Kato Tomonori, Komiya Akira, Yuasa Joji, Kaga Kanya, Kaga Mayuko, Kojima Satoko, Naya Yukio, Isaka Shigeo
Division of Urology, Kuki General Hospital (Formerly Satte General Hospital), Saitama 346-8530, Japan.
Department of Urology, Teikyo University Chiba Medical Center, Chiba 299-0111, Japan.
Oncol Lett. 2018 Feb;15(2):2669-2672. doi: 10.3892/ol.2017.7628. Epub 2017 Dec 14.
A 72-year-old man initially presented with lumbar and right chest pain, but was later found out to also have an elevated prostate-specific antigen (PSA) level at 2,000.0 ng/ml. Further evaluation disclosed metastatic prostate cancer involving the bones and lymph nodes. The patient was initially treated with combined androgen blockade (CAB) with leuprolide acetate and bicalutamide. After 6 months of CAB, the patient's PSA level began to rise from the nadir (85.1 ng/ml) to 113.3 ng/ml. Bicalutamide was withdrawn in anticipation of anti-androgen withdrawal syndrome and the PSA level declined temporally. However, it increased up to 517.0 ng/ml thereafter. Consequently, a year after CAB, abiraterone acetate (AA) was initiated at a standard dose of 1,000 mg daily in combination with 10 mg of prednisolone. PSA rapidly decreased to the nadir of 20.1 ng/ml thereafter. The PSA level remained stable until 2 years after AA administration. However, he decided to reduce the dose of AA to half of the standard dose (500 mg daily). Contrary to our expectations, the serum PSA level promptly decreased to a nadir of 8.1 ng/ml. Thereafter, the PSA level remained stable until 3 years and 9 months after AA administration. Subsequently, the patient stopped taking AA and prednisolone. However, to our surprise, the patient's serum PSA level decreased further to <1.0 ng/ml after AA discontinuation. His PSA remained <1.0 ng/ml without clinical or radiological progression for 1 year after AA withdrawal. Recently, it was reported that cessation of AA is associated with AA withdrawal syndrome in metastatic castration-resistant prostate cancer, defined as a PSA decrease after AA discontinuation, mimicking anti-androgen withdrawal syndrome. In the present study, explanations of the mechanisms underlying this phenomenon were explored, including mutant AR activation by alternative ligands.
一名72岁男性最初表现为腰背部及右胸痛，后来发现其前列腺特异性抗原（PSA）水平升高至2000.0 ng/ml。进一步评估发现为转移性前列腺癌，累及骨骼和淋巴结。患者最初接受了醋酸亮丙瑞林和比卡鲁胺联合雄激素阻断（CAB）治疗。CAB治疗6个月后，患者的PSA水平开始从最低点（85.1 ng/ml）升至113.3 ng/ml。因预期出现抗雄激素撤药综合征停用了比卡鲁胺，PSA水平暂时下降。然而，此后又升至517.0 ng/ml。因此，CAB治疗1年后，开始每日标准剂量服用1000 mg醋酸阿比特龙（AA）并联合10 mg泼尼松龙。此后PSA迅速降至最低点20.1 ng/ml。PSA水平在AA给药后2年内保持稳定。然而，他决定将AA剂量减至标准剂量的一半（每日500 mg）。与我们的预期相反，血清PSA水平迅速降至最低点8.1 ng/ml。此后，PSA水平在AA给药后3年9个月内保持稳定。随后，患者停止服用AA和泼尼松龙。然而，令我们惊讶的是，停用AA后患者的血清PSA水平进一步降至<1.0 ng/ml。AA停药后1年内，其PSA水平保持<1.0 ng/ml，无临床或影像学进展。最近有报道称，在转移性去势抵抗性前列腺癌中，停用AA与AA撤药综合征有关，定义为停用AA后PSA下降，类似于抗雄激素撤药综合征。在本研究中，探讨了这一现象潜在机制的解释，包括替代配体激活突变型雄激素受体。
