ESPE Yearbook of Paediatric Endocrinology

Int J Radiat Oncol Biol Phys. 2024 Jun 1;119(2):610-624. PMID: 37791936. doi: 10.1016/j.ijrobp.2023.08.010. [email protected]

Brief summary: This systematic review, by the PENTEC initiative, addresses a critical but often underexamined long-term effect of childhood cancer therapy: testicular dysfunction in male survivors treated with RT.

Following PRISMA guidelines, the authors searched PubMed, Embase, and Web of Science for studies reporting on testicular function after radiation therapy (RT) in male childhood cancer survivors. A total of 1,496 articles were initially identified, 31 studies were analysed, and only 4 studies showed data on testicular dose to generate descriptive scatter plots. Two cohorts were identified: cohort 1 consisted of pediatric and young adult patients with cancer who received scattered (incidental) testis exposure during pelvic RT; cohort 2 consisted of pediatric and young adult patients with cancer who received direct testicular radiation therapy as part of their cancer therapy. The use of chemotherapy, especially alkylating agents and anthracyclines was also analysed.

The risk of oligospermia varied from 44% to 80% when the mean testicular dose was <1 Gy, but this recovered by >12 months in 75% to 100% of patients. At doses >1 Gy, the rate of oligospermia increased to >90% at 12 months. Testosterone levels were generally unaffected at mean testicular doses <0.2 Gy but were abnormal in up to 25% of patients receiving doses between 0.2 and 12 Gy. Doses between 12 and 19 Gy led to low testosterone levels in 40% of patients, while doses above 20 Gy were associated with low testosterone levels in at least 68% of patients. FSH levels were unaffected by a mean testicular dose <0.2 Gy, whereas at doses above 0.5 Gy, the risk was between 40% and 100%. LH levels were affected at doses above 0.5 Gy in 33% to 75% of patients between 10 and 24 months after radiation. Despite differences in patient populations and treatment regimens, the authors generated a preliminary dose–risk curve, indicating that the risk of testicular dysfunction increases sharply with higher radiation doses.

Comment: This comprehensive review evaluates the dose–response relationship between testicular exposure to radiotherapy (RT) and subsequent impairment of testicular function. Only 4 studies met the criteria for dose–response modelling, highlighting the scarcity of high-quality, detailed data in this area. Even low doses (< 2 Gy) can impair spermatogenesis, while higher doses (> 20 Gy) are associated with Leydig cell damage, leading to testosterone deficiency. Damage to the testes is often long-lasting or irreversible, especially when high-dose RT is used. Recovery of function is rare once damage has occurred, particularly for testosterone production. Anthracyclines, when combined with RT, may have an additive effect on testicular damage. These findings underscore the importance of minimizing testicular dose during radiotherapy planning in boys, especially when long-term survivorship is expected. Modern and less damaging RT techniques as proton therapy, intensity-modulated radiation therapy (IMRT), and testicular shielding should be strongly considered when feasible.

Parents and patients should be counselled about the potential long-term effects on fertility and endocrine health, including options for fertility preservation. Lifelong monitoring for hypogonadism and infertility is warranted in patients who received significant gonadal irradiation.