perceived malignancy risk. However, this practice has been questioned given the benefits of hormone production, low prepubertal tumor risk, and unclear long-term malignancy risk. An ideal screening strategy would detect premalignant/malignant changes at an early stage and improve the safety of leaving gonads in situ. This review summarizes existing screening protocols and the evidence supporting their effectiveness.

A systematic review was conducted per PRISMA-P guidelines to examine malignancy screening in AIS. We searched PubMed, CINAHL, Web of Science, Cochrane, Scopus, Google Scholar, BioRxiv, and MedRxiv using terms related to AIS, gonadal tumors, and screening. We abstracted data from included studies focusing on three major questions: 1. What modality/frequency for screening recommendations are mentioned for AIS patients, 2. What evidence is there for the sensitivity and/or specificity of imaging, and 3. What evidence is there for the effectiveness of any screening protocol to detect neoplasia?

After reviewing 538 studies, 28 met the inclusion criteria. Most recommendations were based on expert opinion. Modalities included biopsy (recommended in 14 studies), physical exams (8 studies), serum tumor markers (4 studies), ultrasound (14 studies), and MRI (6 studies). Biopsy and ultrasound were the most frequently cited, though protocols varied. Only 3 studies had indirect data regarding screening modality effectiveness, and imaging prior to gonadectomy showed limitations in identifying pre-malignant lesions. Three cohort studies included screening protocols but lacked consistency or strong evidence supporting specific strategies.

There is a lack of standardized screening strategies for detecting malignancy in patients with Androgen Insensitivity Syndrome. Current screening methods have limitations and are mostly based on expert opinion rather than clinical evidence. No method has proven effective, and the variability in protocols reflects the uncertainty. Patients retaining their gonads should be informed of the potential risks, as there is limited evidence supporting existing screening strategies.