Köllermann Jens, Weikert Steffen, Schostak Martin, Kempkensteffen Carsten, Kleinschmidt Klaus, Rau Thomas, Pantel Klaus
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Clin Oncol. 2008 Oct 20;26(30):4928-33. doi: 10.1200/JCO.2007.15.0441. Epub 2008 Sep 15.
To explore whether the presence of occult disseminated tumor cells (DTCs) in the bone marrow before neoadjuvant hormone therapy influences the prognosis of patients with organ confined prostate cancer treated by radical prostatectomy.
Pretreatment bone marrow aspirates from 193 cT (1-4) pN0M0 prostate cancer patients submitted to neoadjuvant hormone therapy (mean, 8 months) followed by radical prostatectomy were immunohistochemically evaluated by anticytokeratin antibody A45-B/B3 previously validated for the detection of DTCs. Bone marrow status was compared with established clinical and histopathologic risk parameters. Patients' outcome was evaluated using prostate-specific antigen (PSA) blood serum measurements as surrogate marker for recurrence over a median follow-up of 44 months.
DTCs were detected in 44.6% of patients. Bone marrow status neither correlated with tumor grade and stage, nor with the pretreatment PSA risk category (all P values > .05). In the univariate Kaplan-Meier analysis, the presence of DTCs was a significant prognostic factor with respect to poor PSA progression-free survival (log-rank test P = .0035). Using a multivariable piecewise Cox regression model, the presence of DTCs was an independent predictor of PSA relapse (relative risk 1.82; P = .014).
The presence of DTCs in the bone marrow of patients with prostate cancer before neoadjuvant hormone therapy and subsequent surgery represents an independent prognostic parameter, suggesting that DTCs may contribute to the failure of current neoadjuvant hormone therapy regimens.
探讨新辅助激素治疗前骨髓中隐匿性播散肿瘤细胞(DTCs)的存在是否会影响接受根治性前列腺切除术的器官局限性前列腺癌患者的预后。
对193例cT(1 - 4)pN0M0前列腺癌患者进行新辅助激素治疗(平均8个月)后行根治性前列腺切除术,术前骨髓穿刺液采用先前经验证可用于检测DTCs的抗细胞角蛋白抗体A45 - B/B3进行免疫组化评估。将骨髓状态与既定的临床和组织病理学风险参数进行比较。使用前列腺特异性抗原(PSA)血清测量作为复发的替代标志物,在中位随访44个月期间评估患者的预后。
44.6%的患者检测到DTCs。骨髓状态与肿瘤分级和分期均无相关性,与术前PSA风险类别也无相关性(所有P值>0.05)。在单因素Kaplan - Meier分析中,DTCs的存在是PSA无进展生存期较差的显著预后因素(对数秩检验P = 0.0035)。使用多变量分段Cox回归模型,DTCs的存在是PSA复发的独立预测因素(相对风险1.82;P = 0.014)。
新辅助激素治疗及后续手术前前列腺癌患者骨髓中DTCs的存在是一个独立的预后参数,提示DTCs可能导致当前新辅助激素治疗方案的失败。