Long-term follow-up after high-risk gonadotoxic treatment and immature testicular tissue banking

Introduction: Long-term consequences of oncological treatments become clinically more relevant due to the growing population of long-term childhood cancer survivors. Various malignant and non-malignant conditions are treated by hematopoietic stem cell transplantation (HSCT) or high-risk chemo/radiotherapy (HR-CR) with known long-term effects such as endocrine and gonadal dysfunction. Therefore, fertility preservation programs have emerged to safeguard the future fertility of patients needing high-risk gonadotoxic treatment. For pediatric boys, cryopreservation of immature testicular tissue containing spermatogonial stem cells is currently the only fertility preservation option. Long-term follow-up after high-risk gonadotoxic treatment with or without testicular tissue banking is needed to adapt patients’ selection criteria and to better inform patients about their fertility preservation and restoration opportunities. The aim is to evaluate the long-term effects of the high-risk gonadotoxic treatment and the testicular biopsy procedure.
Methods: Pediatric boys treated by HSCT or HR-CR at two Brussels hospital between 2002-2016 and accepting or refusing testicular tissue banking were included. Changes in testicular volume and in the reproductive hormones LH, FSH, testosterone and INHB were evaluated after treatment completion and compared between HSCT and HR-CR treatment as well as between boys accepting and refusing banking.
Results: Of 60 pediatric boys included, 34 were treated by HCST and 26 required HR-CR. Testicular tissue banking was accepted by 39 boys and refused by 21 boys. Most boys were prepubertal at diagnosis (87%), at treatment completion (78%) and at testicular tissue banking (79%). At the last follow-up visit, 20 boys were still prepubertal (33%) and 40 boys spontaneously initiated or completed their pubertal development (67%). Most patients presented with (sub)normal testicular volumes (86%) and normal LH (81%), FSH (81%), testosterone (70%) and INHB (65%) serum levels at 5.0 (1.0-11.0) years post-treatment. Testicular volumes and LH, FSH and INHB serum levels were not significantly different between the treatment groups. However, significantly more low testosterone serum levels (43%) were recorded after HSCT compared to HR-CR (10%). No significant differences were recorded between the banking groups.
Conclusion: Follow-up data demonstrate more impaired testosterone levels after HSCT compared to HR-CR and (sub)normal testicular volumes after high-risk gonadotoxic treatment. The testicular biopsy procedure has no long-term effects on the gonadal development of cancer patients. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings.