Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Finnish Cancer Registry, Helsinki, Finland.
Cancer. 2023 Nov 15;129(22):3633-3644. doi: 10.1002/cncr.34971. Epub 2023 Aug 8.
Childhood cancer therapy may cause long-term effects. This cross-sectional study evaluated adulthood milestones in male childhood cancer survivors (CCS).
The study population comprised 252 male CCS with 6 to 42 years of survival diagnosed at the Children's Hospital in Helsinki (1964-2000) at the age of 0 to 17 years. Sex-, age-, and area of residence-matched population controls were randomly selected from the Finnish national registries. Data on moving away from the parental home, marital status, offspring, and adoption in CCS were compared with the population controls. We analyzed the influence of chemotherapy and radiation exposures and testicular dysfunction (ever nontestosterone-substituted serum follicle stimulating hormone >15 IU/L, luteinizing hormone >15 IU/L, testosterone <2 ng/mL (5 nmol/L), need of testosterone replacement therapy, or testicular volume <12 mL at the end of puberty) during pubertal maturation on long-term social outcomes.
CCS moved away from their parental home as frequently as population controls (97.8% vs. 98.5%, p = .45). CCS were less likely to marry or live in a registered relationship (46.4% vs. 57.5%, p < .001), especially when diagnosed at a young age (<4 years). Among those married, the probability of divorce was similar between CCS and population controls (27.4% vs. 23.8%, p = .41). Survivors were less likely to sire a child (38.5% vs. 59.1%, p < .001) and more likely to adopt (2% vs. 0.4%, p = .015). Lower probability of paternity was associated with hematopoietic stem cell therapy, testicular radiation dose >6 Gy, pubertal signs of testicular dysfunction (nontestosterone-substituted serum follicle stimulating hormone >15 IU/L, luteinizing hormone >15 IU/L, testosterone <2 ng/mL (5 nmol/L), or need of testosterone replacement therapy during puberty, or testicular volume <12 mL at the end of puberty) or azoospermia after puberty.
This study emphasizes the value of pubertal monitoring of testicular function to estimate future probability of paternity. If no signs of dysfunction occurred during pubertal follow-up, paternity was comparable to population controls. Testicular radiation dose >6 Gy appeared to be the strongest risk factor for decreased paternity.
Treatment with intensive therapies, including hematopoietic stem cell therapy, testicular radiation dose >6 Gy, and signs of testicular dysfunction, during puberty are important risk factors for lower rates of fertility. Intensive therapies and testicular dysfunction itself do not similarly hamper psychosocial milestones in adulthood; cancer diagnosis at a very young age (<4 years) lower the probability of marriage. This study accentuates the importance of monitoring of pubertal development, emphasizing on testicular function, not only sperm analysis, to estimate future fertility among male childhood cancer survivors.
儿童癌症治疗可能会产生长期影响。本横断面研究评估了男性儿童癌症幸存者（CCS）成年后的重要里程碑。
研究人群包括 252 名男性 CCS，他们在赫尔辛基儿童医院（1964-2000 年）被诊断患有癌症，年龄在 0 至 17 岁之间，生存时间为 6 至 42 年。从芬兰国家登记处随机选择了与性别、年龄和居住地区相匹配的人口对照。将 CCS 中离开父母家、婚姻状况、后代和收养的数据与人口对照进行比较。我们分析了青春期时化疗和放疗暴露以及睾丸功能障碍（青春期结束时血清卵泡刺激素替代治疗后非睾酮水平>15 IU/L、黄体生成素>15 IU/L、睾酮<2ng/mL（5nmol/L）、需要睾酮替代治疗或睾丸体积<12mL）对长期社会结局的影响。
CCS 离开父母家的频率与人口对照组相同（97.8%比 98.5%，p=0.45）。CCS 结婚或处于注册关系的可能性较小（46.4%比 57.5%，p<0.001），尤其是在很小的时候（<4 岁）被诊断出癌症。在已婚人群中，CCS 和人口对照组的离婚概率相似（27.4%比 23.8%，p=0.41）。幸存者生育孩子的可能性较低（38.5%比 59.1%，p<0.001），收养的可能性较高（2%比 0.4%，p=0.015）。较低的生育能力与造血干细胞治疗、睾丸放疗剂量>6Gy、青春期睾丸功能障碍的迹象（血清卵泡刺激素替代治疗后非睾酮水平>15IU/L、黄体生成素>15IU/L、睾酮<2ng/mL（5nmol/L）或青春期需要睾酮替代治疗，或青春期结束时睾丸体积<12mL）或青春期后无精子症有关。
本研究强调了监测青春期睾丸功能以估计未来生育能力的重要性。如果在青春期随访期间没有出现功能障碍迹象，则生育能力与人口对照组相当。睾丸放疗剂量>6Gy 似乎是生育能力下降的最强危险因素。
