Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Eur Urol Oncol. 2019 Nov;2(6):656-663. doi: 10.1016/j.euo.2018.12.012. Epub 2019 Jan 31.
Current pathological nodal staging for bladder cancer is based on lymph node (LN) location but not on the number of positive LNs.
We sought to improve prognostic classification by creating a novel staging system incorporating positive LN burden.
DESIGN, SETTING, AND PARTICIPANTS: We sampled 12515 patients with muscle-invasive bladder cancer (MIBC) from the National Cancer Database (NCDB) and 5928 MIBC patients from the Surveillance, Epidemiology, and End Results (SEER) database for our development and validation cohorts, respectively.
Multivariable Cox proportional hazards analysis with restricted cubic splines was used to assess the association between the number of metastatic LNs and overall mortality (OM). A novel staging system was derived by recursive partitioning analysis (RPA) in NCDB and was validated in SEER by assessing discrimination (Harrel's c-index) and calibration (mean absolute prediction error).
Mortality risk increased continuously with more metastatic LNs; the effect was most pronounced up to four LNs (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.12-1.22) and attenuated beyond four nodes (HR 1.03, 95% CI 1.02-1.05). RPA generated a novel staging system predicting mortality by metastatic nodal number with cutpoints at zero (reference), one (HR 1.57, 95% CI 1.46-1.69), two to three (HR 2.03, 95% CI 1.88-2.19), four to seven (HR 2.46, 95% CI 2.25-2.70), and more than seven (HR 3.83, 95% CI 3.38-4.33) positive LNs. Location of LN involvement was not a significant predictor of OM. In external validation, the novel staging system showed good risk discrimination (optimism corrected c-index 0.677, 95% CI 0.672-0.682) and calibration (mean absolute prediction error 0.011 for 5-yr OM). Results are limited by development and validation using secondary data.
The number of metastatic LNs predicts mortality better than LN location and may improve pathological nodal staging in MIBC.
This retrospective study found that the number of metastatic lymph nodes more accurately predicts survival than the location of metastatic lymph nodes in patients with muscle-invasive bladder cancer. This finding argues for change to the current bladder cancer staging system.
目前膀胱癌的病理淋巴结分期基于淋巴结（LN）位置而非阳性 LN 数量。
我们试图通过创建一个包含阳性 LN 负担的新分期系统来改善预后分类。
设计、设置和参与者：我们分别从国家癌症数据库（NCDB）中采样了 12515 例肌层浸润性膀胱癌（MIBC）患者和 5928 例 MIBC 患者作为开发和验证队列。
使用受限立方样条的多变量 Cox 比例风险分析来评估转移性 LN 数量与总死亡率（OM）之间的关联。通过递归分区分析（RPA）在 NCDB 中得出一个新的分期系统，并通过评估判别（Harrell 的 c 指数）和校准（平均绝对预测误差）在 SEER 中进行验证。
死亡率风险随转移性 LN 数量的增加而持续增加；这种影响在四个 LN 之前最为显著（HR 1.17，95%CI 1.12-1.22），超过四个 LN 后则减弱（HR 1.03，95%CI 1.02-1.05）。RPA 生成了一个新的分期系统，通过转移性淋巴结数量预测死亡率，截点为零（参考）、一（HR 1.57，95%CI 1.46-1.69）、二至三（HR 2.03，95%CI 1.88-2.19）、四至七（HR 2.46，95%CI 2.25-2.70）和大于七个（HR 3.83，95%CI 3.38-4.33）阳性 LN。LN 受累部位不是 OM 的显著预测因素。在外部验证中，新的分期系统显示出良好的风险判别能力（校正后的乐观 c 指数为 0.677，95%CI 0.672-0.682）和校准（5 年 OM 的平均绝对预测误差为 0.011）。结果受到使用二次数据进行开发和验证的限制。
转移性 LN 数量比 LN 位置更能准确预测死亡率，可能改善 MIBC 的病理淋巴结分期。
这项回顾性研究发现，在肌层浸润性膀胱癌患者中，转移性淋巴结的数量比转移性淋巴结的位置更能准确预测生存率。这一发现表明需要改变当前的膀胱癌分期系统。
