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This study correlated cancer therapy exposures with testicular volumes from puberty to adulthood, spermatogenesis, and paternity outcomes in adulthood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study population comprised 255 male childhood cancer survivors (CCS) (survival \u22655 years, diagnosed in 1964\u20132000 at the Helsinki Children's Hospital) whose testicular volume was measured at ages 12 years (<jats:italic>n<\/jats:italic>\u00a0=\u00a038), 14 years (<jats:italic>n<\/jats:italic>\u00a0=\u00a057), 16 years (<jats:italic>n<\/jats:italic>\u00a0=\u00a063), 18 years (<jats:italic>n<\/jats:italic>\u00a0=\u00a0105), and in adulthood (<jats:italic>n<\/jats:italic>\u00a0=\u00a043; median age, 27 years). Testicular volumes were converted to age\u2010specific z scores. In addition, 92 CCS provided semen sample in adulthood (median age, 25.2 years); and paternity was evaluated through national register data (mean age at assessment, 37.6 years; <jats:italic>n<\/jats:italic>\u00a0=\u00a0252).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with age\u2010specific reference values, CCS generally exhibited low testicular volume z scores at ages 12\u201318 years. Testicular volume z scores in CCS treated exclusively with chemotherapy returned to the reference range in adulthood. In contrast, patients exposed to testicular radiation \u22651 gray (Gy) (median dose, 12 Gy) showed no late recovery in testicular size. Testicular radiation \u22651 Gy and a cyclophosphamide equivalent dose \u226512 g\/m<jats:sup>2<\/jats:sup> were identified as risk factors for azoospermia in adulthood. Patients exposed to testicular radiation \u22651 Gy and a cyclophosphamide equivalent dose \u22654 g\/m<jats:sup>2<\/jats:sup> had lower paternity rates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Testicular volume growth after prolonged follow\u2010up suggests a potential late recovery of spermatogenesis in CCS treated exclusively with chemotherapy. However, alkylating agents increased the risk of having prolonged azoospermia and nonpaternity. High\u2010dose testicular radiation causes long\u2010term depletion of spermatogonia and was the strongest risk factor for azoospermia and nonpaternity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.35623","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T10:19:37Z","timestamp":1730197177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Longitudinal trends in testicular volume z scores from puberty to adulthood, sperm quality, and paternity outcomes after childhood cancer"],"prefix":"10.1002","volume":"131","author":[{"given":"Melanie","family":"Korhonen","sequence":"first","affiliation":[{"name":"New Children's Hospital University of Helsinki and Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsi","family":"Jahnukainen","sequence":"additional","affiliation":[{"name":"New Children's Hospital University of 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