Fair W R, Cookson M S, Stroumbakis N, Cohen D, Aprikian A G, Wang Y, Russo P, Soloway S M, Sogani P, Sheinfeld J, Herr H, Dalgabni G, Begg C B, Heston W D, Reuter V E
Department of Surgery, Pathology, and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Urology. 1997 Mar;49(3A Suppl):46-55. doi: 10.1016/s0090-4295(97)00169-6.
The use of neoadjuvant chemotherapy prior to definitive surgery has been firmly established in other areas of oncology, most notably in the treatment to testis and Wilm's tumors. The use of neoadjuvant androgen deprivation therapy (ADT) in conjunction with radical prostatectomy remains a source of controversy. We have conducted phase II and phase III studies to assess the effects of 3 months of preoperative ADT (goserelin and flutamide) on the pathologic staging and postsurgery prostate-specific antigen (PSA) relapse rate. We also reviewed the data confirming the understaging of clinically localized prostatic cancer and the experimental data providing the conceptual support for ADT.
We report the results of 141 patients, Stage T0-T0, in a Phase II study with concurrent, nonrandomized controls (N = 72) versus a treatment arm (N = 69) of men receiving 3 months of ADT with 3.6 mg goserelin for 28 days and 750 mg flutamide daily. We also report the interim results in 114 men participating in a prospective, randomized study of ADT versus surgery alone.
The 69 patients who received 3 months of goserelin and flutamide followed by radical prostatectomy had a pathologic organ-confined cancer rate of 74%, versus 48% in the control group who received no ADT prior to surgery. The margin-positive rate was 10% in the ADT group versus 33% in the control group. In an interim analysis of 114 patients (59 ADT, 55 control), the organ-confined and margin-positive rates were 73% and 17% in the ADT group versus 56% and 36% in the control arm, respectively. The PSA disease-free rate at a mean follow-up of 28.6 months (range 6.2 to 49.5 months) was 89% in the ADT-treated patients (N = 98) and 84% in the control patients (N = 96). There was no statistical difference demonstrated between the arms with respect to biochemical failure.
While the pathologic staging of tumors following ADT treatment was improved compared with surgical controls, to date the PSA disease-free survival rates are similar. Patients with residual extracapsular (P3) disease after ADT manifest an increased PSA failure rate compared with those with P3 tumors treated by surgery alone. This suggests that ADT may identify a subset of patients with aggressive tumors that may be candidates for additional therapeutic interventions even before PSA failure occurs.
在肿瘤学的其他领域，尤其是睾丸癌和威尔姆斯瘤的治疗中，术前新辅助化疗的应用已得到明确确立。新辅助雄激素剥夺疗法（ADT）联合根治性前列腺切除术的应用仍存在争议。我们开展了II期和III期研究，以评估3个月的术前ADT（戈舍瑞林和氟他胺）对病理分期及术后前列腺特异性抗原（PSA）复发率的影响。我们还回顾了证实临床局限性前列腺癌分期过低的数据以及为ADT提供理论支持的实验数据。
我们报告了141例T0 - T0期患者的II期研究结果，该研究设有同期非随机对照组（N = 72）和治疗组（N = 69），治疗组男性接受3个月的ADT，使用3.6 mg戈舍瑞林，皮下注射28天，每日口服750 mg氟他胺。我们还报告了114例参与ADT与单纯手术前瞻性随机研究的男性患者的中期结果。
69例接受3个月戈舍瑞林和氟他胺治疗后行根治性前列腺切除术的患者，病理分期为器官局限性癌的比例为74%，而术前未接受ADT的对照组这一比例为48%。ADT组切缘阳性率为10%，对照组为33%。在对114例患者（59例ADT组，55例对照组）的中期分析中，ADT组器官局限性和切缘阳性率分别为73%和17%，对照组分别为56%和36%。在平均随访28.6个月（范围6.2至49.5个月）时，ADT治疗患者（N = 98）的PSA无病生存率为89%，对照组患者（N = 96）为84%。两组在生化复发方面无统计学差异。
虽然与手术对照组相比，ADT治疗后肿瘤的病理分期有所改善，但迄今为止，PSA无病生存率相似。与单纯手术治疗的P3期肿瘤患者相比，ADT治疗后有残留包膜外（P3）疾病的患者PSA复发率更高。这表明ADT可能识别出一部分具有侵袭性肿瘤的患者，即使在PSA复发之前，这些患者也可能是额外治疗干预的候选对象。
