Ghezzi Marco, Berretta Massimiliano, Bottacin Alberto, Palego Pierfrancesco, Sartini Barbara, Cosci Ilaria, Finos Livio, Selice Riccardo, Foresta Carlo, Garolla Andrea
Unit of Andrology and Reproductive Medicine, Department of Medicine, University of PadovaPadova, Italy; Istituto Oncologico Veneto - Istituto di Ricovero e Cura a Carattere ScientificoPadova, Italy.
Department of Medical Oncology, CRO Aviano National Cancer Institute IRCCS Aviano, Italy.
Front Pharmacol. 2016 May 13;7:122. doi: 10.3389/fphar.2016.00122. eCollection 2016.
Young males have testicular germ cells tumors (TGCT) as the most common malignancy and its incidence is increasing in several countries. Besides unilateral orchiectomy (UO), the treatment of TGCT may include surveillance, radiotherapy, or chemotherapy (CT), basing on tumor histology and stage of disease. It is well known that both radio and CT may have negative effects on testicular function, affecting spermatogenesis, and sex hormones. Many reports investigated these aspects in patients treated with bleomycin, etoposide, and cisplatin (BEP), after UO. In contrast no data are available on the side effects of carboplatin treatment in these patients. We included in this study 212 consecutive subjects who undergone to sperm banking at our Andrology and Human Reproduction Unit after UO for TGCT. Hundred subjects were further treated with one or more BEP cycles (BEP-group), 54 with carboplatin (CARB group), and 58 were just surveilled (S-group). All patients were evaluated for seminal parameters, sperm aneuploidy, sperm DNA, sex hormones, volume of the residual testis at baseline (T0) and after 12 (T1) and 24 months (T2) from UO or end of CT. Seminal parameters, sperm aneuploidies, DNA status, gonadic hormones, and testicular volume at baseline were not different between groups. At T1, we observed a significant reduction of sperm concentration and sperm count in the BEP group versus baseline and versus both Carb and S-group. A significant increase of sperm aneuploidies was present at T1 in the BEP group. Similarly, the same group at 1 had altered sperm DNA integrity and fragmentation compared with baseline, S-group and Carb group. These alterations were persistent after 2 years from the end of BEP treatment. Despite a slight improvement at T2, the BEP group had still higher percentages of sperm aneuploidies than other groups. No impairment of sperm aneuploidies and DNA status were observed in the Carb group both after 1 and 2 years from the end of treatment. Despite preliminary, these data demonstrate that in selected patients with TGCTs CT with carboplatin represents a therapeutic option that that seems to not affect sex hormones, spermatogenesis, and sperm nucleus.
年轻男性中睾丸生殖细胞肿瘤(TGCT)是最常见的恶性肿瘤,在多个国家其发病率都在上升。除了单侧睾丸切除术(UO)外,TGCT的治疗可能包括监测、放疗或化疗(CT),具体取决于肿瘤组织学和疾病分期。众所周知,放疗和CT都可能对睾丸功能产生负面影响,影响精子发生和性激素。许多报告研究了接受UO后使用博来霉素、依托泊苷和顺铂(BEP)治疗的患者的这些方面。相比之下,关于这些患者接受卡铂治疗的副作用尚无数据。我们纳入了本研究的212名连续受试者,他们在因TGCT接受UO后,在我们的男科和人类生殖科进行了精子冷冻保存。100名受试者进一步接受了一个或多个BEP周期的治疗(BEP组),54名接受卡铂治疗(CARB组),58名仅接受监测(S组)。对所有患者在基线(T0)、UO或CT结束后12个月(T1)和24个月(T)时的精液参数、精子非整倍体、精子DNA、性激素、残余睾丸体积进行了评估。各组在基线时的精液参数、精子非整倍体、DNA状态、性腺激素和睾丸体积没有差异。在T1时,我们观察到BEP组与基线相比以及与卡铂组和S组相比,精子浓度和精子数量显著降低。BEP组在T1时精子非整倍体显著增加。同样,与基线、S组和卡铂组相比,该组在T1时精子DNA完整性和片段化发生了改变。这些改变在BEP治疗结束2年后仍然存在。尽管在T2时有轻微改善,但BEP组的精子非整倍体百分比仍高于其他组。在治疗结束1年和2年后,卡铂组均未观察到精子非整倍体和DNA状态受损。尽管这些数据尚属初步,但表明在选定的TGCT患者中,卡铂化疗是一种似乎不影响性激素、精子发生和精子细胞核的治疗选择。