5年以上长期生存肾透明细胞癌伴静脉瘤栓患者的临床病理特征及预后因素

Clinicopathological features and prognostic factors associated with long-term survival （⩾5 years）in patients with clear cell renal cell carcinoma and venous tumor thrombus

摘要

目的：分析接受手术治疗的肾透明细胞癌（clear cell renal cell carcinoma，ccRCC）伴静脉瘤栓（venous tumor thrombus，VTT）长期生存患者的临床病理特征，并探究除肿瘤生物学特征外的潜在影响因素，特别关注个体炎症及营养指标。方法：回顾性分析2014—2019年于北京大学第三医院接受根治性肾切除术联合瘤栓取出术的ccRCC 伴 VTT 患者，将患者分为长期生存组（总生存期 ⩾60 个月）和非长期生存组（总生存期<60个月），比较两组患者的临床特征（年龄、性别、体重指数、Mayo 分级）、病理特征（T 分期、M 分期、组织学分级、肉瘤样变、肾周脂肪侵犯）、围术期指标（手术方式、手术时间、术中失血量、并发症）及实验室指标（血小板计数、白蛋白水平、中性粒细胞计数等）的差异。年龄、体重指数、血小板计数、白蛋白水平的最佳截断值采用 X-tile 软件基于最小 P 值原则确定。在长期生存组内进一步采用 Kaplan-Meier 生存分析及 Log-rank 检验，评估上述指标与远期生存的相关性。结果：397 例 ccRCC 伴 VTT 患者中有 13.9% 实现了长期生存。长期生存组（n=55）和非长期生存组（n=342）在基线血小板计数（P=0.040）、病理 T 分期（P=0.001）、组织学分级（P=0.006）、手术方式（P<0.001），以及是否接受系统治疗（P=0.028）和治疗时机（P=0.003）、治疗方案（P<0.001）方面差异均有统计学意义。在 T 分期方面，长期生存组中 pT3a 期肿瘤的比例显著高于非长期生存组（63.6% vs.42.4％），而 pT4 期肿瘤的比例显著低于非长期生存组（10.9% vs. 33.0%）。长期生存组中低级别肿瘤（G1/G2）的比例也更高（50.9% vs. 31.9%）。在手术方式方面，长期生存组以腹腔镜手术为主（35/55,63.6\%），而非长期生存组的手术方式分布更为均衡，包括开放手术102 例（29.8%）、腹腔镜手术 123 例（36.0%）和机器人手术 117 例（34.2%）。在系统治疗方面，长期生存组有26 例（47.3%）患者接受了系统治疗，且全部为术后辅助治疗（100.0%），而非长期生存组有 215 例（62.9%）患者接受了系统治疗，其中160例（74.4%）接受了术后辅助治疗， 55 例（25.6%）为术前新辅助治疗；长期生存组以靶向单药治疗为主（25/26,96.2\%），而非长期生存组中靶向治疗联合免疫治疗的比例更高（64/215,29.8\%）。长期生存组的中位随访时间为81.7个月，对该组的进一步亚组分析表明，年龄<70岁（P=0.038）、体重指数 ⩾18.5 kg/m²（P=0.032）、血小板计数 $159\times {10}^{9}/\mathrm{L}\sim 273\times {10}^{9}/\mathrm{L}\text{ }(\mathit{P}=0.003)\text{ }$ 及白蛋白 $>41.4\text{ }\mathrm{g}/\mathrm{L}\text{ }(\mathit{P}=0.028)\text{ }$ 与更好的远期生存显著相关，而瘤栓 Mayo 分级与远期生存无显著相关性（P=0.250）。结论：ccRCC 伴 VTT 患者中存在一定比例长期生存者。除肿瘤病理分期和分级外，个体炎症及营养状态可能是影响其长期生存的相关因素，探索与长期生存相关的预后因素有助于进一步优化高危患者风险分层及治疗策略。

Abstract

Objective：To characterize the clinicopathological features of long-term survivors among pa- tients with clear cell renal cell carcinoma（ccRCC）and venous tumor thrombus（VTT）who underwent surgical treatment，and to explore potential prognostic factors beyond tumor-related variables，with parti- cular emphasis on host-related inflammatory and nutritional indicators. Methods：The patients with ccRCC and VTT who underwent radical nephrectomy combined with tumor thrombectomy at Peking Uni- versity Third Hospital between 2014 and 2019 were retrospectively analyzed.The patients were stratified into a long-term survival group（overall survival ⩾60 months）and a non-long-term survival group（overall survival<60 months）.The following parameters were compared between the two groups：clinical cha- racteristics（age，sex，body mass index，Mayo classification），pathological features（T stage，M stage， histological grade，sarcomatoid change，perirenal fat invasion），perioperative parameters（surgical ap- proach，operative time，intraoperative blood loss，complications），and laboratory parameters（platelet count，albumin，neutrophil count，etc.）.Optimal cutoff values for continuous variables，such as age， body mass index（BMI），platelet count and serum albumin level，were determined using X-tile software based on the minimum P-value principle.Subsequently，Kaplan-Meier survival analysis with Log-rank test was performed within the long-term survival cohort to evaluate the association of the above-mentioned factors with long-term survival. Results：Long-term survival was achieved in 13.9% of 397 patients with ccRCC and VTT.Significant differences were observed between the long-term survival group (n=55) and the non-long-term survival group (n=342) in baseline platelet count (P=0.040) ，pathological T stage (P=0.001) ，histological grade (P=0.006) ，surgical approach (P<0.001) ，as well as receipt of systemic therapy (P=0.028) ，treatment timing (P=0.003) ，and treatment regimen (P<0.001). Regarding T stage，the long-term survival group had a significantly higher proportion of pT3a tumors （63.6% vs. 42.4%）and a significantly lower proportion of pT4 tumors（10.9% vs. 33.0%）compared with the non-long-term survival group.The long-term survival group also had a higher proportion of low-grade tumors（G1/G2 ：50.9％vs.31.9％）.Regarding surgical approach，laparoscopic surgery predominated in the long-term survival group (35/55,63.6\%) ，whereas the non-long-term survival group had a more balanced distribution，including open surgery（102/342,29.8\%），laparoscopic surgery（123/342 ， 36.0%），and robotic surgery（117/342,34.2\%）.Regarding systemic therapy，in the long-term sur- vival group， 26 patients（47.3%）received systemic therapy，all of whom（100.0%）received adjuvant therapy.In the non-long-term survival group， 215 patients（62.9％）received systemic therapy，of whom 160(74.4%) received adjuvant therapy and 55(25.6%) received neoadjuvant therapy.Regar- ding treatment regimen，the long-term survival group was predominantly treated with targeted monotherapy （25/26,96.2\%），whereas the non-long-term survival group had a higher proportion of targeted therapy plus immunotherapy combination (64/215,29.8\%).The median follow-up time for the long-term sur- vival group was 81.7 months.Further subgroup analysis of this group showed that age <70 years（P= $0.038),\mathrm{B}\mathrm{M}\mathrm{I}⩾18.5\text{ }\mathrm{k}\mathrm{g}/{\mathrm{m}}^{2}(\mathit{P}=0.032)$ ，platelet count $159\times {10}^{9}/\mathrm{L}-273\times {10}^{9}/\mathrm{L}(\mathit{P}=0.003)$ ，and albumin level $>41.4\text{ }\mathrm{g}/\mathrm{L}(\mathit{P}=0.028)$ were significantly associated with better long-term survival， whereas Mayo classification of tumor thrombus showed no significant association with long-term survival （P=0.250）. Conclusion：A subset of patients with ccRCC and VTT can achieve long-term survival. Beyond pathological tumor stage and grade，patient-related inflammatory and nutritional status may be associated with long-term survival.Exploring prognostic factors related to long-term survival may help further optimize risk stratification and treatment strategies for high-risk patients.

关键词

癌，肾细胞 / 肿瘤浸润 / 静脉血栓形成 / 预后 / 癌症幸存者

Key words

Carcinoma，renal cell / Neoplasm invasiveness / Venous thrombosis / Prognosis / Cancer survivors

参考文献

[1] Tumkur Sitaram R, Landström M, Roos G, et al. Significance of PI3K signalling pathway in clear cell renal cell carcinoma in rela- tion to VHL and HIF status[J]. J Clin Pathol, 2021, 74 (4): 216-222.

[2] Martínez-Salamanca JI, Huang WC, Millán I, et al. Prognostic impact of the 2009 UICC/AJCC TNM staging system for renal cell carcinoma with venous extension[J]. Eur Urol, 2011, 59(1): 120-127.

[3] Blute ML, Leibovich BC, Lohse CM, et al. The Mayo Clinic ex- perience with surgical management,complications and outcome for patients with renal cell carcinoma and venous tumour thrombus[J]. BJU Int, 2004, 94(1):33-41.

[4] Barashi NS, Friedman D, Shiang A, et al. Growth kinetics of ve- nous tumor thrombus in patients with renal cell carcinoma[J]. Urol Oncol, 2024, 42(2):31.e17-31.e23.

[5] Hu B, Yang XR, Xu Y, et al. Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma[J]. Clin Cancer Res, 2014, 20(23): 6212-6222.

[6] Gupta D, LIS CG. Pretreatment serum albumin as a predictor of cancer survival:A systematic review of the epidemiological litera- ture[J]. Nutr J, 2010, 9(1): 69.

[7] Qu N, Shi RL, Luo TX, et al. Prognostic significance and optimal cutoff of age in medullary thyroid cancer[J]. Oncotarget, 2016, 7 (13):15937-15947.

[8] Hirono M, Kobayashi M, Tsushima T, et al. Impacts of clinico- pathologic and operative factors on short-term and long-term survi- val in renal cell carcinoma with venous tumor thrombus extension: A multi-institutional retrospective study in Japan[J]. BMC Cancer, 2013, 13(1): 447.

[9] Chang TW, Cheng WM, Fan YH, et al. Predictive factors for disease recurrence in patients with locally advanced renal cell carcinoma treated with curative surgery[J]. J Chin Med Assoc, 2021, 84(4):405-409.

[10] Baboudjian M, Gondran-Tellier B, Khene Z, et al. Predictive fac- tors of recurrence after surgery in patients with non-metastatic renal cell carcinoma with venous tumor thrombus(UroCCR-56 Study)[J]. World J Urol, 2023, 41(2):295-302.

[11] Masic S, Smaldone MC. Robotic renal surgery for renal cell carci- noma with inferior vena cava thrombus[J]. Transl Androl Urol, 2021, 10(5):2195-2198.

[12] Motzer RJ, Ravaud A, Patard JJ, et al. Adjuvant sunitinib for high-risk renal cell carcinoma after nephrectomy:Subgroup analy- ses and updated overall survival results[J]. Eur Urol, 2018, 73 (1):62-68.

[13] Bedke J, Abu Ghanem Y, Albiges L, et al. Updated European association of urology guidelines on the use of adjuvant immune checkpoint inhibitors and subsequent therapy for renal cell carcino- ma[J]. Eur Urol, 2025, 87 (4):491-496.

[14] Choueiri TK, Tomczak P, Park SH, et al. Adjuvant pembroli- zumab after nephrectomy in renal-cell carcinoma[J]. N Engl J Med, 2021, 385(8):683-694.

[15] Gan J, Zhang X, Guo J. The role of platelets in tumor immune evasion and metastasis:Mechanisms and therapeutic implications[J]. Cancer Cell Int, 2025, 25(1): 258.

[16] Attawettayanon W, Choorit T, Chalieopanyarwong V, et al. Sig- nificance of preoperative hematologic scoring in predicting death among patients with non-metastatic renal cell carcinoma undergoing nephrectomy[J]. Asian J Surg, 2021, 44(7):952-956.

[17] Xu J, Chen P, Cao S, et al. Prognostic value of systemic immune- inflammation index in patients with metastatic renal cell carcinoma treated with systemic therapy:A meta-analysis[J]. Front Oncol, 2024, 14: 1404753.

[18] Takahara K, Ando R, Kanao K, et al. Prognostic stratification of the IMDC intermediate risk group after treatment with first-line molecular-targeted therapy for metastatic renal cell carcinoma[J]. Anticancer Res, 2020, 40(8):4395-4400.

[19] Li S, Zhang W, Yang Z, et al. Systemic inflammation score as a novel prognostic indicator for patients undergoing video-assisted thoracoscopic surgery lobectomy for non-small-cell lung cancer[J]. J Invest Surg, 2021, 34(4):428-440.

[20] Zhang B, Ren W, Yang T, et al. Nomograms based on SIRI for predicting postoperative survival outcomes in patients with non- metastatic clear cell renal cell carcinoma[J]. BMC Surg, 2025, 25(1): 593.

[21] Tamagawa H, Aoyama T, Numata M, et al. Prognostic signifi- cance of the preoperative C-reactive protein-to-albumin ratio in pa- tients with colorectal cancer[J]. J Cancer Res Ther, 2021, 17 (4):1075-1080.

[22] Tsutsumi T, Komura K, Hashimoto T, et al. Distinct effect of body mass index by sex as a prognostic factor in localized renal cell carcinoma treated with nephrectomy-data from a multi-institutional study in Japan-[J]. BMC Cancer, 2021, 21 (1): 201.

[23] Onal B, Simsekoglu MF, Gultekin MH, et al. Clinical outcomes of radical surgery in patients with renal carcinoma and associated venous thrombosis:Single-centre experience in a tertiary care institution[J]. Int J Clin Pract, 2021, 75(4):e13811.

[24] Chen Z, Yang F, Ge L, et al. Outcomes of renal cell carcinoma with associated venous tumor thrombus:Experience from a large cohort and short time span in a single center[J]. BMC Cancer, 2021, 21(1): 766.

基金资助

北京市自然科学基金(7254443)

国家自然科学基金(82504235)