Gleave M E, Goldenberg S L, Jones E C, Bruchovsky N, Sullivan L D
Department of Surgery, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Canada.
J Urol. 1996 Jan;155(1):213-9.
A prospective, nonrandomized trial was initiated to determine the duration of neoadjuvant therapy required for prostate specific antigen (PSA) to reach its nadir, evaluate the ability of an ultrasensitive assay to measure decreases in PSA less than 0.2 microgram./l., and characterize the effects of 8 months of neoadjuvant therapy on pathological stage, positive margin rates, proliferation and tumor marker immuno-staining.
We evaluated 50 patients with clinically localized prostate cancer treated by 8 months of reversible androgen ablation before radical prostatectomy. Serum PSA and testosterone levels were measured monthly.
Serum PSA decreased by 84% after 1 month and by a further 52% between 3 and 8 months. Using an ultrasensitive assay, serum PSA decreased to undetectable levels (less than 0.1 microgram./l.) or reached its nadir in 22% of the cases after 3 months, 42% after 5 months and 84% after 8 months. Overall, the positive margin rate was 4%. Of the cases 68% were organ-confined and 24% were specimen-confined. The positive margin rate was not increased after reevaluation with cytokeratin, PSA and prostatic acid phosphatase immuno-staining but of 4 cases initially staged as P0 on hematoxylin and eosin evaluation 2 had microscopic foci of cancer with prostatic acid phosphatase staining. Immuno-staining with the proliferation markers proliferation cell nuclear antigen and Ki-67 showed decreased staining in surgical specimens relative to pretreatment needle biopsy specimens, which suggests that outgrowth of androgen independent clones does not develop during prolonged neoadjuvant therapy.
Eight months of neoadjuvant androgen withdrawal therapy results in low positive margin rates and PSA nadir levels. The initial rapid decrease in PSA results from cessation of androgen regulated PSA synthesis and apoptosis, while the ongoing slower decrease reflects decreasing tumor volume.
开展一项前瞻性、非随机试验，以确定前列腺特异性抗原（PSA）降至最低点所需的新辅助治疗持续时间，评估超敏检测法测量低于0.2微克/升的PSA下降情况的能力，并描述8个月新辅助治疗对病理分期、切缘阳性率、增殖及肿瘤标志物免疫染色的影响。
我们评估了50例临床局限性前列腺癌患者，这些患者在根治性前列腺切除术前行8个月的可逆性雄激素剥夺治疗。每月测量血清PSA和睾酮水平。
血清PSA在1个月后下降了84%，在3至8个月间又下降了52%。使用超敏检测法，血清PSA在3个月后降至不可检测水平（低于0.1微克/升）或达到最低点的病例占22%，5个月后为42%，8个月后为84%。总体而言，切缘阳性率为4%。病例中68%为器官局限性，24%为标本局限性。用细胞角蛋白、PSA和前列腺酸性磷酸酶免疫染色重新评估后，切缘阳性率未增加，但在苏木精和伊红评估中最初分期为P0的4例病例中，有2例经前列腺酸性磷酸酶染色显示有微小癌灶。用增殖标志物增殖细胞核抗原和Ki-67进行免疫染色显示，手术标本中的染色相对于治疗前穿刺活检标本减少，这表明在长期新辅助治疗期间未出现雄激素非依赖性克隆的生长。
8个月的新辅助雄激素剥夺治疗导致低切缘阳性率和PSA最低点水平。PSA最初的快速下降是由于雄激素调节的PSA合成停止和细胞凋亡，而持续的缓慢下降反映了肿瘤体积的减小。
