Østergren Peter B, Kistorp Caroline, Fode Mikkel, Henderson James, Bennedbæk Finn N, Faber Jens, Sønksen Jens
Department of Urology, Herlev and Gentofte University Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Endocrinology, Herlev and Gentofte University Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Urol. 2017 Jun;197(6):1441-1447. doi: 10.1016/j.juro.2016.12.003. Epub 2016 Dec 9.
Recent evidence suggests that reaching the lowest achievable levels of testosterone with androgen deprivation therapy delays disease progression and increases overall survival in men with advanced prostate cancer. The aim of this analysis was to compare posttreatment serum testosterone levels between patients undergoing subcapsular orchiectomy and patients treated with the luteinizing hormone-releasing hormone agonist triptorelin.
In this randomized clinical trial we included 58 consecutive hormone naïve men diagnosed with advanced prostate cancer at Herlev and Gentofte University Hospital, Herlev, Denmark from September 2013 to March 2015. Followup was 48 weeks. Participants were randomly assigned 1:1 to subcapsular orchiectomy or triptorelin 22.5 mg given as 24-week depot injections. Androgen status was measured by liquid chromatography-tandem mass spectrometry prior to treatment and after 12, 24 and 48 weeks. Between group differences in achieved hormone levels were analyzed by longitudinal Tobit regression.
Triptorelin injections resulted in 29% lower testosterone levels (95% CI 17.2-41.7) compared to subcapsular orchiectomy (p <0.001). A significantly higher proportion of men receiving triptorelin had testosterone levels less than 20 ng/dl at 12 and 48 weeks compared to men undergoing orchiectomy (97% vs 79% and 100% vs 87%, respectively, p <0.05). There was no detectable difference in the adrenal androgen reduction between the treatment groups.
The use of 24-week depot triptorelin injections results in significantly lower testosterone levels compared to subcapsular orchiectomy. To our knowledge this is the first randomized study to demonstrate a difference in treatment effect between surgical and medical castration on testosterone levels.
近期证据表明,雄激素剥夺疗法使睾酮水平降至可达到的最低水平可延缓疾病进展,并提高晚期前列腺癌男性的总生存率。本分析的目的是比较接受包膜下睾丸切除术的患者与接受促黄体生成素释放激素激动剂曲普瑞林治疗的患者治疗后的血清睾酮水平。
在这项随机临床试验中,我们纳入了2013年9月至2015年3月在丹麦赫勒夫市赫勒夫和根措夫特大学医院连续诊断为晚期前列腺癌的58例初治激素患者。随访48周。参与者按1:1随机分配接受包膜下睾丸切除术或每24周注射一次22.5 mg曲普瑞林。在治疗前以及治疗12周、24周和48周后,通过液相色谱-串联质谱法测量雄激素状态。通过纵向 Tobit 回归分析两组间达到的激素水平差异。
与包膜下睾丸切除术相比,注射曲普瑞林导致睾酮水平降低29%(95%CI 17.2 - 41.7)(p<0.001)。与接受睾丸切除术的男性相比,接受曲普瑞林治疗的男性在12周和48周时睾酮水平低于20 ng/dl的比例显著更高(分别为97%对79%和100%对87%,p<0.05)。治疗组之间肾上腺雄激素减少没有可检测到的差异。
与包膜下睾丸切除术相比,每24周注射一次曲普瑞林可使睾酮水平显著降低。据我们所知,这是第一项证明手术去势和药物去势对睾酮水平的治疗效果存在差异的随机研究。