Yossepowitch Ofer, Sircar Kanishka, Scardino Peter T, Ohori Makoto, Kattan Michael W, Wheeler Thomas M, Reuter Victor E
Department of Urology and Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
J Urol. 2002 Nov;168(5):2011-5. doi: 10.1016/S0022-5347(05)64284-X.
Bladder neck invasion by prostate cancer in radical prostatectomy specimens is uncommon and, thus, its influence on disease recurrence has not been well defined. Consequently the classification of bladder neck invasion in the TNM staging system is controversial. We studied our cohort of patients with stage pT4 disease and bladder neck invasion to clarify the true clinical behavior and prognostic significance of bladder neck invasion in radical prostatectomy specimens.
The study group consisted of 4,090 consecutive patients treated with radical prostatectomy at one of our institutions between 1983 and 2001. Median followup was 53.1 months (range 1 to 189). After excluding from analysis patients treated with neoadjuvant androgen withdrawal or preoperative irradiation 72 of the remaining 2,571 (2.8%) with bladder neck invasion were classified with stage pT4 disease and their specimens were reviewed. Progression-free probability was determined by Kaplan-Meier analysis. Using the Cox proportional hazards model the independent prognostic significance of bladder neck invasion was assessed after controlling for pretreatment prostate specific antigen, final Gleason sum, extracapsular extension, surgical margins status, seminal vesicle invasion and lymph node involvement.
Of the 72 patients categorized with stage pT4 disease 14 (19%) had poorly differentiated Gleason sum 8 to 10 cancer, 38 (53%) had established extracapsular extension, 24 (33%) had seminal vesicle invasion and 8 (11%) had lymph node involvement. However, 26 patients (36%) had cancer confined to the prostate and 28 (39%) had negative surgical margins except for the bladder neck site. The mean 5-year progression-free probability plus or minus SD in all stage pT4 cases was 68% +/- 7%, which was better than in cases of seminal vesicle invasion (52% +/- 5%, log rank test p = 0.0156) but worse than in those of extracapsular extension (84% +/- 4.1%). Univariate analysis of the stage pT4 cohort revealed that higher prostatectomy Gleason sum, more extensive extracapsular extension and seminal vesicle invasion were significantly associated with an adverse prognosis. However, in a multivariate model that included all radical prostatectomy cases the finding of bladder neck invasion or stage pT4 disease did not independently predict prostate specific antigen recurrence.
Stage pT4 disease comprises a heterogeneous group of tumors with various pathological features and inconsistent outcomes. Assigning the pT4 stage to cases of microscopic bladder neck invasion provides no independent ability for predicting disease progression after adjusting for other adverse disease features. Due to this and previously reported data the definition of stage pT4 disease should be modified in the next version of the TNM staging system.
前列腺癌根治术标本中出现膀胱颈侵犯的情况并不常见，因此其对疾病复发的影响尚未明确界定。所以，TNM分期系统中膀胱颈侵犯的分类存在争议。我们对一组pT4期且伴有膀胱颈侵犯的患者进行研究，以阐明前列腺癌根治术标本中膀胱颈侵犯的真实临床行为和预后意义。
研究组包括1983年至2001年间在我们其中一家机构接受前列腺癌根治术的4090例连续患者。中位随访时间为53.1个月（范围1至189个月）。在排除接受新辅助雄激素剥夺或术前放疗的患者后，对其余2571例患者中的72例（2.8%）出现膀胱颈侵犯且被分类为pT4期疾病的患者标本进行回顾性分析。无进展概率通过Kaplan-Meier分析确定。使用Cox比例风险模型，在控制了术前前列腺特异性抗原、最终Gleason评分、包膜外侵犯、手术切缘状态、精囊侵犯和淋巴结受累情况后，评估膀胱颈侵犯的独立预后意义。
在72例被分类为pT4期疾病的患者中，14例（19%）为高分化Gleason评分8至10分的癌，38例（53%）已出现包膜外侵犯扩展，24例（33%）有精囊侵犯，8例（11%）有淋巴结受累。然而，26例患者（36%）的癌局限于前列腺内，28例（39%）除膀胱颈部位外手术切缘阴性。所有pT4期病例的平均5年无进展概率±标准差为68%±7%，这优于精囊侵犯病例（52%±5%，对数秩检验p = 0.0156），但差于包膜外侵犯扩展病例（84%±4.1%）。对pT4期队列的单因素分析显示，前列腺癌根治术Gleason评分越高、包膜外侵犯扩展越广泛以及精囊侵犯与不良预后显著相关。然而，在一个纳入所有前列腺癌根治术病例的多因素模型中，发现膀胱颈侵犯或pT4期疾病并不能独立预测前列腺特异性抗原复发。
pT4期疾病包含一组具有不同病理特征和不一致预后的异质性肿瘤。将pT4期指定给显微镜下膀胱颈侵犯的病例，在调整其他不良疾病特征后，没有独立预测疾病进展的能力。鉴于此及先前报道的数据，TNM分期系统的下一版应修改pT4期疾病的定义。
