Predicting Model Based on Evidence-based Pathological Diagnose Criteria for RCC Tumor Thrombus With IVC Wall Invasion

Carcinoma, Renal Cell Clinical Trial

Official title:

Preoperative Imaging Diagnostic Evaluation Model Based on Evidence-based Pathological Diagnose Criteria for Renal Cell Carcinoma Tumor Thrombus With Inferior Vena Cava Wall Invasion

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05589207
• Other study ID #: M2022597
• Status: Recruiting
• Start date: January 1, 2023
• Est. completion date: January 1, 2027

Study information

• Verified date: February 2023
• Source: Peking University Third Hospital
• Contact: Jiyuan Chen, MD
• Phone: +86 18801430995
• Email: 1910301319[@]pku.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to establish a preoperative imaging diagnostic model which highly consistent with the histopathological examinations, as well as a accurate and systematic pathological grading standard of inferior vena cava (IVC) vascular wall invasion in renal cell carcinoma (RCC) with tumor thrombus invading vascular wall.The main questions it aims to answer are:

• To establish a preoperative imaging diagnostic model which highly consistent with the histopathological examinations.

• To determine what impact does different vascular wall layer invasion make on the long-term prognosis in RCC with IVC tumor thrombus;

• To determine which layer invasion according to pathological examination make sense to clinical treatment (can significantly affect prognosis); Participants with IVC vascular wall invasion/ non-invasion are divided into experimental group (invaded group) or control group (non-invaded group) respectively according to pathological examinations, in order to establish a prospective cohort with three-year follow-up. The pathological characteristics of local recurrence and poor prognosis are summarized, and postoperative pathological diagnostic criteria of IVC vascular wall invasion and established. The local recurrence and distant recurrence outcomes are compared between experiment group and control group, in order to analyze the long-term influence of vascular wall invasion. Then the preoperative imaging diagnostic evaluation model will be established.

Description:

Radical nephrectomy and thrombectomy are essential surgical treatments for renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus. IVC vascular wall invasion leads to higher recurrence risk and worse long-term prognosis. The diagnosis and treatment of RCC tumor thrombus with IVC vascular wall invaded are affected by prominent difficulties: First, there is a lack of the preoperative diagnostic evaluation system consisting to the postoperative histopathological examinations, which is regarded as the gold standard of vascular wall invasion, therefore hinders the development of the neoadjuvant therapy strategy and surgery plan; Besides, the pathological diagnostic criteria of IVC vascular wall adhesion or invasion is inconsistent among different centers, an accurate and systematic criteria is needed.

This study consecutively includes patients admitted in Peking University Third Hospital between January 2023 to January 2026, who were diagnosed with primary renal cell carcinoma with IVC tumor thrombus with/without vascular wall invasion, and accepted radical nephrectomy and at least one IVC thrombectomy (including IVC incision only, IVC partial resection, IVC diagonal resection, and IVC segmental resection). The patients with IVC vascular wall invasion/ non-invasion are divided into experimental group (invaded group) or control group (non-invaded group) respectively according to pathological examinations, in order to establish a prospective cohort with three-year follow-up. For the invaded group, micro invasion subgroup and tumor thrombus capsule subgroup analysis are conducted. The pathological characteristics of local recurrence and poor prognosis are summarized, and postoperative pathological diagnostic criteria of IVC vascular wall invasion and established. The local recurrence and distant recurrences outcomes are compared between experiment group and control group, in order to analyze the long-term influence of vascular wall invasion. Then the preoperative imaging diagnostic evaluation model were established: re-diagnose patients in two groups according to the established pathological diagnostic criteria, and divide them into truly-invaded group and truly-non-invaded group. Analyzing the preoperative abdominal ultrasound scan, contrast-enhanced ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI), thus explore the imaging characteristics of vascular wall invasion and establish the preoperative diagnostic model. This study aims at establish a preoperative imaging diagnostic model which highly consistent with the histopathological examinations, as well as a accurate and systematic pathological grading standard of IVC vascular wall invasion, therefore contribute to the development of a more accurate and effective preoperative treatment strategy and surgery plan.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 232
• Est. completion date: January 1, 2027
• Est. primary completion date: January 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults =18 years of age;

• Accepted abdominal ultrasonography, contrast-induced ultrasonography, enhanced CT and MRI before the surgery;

• Diagnosis of primary renal cell carcinoma with tumor thrombus before and during the surgery;

• Received radical nephrectomy and at least one kind of thrombectomy (including IVC incision only, IVC partial resection, IVC diagonal resection, and IVC segmental resection)

• Can tolerate the surgery;

• Eastern Cooperative Oncology Group Performance Status Scale (ECOG-PS) 0~2;

• No previous history of malignant tumor;

• Willing to return for required follow-up visits

Exclusion Criteria:

• Failed to receive standard nephrectomy for any reason;

• Attached other addition operations in the surgery;

• Received neoadjuvant treatment before the surgery;

• Experience any other conditions that may affect the curative effect (e.g. active tuberculosis, autoimmune disease, or oral glucocorticoids treatment);

• Experience serious consequences or death due to anesthesia accident during operation;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Thrombosis
• Tumor Thrombus

Intervention

Diagnostic Test:
• Vascular wall invaded
Inferior vena cava vascular wall is invaded according to pathologic examination on the postoperative tumor thrombus/ vascular wall specimen.

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University Third Hospital

Country where clinical trial is conducted

China, 

References & Publications (23)

Abaza R. Initial series of robotic radical nephrectomy with vena caval tumor thrombectomy. Eur Urol. 2011 Apr;59(4):652-6. doi: 10.1016/j.eururo.2010.08.038. Epub 2010 Sep 16. — View Citation

Adams LC, Ralla B, Bender YY, Bressem K, Hamm B, Busch J, Fuller F, Makowski MR. Renal cell carcinoma with venous extension: prediction of inferior vena cava wall invasion by MRI. Cancer Imaging. 2018 May 3;18(1):17. doi: 10.1186/s40644-018-0150-z. — View Citation

Bocardo Fajardo G, Arellano Ganan R, Gonzalez Lopez L, Fernandez Gonzalez I, Blanco Gonzalez J, Garrido Abad P, Coloma del Peso A, Pereira Sanz I. [Prognostic significance of the microscopic invasion of the renal vein wall in renal cell cancer]. Arch Esp Urol. 2009 Oct;62(8):630-8. doi: 10.4321/s0004-06142009000800004. Spanish. — View Citation

Hirono M, Kobayashi M, Tsushima T, Obara W, Shinohara N, Ito K, Eto M, Takayama T, Fujii Y, Nishikido M, Kimura G, Kishida T, Takahashi M, Miyao N, Naya Y, Abe T, Fujioka T, Ito K, Naito S; Members of the Japanese Society of Renal Cancer. Impacts of clinicopathologic and operative factors on short-term and long-term survival in renal cell carcinoma with venous tumor thrombus extension: a multi-institutional retrospective study in Japan. BMC Cancer. 2013 Oct 2;13:447. doi: 10.1186/1471-2407-13-447. — View Citation

Ingels A, Campi R, Capitanio U, Amparore D, Bertolo R, Carbonara U, Erdem S, Kara O, Klatte T, Kriegmair MC, Marchioni M, Mir MC, Ouzaid I, Pavan N, Pecoraro A, Roussel E, de la Taille A. Complementary roles of surgery and systemic treatment in clear cell renal cell carcinoma. Nat Rev Urol. 2022 Jul;19(7):391-418. doi: 10.1038/s41585-022-00592-3. Epub 2022 May 11. — View Citation

Labbate C, Hatogai K, Werntz R, Stadler WM, Steinberg GD, Eggener S, Sweis RF. Complete response of renal cell carcinoma vena cava tumor thrombus to neoadjuvant immunotherapy. J Immunother Cancer. 2019 Mar 11;7(1):66. doi: 10.1186/s40425-019-0546-8. — View Citation

Lakatos E. Designing complex group sequential survival trials. Stat Med. 2002 Jul 30;21(14):1969-89. doi: 10.1002/sim.1193. — View Citation

Lakatos E. Sample sizes based on the log-rank statistic in complex clinical trials. Biometrics. 1988 Mar;44(1):229-41. Erratum In: Biometrics 1988 Sep;44(3):923. — View Citation

Lang H, Lindner V, Saussine C, Havel D, Faure F, Jacqmin D. Microscopic venous invasion: a prognostic factor in renal cell carcinoma. Eur Urol. 2000 Nov;38(5):600-5. doi: 10.1159/000020338. — View Citation

Lardas M, Stewart F, Scrimgeour D, Hofmann F, Marconi L, Dabestani S, Bex A, Volpe A, Canfield SE, Staehler M, Hora M, Powles T, Merseburger AS, Kuczyk MA, Bensalah K, Mulders PF, Ljungberg B, Lam TB. Systematic Review of Surgical Management of Nonmetastatic Renal Cell Carcinoma with Vena Caval Thrombus. Eur Urol. 2016 Aug;70(2):265-80. doi: 10.1016/j.eururo.2015.11.034. Epub 2015 Dec 23. — View Citation

Li QY, Li N, Huang QB, Luo YK, Wang BJ, Guo AT, Ma X, Zhang X, Tang J. Contrast-enhanced ultrasound in detecting wall invasion and differentiating bland from tumor thrombus during robot-assisted inferior vena cava thrombectomy for renal cell carcinoma. Cancer Imaging. 2019 Dec 2;19(1):79. doi: 10.1186/s40644-019-0265-x. — View Citation

Liu Z, Li L, Hong P, Zhu G, Tang S, Zhao X, Zhang Q, Wang G, He W, Zhang H, Xue H, Cui L, Ge H, Jiang J, Zhang S, Cao F, Yan J, Ma F, Liu C, Ma L, Wang S. A Predictive Model for Tumor Invasion of the Inferior Vena Cava Wall Using Multimodal Imaging in Patients with Renal Cell Carcinoma and Inferior Vena Cava Tumor Thrombus. Biomed Res Int. 2020 Oct 6;2020:9530618. doi: 10.1155/2020/9530618. eCollection 2020. — View Citation

Liu Z, Li Y, Zhao X, Ge L, Zhu G, Hong P, Tang S, Zhang S, Tian X, Wang S, Liu C, Zhang H, Ma L. Renal cell carcinoma with tumor thrombus growing against the direction of venous return: an indicator of complicated surgery and poor prognosis. BMC Surg. 2021 Dec 28;21(1):443. doi: 10.1186/s12893-021-01448-0. — View Citation

Liu Z, Zhang Q, Zhao X, Zhu G, Tang S, Hong P, Ge L, Zhang S, Wang G, Tian X, Zhang H, Liu C, Ma L. Inferior vena cava interruption in renal cell carcinoma with tumor thrombus: surgical strategy and perioperative results. BMC Surg. 2021 Nov 21;21(1):402. doi: 10.1186/s12893-021-01400-2. — View Citation

Liu Z, Zhao X, Zhang HX, Li LW, Tang SY, Wang GL, Zhang SD, Wang SM, Ma LL, Tian XJ. Surgical complexity and prognostic outcome of small volume renal cell carcinoma with high-level venous tumor thrombus and large volume renal cell carcinoma with low-level thrombus. Chin Med J (Engl). 2019 Aug 5;132(15):1780-1787. doi: 10.1097/CM9.0000000000000352. — View Citation

Rodriguez Faba O, Linares E, Tilki D, Capitanio U, Evans CP, Montorsi F, Martinez-Salamanca JI, Libertino J, Gontero P, Palou J. Impact of Microscopic Wall Invasion of the Renal Vein or Inferior Vena Cava on Cancer-specific Survival in Patients with Renal Cell Carcinoma and Tumor Thrombus: A Multi-institutional Analysis from the International Renal Cell Carcinoma-Venous Thrombus Consortium. Eur Urol Focus. 2018 Apr;4(3):435-441. doi: 10.1016/j.euf.2017.01.009. Epub 2017 Feb 9. — View Citation

Shi T, Huang Q, Liu K, Du S, Fan Y, Yang L, Peng C, Shen D, Wang Z, Gao Y, Gu L, Niu S, Ai Q, Li H, Liu F, Li Q, Wang H, Guo A, Fu B, Yang X, Zhang X, Wang D, Wang D, Guo H, Li H, Olivero A, Fam XI, Ma X, Wang B, Zhang X. Robot-assisted Cavectomy Versus Thrombectomy for Level II Inferior Vena Cava Thrombus: Decision-making Scheme and Multi-institutional Analysis. Eur Urol. 2020 Oct;78(4):592-602. doi: 10.1016/j.eururo.2020.03.020. Epub 2020 Apr 15. — View Citation

Sun Z, Cui Y, Xu C, Yu Y, Han C, Liu X, Lin Z, Wang X, Li C, Zhang X, Wang X. Preoperative Prediction of Inferior Vena Cava Wall Invasion of Tumor Thrombus in Renal Cell Carcinoma: Radiomics Models Based on Magnetic Resonance Imaging. Front Oncol. 2022 Jun 6;12:863534. doi: 10.3389/fonc.2022.863534. eCollection 2022. — View Citation

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. — View Citation

Ueki H, Terakawa T, Ueno Y, Sofue K, Horii S, Okamura Y, Bando Y, Hara T, Furukawa J, Harada K, Hinata N, Nakano Y, Murakami T, Fujisawa M. Efficacy of preoperative cine magnetic resonance imaging in evaluation of adhesion of renal cancer thrombus to inferior vena cava wall. J Vasc Surg Venous Lymphat Disord. 2022 Jul;10(4):908-915. doi: 10.1016/j.jvsv.2022.02.016. Epub 2022 Mar 18. — View Citation

Wagner B, Patard JJ, Mejean A, Bensalah K, Verhoest G, Zigeuner R, Ficarra V, Tostain J, Mulders P, Chautard D, Descotes JL, de la Taille A, Salomon L, Prayer-Galetti T, Cindolo L, Valeri A, Meyer N, Jacqmin D, Lang H. Prognostic value of renal vein and inferior vena cava involvement in renal cell carcinoma. Eur Urol. 2009 Feb;55(2):452-9. doi: 10.1016/j.eururo.2008.07.053. Epub 2008 Aug 5. — View Citation

Wang B, Huang Q, Liu K, Fan Y, Peng C, Gu L, Shi T, Zhang P, Chen W, Du S, Niu S, Liu R, Zhao G, Li Q, Xiao C, Wang R, Li S, Wang M, Liu F, Wang H, Li H, Ma X, Zhang X. Robot-assisted Level III-IV Inferior Vena Cava Thrombectomy: Initial Series with Step-by-step Procedures and 1-yr Outcomes. Eur Urol. 2020 Jul;78(1):77-86. doi: 10.1016/j.eururo.2019.04.019. Epub 2019 May 16. — View Citation

Wang BS, Li YZ, Fang YY, Zhang SD, Ma LL. Imaging predictors for assessment of inferior vena cava wall invasion in patients with renal cell carcinoma and inferior vena cava tumor thrombus: a retrospective study. Chin Med J (Engl). 2020 Sep 5;133(17):2078-2083. doi: 10.1097/CM9.0000000000000828. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	The duration from the date of diagnosis to death or last follow-up, with no restriction on the cause of death.	From date of randomization until the date of lost follow-up or date of death from any cause, whichever came first, assessed up to 120 months
Secondary	Clinical manifestation	Clinical manifestation related to the renal carcinoma	From the clinical diagnosis until the surgery, an average of 3 weeks
Secondary	Mayo classification	A universal grading system for renal tumor thrombus.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	Primary tumor diameter	Diameter of the primary tumor.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	Preoperative tumor node metastasis (TNM) stage	TNM stage according to the preoperative imaging.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	IVC residual blood flow	Inferior vena cava residual blood flow according to ultrasonography.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	IVC vascular wall continuity	Inferior vena cava vascular wall continuity according to ultrasonography.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	IVC complete occlusion	Whether the inferior vena cava is completely occluded according to ultrasonography.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	IVC enhanced synchronization with tumor thrombus	Whether the inferior vena cava enhanced synchronization with tumor thrombus according to ultrasonography.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	Tumor thrombus move when breathe	Whether the tumor thrombus move when breathe according to ultrasonography.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	Maximum IVC anterior-posterior (AP) diameter	Maximum inferior vena cava anterior-posterior diameter according to CT/ MRI.	The time once the preoperative imaging was assessed, up to 1 weeks.
Secondary	Maximum coronal IVC diameter	Maximun coronal inferior vena cava diameter according to CT/ MRI.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	Maximum IVC AP diameter at the Rvo	Maximum inferior vena cava anterior-posterior diameter at the renal vein ostium according to CT/ MRI.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	Maximum coronal IVC diameter at the Rvo	Maximun coronal inferior vena cava diameter at the renal vein ostium according to CT/ MRI.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	Bland thrombus	The presence of bland thrombus in inferior vena cava according to CT/ MRI.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	growing against the direction of venous return (GADVR)	The presence of tumor thrombus growing against the direction of venous return according to CT/ MRI.	The time once the preoperative imaging is assessed, up to 1 weeks.
Secondary	Surgery approach	Radical nephrectomy and at least one kind of IVC thrombectomy (including IVC incision only, IVC partial resection, IVC diagonal resection, and IVC segmental resection)	The time once the surgery finished, an average of 10 days.
Secondary	Surgery time	Surgery time	The time once the surgery finished, an average of 10 days.
Secondary	Blood loss	Blood loss during surgery	The time once the surgery finished, an average of 10 days.
Secondary	Histological type	Histological type of the tumor according to pathological examination.	The time once the pathological specimen is assessed, up to 1 weeks.
Secondary	Postoperative TNM stage	TNM stage according to pathological examination.	The time once the pathological specimen is assessed, up to 1 weeks.
Secondary	Invaded vascular wall layer	The deepest Inferior vane cava vascular wall layer the tumor thrombus invaded.	The time once the pathological specimen is assessed, up to 1 weeks.
Secondary	Comorbidity occurence	The comorbidity occurence after surgery.	From the end of surgery until discharge, up to 3 weeks.
Secondary	Recurrence free survival	The duration from the date of diagnosis to death, last follow-up, or cancer recurrence.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 120 months
Secondary	Tumor metastasis	Location and time that the metastasis occurs.	Through study completion, an average of 3 year.