Marks Phillip, Gild Philipp, Soave Armin, Janisch Florian, Minner Sarah, Engel Oliver, Vetterlein Malte W, Shariat Shahrokh F, Sauter Guido, Dahlem Roland, Fisch Margit, Rink Michael
University Medical Center Hamburg-Eppendorf, Department of Urology, Hamburg, Germany.
University Medical Center Hamburg-Eppendorf, Department of Pathology, Hamburg, Germany.
Surg Oncol. 2019 Mar;28:208-213. doi: 10.1016/j.suronc.2019.01.008. Epub 2019 Jan 30.
To investigate the impact of variant urothelial carcinoma of the bladder (UCB) histologies on extra nodal extension (ENE) and survival in lymph node (LN) positive bladder cancer patients undergoing radical cystectomy (RC).
We meticulously reviewed all bladder specimens for presence of variant UCB histologies and LN specimen for presence and extent of ENE in 517 UCB patients treated with RC. Descriptive statistics, the Kaplan Meier method and multivariable Cox regression models evaluated the association between variant UCB histology, ENE and survival metrics including disease recurrence-free, cancer-specific, and overall survival, respectively.
Overall, 138 patients had LN metastasis (27%), with a median number of 15 (IQR 9; 18) LNs removed. Among LN positive patients, 43 (31%) had ENE with a median length of 10 mm. Variant histology was present in 96 patients (18.6%) with squamous cell (12.0%) and sarcomatoid (2.5%) differentiation being the most common. In all patients, the presence of variant histology was neither associated with presence of LN metastasis nor ENE (all p-values = n.s.). In Kaplan-Meier analyses the presence of LN metastases and ENE in LN positive patients was significantly associated with disease recurrence and cancer-specific mortality, respectively (all p < 0.001). The presence of variant histology did not influence these outcomes (p = n.s.). In multivariable analyses, adjusted for standard UCB prognosticators, ENE, but not variant histology, independently predicted disease recurrence-free (hazard ratio (HR) 3.88, 95% confidence intervall (CI) 2.24-6.71, p < 0.001), cancer-specific (HR 4.60; 95% CI, 2.57-8.23, p < 0.001), and overall survival (HR 3.51; 95% CI, 2.10-5.86, p < 0.001).
Variant UCB histologies do not seem to increase the incidence of LN metastasis or ENE. This study confirms ENE being a powerful predictor for outcomes in node positive UCB patients - regardless of variant histological differentiation. Our findings warrant validation in larger cohort setting.
探讨膀胱尿路上皮癌（UCB）组织学变异对接受根治性膀胱切除术（RC）的淋巴结（LN）阳性膀胱癌患者的淋巴结外侵犯（ENE）及生存的影响。
我们仔细检查了517例接受RC治疗的UCB患者的所有膀胱标本，以确定是否存在UCB组织学变异，并检查LN标本以确定ENE的存在及范围。描述性统计、Kaplan-Meier法和多变量Cox回归模型分别评估了UCB组织学变异、ENE与生存指标（包括无疾病复发、癌症特异性生存和总生存）之间的关联。
总体而言，138例患者发生LN转移（27%），切除的LN中位数为15个（四分位间距9；18）。在LN阳性患者中，43例（31%）发生ENE，中位数长度为10毫米。96例患者（18.6%）存在组织学变异，最常见的是鳞状细胞分化（12.0%）和肉瘤样分化（2.5%）。在所有患者中，组织学变异的存在与LN转移或ENE的存在均无关联（所有p值均无统计学意义）。在Kaplan-Meier分析中，LN阳性患者中LN转移和ENE的存在分别与疾病复发和癌症特异性死亡率显著相关（所有p<0.001）。组织学变异的存在并未影响这些结果（p值无统计学意义）。在多变量分析中，校正标准UCB预后因素后，ENE而非组织学变异独立预测无疾病复发（风险比（HR）3.88，95%置信区间（CI）2.24 - 6.71，p<0.001）、癌症特异性生存（HR 4.60；95%CI，2.57 - 8.23，p<0.001）和总生存（HR 3.51；95%CI，2.10 - 5.86，p<0.001）。
UCB组织学变异似乎不会增加LN转移或ENE的发生率。本研究证实ENE是LN阳性UCB患者预后的有力预测指标——无论组织学分化如何。我们的研究结果有待在更大的队列中进行验证。
