Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group

Abstract

Children, adolescent and young adult (CAYA) males with cancer are at an increased risk for infertility, if their treatment adversely impacts reproductive organ function. Future fertility is a primary concern of patients and their families. Variations in clinical practice are barriers to the timely implementation of fertility preserving interventions. The PanCareLIFE consortium in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) reviewed the current literature and developed a clinical practice guideline (CPG) for fertility preservation in male CAYA cancer patients diagnosed before age 25 years, including guidance on risk assessment and available fertility preservation methods. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to grade the evidence and recommendations. Recognizing the need for global consensus, this CPG used existing evidence and international expertise to develop transparent, easy-touse and rigorously-developed recommendations that can facilitate the care of CAYA males with cancer at risk of fertility impairment and enhance their quality of life.

Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review

“…First, regarding primary hypogonadism, it is essential to discuss with the patient the possibility of altered gametogenesis and the subsequent reduced fertility. Accordingly, fertility-preservation strategies 62 , 63 , 64 (gamete cryopreservation) should be offered, especially in the curative setting where a cure can be achieved and family planning can be made. Although such a strategy could be pursued in a metastatic setting, it is better to avoid a delayed therapy initiation in favor of a fertility-preservation strategy, especially in high-burden disease.…”

Effect of Genetic Variation in CYP450 on Gonadal Impairment in a European Cohort of Female Childhood Cancer Survivors, Based on a Candidate Gene Approach: Results from the PanCareLIFE Study

“…Our findings may enhance clinical practice by identifying patients at high risk of ovarian impairment who more than others may benefit from referral and counseling about fertility preservation options. Recently, the International Guideline Harmonisation Group (IGHG) published recommendations advising that all patients should be informed about their potential risk of gonadal damage [ 74 , 75 , 76 ]. This is in line with the current views and wishes of both healthcare providers and patients and their families [ 77 , 78 ].…”

Multidisciplinary consensus on the criteria for fertility preservation in cancer patients

“…Additionally, vascular damage, stromal injury or fibrosis may occur. To calculate the gonadotoxic risk [70][71][72], the patient should receive an equivalent dose of CFM (cyclophosphamide equivalent dose, CED) according to the formula of Green et al: > 6000-8000 mg/ m 2 in women and > 4000 mg/m 2 in men, ovarian or testicular RT or HSCT (73). The following equivalences were used (CFM = 1; ifosfamide × 0.244; procarbazine × 0.857; chlorambucil × 14.28; BCNU × 16; melphalan × 40; thiotepa × 40; nitrogen mustard × 100; busulfan × 8.82).…”

“…ALL acute lymphoblastic leukaemia; AML acute myeloid leukaemia; CNS central nervous system; CNS3 CNS with cerebrospinal fluid 5 ≥ leukocytes/µl and blast positives Colli et al, 205; CYP cyclophosphamide; GCTs germ cell tumors; HL Hodgkin lymphoma; HCT hematopoietic cell transplantation; HSCT hematopoietic stem cell transplantation; LBL lymphoblastic lymphoma; NHL non-Hodgkin lymphoma; PMBCL primary mediastinal B-cell lymphoma; PNET primitive neuroectodermal tumour; RMS rhabdomyosarcoma; RT radiotherapy; TBI total body irradiation. To calculate the gonadotoxic risk[70][71][72], the patient should receive an equivalent dose of CFM (cyclophosphamide equivalent dose, CED) according to the formula of Green et al: > 6000-8000 mg/ m 2 in women and > 4000 mg/m 2 in men, ovarian or testicular RT or HSCT (73). The following equivalences were used (CFM = 1; ifosfamide × 0.244; procarbazine × 0.857; chlorambucil × 14.28; BCNU × 16; melphalan × 40; thiotepa × 40; nitrogen mustard × 100; busulfan × 8.82).…”