Testicular germ cell tumor (TGCT) is the most frequent neoplasia in men of reproductive age, with a 5-year survival rate of 95%. Antineoplastic treatments induce sperm DNA fragmentation (SDF), especially within the first year post-therapy. Data in the literature are heterogeneous concerning longer follow-up periods and the large majority is limited to 2 years.
To define the timing for the recovery of sperm DNA damage and the proportion of patients with severe DNA damage (SDD) at 2 and 3 years from the end of therapy.
SDF was evaluated in 115 TGCT patients using TUNEL assay coupled with flow cytometry before (T0 ) and 2 (T2 ) and 3 (T3 ) years post-treatment. Patients were divided based on the type of treatment: carboplatin (CP), bleomycin-etoposide-cisplatin (BEP), radiotherapy (RT). For 24 patients paired SDF data were available at all time-points (T0 -T2 -T3 ). 79 cancer-free, fertile normozoospermic men served as controls. SDD was defined as the 95th percentile in controls (SDF = 50%).
Comparing patients versus controls we observed: i) no differences at T0 and T3 ; ii) significantly higher SDF levels (p<0.05) at T2 in all treatment groups. Comparing pre and post-therapy in the 115 patients, the median SDF values were higher in all groups at T2 , reaching significance (p<0.05) only in the CP group. While the median SDF values were higher also in the strictly paired cohort at T2 , about 50% of patients returned to baseline. The proportion of SDD in the entire cohort was 23.4% and 4.8% of patients at T2 and T3 , respectively.
Currently, TGCT patients are advised to wait two years post-therapy before seeking natural pregnancy. Our results suggest that this period may not be sufficient for all patients.
The analysis of SDF may represent a useful biomarker for pre-conception counselling following cancer treatment. This article is protected by copyright. All rights reserved.
Andrology. 2023 Mar 17 [Epub ahead of print]
Ginevra Farnetani, Maria Grazia Fino, Francesca Cioppi, Antoni Riera-Escamilla, Lara Tamburrino, Matteo Vannucci, Viktoria Rosta, Serena Vinci, Elena Casamonti, Leila Turki, Selene Degl'Innocenti, Matilde Spinelli, Sara Marchiani, Francesco Lotti, Monica Muratori, Csilla Krausz
Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy., University Hospital Careggi (AOUC), Florence, Italy., Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.