Heidenreich A, Ohlmann C H
Sektion für Urologische Onkologie, Klinik und Poliklinik für Urologie, Universität, Köln.
Urologe A. 2005 Nov;44(11):1303-4, 1306-14. doi: 10.1007/s00120-005-0928-z.
Surgical or medical androgen deprivation therapy in its multiple variants represents the standard therapeutic approach in the management of metastatic prostate cancer resulting in a primary response rate of about 90%. However, about 90% of the men treated will develop PSA progression within 3-4 years resulting in androgen-independent and later on hormone-refractory prostate cancer. Management of AIPCA and HRPCA still represents a therapeutic challenge despite the development of new and effective treatment options. PSA progression following primary ADT defines an androgen-refractory but still hormone-sensitive PCA which might respond to secondary hormonal manipulations such as antiandrogen withdrawal, addition of nonsteroidal antiandrogens, and administration of estrogens, ketoconazole and hydrocortisone, and somatostatin analogues. Secondary hormonal manipulations will result in a PSA decline >50% in about 60-80% of the patients with a mean duration of 7-17 months depending on the type of treatment. PSA progression following secondary endocrine treatment defines hormone-refractory prostate cancer (HRPCA) which might be treated by systemic chemotherapy. Based on the results of two prospective, randomized clinical phase III trials comparing docetaxel and mitoxantrone, docetaxel results in a statistically significant survival benefit of 2.5 months, a significantly higher PSA and pain response, and represents the treatment of choice in the management of HRPCA. Bisphosphonates such as zoledronate represent another cornerstone in the management of PSA-progressive PCA demonstrating a significant benefit with regard to the prevention of skeletal-related events. Furthermore, bisphosphonates might be indicated in the treatment of symptomatic bone pain as has been demonstrated for ibandronate and zoledronate. The current article critically reflects on the various therapeutic options in the management of PSA progression following primary androgen deprivation for advanced prostate cancer. The development, rationale, and results of systemic chemotherapy are discussed critically and a therapeutic algorithm is demonstrated.
手术或药物去雄激素疗法的多种变体是转移性前列腺癌管理中的标准治疗方法,其初始缓解率约为90%。然而,约90%接受治疗的男性会在3至4年内出现前列腺特异性抗原(PSA)进展,进而发展为雄激素非依赖性及随后的激素难治性前列腺癌。尽管有了新的有效治疗选择,但雄激素非依赖性前列腺癌(AIPCA)和激素难治性前列腺癌(HRPCA)的管理仍然是一个治疗挑战。初始雄激素剥夺治疗(ADT)后出现的PSA进展定义了一种雄激素难治但仍对激素敏感的前列腺癌(PCA),它可能对诸如抗雄激素撤药、添加非甾体抗雄激素、给予雌激素、酮康唑、氢化可的松以及生长抑素类似物等二线激素治疗有反应。二线激素治疗将使约60%至80%的患者PSA下降>50%,根据治疗类型,平均持续时间为7至17个月。二线内分泌治疗后出现的PSA进展定义了激素难治性前列腺癌(HRPCA),它可能通过全身化疗进行治疗。基于两项比较多西他赛和米托蒽醌的前瞻性、随机临床III期试验结果,多西他赛在统计学上有显著的生存获益,生存期延长2.5个月,PSA和疼痛反应显著更高,是HRPCA管理中的首选治疗方法。唑来膦酸等双膦酸盐是PSA进展性PCA管理中的另一个基石,在预防骨相关事件方面显示出显著益处。此外,如伊班膦酸和唑来膦酸所示,双膦酸盐可能适用于有症状的骨痛治疗。本文批判性地反思了晚期前列腺癌初始雄激素剥夺治疗后PSA进展管理中的各种治疗选择。对全身化疗的发展、原理和结果进行了批判性讨论,并展示了一种治疗算法。