Background/Objectives:Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor initially causes a surge in LH and testosterone, defined as the “flare-up phenomenon”, leading to increased bone pain, spinal cord compression, bladder outlet obstruction and cardiovascular issues. To mitigate this effect, combining a first-generation antiandrogen agent (FGA) with aGnRH is recommended. However, second-generation anti-androgens, such as apalutamide, bind selectively and irreversibly to the androgen receptor (AR), exhibiting a more efficient inhibition of the AR pathway.Methods:This is a descriptive retrospective study of 27 patients (pts) with mHSPC, treated at a single center (“Santa Maria delle Grazie” Hospital in Pozzuoli, ASL Napoli 2 Nord, Italy) between June 2022 and April 2024. Patients received apalutamide monotherapy for 14 days followed by continuous combination with aGnRH plus apalutamide. Serum PSA and testosterone levels were measured at baseline, at day 14 (after 13 days of apalutamide monotherapy), at day 28 (after an additional 15 days of apalutamide plus a aGnRH), and at day 60.Results:PSA levels decreased from a mean of 45.2 (±63.1) ng/mL at baseline to a mean of 12.6 (±23.4) ng/mL at day 14 and to 3.3 ng/mL (±6.0) at day 28 of treatment. After 14 days of apalutamide monotherapy, 21 patients (77.8%) achieved a >50% PSA reduction and 4 (14.8%) a >90% PSA reduction. The number of patients with undetectable PSA was one (3.7%) at day 14, two (7.4%) at day 28, and nine (33.3%) at day 60. The mean serum testosterone levels were 6.56 (±4.46) ng/mL at baseline, 6.58 (±4.42) ng/mL at day 14, and 2.40 (± 3.38) ng/mL at day 28. No significant difference in PSA and testosterone level reduction during treatment emerged between subgroups of patients with low- vs. high-volume disease.Conclusions:Apalutamide alone is a viable option for mitigating the flare-up phenomenon, avoiding first generation anti-androgen therapy, and it can achieve rapid and deep biochemical control.
背景/目的：雄激素剥夺疗法（ADT）是前列腺癌治疗的主要手段，尤其在晚期疾病中。促性腺激素释放激素激动剂（aGnRH）通过降低促性腺激素的生成，进而减少睾酮水平。然而，约10%的患者在接受非脉冲式GnRH受体刺激初期，会出现黄体生成素和睾酮水平的激增，即“反跳现象”，可能导致骨痛加剧、脊髓压迫、膀胱出口梗阻及心血管问题。为缓解此现象，建议将第一代抗雄激素药物（FGA）与aGnRH联合使用。而第二代抗雄激素药物如阿帕他胺，能选择性地不可逆结合雄激素受体（AR），更有效地抑制AR通路。 方法：本研究为一项描述性回顾性研究，纳入2022年6月至2024年4月期间在意大利波佐利“Santa Maria delle Grazie”医院（ASL Napoli 2 Nord）接受治疗的27例转移性激素敏感性前列腺癌（mHSPC）患者。患者先接受阿帕他胺单药治疗14天，随后持续联合aGnRH与阿帕他胺治疗。分别在基线、第14天（阿帕他胺单药治疗13天后）、第28天（联合治疗15天后）及第60天检测血清前列腺特异性抗原（PSA）和睾酮水平。 结果：PSA水平从基线的平均45.2（±63.1）ng/mL降至治疗第14天的平均12.6（±23.4）ng/mL，第28天进一步降至3.3（±6.0）ng/mL。在阿帕他胺单药治疗14天后，21例患者（77.8%）的PSA下降超过50%，4例患者（14.8%）的PSA下降超过90%。PSA降至不可检测水平的患者数量在第14天为1例（3.7%），第28天为2例（7.4%），第60天为9例（33.3%）。血清睾酮平均水平在基线时为6.56（±4.46）ng/mL，第14天为6.58（±4.42）ng/mL，第28天降至2.40（±3.38）ng/mL。在低肿瘤负荷与高肿瘤负荷亚组患者之间，治疗期间PSA和睾酮水平的下降无显著差异。 结论：阿帕他胺单药治疗是缓解反跳现象的可行选择，可避免使用第一代抗雄激素药物，并能实现快速且深度的生化控制。
肿瘤(癌症)患者之家