Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium

Abstract

Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.

Hypogonadism in Children with a Previous History of Cancer: Endocrine Management and Follow-Up

“…Primary gonadal failure with androgen deficiency and impaired spermatogenesis may be the result of the tumor itself (testis tumor), or its treatment. Surgery, chemotherapy or radiation to the testes may all lead to testicular dysfunction due to direct damage to Leydig-, Sertoli- or the testicular germ cells [7, 31]. Indirect damage may also cause dysfunction of the Sertoli or Leydig cells, such as by vascular damage, damage by changes in hormone concentrations, growth factors or the structure of the seminiferous tubule structure that will indirectly mediate the effects of chemo-/radiotherapy on the germ cells.…”

“…There is good published evidence for impaired spermatogenesis in males after treatment with busulphan, cyclophosphamide, chlormethine, ifosfamide, fludarabine/melphalan and procarbazine [7]. Similar to the studies performed in females, as in most studies patients were treated with combination therapy, it remains difficult to determine the absolute risk of a single agent.…”

“…Premature ovarian insufficiency (POI) is a clinical condition that develops under the age of 40 years and is characterized by the absence of menstrual cycles for ≥4 months and 2 sequential elevated FSH levels in the postmenopausal range [6]. In males, primary gonadal failure is defined as decreased androgen concentrations in combination with elevated LH and FSH levels or failure to develop signs of puberty by age 14 or no change in pubertal stage for at least 6 months at the age at which progression would be expected in combination with elevated levels of LH and FSH [7]. …”

The Role of Exercise in Pediatric and Adolescent Cancers: A Review of Assessments and Suggestions for Clinical Implementation

“…In CCS, as well as adults who are survivors of childhood cancer, the risk of clinical metabolic syndrome is high [26]. Metabolic syndrome (MS) is characterized by a clustering of hypertension, dyslipidemia, type 2 diabetes or preclinical conditions, and obesity.…”

“…As a result, adult survivors of childhood cancer may suffer from cardiomyopathy, heart valve and conduction disorders [14,15], increased cardiovascular risk factors including hypertension, dyslipidemia [16][17][18], and obesity [19,20], pulmonary disorders [21,22], endocrine disorders [23] including hypothalamic-pituitary-adrenal disorders [24], diabetes mellitus [25], ovarian and Leydig cell dysfunction [26], and hypothyroidism [27]. Survivors of childhood cancer are also at increased risk for neurocognitive and neurosensory impairment including ocular degeneration, hearing loss and neuropathy [28][29][30][31], metabolic disturbances (abnormal blood counts, liver and kidney dysfunction, and osteoporosis) [28][29][30]32,33], transfusion-associated infections [30], and increased risk of subsequent neoplasm [14].…”