Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: The concept of lymph node density
Risk factors for patients with pelvic lymph node metastases following radical cystectomy with en bloc pelvic lymphadenectomy: The concept of lymph node density
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DOI：
10.1097/01.ju.0000072422.69286.0e
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发表时间：
2003-07-01
影响因子：
6.6
通讯作者：
Skinner, DG
中科院分区：
文献类型：
--
作者：
Stein, JP;Cai, J;Skinner, DG
目的：我们评估了一个大型队列的淋巴结转移患者在整体根治性膀胱切除术和双侧盆腔淋巴结切除术后的临床结局和进展的风险因素。材料和方法：从1971年7月到1997年12月，1，054名患者接受了根治性膀胱切除术和双侧盆腔-髂淋巴结切除术治疗高级别、侵袭性膀胱移行细胞癌。在这些患者中，244例（23%）中位年龄为66岁（范围36 - 90岁），有病理性淋巴结转移。244例患者中有139例（57%）接受了某种形式的化疗。在中位随访时间超过10年（范围0 - 28年）时，根据肿瘤分级、原位癌、原发性膀胱肿瘤分期、病理亚组、切除的和累及肿瘤的淋巴结总数和淋巴结密度（阳性淋巴结总数/切除的淋巴结总数），在单变量分析中分析结局数据。此外，还对尿流改道的形式和化疗的给药进行了评价。结果：淋巴结阳性率随p分期和病理亚组的增高而增高。669例原发性肿瘤中，75例（11%）累及器官，385例（44%）累及膀胱外淋巴结。在244例淋巴结阳性病例中，切除淋巴结的中位数为30个（范围1 - 96），而阳性淋巴结的中位数为2个（范围1 - 63）。244例淋巴结阳性患者的5年和10年总无复发生存率分别为35%和34%。与膀胱外肿瘤扩散患者相比，淋巴结阳性疾病和器官局限性原发性膀胱肿瘤患者的10年无复发生存率显著提高（44% vs 30%，p = 0.003）。手术切除的淋巴结总数也是预后指标。切除15个或更少淋巴结的患者10年无复发生存率为25%，而切除15个以上淋巴结的患者10年无复发生存率为36%。8个或更少阳性淋巴结的患者10年无复发生存率显著高于8个以上阳性淋巴结的患者（40% vs 10%，p <0.001）。淋巴结密度的新概念也是一个重要的预后因素。淋巴结密度小于等于20%的患者10年无复发生存率为43%，而淋巴结密度大于20%的患者10年无复发生存率仅为17%（p < 0.001）。在多变量分析中，受累淋巴结总数、原发性膀胱肿瘤的病理亚组、淋巴结密度和辅助化疗仍然是无复发和总生存率的重要独立危险因素。根治性膀胱切除术后淋巴结肿瘤受累的患者可根据原发性膀胱肿瘤、病理亚组切除的淋巴结数量和涉及的淋巴结总数。淋巴结密度是一种新的预后指标，可以更好地对淋巴结阳性病例进行分层，因为这个概念共同解释了阳性淋巴结的总数（肿瘤负荷）和切除的淋巴结总数（淋巴结切除术的范围）。未来的分期系统和辅助治疗在临床试验中的应用应考虑应用淋巴结密度来帮助标准化根治性膀胱癌后的高危患者。
Purpose: We evaluated the clinical outcomes and risk factors for progression in a large cohort of patients with lymph node metastases following en bloc radical cystectomy and bilateral pelvic lymphadenectomy.Materials and Methods: From July 1971 through December 1997, 1,054 patients underwent radical cystectomy and bilateral pelvic-iliac lymphadenectomy for high grade, invasive transitional cell carcinoma of the bladder. Of these patients 244 (23%) with a median age of 66 years (range 36 to 90) had pathological lymph node metastases. Overall 139 of the 244 patients (57%) received some form of chemotherapy. At a median followup of greater than 10 years (range 0 to 28) outcomes data were analyzed in univariate analysis according to tumor grade, carcinoma in situ, primary bladder tumor stage, pathological subgroups, total number of lymph nodes removed and involved with tumor, and lymph node density (total number of positive lymph nodes/total number removed). In addition, the form of urinary diversion and the administration of chemotherapy were also evaluated. Multivariate analysis was then performed to analyze these variables independently.Results: The incidence of positive lymph nodes increased with higher p stage and pathological subgroups. Of 669 patients 75 (11%) with organ confined primary tumors and 169 of 385 (44%) with extravesical tumor extension had involved lymph nodes. The median number of lymph nodes removed in the 244 lymph node positive cases was 30 (range 1 to 96), while the median number of positive lymph nodes was 2 (range 1 to 63). Overall recurrence-free survival at 5 and 10 years for the 244 patients with lymph node positive disease was 35% and 34%, respectively. Patients with lymph node positive disease and an organ confined primary bladder tumor had significantly improved 10-year recurrence-free survival compared with those with extravesical tumor extension (44% vs 30%, p = 0.003). The total number of lymph nodes removed at surgery was also prognostic. Patients with 15 or less lymph nodes removed had 25% 10-year recurrence-free survival compared with 36% when greater than 15 lymph nodes were removed. Recurrence-free survival at 10 years for patients with 8 or less positive lymph nodes was significantly higher than in those with greater than 8 positive lymph nodes (40% vs 10%, p < .001). The novel concept of lymph node density was also a significant prognostic factor. Patients with a lymph node density of 20% or less had 43% 10-year recurrence-free survival compared with only 17% survival at 10 years when lymph node density was greater than 20% (p < 0.001). On multivariate analysis the total number of lymph nodes involved, pathological subgroups of the primary bladder tumor, lymph node density and adjuvant chemotherapy remained significant and independent risk factors for recurrence-free and overall survival.Conclusions: Patients with lymph node tumor involvement following radical cystectomy may be stratified into high risk groups based on the primary bladder tumor, pathological subgroup, number of lymph nodes removed and total number of lymph nodes involved. Lymph node density, which is a novel prognostic indicator, may better stratify lymph node positive cases because this concept collectively accounts for the total number of positive lymph nodes (tumor burden) and the total number of lymph nodes removed (extent of lymphadenectomy). Future staging systems and the application of adjuvant therapies in clinical trials should consider applying lymph node density to help standardize this high risk group of patients following radical cystectomy.