Segmental Renal Vein Tumor Thrombus in Early-stage RCC: Intraoperative Diagnosis, Clinical Significance, and a Systematic Review with Meta-analysis

Segmental Renal Vein Tumor Thrombus in Early-stage RCC: Intraoperative Diagnosis, Clinical Significance, and a Systematic Review with Meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Segmental Renal Vein Tumor Thrombus in Early-stage RCC: Intraoperative Diagnosis, Clinical Significance, and a Systematic Review with Meta-analysis Fabrice Kayitare, Geng Tian, Tang Xiaoshuang, Li Xue, Tie Chong, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8609799/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Objective: To summarize the clinical characteristics of renal cell carcinoma (RCC) patients with segmental vein tumor thrombus detected during partial nephrectomy (PN) and explore its clinical significance, so as to deepen the understanding of the pathogenesis of RCC-associated tumor thrombus. Additionally, we aim to evaluate the prognostic impact of renal vein invasion (RVI) in RCC, particularly its influence on recurrence-free survival (RFS), through a meta-analysis. Methods: A retrospective analysis was conducted on the clinical data of 209 RCC patients (162 cases of T1a stage, 47 cases of T1b stage) who underwent PN in The Second Affiliated Hospital of Xi'an Jiaotong University from September 2023 to July 2025. Among them, 8 patients were intraoperatively identified with extracapsular segmental venous tumor thrombus. in this study, “grossly visible vascular invasion (GVI)” refers to intraoperatively observed, macroscopic segmental venous tumor thrombus (ESVTT/SRVI) detected during nephron-sparing surgery, regardless of preoperative imaging findings. Intraoperative findings, pathological characteristics, and follow-up outcomes were recorded and analyzed. Furthermore, a meta-analysis of 12 studies (141,504 patients) was conducted to assess the impact of RVI on RFS, comparing it to other invasion patterns such as perinephric fat invasion (PFI). Results: Among the 8 cases of extracapsular segmental vein tumor thrombus, 1 was at T1a stage and 7 at T1b stage. Preoperative computed tomography (CT) showed round or roundish solid renal masses with heterogeneous density on non-contrast scans, significant enhancement on contrast-enhanced scans, and markedly weaker enhancement in the renal parenchymal phase compared with normal renal tissue. The average tumor diameter was (4.9±0.2) cm, with clear boundaries and no evidence of vascular invasion. Postoperative pathology confirmed pT3a clear cell carcinoma in all cases, with International Society of Urological Pathology (ISUP) grades ranging from Ⅰ to Ⅳ, and all surgical margins were negative. After surgery, 5 patients received adjuvant immunotherapy. During a median follow-up of 10.3 (3.8-22.8) months, no tumor recurrence or metastasis was observed. The meta-analysis revealed that RVI significantly increased recurrence risk, with a pooled hazard ratio (HR) of 1.76 (95% CI 1.23–2.51) for RVI compared to perinephric fat invasion (PFI), and a pooled HR of 1.85 (95% CI 1.35–2.53) compared to non-RVI patients. Furthermore, multiple patterns of vascular invasion (HR 1.60, 95% CI 1.31–1.94) and sarcomatoid differentiation (HR 2.81, 95% CI 2.12–3.72) were strongly correlated with higher recurrence risks. Conclusion: Renal cell carcinoma (RCC) has a strong tendency for vascular invasion, and this study highlights that even clinically T1 tumors can harbor glossly visible segmental venous tumor thrombus (ESVTT/GVI) detected only at surgery. In this context, ESVTT represents a macroscopic manifestation of segmental renal vein involvement along the continuum from microscopic vascular invasion to main renal vein thrombus, with potential impact on staging, choice of nephron-sparing versus radical surgery, and postoperative surveillance. Complementing these institutional observations, the meta-analysis demonstrates that renal vein invasion (RVI) is consistently associated with significantly worse recurrence-free survival (RFS), supporting the need to recognize and systematically record grossly visible segmental venous invasion as a clinically meaningful risk feature. Together, these findings justify larger multi-center and prospective efforts to standardize intraoperative documentation of GVI/ESVTT, correlate it with imaging and pathology, and ultimately refine risk stratification and treatment strategies for patients with RCC. Early-stage renal cell carcinoma vascular invasion nephron-sparing surgery grossly visible vascular invasion segmental renal vein tumor thrombus renal vein invasion recurrence-free survival pT3a renal cell carcinoma Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction evidence Renal cell carcinoma (RCC) is a type of cancer that behaves in different ways and has a wide range of outcomes[1]. Accurate staging of the tumor is crucial for predicting the disease course and informing treatment decisions[2]. the American Joint Committee on Cancer (AJCC) TNM classification. Currently, pT3a RCC is defined as tumors that have grown beyond the outer layer of the kidney, spreading into adjacent areas, including the renal vein and its branches, the fat surrounding the kidney, and the fat within the kidney[3]. Despite covering a wide range of areas, pT3a is still treated as one uniform category. However, growing suggests that this continuum approach doesn't fully reflect the differences in how these tumors behave.[4],[5], [6]. Vascular invasion, especially when it involves the renal vein, is a sign of a worse prognosis[7]. However, the impact of invasion limited to the segmental renal veins is often overlooked. This is partly because preoperative imaging struggles to detect it, and it's usually not fully reported in pathology reports. Grossly visible vascular invasion (GVI) is often seen during surgery but can be missed on imaging. Its presence may indicate a more aggressive tumor and advanced disease. This mismatch highlights a key gap in the current staging system, which affects the accuracy of our risk assessments and treatment decisions. Renal cell carcinoma (RCC) is characterized by a strong propensity for vascular invasion, and growing evidence indicates that even clinically T1 tumors may harbor occult venous involvement. In this context, the present study focuses on extracapsular segmental venous tumor thrombus (ESVTT), which is conceptualized as a macroscopic, grossly visible form of vascular invasion arising in the segmental renal veins and detected intraoperatively during nephron-sparing surgery. For clarity, ESVTT in this manuscript is explicitly defined as grossly visible segmental venous tumor thrombus (a form of grossly visible vascular invasion, GVI), situated along the continuum between microscopic vascular invasion and overt main renal vein thrombus. Recent clinical series and meta-analytic data suggest that renal vein invasion particularly when segmental branches are involved adversely affects recurrence-free survival (RFS), alongside other adverse features such as larger tumor size, sarcomatoid differentiation, and positive surgical margins in pT3a RCC. However, current TNM staging does not distinguish these patterns or incorporate grossly visible segmental venous invasion as a separate risk category, underscoring the rationale for this study, which aims to characterize ESVTT/GVI in early-stage RCC and to situate it within an evidence-based framework for refined pT3a subclassification and risk stratification. This study investigates the diagnostic characterization and staging implications of grossly visible vascular invasion (GVI), defined as macroscopic extracapsular segmental venous tumor thrombus (ESVTT), and segmental renal vein invasion (SRVI) within the spectrum of pT3a renal cell carcinoma (RCC), using an institutional case series. Complementing this, a comprehensive meta-analysis evaluates the prognostic impact of renal vein invasion patterns on recurrence-free survival, thereby situating GVI/ESVTT and SRVI within an evidence-based from microscopic vascular invasion to main renal vein thrombus. Together, these approaches aim to refine the diagnostic recognition and risk stratification of venous invasion in RCC, support more accurate staging, and ultimately inform individualized surgical and follow-up strategies for patients with this complex disease subgroup. Table 1 Baseline Characteristics Patient ID Gender Age Tumor size/cm Pre-surgery stage Tumor Side Post-surgery pathological diagnosis Post-surgery Stage 1 Male 48 5.0 cT1bN0M0 Left Clear cell carcinoma cT3a 2 Male 67 5.2 cT1bN0M0 Right Clear cell carcinoma cT3a 3 Male 72 5.0 cT1bN0M0 Right Clear cell carcinoma cT3a 4 Male 53 5.1 cT1bN0M0 Left Clear cell carcinoma cT3a 5 Male 74 3.8 cT1aN0M0 Right Mixed-type carcinoma cT3b 6 Male 39 4.6 cT1bN0M0 Left Clear cell carcinoma cT3a 7 Female 66 5.3 cT1bN0M0 Right Clear cell carcinoma cT3a 8 Male 66 5.0 cT1bN0M0 Left Clear cell carcinoma cT3a Figure 1 : Study selection : PRISMA flow diagram illustrating the rigorous multi-database search, de-duplication, and stepwise screening process that yielded 12 eligible studies from 1,684 records initially identified. This transparent selection pathway underscores the comprehensiveness and methodological robustness of the evidence base synthesized in this review. Methodology Study Design This study combines a retrospective case series with a meta-analysis to provide a comprehensive understanding of vascular invasion in renal cell carcinoma (RCC). The case series focuses on an intraoperative finding of extracapsular segmental venous tumor thrombus, while the meta-analysis consolidates data from multiple studies to evaluate the prognostic significance of renal vein invasion (RVI) on recurrence-free survival (RFS) in pT3a RCC. The complementary nature of these two approaches allow us to combine exploratory findings from a small cohort with broader, validated evidence from larger studies, creating a comprehensive assessment of vascular invasion patterns in RCC. Case Series Patient Selection We retrospectively reviewed the clinical data of 209 patients who underwent robot-assisted nephron-sparing surgery (NSS) for RCC at The Second Affiliated Hospital of Xi'an Jiaotong University between September 2023 and May 2025. The inclusion criteria were as follows: Clinical Stage: Patients initially diagnosed with clinical stage T1 (cT1) RCC based on preoperative imaging. Procedure: T1 stage tumor; age > 18 years; no conversion to other surgical methods; postoperative pathology confirmed renal malignant tumor. Exclusion: benign tumor confirmed by pathology; incomplete clinical and surgical data. Among these, 8 patients were intraoperatively identified with extracapsular segmental venous tumor thrombus, a finding that had not been detected in their preoperative imaging. These patients serve as the focus of our case series, providing valuable insights into a form of vascular invasion that has important clinical implications. Ethical Considerations This study was approved by the Institutional Review Board (IRB) of The Second Affiliated Hospital of Xi'an Jiaotong University. All patients provided written informed consent for the use of their clinical data for research purposes. Meta-Analysis Search Strategy We performed a systematic review and meta-analysis to assess the prognostic value of renal vein invasion (RVI) in recurrence-free survival (RFS) in pT3a RCC. The meta-analysis involved studies that reported on vascular invasion in RCC, specifically those examining the impact of RVI and perinephric fat invasion (PFI) on survival outcomes. The following steps were followed: Databases Searched: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science up to May 2025, using keywords related to RCC, vascular invasion, renal vein invasion, and recurrence-free survival. Study Inclusion Criteria: We included studies that: Focused on patients with pT3a RCC. Reported hazard ratios (HR) or other metrics related to recurrence-free survival (RFS). Compared RVI to other forms of invasion, such as perinephric fat invasion (PFI). Exclusion Criteria: Studies were excluded if they focused on non-surgical treatments, non-clear cell RCC, or lacked survival data. Data Extraction and Statistical Analysis Data were independently extracted by two reviewers (FK and TG) and discrepancies were resolved with a senior author (FL). Extracted data included: Study design, sample size, and patient demographics (age, sex, tumor size). Prognostic factors, including vascular invasion patterns (RVI, PFI, and others). Outcome measures, particularly recurrence-free survival (RFS). The meta-analysis used a random-effects model due to high heterogeneity between studies. The Cochrane Q test and I² statistic were employed to assess the heterogeneity of study results. We pooled hazard ratios (HRs) for RFS and conducted sensitivity analysis to check the robustness of the results. PRISMA Guidelines The meta-analysis followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to ensure methodological transparency[8]. The protocol for this meta-analysis was registered with PROSPERO (CRD420251061560). Complementarity of Case Series and Meta-Analysis The case series and meta-analysis are complementary in this study. The case series provides detailed, real-world insights into a clinical phenomenon of extracapsular basal venous tumor thrombus, which has not been well-documented in the literature. These findings offer valuable hypothesis-generating data on an unrecognized pattern of vascular invasion in RCC. By contrast, the meta-analysis synthesizes larger cohort data and offers statistical validation for the prognostic role of vascular invasion, including renal vein invasion, in predicting recurrence risk in RCC. Together, these two components contribute to a comprehensive understanding of the clinical significance of vascular invasion in RCC. The case series helps introduce new findings, while the meta-analysis places these findings within the broader context of existing evidence, validating the association of vascular invasion with recurrence-free survival and providing robust statistical backing for its prognostic value. Quality Assessment Study quality was assessed using the Covidence framework, covering key domains such as participation, prognostic factors, and statistical reporting. Most studies had low bias, with low risk in prognostic factors and confounding, indicating robust evidence. Data Synthesis and Statistical Analysis Pooled hazard ratios (HRs) for recurrence-free survival (RFS) were calculated using inverse variance methods. Heterogeneity was assessed with the Cochrane Q test and I² statistic, applying fixed or random-effects models. Sensitivity analyses, risk differences (Mantel-Haenszel), and publication bias (Egger’s test) were also evaluated. All analyses used RevMan 5.4 (p < 0.05). Results are shown in forest plots (Fig. 4 ). Results i. Case Series Our case series identifies extracapsular segmental vein tumor thrombus (ESVTT) a grossly visible vascular invasion (GVI) as an early, under-recognized marker of vascular invasion, impacting prognosis and surgical decisions. This is supported by our meta-analysis on renal vein invasion (RVI) in early-stage clear cell RCC (ccRCC). The tumors (mean size 5.13 cm, Table 1) were incidentally diagnosed with preoperative CT showing typical ccRCC patterns but no signs of advanced features like calcification, necrosis, or vascular invasion (Fig. 2). During robot-assisted NSS, tumor thrombus was confirmed (Fig. 3). Histopathology showed ISUP grade III ccRCC with negative margins. Five patients (56%) received adjuvant toripalimab, with long-term outcomes still under observation. These findings highlight extracapsular segmental vein tumor thrombus as an early marker of vascular invasion and a risk factor for recurrence after NSS, offering insights into early ccRCC progression and management when combined with meta-analysis evidence on RVI. iiMeta-Analysis The meta-analysis included 12 studies[9],[10],[11, 12],[13],[7],[14],[15],[16],[17],[18],[19] with 141,504 patients, conducted following PRISMA guidelines[8]. The study selection process was carried out using Covidence for screening, extraction, and risk of bias assessment. Statistical analysis was performed using RevMan 5.4 with a fixed-effect model. The search covered studies from inception to May 2025. The baseline characteristics of the comparative studies are presented in (Supplementary Table 2). The following significant findings emerged from the analysis (Fig. 4): RVI Alone vs. PFI Alone: The pooled hazard ratio (HR) was 1.76 (95% CI: 1.23, 2.51), indicating that RVI alone is significantly associated with increased recurrence risk compared to PFI alone. (Fig. 4A). RVI vs. Non-RVI: The pooled HR was 1.85 (95% CI: 1.35, 2.53), suggesting that patients with RVI face a significantly higher recurrence risk than those without RVI. (Fig. 4B) RVI vs. RVI + PFI: The pooled HR was 1.34 (95% CI: 1.06, 1.70), highlighting the increased recurrence risk for patients with RVI + PFI compared to RVI alone. (Fig. 4C) Single Pattern vs. Multiple Patterns: The pooled HR was 1.60 (95% CI: 1.31, 1.94), showing that patients with multiple patterns of vascular invasion have a significantly higher recurrence risk. (Fig. 4D) Sarcomatoid vs Non-Sarcomatoid: The pooled HR was 2.81 (95% CI: 2.12, 3.72), emphasizing the much higher recurrence risk in patients with sarcomatoid features. (Fig. 4E) Fuhrman Grade III or IV vs. I or II: The pooled HR was 2.01 (95% CI: 1.63, 2.48), indicating a significantly higher recurrence risk in patients with high Fuhrman grades. (Fig. 4F) Tumor Necrosis vs No Tumor Necrosis: The pooled HR was 1.73 (95% CI: 1.35, 2.21), highlighting the poor prognosis associated with tumor necrosis. (Fig. 4G) Tumor Size (≤ 7 cm vs > 7 cm): The pooled HR was 1.13 (95% CI: 1.10, 1.17), indicating a significant increase in recurrence risk for tumors > 7 cm. (Fig. 4H) Positive Surgical Margins (PSM vs Non-PSM): The pooled HR was 3.56 (95% CI: 1.85, 6.85), emphasizing the critical role of achieving negative surgical margins in preventing recurrence. (Fig. 4I) This analysis links RVI, sarcomatoid histology, high Fuhrman grade, tumor necrosis, and larger tumor size to poor RCC prognosis. Positive surgical margins (PSM) increase recurrence risk, highlighting the need for precise surgery. The meta-analysis confirms RVI as a strong recurrence predictor, while GVI may signal early vascular invasion and potential recurrence. Discussion Renal cell carcinoma (RCC) presents a diverse spectrum of biological behavior, particularly in tumors classified as pathologic T3a (pT3a). While the current AJCC and UICC guidelines recognize vascular invasion as a key prognostic factor, they do not differentiate between various forms of renal vein invasion (RVI), including segmental renal vein invasion (SRVI), which is often missed preoperatively. In this study, we found that extracapsular segmental vein tumor thrombus which was glossily visible specifically SRVI, highlighting its potential as a crucial intraoperative marker. Our meta-analysis further confirmed that RVI is associated with a significantly increased risk of recurrence, with a pooled hazard ratio (HR) of 1.76 compared to perinephric fat invasion (PFI). Although preoperative imaging, particularly contrast-enhanced CT, remains the gold standard for RCC staging, its ability to detect vascular invasion is limited. Our study identified SRVI intraoperatively in patients whose preoperative scans showed no vascular involvement. This discrepancy underscores a critical gap in current RCC staging, as overlooked vascular involvement may lead to misclassification, affecting surgical planning and subsequent treatment strategies. Surgeons and oncologists should consider intraoperative SRVI as an important indicator of tumor aggressiveness and incorporate this finding into their decision-making process for follow-up and adjuvant therapy. This case series and meta-analysis provide further clarity on the prognostic significance of tumor invasion patterns in pT3a renal cell carcinoma (RCC). This subgroup has long been recognized for its biological heterogeneity[20]. While the AJCC 8th and UICC 8th editions have eliminated the term "grossly" to describe renal vein invasion (RVI) in the pT3a classification[21], this revision, though methodologically precise, does not diminish the clinical importance of grossly visible vascular invasion (GVI). The updated guidelines acknowledge that microscopic vascular invasion (MVI) and its detection are sufficient for pT3a categorization[22]. However, glossly visible segmental renal vein invasion remains a pivotal finding that straddles the continuum from microscopic vascular invasion (MVI) to renal vein invasion (RVI) (Fig. 2 ). Its presence, often evident intraoperatively despite being missed preoperatively, offers critical insights into disease aggressiveness, potentially identifying more advanced stages of RCC that might otherwise be underappreciated (Fig. 2 ). In our case series, extracapsular segmental vein invasion revealed invasions missed on imaging, serving as a key predictor of tumor aggressiveness. Patients with this finding had poorer outcomes, highlighting its role in staging, surgical planning, and postoperative surveillance. While the current TNM8 classification no longer explicitly requires Glossly Visible Invasion for T3a categorization, our findings suggest that it should not be dismissed. Rather, Glossly visible segmental vein invasion offers an invaluable clinical tool for refining the assessment of RCC's biological behavior and guiding therapeutic interventions. By recognizing glossly visible segmental vein tumor invasion, clinicians can gain a more nuanced understanding of tumor progression, particularly in cases where microscopic invasion could be overlooked, ultimately enhancing the precision of treatment planning and improving patient outcomes. This discrepancy in the current staging paradigm, where segmental vein invasion may be missed preoperatively but identified intraoperatively, underscores the potential for misclassification and suboptimal surgical planning. Clinically, undetected vascular invasion may lead to under-classification of the disease, denying patients the opportunity for more aggressive surveillance or adjuvant therapy. Additionally, the decision between nephron-sparing surgery (NSS) and radical nephrectomy often depends heavily on preoperative imaging; therefore, missed segmental venous involvement could jeopardize oncologic safety by influencing surgical decisions. Ma et al[23]found that while CT demonstrates an acceptable diagnostic performance for both PFI and RSFI, the sensitivity remains moderate (0.69 for PFI and 0.81 for RSFI) with specificity at 82% for PFI and 79% for RSFI. These results highlight the diagnostic challenges, particularly given the low positive sample rate in the studies assessed. Further, the positive likelihood ratio (PLR) for PFI and RSFI was found to be low (3.85 for PFI and 3.91 for RSFI), which limits the utility of CT for robust diagnostic decisions. The moderate to low sensitivity of CT in detecting these invasions implies that undetected vascular involvement may lead to staging misclassification, ultimately affecting treatment decisions such as nephron-sparing surgery (NSS) versus radical nephrectomy. Recent innovations in imaging, particularly machine learning-based models, are showing promise in addressing these diagnostic gaps. For instance, Xu et al[24]. demonstrated that a multiparametric CT radiomics model could predict MVI preoperatively with high accuracy, integrating radiomic features and clinical variables. Similarly, Yang et al[25] developed a deep learning model that accurately identified venous tumor thrombus using venous-phase CT, enhancing the potential for more accurate preoperative assessments. In a study by Boulenger de Hauteclocque et al[26] The study highlighted the potential of machine-learning technology in predicting upstaging to pT3a, moreover In a study conducted by Mei et al[27], a predictive model was constructed to assess the risk of upstaging from cT1 to pT3 renal cell carcinoma (RCC) based on perioperative characteristics. These innovations underscore the need for more sophisticated imaging techniques to improve the detection of vascular invasion and inform treatment planning. Although CT remains essential for RCC staging, these emerging technologies may help bridge the gap left by traditional imaging, particularly in detecting subtle forms of vascular invasion that may be missed by conventional methods. Our meta-analysis reinforces the idea that not all T3a invasion patterns in renal cell carcinoma (RCC) carry the same prognostic weight. Studies, including a large analysis of the SEER registry, [5] show that renal vein invasion (RVI) carries the worst prognosis, followed by renal sinus fat invasion (RSFI), with perinephric fat invasion (PFI) associated with more favorable outcomes. These findings emphasize the need to reconsider the broad classification of pT3a RCC, as tumors with multiple invasion patterns often exhibit worse survival outcomes compared to those with a single invasion type. Current pT3a staging may not adequately reflect the heterogeneity in tumor aggressiveness, potentially leading to staging misclassification and influencing treatment decisions. This underscores the importance of refining the staging criteria to better differentiate between distinct invasion patterns, ultimately improving risk stratification and guiding individualized treatment strategies, including neoadjuvant and adjuvant therapies, to reduce recurrence and metastasis risks. Our institutional cases also raise important questions about the role of NSS in selected T3a cases. While NSS has historically been contraindicated in T3a tumors due to concerns over oncologic adequacy, emerging evidence suggests that it may be appropriate in non-metastatic patients with limited invasion and strong nephron-sparing indications (e.g., solitary kidney or pre-existing renal insufficiency)[28],[16],[29],[30]. A key limitation of this study is the small sample size and relatively short follow-up in the institutional case series, which restrict the ability to draw firm conclusions about long-term oncologic outcomes and recurrence patterns in patients with extracapsular segmental venous tumor thrombus (ESVTT) with grossly visible vascular invasion (GVI) detected during nephron-sparing surgery. In addition, assessment of GVI is inherently subjective and operator-dependent, as it relies on intraoperative visual and tactile impressions rather than standardized criteria, which may introduce variability and potential misclassification. These constraints underscore the need for future multi-center registries that systematically capture intraoperative vascular findings, prospective studies correlating preoperative imaging and emerging radiomics or AI-based markers with intraoperative and pathological evidence of vascular invasion, and the development of standardized intraoperative documentation protocols (including predefined photographic or video recording of suspected GVI) to improve reproducibility and external validity. Conclusion This study emphasizes the need for better subclassification and preoperative detection of vascular invasion in pT3a RCC. Advanced imaging holds promise, but histopathology is key. Findings support personalized surveillance and selective NSS in non-metastatic pT3a RCC, with future studies needed to refine imaging and molecular markers. Declarations Ethics approval and consent to participate This study was approved by the Institutional Review Board of The Second Affiliated Hospital of Xi'an Jiaotong University. Written informed consent was obtained from all patients for the use of their clinical data for research purposes. Consent for publication Written informed consent for publication was obtained from all participants. Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due to patient privacy considerations but are available from the corresponding author upon reasonable request. Requests for data or study-related inquiries should be directed to De laifu. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Authors’ contributions FK conceived and designed the study. FK, GT, and TX collected the data. FK and GT performed the data analysis. FK drafted the manuscript. LX, TC, and DF critically revised the manuscript. All authors read and approved the final manuscript. References Cairns, P., Renal cell carcinoma. Cancer Biomark, 2010. 9 (1-6): p. 461-73. Powles, T., et al., Renal cell carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol, 2024. 35 (8): p. 692-706. Amin, M.B., et al., The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin, 2017. 67 (2): p. 93-99. DiBianco, J.M., P.T. Gomella, and M.W. Ball, Pathologic T3a renal cell carcinoma: a classification in need of further refinement. 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Supplementary Files Qualityassesssment.pdf Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 23 Mar, 2026 Reviews received at journal 19 Mar, 2026 Reviewers agreed at journal 13 Mar, 2026 Reviewers agreed at journal 12 Mar, 2026 Reviews received at journal 11 Mar, 2026 Reviewers agreed at journal 11 Mar, 2026 Reviewers invited by journal 11 Mar, 2026 Editor assigned by journal 05 Feb, 2026 Editor invited by journal 27 Jan, 2026 Submission checks completed at journal 23 Jan, 2026 First submitted to journal 23 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8609799","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":605355428,"identity":"a48fa715-8cd4-41c5-aafe-ea6ef6ba0526","order_by":0,"name":"Fabrice Kayitare","email":"","orcid":"","institution":"Second Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Fabrice","middleName":"","lastName":"Kayitare","suffix":""},{"id":605355429,"identity":"053c6db3-0fb1-4599-80fa-4f154c56931d","order_by":1,"name":"Geng Tian","email":"","orcid":"","institution":"Second Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Geng","middleName":"","lastName":"Tian","suffix":""},{"id":605355430,"identity":"fc8560fa-a2a5-4378-b8ee-e1fb675c3a62","order_by":2,"name":"Tang Xiaoshuang","email":"","orcid":"","institution":"Second Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Tang","middleName":"","lastName":"Xiaoshuang","suffix":""},{"id":605355431,"identity":"b42a5d60-ccfe-45a6-a999-bd0069e96a73","order_by":3,"name":"Li Xue","email":"","orcid":"","institution":"Second Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Xue","suffix":""},{"id":605355432,"identity":"f7d4a278-f147-4cb3-b5f4-1127a2733be3","order_by":4,"name":"Tie Chong","email":"","orcid":"","institution":"Second Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Tie","middleName":"","lastName":"Chong","suffix":""},{"id":605355433,"identity":"647e8656-c5bb-4cf8-9946-8c6b29e0dfd1","order_by":5,"name":"Delai Fu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuElEQVRIiWNgGAWjYBAC9gYGA4YHDBJybOzNB4jTwnMAqCWBQcKYj+dYAklaGBLnSeQoEKlFInnjg4Qai/Q2hhwGhh8V24jRklZskHBMIreN4ewBxp4ztwlrsZfIMZNIYANqYexLYGZsI0ILj0SO+Y+EfxLpbMw8BkRrMWNIbANaxEa0Fp5nxRKJfRKGbTxsCQeJ8gsPe/LGDx++1cnLz3988MGPCiK0oIADJKofBaNgFIyCUYALAADtsDZQJwGnvQAAAABJRU5ErkJggg==","orcid":"","institution":"Second Affiliated Hospital of Xi'an Jiaotong University","correspondingAuthor":true,"prefix":"","firstName":"Delai","middleName":"","lastName":"Fu","suffix":""}],"badges":[],"createdAt":"2026-01-15 11:08:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8609799/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8609799/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104782821,"identity":"df712fe8-d4a5-446a-b8d9-73e8f265abb7","added_by":"auto","created_at":"2026-03-17 07:57:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":122066,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy selection\u003c/strong\u003e: PRISMA flow diagram illustrating the rigorous multi-database search, de-duplication, and stepwise screening process that yielded 12 eligible studies from 1,684 records initially identified. This transparent selection pathway underscores the comprehensiveness and methodological robustness of the evidence base synthesized in this review.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8609799/v1/4e0945c3e7c477453f411b7c.png"},{"id":104782284,"identity":"dead8981-da4d-4e9a-bec9-29b7d6ec6712","added_by":"auto","created_at":"2026-03-17 07:57:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":868367,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 1. \u003c/strong\u003eIntraoperative images showing visible vascular system masses during surgery. The orange arrows indicate the masses, and the blue arrows point to the transected vascular ends\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"01.png","url":"https://assets-eu.researchsquare.com/files/rs-8609799/v1/37db13f304853fdcaeed5898.png"},{"id":104782459,"identity":"91a57717-517c-42f7-8649-cd2c5b4e9df2","added_by":"auto","created_at":"2026-03-17 07:57:21","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":505088,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 2. \u003c/strong\u003ePreoperative contrast-enhanced CT showing renal masses with typical irregular enhancement patterns of ccRCC, without evidence of vascular invasion, necrosis, or perirenal fat infiltration.\u003c/p\u003e","description":"","filename":"02.png","url":"https://assets-eu.researchsquare.com/files/rs-8609799/v1/12fd17d9b54032d8a5180ab0.png"},{"id":104689585,"identity":"6f26117c-45a0-4f2a-a202-d5d3baeba757","added_by":"auto","created_at":"2026-03-16 06:00:58","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":874358,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 3. \u003c/strong\u003ePostoperative gross pathology specimens showing tumor thrombus protruding externally from the tumor base (yellow arrows).\u003c/p\u003e","description":"","filename":"03.png","url":"https://assets-eu.researchsquare.com/files/rs-8609799/v1/d908afff6a13951829f7846b.png"},{"id":104689583,"identity":"8ed708c3-41b6-48d7-9618-e87dfd046c5c","added_by":"auto","created_at":"2026-03-16 06:00:58","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1087662,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 4: The forest plots display the hazard ratios (HR) A-I\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8609799/v1/ed3ab3eae34432179a67969e.png"},{"id":104784774,"identity":"8005e0f9-7664-4c80-ad1a-e855774374c7","added_by":"auto","created_at":"2026-03-17 08:08:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4665296,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8609799/v1/7d4b9e73-4c57-4d32-9efa-42a92366024a.pdf"},{"id":104689586,"identity":"dbc6d6a3-2208-441c-b33a-03cb1f5e650b","added_by":"auto","created_at":"2026-03-16 06:00:58","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":211898,"visible":true,"origin":"","legend":"","description":"","filename":"Qualityassesssment.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8609799/v1/25a46dafad866872aa490348.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Segmental Renal Vein Tumor Thrombus in Early-stage RCC: Intraoperative Diagnosis, Clinical Significance, and a Systematic Review with Meta-analysis","fulltext":[{"header":" Introduction","content":"\u003cp\u003eevidence Renal cell carcinoma (RCC) is a type of cancer that behaves in different ways and has a wide range of outcomes[1]. Accurate staging of the tumor is crucial for predicting the disease course and informing treatment decisions[2]. the American Joint Committee on Cancer (AJCC) TNM classification. Currently, pT3a RCC is defined as tumors that have grown beyond the outer layer of the kidney, spreading into adjacent areas, including the renal vein and its branches, the fat surrounding the kidney, and the fat within the kidney[3]. Despite covering a wide range of areas, pT3a is still treated as one uniform category. However, growing suggests that this\u003c/p\u003e \u003cp\u003econtinuum approach doesn't fully reflect the differences in how these tumors behave.[4],[5], [6].\u003c/p\u003e \u003cp\u003eVascular invasion, especially when it involves the renal vein, is a sign of a worse prognosis[7]. However, the impact of invasion limited to the segmental renal veins is often overlooked. This is partly because preoperative imaging struggles to detect it, and it's usually not fully reported in pathology reports. Grossly visible vascular invasion (GVI) is often seen during surgery but can be missed on imaging. Its presence may indicate a more aggressive tumor and advanced disease. This mismatch highlights a key gap in the current staging system, which affects the accuracy of our risk assessments and treatment decisions.\u003c/p\u003e \u003cp\u003eRenal cell carcinoma (RCC) is characterized by a strong propensity for vascular invasion, and growing evidence indicates that even clinically T1 tumors may harbor occult venous involvement. In this context, the present study focuses on extracapsular segmental venous tumor thrombus (ESVTT), which is conceptualized as a macroscopic, grossly visible form of vascular invasion arising in the segmental renal veins and detected intraoperatively during nephron-sparing surgery. For clarity, ESVTT in this manuscript is explicitly defined as grossly visible segmental venous tumor thrombus (a form of grossly visible vascular invasion, GVI), situated along the continuum between microscopic vascular invasion and overt main renal vein thrombus. Recent clinical series and meta-analytic data suggest that renal vein invasion particularly when segmental branches are involved adversely affects recurrence-free survival (RFS), alongside other adverse features such as larger tumor size, sarcomatoid differentiation, and positive surgical margins in pT3a RCC. However, current TNM staging does not distinguish these patterns or incorporate grossly visible segmental venous invasion as a separate risk category, underscoring the rationale for this study, which aims to characterize ESVTT/GVI in early-stage RCC and to situate it within an evidence-based framework for refined pT3a subclassification and risk stratification.\u003c/p\u003e \u003cp\u003eThis study investigates the diagnostic characterization and staging implications of grossly visible vascular invasion (GVI), defined as macroscopic extracapsular segmental venous tumor thrombus (ESVTT), and segmental renal vein invasion (SRVI) within the spectrum of pT3a renal cell carcinoma (RCC), using an institutional case series. Complementing this, a comprehensive meta-analysis evaluates the prognostic impact of renal vein invasion patterns on recurrence-free survival, thereby situating GVI/ESVTT and SRVI within an evidence-based from microscopic vascular invasion to main renal vein thrombus. Together, these approaches aim to refine the diagnostic recognition and risk stratification of venous invasion in RCC, support more accurate staging, and ultimately inform individualized surgical and follow-up strategies for patients with this complex disease subgroup.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient ID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTumor size/cm\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePre-surgery stage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTumor Side\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePost-surgery pathological diagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePost-surgery Stage\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ecT1bN0M0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ecT3a\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ecT1bN0M0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ecT3a\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ecT1bN0M0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ecT3a\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ecT1bN0M0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ecT3a\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ecT1aN0M0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMixed-type carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ecT3b\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ecT1bN0M0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ecT3a\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ecT1bN0M0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ecT3a\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ecT1bN0M0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eClear cell carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ecT3a\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e: \u003cb\u003eStudy selection\u003c/b\u003e: PRISMA flow diagram illustrating the rigorous multi-database search, de-duplication, and stepwise screening process that yielded 12 eligible studies from 1,684 records initially identified. This transparent selection pathway underscores the comprehensiveness and methodological robustness of the evidence base synthesized in this review.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003e \u003cb\u003eStudy Design\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThis study combines a retrospective case series with a meta-analysis to provide a comprehensive understanding of vascular invasion in renal cell carcinoma (RCC). The case series focuses on an intraoperative finding of extracapsular segmental venous tumor thrombus, while the meta-analysis consolidates data from multiple studies to evaluate the prognostic significance of renal vein invasion (RVI) on recurrence-free survival (RFS) in pT3a RCC. The complementary nature of these two approaches allow us to combine exploratory findings from a small cohort with broader, validated evidence from larger studies, creating a comprehensive assessment of vascular invasion patterns in RCC.\u003c/p\u003e \u003cp\u003e \u003cb\u003eCase Series\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003ePatient Selection\u003c/b\u003e \u003c/p\u003e \u003cp\u003e We retrospectively reviewed the clinical data of 209 patients who underwent robot-assisted nephron-sparing surgery (NSS) for RCC at The Second Affiliated Hospital of Xi'an Jiaotong University between September 2023 and May 2025. The inclusion criteria were as follows:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eClinical Stage: Patients initially diagnosed with clinical stage T1 (cT1) RCC based on preoperative imaging.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eProcedure: T1 stage tumor; age\u0026thinsp;\u0026gt;\u0026thinsp;18 years; no conversion to other surgical methods; postoperative pathology confirmed renal malignant tumor.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eExclusion: benign tumor confirmed by pathology; incomplete clinical and surgical data.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eAmong these, 8 patients were intraoperatively identified with extracapsular segmental venous tumor thrombus, a finding that had not been detected in their preoperative imaging. These patients serve as the focus of our case series, providing valuable insights into a form of vascular invasion that has important clinical implications.\u003c/p\u003e \u003cp\u003eEthical Considerations\u003c/p\u003e \u003cp\u003e This study was approved by the Institutional Review Board (IRB) of The Second Affiliated Hospital of Xi'an Jiaotong University. All patients provided written informed consent for the use of their clinical data for research purposes.\u003c/p\u003e \u003cp\u003eMeta-Analysis\u003c/p\u003e \u003cp\u003e \u003cb\u003eSearch Strategy\u003c/b\u003e \u003c/p\u003e \u003cp\u003e We performed a systematic review and meta-analysis to assess the prognostic value of renal vein invasion (RVI) in recurrence-free survival (RFS) in pT3a RCC. The meta-analysis involved studies that reported on vascular invasion in RCC, specifically those examining the impact of RVI and perinephric fat invasion (PFI) on survival outcomes. The following steps were followed:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eDatabases Searched: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science up to May 2025, using keywords related to RCC, vascular invasion, renal vein invasion, and recurrence-free survival.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eStudy Inclusion Criteria: We included studies that:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eFocused on patients with pT3a RCC.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eReported hazard ratios (HR) or other metrics related to recurrence-free survival (RFS).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eCompared RVI to other forms of invasion, such as perinephric fat invasion (PFI).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eExclusion Criteria: Studies were excluded if they focused on non-surgical treatments, non-clear cell RCC, or lacked survival data.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eData Extraction and Statistical Analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eData were independently extracted by two reviewers (FK and TG) and discrepancies were resolved with a senior author (FL). Extracted data included:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eStudy design, sample size, and patient demographics (age, sex, tumor size).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePrognostic factors, including vascular invasion patterns (RVI, PFI, and others).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eOutcome measures, particularly recurrence-free survival (RFS).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eThe meta-analysis used a random-effects model due to high heterogeneity between studies. The Cochrane Q test and I\u0026sup2; statistic were employed to assess the heterogeneity of study results. We pooled hazard ratios (HRs) for RFS and conducted sensitivity analysis to check the robustness of the results.\u003c/p\u003e \u003cp\u003e\u003cb\u003e PRISMA Guidelines\u003c/b\u003e\u003c/p\u003e \u003cp\u003e The meta-analysis followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to ensure methodological transparency[8]. The protocol for this meta-analysis was registered with PROSPERO (CRD420251061560).\u003c/p\u003e \u003cp\u003e \u003cb\u003eComplementarity of Case Series and Meta-Analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe case series and meta-analysis are complementary in this study. The case series provides detailed, real-world insights into a clinical phenomenon of extracapsular basal venous tumor thrombus, which has not been well-documented in the literature. These findings offer valuable hypothesis-generating data on an unrecognized pattern of vascular invasion in RCC. By contrast, the meta-analysis synthesizes larger cohort data and offers statistical validation for the prognostic role of vascular invasion, including renal vein invasion, in predicting recurrence risk in RCC.\u003c/p\u003e \u003cp\u003eTogether, these two components contribute to a comprehensive understanding of the clinical significance of vascular invasion in RCC. The case series helps introduce new findings, while the meta-analysis places these findings within the broader context of existing evidence, validating the association of vascular invasion with recurrence-free survival and providing robust statistical backing for its prognostic value.\u003c/p\u003e \u003cp\u003e \u003cb\u003eQuality Assessment\u003c/b\u003e \u003c/p\u003e \u003cp\u003eStudy quality was assessed using the Covidence framework, covering key domains such as participation, prognostic factors, and statistical reporting. Most studies had low bias, with low risk in prognostic factors and confounding, indicating robust evidence.\u003c/p\u003e \u003cp\u003e \u003cb\u003eData Synthesis and Statistical Analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003ePooled hazard ratios (HRs) for recurrence-free survival (RFS) were calculated using inverse variance methods. Heterogeneity was assessed with the Cochrane Q test and I\u0026sup2; statistic, applying fixed or random-effects models. Sensitivity analyses, risk differences (Mantel-Haenszel), and publication bias (Egger\u0026rsquo;s test) were also evaluated. All analyses used RevMan 5.4 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Results are shown in forest plots (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ei. Case Series\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur case series identifies extracapsular segmental vein tumor thrombus (ESVTT) a grossly visible vascular invasion (GVI) as an early, under-recognized marker of vascular invasion, impacting prognosis and surgical decisions. This is supported by our meta-analysis on renal vein invasion (RVI) in early-stage clear cell RCC (ccRCC). The tumors (mean size 5.13 cm, Table\u0026nbsp;1) were incidentally diagnosed with preoperative CT showing typical ccRCC patterns but no signs of advanced features like calcification, necrosis, or vascular invasion (Fig.\u0026nbsp;2).\u003c/p\u003e\n\u003cp\u003eDuring robot-assisted NSS, tumor thrombus was confirmed (Fig.\u0026nbsp;3). Histopathology showed ISUP grade III ccRCC with negative margins. Five patients (56%) received adjuvant toripalimab, with long-term outcomes still under observation.\u003c/p\u003e\n\u003cp\u003eThese findings highlight extracapsular segmental vein tumor thrombus as an early marker of vascular invasion and a risk factor for recurrence after NSS, offering insights into early ccRCC progression and management when combined with meta-analysis evidence on RVI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eiiMeta-Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe meta-analysis included 12 studies[9],[10],[11, 12],[13],[7],[14],[15],[16],[17],[18],[19] with 141,504 patients, conducted following PRISMA guidelines[8]. The study selection process was carried out using Covidence for screening, extraction, and risk of bias assessment. Statistical analysis was performed using RevMan 5.4 with a fixed-effect model. The search covered studies from inception to May 2025. The baseline characteristics of the comparative studies are presented in (Supplementary Table\u0026nbsp;2). The following significant findings emerged from the analysis (Fig.\u0026nbsp;4):\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\n \u003cp\u003eRVI Alone vs. PFI Alone: The pooled hazard ratio (HR) was 1.76 (95% CI: 1.23, 2.51), indicating that RVI alone is significantly associated with increased recurrence risk compared to PFI alone. (Fig.\u0026nbsp;4A).\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eRVI vs. Non-RVI: The pooled HR was 1.85 (95% CI: 1.35, 2.53), suggesting that patients with RVI face a significantly higher recurrence risk than those without RVI. (Fig.\u0026nbsp;4B)\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eRVI vs. RVI\u0026thinsp;+\u0026thinsp;PFI: The pooled HR was 1.34 (95% CI: 1.06, 1.70), highlighting the increased recurrence risk for patients with RVI\u0026thinsp;+\u0026thinsp;PFI compared to RVI alone. (Fig.\u0026nbsp;4C)\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eSingle Pattern vs. Multiple Patterns: The pooled HR was 1.60 (95% CI: 1.31, 1.94), showing that patients with multiple patterns of vascular invasion have a significantly higher recurrence risk. (Fig.\u0026nbsp;4D)\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eSarcomatoid vs Non-Sarcomatoid: The pooled HR was 2.81 (95% CI: 2.12, 3.72), emphasizing the much higher recurrence risk in patients with sarcomatoid features. (Fig.\u0026nbsp;4E)\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eFuhrman Grade III or IV vs. I or II: The pooled HR was 2.01 (95% CI: 1.63, 2.48), indicating a significantly higher recurrence risk in patients with high Fuhrman grades. (Fig.\u0026nbsp;4F)\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eTumor Necrosis vs No Tumor Necrosis: The pooled HR was 1.73 (95% CI: 1.35, 2.21), highlighting the poor prognosis associated with tumor necrosis. (Fig.\u0026nbsp;4G)\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003eTumor Size (\u0026le;\u0026thinsp;7 cm vs\u0026thinsp;\u0026gt;\u0026thinsp;7 cm): The pooled HR was 1.13 (95% CI: 1.10, 1.17), indicating a significant increase in recurrence risk for tumors\u0026thinsp;\u0026gt;\u0026thinsp;7 cm. (Fig.\u0026nbsp;4H)\u003c/p\u003e\n \u003c/li\u003e\n \u003cli\u003e\n \u003cp\u003ePositive Surgical Margins (PSM vs Non-PSM): The pooled HR was 3.56 (95% CI: 1.85, 6.85), emphasizing the critical role of achieving negative surgical margins in preventing recurrence. (Fig.\u0026nbsp;4I)\u003c/p\u003e\n \u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThis analysis links RVI, sarcomatoid histology, high Fuhrman grade, tumor necrosis, and larger tumor size to poor RCC prognosis. Positive surgical margins (PSM) increase recurrence risk, highlighting the need for precise surgery. The meta-analysis confirms RVI as a strong recurrence predictor, while GVI may signal early vascular invasion and potential recurrence.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRenal cell carcinoma (RCC) presents a diverse spectrum of biological behavior, particularly in tumors classified as pathologic T3a (pT3a). While the current AJCC and UICC guidelines recognize vascular invasion as a key prognostic factor, they do not differentiate between various forms of renal vein invasion (RVI), including segmental renal vein invasion (SRVI), which is often missed preoperatively. In this study, we found that extracapsular segmental vein tumor thrombus which was glossily visible specifically SRVI, highlighting its potential as a crucial intraoperative marker. Our meta-analysis further confirmed that RVI is associated with a significantly increased risk of recurrence, with a pooled hazard ratio (HR) of 1.76 compared to perinephric fat invasion (PFI).\u003c/p\u003e \u003cp\u003eAlthough preoperative imaging, particularly contrast-enhanced CT, remains the gold standard for RCC staging, its ability to detect vascular invasion is limited. Our study identified SRVI intraoperatively in patients whose preoperative scans showed no vascular involvement. This discrepancy underscores a critical gap in current RCC staging, as overlooked vascular involvement may lead to misclassification, affecting surgical planning and subsequent treatment strategies. Surgeons and oncologists should consider intraoperative SRVI as an important indicator of tumor aggressiveness and incorporate this finding into their decision-making process for follow-up and adjuvant therapy.\u003c/p\u003e \u003cp\u003eThis case series and meta-analysis provide further clarity on the prognostic significance of tumor invasion patterns in pT3a renal cell carcinoma (RCC). This subgroup has long been recognized for its biological heterogeneity[20]. While the AJCC 8th and UICC 8th editions have eliminated the term \"grossly\" to describe renal vein invasion (RVI) in the pT3a classification[21], this revision, though methodologically precise, does not diminish the clinical importance of grossly visible vascular invasion (GVI). The updated guidelines acknowledge that microscopic vascular invasion (MVI) and its detection are sufficient for pT3a categorization[22].\u003c/p\u003e \u003cp\u003eHowever, glossly visible segmental renal vein invasion remains a pivotal finding that straddles the continuum from microscopic vascular invasion (MVI) to renal vein invasion (RVI) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Its presence, often evident intraoperatively despite being missed preoperatively, offers critical insights into disease aggressiveness, potentially identifying more advanced stages of RCC that might otherwise be underappreciated (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn our case series, extracapsular segmental vein invasion revealed invasions missed on imaging, serving as a key predictor of tumor aggressiveness. Patients with this finding had poorer outcomes, highlighting its role in staging, surgical planning, and postoperative surveillance.\u003c/p\u003e \u003cp\u003eWhile the current TNM8 classification no longer explicitly requires Glossly Visible Invasion for T3a categorization, our findings suggest that it should not be dismissed. Rather, Glossly visible segmental vein invasion offers an invaluable clinical tool for refining the assessment of RCC's biological behavior and guiding therapeutic interventions. By recognizing glossly visible segmental vein tumor invasion, clinicians can gain a more nuanced understanding of tumor progression, particularly in cases where microscopic invasion could be overlooked, ultimately enhancing the precision of treatment planning and improving patient outcomes. This discrepancy in the current staging paradigm, where segmental vein invasion may be missed preoperatively but identified intraoperatively, underscores the potential for misclassification and suboptimal surgical planning. Clinically, undetected vascular invasion may lead to under-classification of the disease, denying patients the opportunity for more aggressive surveillance or adjuvant therapy. Additionally, the decision between nephron-sparing surgery (NSS) and radical nephrectomy often depends heavily on preoperative imaging; therefore, missed segmental venous involvement could jeopardize oncologic safety by influencing surgical decisions. Ma et al[23]found that while CT demonstrates an acceptable diagnostic performance for both PFI and RSFI, the sensitivity remains moderate (0.69 for PFI and 0.81 for RSFI) with specificity at 82% for PFI and 79% for RSFI. These results highlight the diagnostic challenges, particularly given the low positive sample rate in the studies assessed.\u003c/p\u003e \u003cp\u003eFurther, the positive likelihood ratio (PLR) for PFI and RSFI was found to be low (3.85 for PFI and 3.91 for RSFI), which limits the utility of CT for robust diagnostic decisions. The moderate to low sensitivity of CT in detecting these invasions implies that undetected vascular involvement may lead to staging misclassification, ultimately affecting treatment decisions such as nephron-sparing surgery (NSS) versus radical nephrectomy. Recent innovations in imaging, particularly machine learning-based models, are showing promise in addressing these diagnostic gaps. For instance, Xu et al[24]. demonstrated that a multiparametric CT radiomics model could predict MVI preoperatively with high accuracy, integrating radiomic features and clinical variables. Similarly, Yang et al[25] developed a deep learning model that accurately identified venous tumor thrombus using venous-phase CT, enhancing the potential for more accurate preoperative assessments. In a study by Boulenger de Hauteclocque et al[26] The study highlighted the potential of machine-learning technology in predicting upstaging to pT3a, moreover In a study conducted by Mei et al[27], a predictive model was constructed to assess the risk of upstaging from cT1 to pT3 renal cell carcinoma (RCC) based on perioperative characteristics. These innovations underscore the need for more sophisticated imaging techniques to improve the detection of vascular invasion and inform treatment planning. Although CT remains essential for RCC staging, these emerging technologies may help bridge the gap left by traditional imaging, particularly in detecting subtle forms of vascular invasion that may be missed by conventional methods.\u003c/p\u003e \u003cp\u003eOur meta-analysis reinforces the idea that not all T3a invasion patterns in renal cell carcinoma (RCC) carry the same prognostic weight. Studies, including a large analysis of the SEER registry, [5] show that renal vein invasion (RVI) carries the worst prognosis, followed by renal sinus fat invasion (RSFI), with perinephric fat invasion (PFI) associated with more favorable outcomes. These findings emphasize the need to reconsider the broad classification of pT3a RCC, as tumors with multiple invasion patterns often exhibit worse survival outcomes compared to those with a single invasion type.\u003c/p\u003e \u003cp\u003eCurrent pT3a staging may not adequately reflect the heterogeneity in tumor aggressiveness, potentially leading to staging misclassification and influencing treatment decisions. This underscores the importance of refining the staging criteria to better differentiate between distinct invasion patterns, ultimately improving risk stratification and guiding individualized treatment strategies, including neoadjuvant and adjuvant therapies, to reduce recurrence and metastasis risks.\u003c/p\u003e \u003cp\u003eOur institutional cases also raise important questions about the role of NSS in selected T3a cases. While NSS has historically been contraindicated in T3a tumors due to concerns over oncologic adequacy, emerging evidence suggests that it may be appropriate in non-metastatic patients with limited invasion and strong nephron-sparing indications (e.g., solitary kidney or pre-existing renal insufficiency)[28],[16],[29],[30].\u003c/p\u003e \u003cp\u003eA key limitation of this study is the small sample size and relatively short follow-up in the institutional case series, which restrict the ability to draw firm conclusions about long-term oncologic outcomes and recurrence patterns in patients with extracapsular segmental venous tumor thrombus (ESVTT) with grossly visible vascular invasion (GVI) detected during nephron-sparing surgery. In addition, assessment of GVI is inherently subjective and operator-dependent, as it relies on intraoperative visual and tactile impressions rather than standardized criteria, which may introduce variability and potential misclassification. These constraints underscore the need for future multi-center registries that systematically capture intraoperative vascular findings, prospective studies correlating preoperative imaging and emerging radiomics or AI-based markers with intraoperative and pathological evidence of vascular invasion, and the development of standardized intraoperative documentation protocols (including predefined photographic or video recording of suspected GVI) to improve reproducibility and external validity.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study emphasizes the need for better subclassification and preoperative detection of vascular invasion in pT3a RCC. Advanced imaging holds promise, but histopathology is key. Findings support personalized surveillance and selective NSS in non-metastatic pT3a RCC, with future studies needed to refine imaging and molecular markers.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board of The Second Affiliated Hospital of Xi'an Jiaotong University. Written informed consent was obtained from all patients for the use of their clinical data for research purposes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to patient privacy considerations but are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003eRequests for data or study-related inquiries should be directed to De laifu.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFK conceived and designed the study.\u003c/p\u003e\n\u003cp\u003eFK, GT, and TX collected the data.\u003c/p\u003e\n\u003cp\u003eFK and GT performed the data analysis.\u003c/p\u003e\n\u003cp\u003eFK drafted the manuscript.\u003c/p\u003e\n\u003cp\u003eLX, TC, and DF critically revised the manuscript.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCairns, P., \u003cem\u003eRenal cell carcinoma.\u003c/em\u003e Cancer Biomark, 2010. \u003cstrong\u003e9\u003c/strong\u003e(1-6): p. 461-73.\u003c/li\u003e\n\u003cli\u003ePowles, T., et al., \u003cem\u003eRenal cell carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.\u003c/em\u003e Ann Oncol, 2024. \u003cstrong\u003e35\u003c/strong\u003e(8): p. 692-706.\u003c/li\u003e\n\u003cli\u003eAmin, M.B., et al., \u003cem\u003eThe Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more \u0026quot;personalized\u0026quot; approach to cancer staging.\u003c/em\u003e CA Cancer J Clin, 2017. \u003cstrong\u003e67\u003c/strong\u003e(2): p. 93-99.\u003c/li\u003e\n\u003cli\u003eDiBianco, J.M., P.T. 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LARCG Group.\u003c/em\u003e Actas Urol\u0026oacute;gicas Espa\u0026ntilde;olas (English Edition), 2019. \u003cstrong\u003e43\u003c/strong\u003e(9): p. 495-502.\u003c/li\u003e\n\u003cli\u003eOh, J.J., et al., \u003cem\u003eAccurate Risk Assessment of Patients with Pathologic T3aN0M0 Renal Cell Carcinoma.\u003c/em\u003e Sci Rep, 2018. \u003cstrong\u003e8\u003c/strong\u003e(1): p. 13914.\u003c/li\u003e\n\u003cli\u003eLai, G.S., et al., \u003cem\u003eTumor Size Significantly Affects Prognosis in Pathological T3a Renal Cell Carcinoma.\u003c/em\u003e Anticancer Res, 2022. \u003cstrong\u003e42\u003c/strong\u003e(4): p. 2185-2191.\u003c/li\u003e\n\u003cli\u003eMusso, G., et al., \u003cem\u003eDifferential Prognostic Value of Extrarenal Involvement in Patients With Non-Metastatic Renal Cell Cancer.\u003c/em\u003e Clin Genitourin Cancer, 2023. \u003cstrong\u003e21\u003c/strong\u003e(4): p. e279-e285 e1.\u003c/li\u003e\n\u003cli\u003ePark, M., et al., \u003cem\u003ePrognostic heterogeneity in T3aN0M0 renal cell carcinoma according to the site of invasion.\u003c/em\u003e Urologic Oncology: Seminars and Original Investigations, 2017. \u003cstrong\u003e35\u003c/strong\u003e(7): p. 458.e17-458.e22.\u003c/li\u003e\n\u003cli\u003ePeng, D., et al., \u003cem\u003ePartial nephrectomy for T3aN0M0 renal cell carcinoma: shall we step forward?\u003c/em\u003e International braz j urol, 2017. \u003cstrong\u003e43\u003c/strong\u003e(5): p. 849-856.\u003c/li\u003e\n\u003cli\u003eShah, P.H., et al., \u003cem\u003ePrognostic evaluation of perinephric fat, renal sinus fat, and renal vein invasion for patients with pathological stage T3a clear\u003c/em\u003e\u003cem\u003e‐cell renal cell carcinoma.\u003c/em\u003e BJU International, 2018. \u003cstrong\u003e123\u003c/strong\u003e(2): p. 270-276.\u003c/li\u003e\n\u003cli\u003eSoltani, M.H., et al., \u003cem\u003eOncologic Outcomes and Predictors in Patients with Stage PT3aNxM0 Renal Cell Carcinoma Following Radical Nephrectomy.\u003c/em\u003e Urol Res Pract, 2023. \u003cstrong\u003e49\u003c/strong\u003e(1): p. 25-32.\u003c/li\u003e\n\u003cli\u003eZhu, D., et al., \u003cem\u003ePrognostic significance of the sub-classification of stage pT3a renal tumors by perinephric and sinus fat invasion.\u003c/em\u003e Oncology Letters, 2020.\u003c/li\u003e\n\u003cli\u003eYoshida, T., et al., \u003cem\u003eClinical impact of segmental renal vein invasion on recurrence in patients with clinical T1 renal cell carcinoma undergoing partial nephrectomy.\u003c/em\u003e Int J Clin Oncol, 2020. \u003cstrong\u003e25\u003c/strong\u003e(3): p. 464-471.\u003c/li\u003e\n\u003cli\u003ePaner, G.P., et al., \u003cem\u003eUpdates in the Eighth Edition of the Tumor-Node-Metastasis Staging Classification for Urologic Cancers.\u003c/em\u003e Eur Urol, 2018. \u003cstrong\u003e73\u003c/strong\u003e(4): p. 560-569.\u003c/li\u003e\n\u003cli\u003eKandori, S., T. 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Nishiyama, \u003cem\u003eThe updated points of TNM classification of urological cancers in the 8th edition of AJCC and UICC.\u003c/em\u003e Jpn J Clin Oncol, 2019. \u003cstrong\u003e49\u003c/strong\u003e(5): p. 421-425.\u003c/li\u003e\n\u003cli\u003eMa, J., et al., \u003cem\u003eDiagnostic performance of CT for extrarenal fat invasion in renal cell carcinoma: a meta-analysis and systematic review.\u003c/em\u003e Insights Imaging, 2025. \u003cstrong\u003e16\u003c/strong\u003e(1): p. 19.\u003c/li\u003e\n\u003cli\u003eXu, J., et al., \u003cem\u003eMachine learning-based multiparametric CT radiomics for predicting microvascular invasion before nephrectomy in clear cell renal cell carcinoma.\u003c/em\u003e Abdom Radiol (NY), 2025.\u003c/li\u003e\n\u003cli\u003eYang, Y., et al., \u003cem\u003eMachine learning-based multiparametric MRI radiomics nomogram for predicting WHO/ISUP nuclear grading of clear cell renal cell carcinoma.\u003c/em\u003e Front Oncol, 2024. \u003cstrong\u003e14\u003c/strong\u003e: p. 1467775.\u003c/li\u003e\n\u003cli\u003eBoulenger de Hauteclocque, A., et al., \u003cem\u003eMachine-learning approach for prediction of pT3a upstaging and outcomes of localized renal cell carcinoma (UroCCR-15).\u003c/em\u003e BJU Int, 2023. \u003cstrong\u003e132\u003c/strong\u003e(2): p. 160-169.\u003c/li\u003e\n\u003cli\u003eMei, J., et al., \u003cem\u003eConstruction of a Model for Predicting the Risk of pT3 Based on Perioperative Characteristics in cT1 Renal Cell Carcinoma: A Retrospective Study at a Single Institution.\u003c/em\u003e Clin Genitourin Cancer, 2024. \u003cstrong\u003e22\u003c/strong\u003e(4): p. 102122.\u003c/li\u003e\n\u003cli\u003eShvero, A., et al., \u003cem\u003eOncologic Outcomes of Partial Nephrectomy for Stage T3a Renal Cell Cancer.\u003c/em\u003e Clin Genitourin Cancer, 2018. \u003cstrong\u003e16\u003c/strong\u003e(3): p. e613-e617.\u003c/li\u003e\n\u003cli\u003eLiu, S., et al., \u003cem\u003eComparison of prognosis between patients undergoing radical nephrectomy versus partial nephrectomy for renal cell carcinoma \u0026lt;/=7 cm T3aN0/xM0: Survival benefit is biased toward partial nephrectomy.\u003c/em\u003e Cancer Med, 2021. \u003cstrong\u003e10\u003c/strong\u003e(24): p. 8909-8923.\u003c/li\u003e\n\u003cli\u003eChung, D.Y., et al., \u003cem\u003eComparison of oncologic outcomes between partial nephrectomy and radical nephrectomy in patients who were upstaged from cT1 renal tumor to pT3a renal cell carcinoma: an updated systematic review and meta-analysis.\u003c/em\u003e Ther Adv Urol, 2020. \u003cstrong\u003e12\u003c/strong\u003e: p. 1756287220981508.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Early-stage renal cell carcinoma, vascular invasion, nephron-sparing surgery, grossly visible vascular invasion, segmental renal vein tumor thrombus, renal vein invasion, recurrence-free survival, pT3a renal cell carcinoma","lastPublishedDoi":"10.21203/rs.3.rs-8609799/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8609799/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e\u003cbr\u003e\n To summarize the clinical characteristics of renal cell carcinoma (RCC) patients with segmental vein tumor thrombus detected during partial nephrectomy (PN) and explore its clinical significance, so as to deepen the understanding of the pathogenesis of RCC-associated tumor thrombus. Additionally, we aim to evaluate the prognostic impact of renal vein invasion (RVI) in RCC, particularly its influence on recurrence-free survival (RFS), through a meta-analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003cbr\u003e\n A retrospective analysis was conducted on the clinical data of 209 RCC patients (162 cases of T1a stage, 47 cases of T1b stage) who underwent PN in The Second Affiliated Hospital of Xi'an Jiaotong University from September 2023 to July 2025. Among them, 8 patients were intraoperatively identified with extracapsular segmental venous tumor thrombus. in this study, “grossly visible vascular invasion (GVI)” refers to intraoperatively observed, macroscopic segmental venous tumor thrombus (ESVTT/SRVI) detected during nephron-sparing surgery, regardless of preoperative imaging findings. Intraoperative findings, pathological characteristics, and follow-up outcomes were recorded and analyzed. Furthermore, a meta-analysis of 12 studies (141,504 patients) was conducted to assess the impact of RVI on RFS, comparing it to other invasion patterns such as perinephric fat invasion (PFI).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 8 cases of extracapsular segmental vein tumor thrombus, 1 was at T1a stage and 7 at T1b stage. Preoperative computed tomography (CT) showed round or roundish solid renal masses with heterogeneous density on non-contrast scans, significant enhancement on contrast-enhanced scans, and markedly weaker enhancement in the renal parenchymal phase compared with normal renal tissue. The average tumor diameter was (4.9±0.2) cm, with clear boundaries and no evidence of vascular invasion. Postoperative pathology confirmed pT3a clear cell carcinoma in all cases, with International Society of Urological Pathology (ISUP) grades ranging from Ⅰ to Ⅳ, and all surgical margins were negative. After surgery, 5 patients received adjuvant immunotherapy. During a median follow-up of 10.3 (3.8-22.8) months, no tumor recurrence or metastasis was observed.\u003c/p\u003e\n\u003cp\u003eThe meta-analysis revealed that RVI significantly increased recurrence risk, with a pooled hazard ratio (HR) of 1.76 (95% CI 1.23–2.51) for RVI compared to perinephric fat invasion (PFI), and a pooled HR of 1.85 (95% CI 1.35–2.53) compared to non-RVI patients. Furthermore, multiple patterns of vascular invasion (HR 1.60, 95% CI 1.31–1.94) and sarcomatoid differentiation (HR 2.81, 95% CI 2.12–3.72) were strongly correlated with higher recurrence risks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003cbr\u003e\n Renal cell carcinoma (RCC) has a strong tendency for vascular invasion, and this study highlights that even clinically T1 tumors can harbor glossly visible segmental venous tumor thrombus (ESVTT/GVI) detected only at surgery. In this context, ESVTT represents a macroscopic manifestation of segmental renal vein involvement along the continuum from microscopic vascular invasion to main renal vein thrombus, with potential impact on staging, choice of nephron-sparing versus radical surgery, and postoperative surveillance. Complementing these institutional observations, the meta-analysis demonstrates that renal vein invasion (RVI) is consistently associated with significantly worse recurrence-free survival (RFS), supporting the need to recognize and systematically record grossly visible segmental venous invasion as a clinically meaningful risk feature. Together, these findings justify larger multi-center and prospective efforts to standardize intraoperative documentation of GVI/ESVTT, correlate it with imaging and pathology, and ultimately refine risk stratification and treatment strategies for patients with RCC.\u003c/p\u003e","manuscriptTitle":"Segmental Renal Vein Tumor Thrombus in Early-stage RCC: Intraoperative Diagnosis, Clinical Significance, and a Systematic Review with Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-16 06:00:53","doi":"10.21203/rs.3.rs-8609799/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-23T12:48:12+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-19T05:30:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8413332503961827947977191637573926299","date":"2026-03-13T09:23:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"82563695986495017483633730188529485813","date":"2026-03-12T11:23:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-11T11:08:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"321046761164643236085321646113143580062","date":"2026-03-11T10:10:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-11T09:57:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-05T11:00:38+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-27T14:56:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-23T11:53:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2026-01-23T11:40:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6702905d-3a89-4fcc-ab37-a66563b3ac49","owner":[],"postedDate":"March 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-16T06:00:53+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-16 06:00:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8609799","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8609799","identity":"rs-8609799","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}