前列腺癌的内分泌治疗

前列腺癌是男性泌尿生殖系统肿瘤中极为重要的一种，本文概述了新近前列癌的内分泌治疗的有关原理，基础研究及临床应用现状。     

前列腺癌内分泌治疗的副作用

前列腺癌的内分泌治疗可以采用不同的方法，这些方法都会产生副作用，它们以不同的方式影响患者的健康和生活质量。本文就内分泌治疗的主要副作用，发病机理和可能的避免方法及治疗作一综述。     

间歇性内分泌治疗前列腺癌

前列腺癌是欧美国家男性最常见的恶性肿瘤,也是全球男性继肺癌之后第二位的恶性肿瘤.随着人口老龄化及诊断水平的提高,我国前列腺癌总体发病率也有增高的趋势,另外,也有发病年龄年轻化及更早期发现的趋势.对于已失去根治机会的晚期前列腺癌,内分泌治疗已成为首选治疗方式.间歇性内分泌治疗(intermittent hormone thempy,IHT)因其有可能提高生活质量、延长雄激素抵抗及存活时间,在近十多年得到广泛关注.     

前列腺癌的内分泌治疗现状及研究进展

目的:前列腺癌发病的流行病学上的改变,导致前列腺癌内分泌治疗的治疗指征和治疗时机也随之改变。本文综述了在新的前列腺癌流行病学背景下,前列腺癌内分泌治疗的现状;同时对内分泌治疗中现存的争议,诸如单纯去势治疗与雄激素联合阻断治疗、间断性雄激素阻断治疗与持续性雄激素阻断治疗、早期内分泌治疗与推迟内分泌治疗等方面的相关研究进展进行了讨论。     

前列腺癌内分泌治疗的几个热点问题

1941年Huggins和Hodges首先报道了去势和注射雌激素在转移性前列腺癌患者中的益处。随后的研究证实前列腺癌细胞广泛表达雄激素受体,且依赖于雄激素而生长,从而确立了内分泌治疗的生物学基础。目前内分泌治疗的手段包括手术去势和药物治疗,国内广泛使用的药物是促黄体激素释放激素激动剂(LHRHa)和非甾体类抗雄药。内分泌治疗是晚期前列腺癌的主要治疗方式,如何提高疗效、减少副作用并最终治愈疾病成为近年来的研究热点。本文就几个热点问题进行探讨。一、最大雄激素阻断(maxi mumandrogen blockage,MAB)去势治疗和抗雄药物的联合构成了M…     

前列腺癌的内分泌治疗

在欧美国家中,前列腺癌是男性的常见恶性肿瘤,且死亡率高。在我国,前列腺癌的发病率亦有明显的增长趋势。1941年Huggins等提出大多数前列腺癌依赖雄激素生长,通过睾丸切除或口服雌激素来减低体内雄激素的作用,可取得治疗前列腺癌的良效。此后,许多研究证实了他们的结果。随着许多疗效好、副作用小的药物用于临床,内分泌疗法已是前列腺癌,特别是晚期病例的主要治疗方法。本文就该疗法作一简要综述。     

前列腺癌内分泌治疗的生存随访

目的:探讨前列腺癌内分泌治疗后患者长期生存情况及相关预后因素。方法:随访124例前列腺癌内分泌治疗后的生存情况,用Kaplan-Meiers生存分析比较不同分型患者的生存时间情况。结果:全组前列腺癌有效随访者平均生存时间为5.912年,中位生存时间为7.81年。按前列腺癌诊断时的特征情况分组分析后仅发现临床未有骨转移者的生存时间相比有骨转移的患者较长(P=0.04)。而不同病理分型和前列腺特异性抗原(PSA)水平对内分泌治疗的预后无显著影响。对58例已死亡的患者分析显示,前列腺癌相关死亡的35例患者生存时间于其他死因患者的生存时间相比并无显著差异(P=0.499)。结论:前列腺癌有无骨转移可能是影响晚期前列腺癌预后的重要因素,其比病理分级情况对生存时间的影响更为显著。     

前列腺癌内分泌治疗的临床应用

内分泌治疗在前列腺癌（尤其是中晚期前列腺癌）的治疗中占有重要地位,但在临床应用中一些问题逐渐凸显并亟待解决.大量有关前列腺癌内分泌治疗的临床试验已经或正在国内外开展,获得的结果指导了治疗指南的制定和更新.作者结合近期临床试验结果及国内外最新指南,对前列腺癌内分泌治疗在临床实践中的一些具体问题,如治疗时机的确定、方法的选择以及联合雄激素阻断、辅助/新辅助治疗、间歇内分泌治疗等的应用进行总结评价.     

前列腺癌的间歇内分泌治疗

1941年，Huggins和Hodges发表了获得诺贝尔奖的有关雄激素去除对晚期前列腺癌作用的研究，开创了前列腺癌内分泌治疗的先河。前列腺癌的内分泌治疗包括联合内分泌治疗（CAB）、单独去势治疗、新辅助内分泌治疗（NHT）、辅助内分泌治疗（AHT）及间歇内分泌治疗（1AD）等，而前列腺癌经内分泌治疗后由激素依赖性转变为非激素依赖性，最终转化为激素不敏感性肿瘤，是前列腺癌患者癌特异性死亡的原因。近年来研究表明完全雄激素阻断并不能延长前列腺癌细胞进展到非雄激素依赖的时间，同时完全雄激素阻断带来患者生活质量的下降，如性欲低下，勃起功能障碍，疲劳，智力下降，心理障碍-精神抑郁，肌力降低，脂肪聚积，生理活动和整体活动能力降低，同时增加了患者的相关治疗费用。     

前列腺癌内分泌治疗方法研究及预后分析

目的:探究延长前列腺癌患者进展为激素非依赖性前列腺癌(AIPC)时间的内分泌治疗方法。方法:经直肠活检穿刺证实前列腺癌患者93例,分为3组:22例患者接受双侧睾丸切除加比卡鲁胺联合治疗,行持续性全雄激素阻断(CAD);71例患者行间歇性内分泌治疗方法,其中29例患者行标准间歇性内分泌治疗(IAD),42例患者行改良型间歇性内分泌治疗;两组治疗期用戈舍瑞林或亮丙瑞林联合比卡鲁胺的用药方案,行雄激素最大阻断(MAB),当患者血清PSA下降至<0.2μg/L,维持用药3个月。进入间歇期,IAD组停药,改良型IAD组停用促黄体生成激素释放激素类似物(LHRH-a),但维持使用比卡鲁胺,两组在间歇期内出现PSA持续升高,且大于4μg/L时,则再次启用MAB,直至患者进展为AIPC。比较CAD、IAD及改良型IAD 3组患者疾病随访时间、疾病进展时间及治疗周期。结果:3组患者人口学特征、基线资料及随访时间相似,中位进展时间分别为(26.50±4.15)月、(30.00±7.83)月和(34.93±5.08)月,CAD与标准IAD组比较差异无统计学意义(P=0.143),改良型IAD组与CAD及IAD组比较差异有统计学意义(P=0.001,0.032)。Kaplan-Meier生存分析显示,改良组中位进展时间明显长于标准IAD治疗组(P=0.01)。标准IAD与改良型IAD组平均治疗周期分别为(16.13±3.33)月和(19.58±4.30)月,两组第1治疗周期间歇期分别为(9.6±3.2)月和(14.2±3.7)月,组间比较差异显著(P=0.001)。结论:与CAD和标准IAD比较,改良型IAD可显著延长前列腺癌患者进展为AIPC的时间。     

Hormonal therapy options for biochemical recurrence of prostate cancer after local therapy

Recurrence after local prostate cancer treatment detectable only by a rise in serum prostate specific antigen (PSA) is a very common problem facing clinicians. Given that the majority of these men are relatively young and otherwise healthy, treatment of PSA-only recurrence requires approaches that not only improve survival but also preserve quality of life. For radical prostatectomy patients, a PSA-only recurrence is broadly defined as persistent or rising PSA in the postoperative period. For radiation-treated patients, the 1997 American Society for Therapeutic Radiology and Oncology guidelines specify three consecutive elevations of PSA after the post-treatment nadir PSA is achieved. Traditional hormonal therapy is the mainstay of systemic treatment for PSA-only recurrence, although nontraditional approaches such as intermittent and oral-only hormonal therapy are under study.     

Hormonal prevention of prostate cancer

Prostate cancer is disease in which the mortality rate is highly variable among populations. An increasing risk with migratory changes suggests that some environmental factor or factors influence prostate cancer risk. It is well established that the prostate is hormonally influenced. Carcinogenesis is a process of malignant transformation evolving over time, involving cellular growth and division. There is evidence suggesting that androgenic influences over a period time encourages the process of prostate carcinogenesis. Studies of prostate biology support the concept that dihydrotestosterone is the principal androgen responsible for both normal and hyperplastic growth of the prostate gland. It may be that androgen causes prostate carcinogenesis. Suppression of dihydrotestosterone synthesis may inhibit carcinogenic transformation. Some preclinical and clinical observations support this hypothesis. A placebo controlled randomized trial using finasteride, an inhibitor of 5-alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone, is ongoing. The endpoint of this trial is reduction of prostate cancer incidence.     

Hormonal predictors of prostate cancer

INTRODUCTION: Androgens are necessary for the development and functioning of the prostate gland. The association of serum testosterone and pituitary hormone levels with prostate cancer development is not completely understood. In this clinical study, we evaluated the role of serum testosterone, free testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in predicting prostate cancer risk in patients who had transrectal ultrasonography-guided prostate biopsy with the suspicion of prostate cancer. MATERIAL AND METHODS: A total of 211 patients who were selected to undergo prostatic biopsy due to abnormal digital rectal examination and/or a serum prostate-specific antigen (PSA) level >2.5 ng/ml were included in the study. The patient characteristics of total PSA, free/total PSA ratio, serum total testosterone, free testosterone, free/total testosterone ratio, FSH and LH levels were compared according to the pathological diagnosis. RESULTS: The mean age was 63.91 years (range 44-83) and the mean PSA level was 9.23 ng/ml (range 0.13-50.41) in the whole group. Of 211 patients, 69 (32.7%) were positive for prostate cancer. The patients who were positive for prostate cancer had statistically lower levels of serum total testosterone compared with the patients who were diagnosed as having benign prostatic hyperplasia (BPH; 405 vs. 450.5 ng/dl, respectively; p = 0.013). The serum FSH level was significantly higher in men with prostatic cancer than in men with BPH (7.56 vs. 6.06 mIU/ml, respectively; p = 0.029). No significant differences between men with prostatic cancer and those with BPH were found for serum LH levels. When normal ranges for serum free and total testosterone levels were defined as 9 pg/ml and 300 ng/dl, respectively, patients who had low free testosterone and total testosterone levels had significantly higher cancer detection rates than patients with high serum androgen levels: 40.8% (40/98) versus 25.6% (29/113) (p = 0.021), and 48.6% (18/37) versus 29.3% (51/174), respectively (p = 0.023). After logistic regression analysis, none of the hormones showed a significant difference in predicting the risk of prostate cancer in patients undergoing prostate biopsy with suspicion of the disease. CONCLUSION: Our data suggest that patients diagnosed with prostate cancer have low levels of serum testosterone and high levels of serum FSH compared with the patients with BPH. No support was found for the theory that high levels of testosterone increase prostate cancer risk. Further studies are needed to clarify the relationship between hormones and prostate cancer etiology.     

Hormonal therapy and chemotherapy in hormone-naive and castration resistant prostate cancer

The management of advanced castration resistant prostate cancer (CRPC) has been rapidly changing and is still evolving. In the last years, there has been an increasing knowledge of prostate cancer biology. New therapeutic agents and approaches have been evaluated demonstrating benefits in survival and quality of life in patients with metastatic prostate cancer.     

晚期前列腺癌膀胱出口梗阻内分泌治疗的价值

目的 探讨晚期前列腺癌BOO内分泌治疗(HT)的价值.方法 晚期前列腺癌伴BOO患者52例,平均年龄72(54～76)岁.既往均未行HT.病程5个月～7年,平均3.6年.治疗前经直肠B超测定前列腺重量为(53.5±15.3)g;IPSS 23.4±4.5;Q_(max)(4.8±2.5)ml/s;PSA(53.4±7.5)ng/ml.有尿潴留6例.52例治疗前均经直肠前列腺穿刺活检病理证实,Whitmore-Jewette临床分期:C期14例,D期38例.所有病例首先给予HT,对治疗3个月LUTS无改善者采用姑息性TURP治疗.结果 HT后LUTS明显改善者占71%(37/52),治疗前后Q_(max)分别为(6.2±4.5)和(13.0±5.5)ml/s、IPSS分别为24.1±5.3和7.8±2.0,治疗前后比较差异均有统计学意义(P＜0.05);LUTS未见缓解者占29%(15/52),治疗前后Q_(max)分别为(6.6±4.3)和(7.0±4.2)ml/s、IPSS分别为23.6±5.1和22.5±4.9,治疗前后比较差异均无统计学意义(P＞0.05).行姑息性TURP后好转12例,尿失禁3例,其中2例经肛提肌训练及药物治疗后有不同程度恢复.结论 HT对大部分晚期前列腺癌患者BOO有明显疗效,并可使无改善者前列腺体积缩小,便于进一步治疗.