阴茎癌改良临床病理肿瘤分期预后意义分析

背景与目的第8版美国癌症联合会-TNM(American Joint Committee on Cancer tumor–node–metastasis,AJCC-TNM)分期基于的是一些回顾性单中心研究。本研究旨在分析分期的预后价值,并探讨加入脉管癌栓的改良的临床病理肿瘤分期能否提高对T2–3期阴茎癌患者预后预测的准确性。方法根据第8版AJCC-TNM分期对2000年至2015年在中国和巴西2个中心接受治疗的411例患者所组成的训练队列进行分期。采用C-indexes一致性系数进行预测模型的评估,Bbootstrap再抽样法(1000次)进行模型验证。采用来自4个大洲15个中心接受治疗的436例患者的数据进行外部验证。结果根据第8版AJCC-TNM分期的T2和T3期患者有存活率重叠(P=0.587)。脉管癌栓是转移和生存的重要预后因素(均P <0.001)。多因素分析显示,仅脉管癌栓对癌症特异性生存(cancer-specific survival,CSS)有显著影响(风险比=1.587,95%置信区间=1.253–2.011;P=0.001)。发生脉管癌栓的T2和T3期患者的CSS显著短于无脉管癌栓的患者(P <0.001)。因此,我们提出一种改良的临床病理分期,将第8版AJCC-TNM分期的T2和T3期细分为如下2个新类别:T2期肿瘤侵犯尿道海绵体和/或阴茎海绵体和/或尿道且无淋巴管侵犯;T3期肿瘤侵犯尿道海绵体和/或阴茎海绵体和/或尿道并有淋巴管侵犯。加入脉管癌栓的改良的分期显示出预后分层改善,各组间CSS差异显著(均P <0.005),患者预后预测的准确性高于第8版AJCC-TNM分期(C-index,0.739 vs. 0.696)。以上结果在外部验证队列中得到了确认。结论 T2–3期阴茎癌是异质性的,加入脉管癌栓的改良临床病理分期比第8版AJCC-TNM分期对阴茎癌患者的预后预测能力更强。

A modified clinicopathological tumor staging system for survival prediction of patients with penile cancer

Background:The 8th American Joint Committee on Cancer tumor-node-metastasis(AJCC-TNM)staging system is based on a few retrospective single-center studies.We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular emboliza-tion could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer.Methods:A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system.The internal validation was analyzed by bootstrap-corrected C-indexes(resampled 1000 times).Data from 436 patients who were treated at 15 centers over four conti-nents were used for external validation.Results:A survivorship overlap was observed between T2 and T3 patients(P=0.587)classified according to the 8th AJCC-TNM staging system.Lymphovascular embolization was a significant prognostic factor for metastasis and survival(all P<0.001).Based on the multivariate analysis,only lymphovascular embolization showed a significant influ-ence on cancer-specific survival(CSS)(hazard ratio=1.587,95%confidence interval=1.253-2.011;P=0.001).T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascu-lar embolization(P<0.001).Therefore,a modified clinicopathological staging system was proposed,with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows:t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion,and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion.The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories(all P<0.005)and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system(C-index,0.739 vs.0.696).These results were confirmed in the external validation cohort.Conclusions:T2-3 penile cancers are heterogeneous,and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system.