Isaacs John T
Department of Oncology, The Chemical Therapeutics Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
Prostate. 2008 Jun 15;68(9):1025-34. doi: 10.1002/pros.20763.
Pharmacological approaches are available to medically-managed patients with symptomatic BPH before surgical intervention is required. These include daily treatment with alpha-blockers and 5-alpha-reductase inhibitors alone or in combination. These medical approaches have two major problems. First, treatments are chronic and must be taken daily. Second, there are significant financial costs and quality of life issues for such chronic treatments. Is it possible to develop effective acute therapy for symptomatic BPH without the long-term androgen deprivation-induced side effects? Two seminal but rarely cited studies of Walsh [Peters, Walsh: N Engl J Med 317:599-604, 1987] and Coffey et al. [Sufrin et al.: Invest Urol 13:418-423, 1976], combined with the growing understanding of the stem cell organization of the prostate stromal (S) and epithelial (E) compartments and their reciprocal paracrine and autocrine interactions provides the rationale for an acute approach.The Walsh study documents that: (1) androgen deprivation disrupts the reciprocal interaction between the prostate S and E thereby decreasing the weight of both compartments and (2) once BPH develops, androgen deprivation does not decrease the number of stem cell units in either the S or E compartments since subsequent androgen restoration fully restores the enlarged gland. The Coffey study documents that acute androgen deprivation sensitizes S-E interactions to radiation induced disruptions so that following radiation, androgen restoration does not induce full gland regrowth. Therefore, effective therapy for symptomatic BPH should be achievable by acute treatment with reversible androgen deprivation for a limited period followed by a single dose of conformal external beam radiation before allowing the man to recovery his normal serum testosterone.
对于有症状的良性前列腺增生（BPH）患者，在需要手术干预之前，可采用药物治疗方法。这些方法包括单独或联合使用α受体阻滞剂和5α还原酶抑制剂进行每日治疗。这些药物治疗方法有两个主要问题。首先，治疗是长期性的，必须每日服用。其次，这种长期治疗存在巨大的经济成本和生活质量问题。是否有可能开发出一种有效的急性治疗方法来治疗有症状的BPH，同时又不会产生长期雄激素剥夺引起的副作用呢？Walsh的两项具有开创性但很少被引用的研究[Peters, Walsh: 《新英格兰医学杂志》317:599 - 604, 1987]以及Coffey等人的研究[Sufrin等人: 《泌尿学研究》13:418 - 423, 1976]，再加上对前列腺基质（S）和上皮（E）区室的干细胞组织及其相互旁分泌和自分泌相互作用的日益了解，为一种急性治疗方法提供了理论依据。Walsh的研究表明：（1）雄激素剥夺会破坏前列腺S和E之间的相互作用，从而使两个区室的重量都减轻；（2）一旦BPH发生，雄激素剥夺并不会减少S或E区室中干细胞单位的数量，因为随后恢复雄激素会使增大的腺体完全恢复。Coffey的研究表明，急性雄激素剥夺会使S-E相互作用对辐射诱导的破坏敏感，因此在辐射后，恢复雄激素不会诱导腺体完全再生。因此，对于有症状的BPH，有效的治疗应该可以通过在有限时间内进行可逆性雄激素剥夺的急性治疗，然后在男性恢复正常血清睾酮之前给予单剂量适形外照射来实现。
