There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.
[1]Nanjing Univ, Jinling Hosp, Affiliated Hosp Med Sch, Dept Urol, Nanjing, Jiangsu, Peoples R China.
[2]Nanjing Med Univ, Jinling Hosp, Jinling Sch Clin Med, Dept Urol, Nanjing, Jiangsu, Peoples R China.
[3]Nanjing Univ, Jinling Hosp, Affiliated Hosp Med Sch, Dept Pathol, Nanjing, Jiangsu, Peoples R China.
[4]Naval Med Univ, Dept Hlth Stat, Shanghai, Peoples R China.
[5]Naval Med Univ, Changhai Hosp, Dept Urol, Shanghai, Peoples R China.
[6]Shandong Univ, Dept Urol, Qilu Hosp, Jinan, Shandong, Peoples R China.
[7]Med Univ Gdansk, Dept Pathomorphol, Gdansk, Poland.
[8]Shanghai Jiao Tong Univ Shanghai, Renji Hosp, Sch Med, Dept Urol, Shanghai, Peoples R China.
[9]Naval Med Univ, Changhai Hosp, Dept Pathol, Shanghai, Peoples R China.
[10]Army Med Univ, Daping Hosp, Dept Urol, Chongqing, Peoples R China.
[11]Shandong Univ, Dept Pathol, Qilu Hosp, Jinan, Shandong, Peoples R China.
[12]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Urol, Wuhan, Hubei, Peoples R China.
[13]Nanjing Univ, Drum Tower Hosp, Clin Sch Med Coll, Dept Pathol, Nanjing, Jiangsu, Peoples R China.
[14]Nanjing Univ, Drum Tower Hosp, Clin Sch Med Coll, Dept Urol, Nanjing, Jiangsu, Peoples R China.
[15]Southeast Univ, Zhongda Hosp, Dept Pathol, Nanjing, Jiangsu, Peoples R China.
[16]Southeast Univ, Zhongda Hosp, Dept Urol, Nanjing, Jiangsu, Peoples R China.
[17]Cent South Univ, Xiangya Hosp, Dept Urol, Changsha, Hunan, Peoples R China.
[18]Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Urol, Hangzhou, Zhejiang, Peoples R China.
[19]Fudan Univ, Huashan Hosp, Dept Urol, Shanghai, Peoples R China.
[20]Qingdao Univ, Affiliated Yantai Yuhuangding Hosp, Dept Urol, Yantai, Shandong, Peoples R China.
[21]Qingdao Univ, Affiliated Yantai Yuhuangding Hosp, Dept Pathol, Yantai, Shandong, Peoples R China.
[22]Dalian Med Univ, Dept Urol, Affiliated Hosp 2, Dalian, Liaoning, Peoples R China.
[23]Anhui Med Univ, Dept Urol, Affiliated Hosp 1, Hefei, Anhui, Peoples R China.
[24]Nanchang Univ, Dept Urol, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China.
[25]Fujian Med Univ, Affiliated Hosp 1, Urol Res Inst, Dept Urol, Fuzhou, Fujian, Peoples R China.
[26]Univ Sci & Technol China, Anhui Prov Hosp, Dept Urol, Hosp 1, Hefei, Anhui, Peoples R China.
[27]Tongji Univ, Shanghai East Hosp, Dept Urol, Shanghai, Peoples R China.
[28]Tongji Univ, Shanghai East Hosp, Dept Pathol, Shanghai, Peoples R China.
[29]Fourth Mil Med Univ, Xijing Hosp, Dept Urol, Xian, Shanxi, Peoples R China.
[30]Fourth Mil Med Univ, Xijing Hosp, Dept Pathol, Xian, Shanxi, Peoples R China.
[31]Nanjing Univ, Jinling Hosp, Affiliated Hosp, Dept Med Oncol,Med Sch, Nanjing, Jiangsu, Peoples R China.
[32]Med Univ Warsaw, Clin Gen Oncol & Funct Urol, Warsaw, Poland.
[33]Nanjing Univ, Jinling Hosp, Affiliated Hosp, Dept Urol,Med Sch, 305 East Zhongshan Rd, Nanjing 210000, Peoples R China.
[34]Naval Med Univ, Changhai Hosp, Dept Urol, 168 Changhai Rd, Shanghai 200433, Peoples R China.
[35]Med Univ Warsaw, Clin Gen Oncol & Funct Urol, PL-02005 Warsaw, Poland.
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