Long-Term Semen Outcomes in Testicular Cancer Survivors: A Longitudinal Study of Clinical, Hormonal, and Semen Parameters

ABSTRACT Background: Testicular cancer (TC) primarily affects men of reproductive age, making the preservation of fertility a critical component of survivorship. While radical orchiectomy and subsequent adjuvant therapies (chemo- and radio-therapy) are highly effective in achieving remission, their impact on long-term spermatogenesis and endocrine function remains a major concern. Aims of the study: This study aims to provide a comprehensive description of the longitudinal evolution of gonadal, hormonal, and spermatogenic functions after the diagnosis and treatment of testicular cancer. It evaluates the principal clinical, oncological, and functional factors associated with medium- and long-term recovery to offer a clear prognostic picture for survivorship and fertility potential. Methods: A retrospective longitudinal study was conducted utilizing the medical records of 766 patients who underwent radical orchiectomy for unilateral testicular cancer, currently in follow-up at the U.O.C. Andrologia e Medicina della Riproduzione of the Padova University Hospital. Seminal parameters, residual testicular volume, and hormonal profiles including Total Testosterone, Luteininzig Hormone and Follicular Stimulating Hormone, were analyzed at three predefined intervals: post-surgery baseline (T1), two years post adjuvant therapies (T2), and the most recent long-term follow-up (T3, median 7 years). Results: Spermatogenic recovery proved to be a prolonged and highly heterogenous process. While the median sperm concentration significantly improved from 18.0 million/mL at T1 to 23.0 million/mL at T3, 39.3% of patients exhibited long-term concentrations below their individual baseline. The early follow-up evaluation at T2 emerged as the primary prognostic landmark: integrating T2 seminal data doubled the long-term predictive accuracy compared to baseline data alone. Heavy chemotherapy regimens (4 cycles of PEB) induced severe early gonadotoxicity, though this gradient substantially attenuated by T3, indicating late recovery. Endocrine function was highly dynamic: while 20.4% of patients presented with biochemical hypogonadism at T2, 52.2% spontaneously recovered normal testosterone levels by T3, whereas 16.2% of initially normogonadal patients experienced late-onset failure. Conclusion: Gonadal recovery following testicular cancer treatment extends well beyond the standard two-years window. The functional and hormonal assessment at two years post treatment serves as the critical prognostic baseline for predicting long-term trajectories. The high incidence of late spermatogenic recovery and dynamic endocrine functions mandates extended and individualized monitoring spanning at least 5 to 7 years.