Increased risk of testis failure in testicular germ cell tumor survivors undergoing radiotherapy

Abstract

Testicular germ cell tumors (TGCTs) are prevalent in males of reproductive age. Among the available therapeutic choices, pelvic radiotherapy (RT) and simple surveillance (SURV) are usually pursued. However, RT is considered to have life-threatening effects on testicular functions. In this study we sought to clarify this issue by evaluating sperm parameters and sex hormones in 131 TGCTs RT-treated-patients at both baseline (T0) and 12 (T1) and 24 months (T2) of follow-up. An age-matched group of 61 SURV patients served as control. Sperm parameters were comparable between SURV and RT at T0.The RT group showed a significant reduction of all sperm parameters at T1 (all P values < 0.05 vs T0 and vs SURV at T1) and increased levels of sperm aneuploidies, with some degree of recovery at T2. On the other hand, despite normal levels of total testosterone being detected in both groups, luteinizing hormone (LH) levels in the RT group progressively increased at T1 and T2 with a relative risk of developing subclinical hypogonadism of 3.03 (95% CI: 1,50–6,11) compared to SURV. Again, compared to SURV, exposure to RT was associated with a 5.78 fold (95% CI: 2,91–11,48) risk of developing vitamin D insufficiency. These data suggest a likely RT-dependent impairment of the Leydig cell compartment.

Testicular Cancer: Genes, Environment, Hormones

“…- Therapeutic evidence: in spite of the aforementioned effectiveness, the treatment of TC itself is frequently associated with an increased risk of developing long lasting adverse effects like infertility, hypogonadism, metabolic/cardiovascular derangements, and osteoporosis, which actually represent the most relevant life threatening consequences of the TC therapy (10– 12).…”

Fertility Outcomes and Sperm-DNA Parameters in Metastatic Melanoma Survivors Receiving Vemurafenib or Dabrafenib Therapy: Case Report

“…As an example, we recently evaluated the effect of chemo-and radiotherapy as adjuvant treatments for testicular cancer, another oncological disease affecting males at reproductive age. We observed that both treatments were equally associated with transient impairment of semen parameters, but long-term increase of sperm aneuploidies and impaired endocrine function of the testis, leading to subclinical hypogonadism and vitamin D deficiency that appeared as matter of concern (16,20). In fact, in addition to infertility, these conditions represent independent risk factors for cardiovascular disease and osteoporosis respectively.…”

“…In fact, in addition to infertility, these conditions represent independent risk factors for cardiovascular disease and osteoporosis respectively. Therefore, an adequate oncological counseling to cancer patients appears as mandatory in order to correctly address the risk/benefit ratio of available adjuvant therapies (20)(21)(22)(23)(24)(25)(26)(27).…”

Vitamin D Deficiency in Testicular Cancer Survivors: A Systematic Review

“…On the contrary, the LH levels progressively increased in the radiotherapy group, leading to a potential risk of subclinical hypogonadism. Moreover, those pretreated with radiotherapy showed a 5.78 relative risk of developing hypovitaminosis D (and consequently, osteopenia/osteoporosis), compared with the surveillance cohort [ 43 ]. The biases of the study were its retrospective nature and the absence of a direct measurement of bone status in the experimental cohort.…”