Comparative analysis of survival rates in patients with renal cell carcinoma and level i-ii tumor thrombus of the renal vein and inferior vena cava undergoing open versus laparoscopic surgical treatment

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Introduction

Renal Cell Carcinoma (RCC) continues to occupy one of the leading places in the structure of oncological urological morbidity and mortality, demonstrating a steady upward trend in the number of cases both in Russia and abroad [1; 2]. According to epidemiological studies conducted in recent years, this nosology is characterized by high variability in clinical course, a significant number of cases debuting at the locally advanced stage, and frequently diagnosed cases of tumor venous invasion [3; 4]. As emphasized by U. Capitanio et al., RCC has a pronounced ability to spread angiotropically, forming tumor thrombi in the renal and inferior vena cava in a significant proportion of patients [5].

The management of patients with RCC complicated by venous thrombosis presents particular clinical and surgical challenges. Performing radical nephrectomy with thrombectomy in such cases is associated with a high risk of intraoperative complications, the need for a multidisciplinary approach, and significant technical equipment requirements [7; 8]. At
the same time, as shown by the works of V.A. Atduev and M.I. Davydov, the immediate and long-term results of surgical treatment depend not only on the level of thrombosis, but also on the extent of the intervention and the chosen surgical approach [9; 10].

Against the backdrop of growing interest in minimally invasive technologies in oncological urology, laparoscopic nephrectomy is increasingly being considered as an alternative to open surgery with potentially equivalent oncological efficacy. However, data on the applicability of the laparoscopic approach in patients with RCC and thrombosis remain limited and contradictory [11–13]. A review conducted by S. Bahadoram et al. emphasizes the importance of individualizing surgical tactics, taking into account prognostic factors and technical limitations [1]. Recent studies also emphasize the importance of comorbid conditions such as obesity, hypertension, and reduced functional reserve in determining surgical risks and survivability [14–16].

Analysis of factors affecting survival after surgical treatment of RCC demonstrates the significant role of morphological and clinical-anamnestic characteristics, including body mass index (BMI), degree of thrombosis, and lymph node involvement [17; 18]. Timely and accurate staging of the tumor process has a direct impact on the choice of treatment tactics and the patient's prognosis [19; 20].

The study, aimed at a comparative analysis of the effectiveness of laparoscopic and laparotomy approaches in performing nephrectomy with thrombectomy in patients with RCC with level I–II tumor thrombosis, allows determining the feasibility of using minimally invasive technologies in complex clinical situations and clarifying the prognostic role of a number of factors that potentially affect patient survival in real clinical practice.

The aim of the study is to compare recurrence-free survival and long-term oncological outcomes in patients with renal cell carcinoma complicated by grade 0–II venous thrombosis after radical nephrectomy with thrombectomy using laparoscopic and open approaches.

Materials and Methods

The study was retrospective in nature and aimed at a comparative analysis of recurrence-free survival rates in patients who underwent surgical treatment for malignant neoplasms using laparotomy and laparoscopic approaches.

Between 2007 and 2024, the Russian Scientific Center for Radiology and Surgical Technologies named after Academician A.M. Granov" conducted a retrospective registry study aimed at assessing long-term oncological outcomes in patients who underwent radical nephrectomy with thrombectomy for RCC complicated by tumor venous thrombosis of grades 0–II according to the Mayo classification.

The study included 100 patients. The inclusion criteria were morphologically confirmed RCC with tumor thrombosis of the renal and/or inferior vena cava of levels I–II, as well as radical nephrectomy with thrombectomy performed in a specialized oncology hospital. The exclusion criteria were the presence of grade III–IV tumor thrombosis, intraoperative complications requiring conversion, and the absence of histological verification.

The sample was stratified based on clinical and anamnestic, morphological, and technical parameters, including the level of tumor thrombosis, the presence of regional metastases, the type of surgical access, BMI (body mass index), and comorbidities. This made it possible to form homogeneous groups for valid comparative analysis and calculation of prognostic survival models. The cohort of patients with verified RCC and tumor venous thrombosis was representative and clinically significant in terms of assessing the efficacy and safety of laparoscopic surgery compared with traditional laparotomy.

Statistical processing of the obtained data was performed using the MedCalc software package. To assess the prognostic factors affecting the time to disease progression, the Cox proportional-hazards regression model was used, which allows determining the relationship between progression-free survival time and a set of clinical, laboratory, and morphological predictors. The dependent variable in the model was time to progression, defined as the interval from the time of surgery to the date of detection of signs of disease progression or the date of last contact (in the absence of an event). Patients who had not progressed by the end of follow-up were considered censored cases. Categorical and continuous variables were included in the model using the Enter method, without stepwise exclusion, with preliminary verification of compliance with the risk proportionality assumption. To assess the significance of the influence of individual factors, the values of regression coefficients (b), standard errors (SE), Wald test values, significance levels (p), and coefficient exponents (Exp (b)), interpreted as hazard ratios (HR) with a 95 % confidence interval (95 % CI). The reliability of the model was assessed based on the change in the -2 logarithmic likelihood function (–2 Log Likelihood) between the zero and full models, the chi-square criterion, and the corresponding significance level (p <  0.05). Progression-free survival was visualized using the cumulative hazard function and survival function as a function of observation time; differences were considered statistically significant at p <  0,05.

Results and Discussion

Analysis of concomitant pathology revealed arterial hypertension in 58 patients (58 %), which may reflect both the severity of comorbid conditions and a pathogenetic link with nephrogenic disorders. Body mass index was distributed as follows: normal BMI (18.5–24.9 kg/m²) in 12 patients, overweight (25.0–29.9 kg/m²) in 54, and obesity (≥ 30 kg/m²) in 34. The mean BMI value was 28.1 ± 2.6 kg/m², indicating a high prevalence of overweight and obesity in this population. Clinical manifestations of RCC with thrombosis were observed in 35 % of patients. The most common symptoms were pain in the lumbar region (11 %), macrohematuria (10 %), prolonged fever of unknown origin (7 %), and rapid weight loss (≥ 10 kg in 6 months) – also in 7 % of patients.

Patients were classified according to the level of tumor thrombosis as follows: 54 (54 %) had renal vein thrombosis (level 0), 30 (30 %) had level I thrombosis, and 16 (16 %) had level II thrombosis. Metastatic involvement of regional lymph nodes (stage N1) was diagnosed in 18 (18 %) patients, while 82 (82 %) patients had no lymphogenous metastasis (stage N0).

According to the results of Kaplan-Meier survival analysis, the differences between laparotomy and laparoscopy did not reach statistical significance (log-rank test: c² = 0.2916; p = 0.5892). The median time to progression was 59.1 ± 4 months in the group of patients who underwent laparotomy and 58.9 ± 4 months in the group who underwent laparoscopy. The median progression-free survival was 68.0 (95 % CI: 52.0–71.0) and 61.0 (95 % CI: 46.0–74.0) months, respectively. The hazard ratio (HR) for laparoscopic access compared to laparotomy was 0.84 (95 % CI: 0.43–1.61), indicating equivalent oncological efficacy of laparoscopic intervention.

Figure 1 shows the generalized survival function calculated using the Cox model based on all included variables, showing a gradual decrease in the probability of recurrence-free disease during the observation period, followed by the curve reaching a plateau at 80 months.

 

Fig. 1. Cumulative survival function according to Cox`s model with mean covariate values in patients with RCC

 

As shown in Fig. 2, a, the recurrence-free survival curves in the laparotomy and laparoscopy groups demonstrate comparable indicators, with the differences between the groups not reaching statistical significance (p = 0.5892).

 

Fig. 2. Recurrence-free survival curves in patients with RCC: a – depending on the type of surgical access (laparotomy vs laparoscopy); b – depending on regional lymph node involvement (N0 vs N1); c – depending on the degree of tumor thrombosis (Mayo levels 0, I, II)

 

The influence of other clinical and morphological factors revealed the following patterns with regional lymph node involvement having a pronounced negative effect on survival: the median time to progression in the subgroup with metastatic involvement was 29 (95 % CI: 23.0–43.0) months versus 69 (95 % CI: 61.0–75.0) months in the group without involvement. The analysis demonstrated a statistically significant difference (c² = 23.55; p <  0.0001) and a hazard ratio (HR) of 24.80 (95 % CI: 6.78–90.70), confirming an unfavorable prognosis in the presence of lymphogenous dissemination. Fig. 2, b shows that the presence of metastatic lymph node involvement (N1) is associated with a significant reduction in recurrence-free survival compared to patients whose lymph nodes were not involved (N0). The statistical significance of the differences has been confirmed (p <  0.0001).

Analysis of the dependence of survival on the degree of thrombosis showed that in patients with severe thrombosis (level II), the median progression-free survival was only 29 (95 % CI: 19.0–41.0) months, while in respondents with level I thrombosis it was 58 (95 % CI: 43.0–69.0) months, and 74 (95 % CI: 68.0–76.0) months for level 0 thrombosis. The hazard ratio for grade II thrombosis compared to level 0 was HR = 7.79 (95 % CI: 2.07–29.36), p <  0.0001. Prolonged thrombosis is associated with a more aggressive course of the tumor process. The average time to progression at thrombosis level 0 was 71.93 ± 3.58 months, at level 1 – 53.60 ± 4.18 months, and at level 2 – 29.24 ± 3.45 months. The differences between the groups were statistically significant (c² = 36.19; df = 2; p <  0.0001) (Fig. 2, c).

Cox's multivariate analysis confirmed the significant influence of a number of predictors on the risk of disease progression. The model included clinical and morphological variables: thrombosis level, tumor morphology type, tumor size, ISUP Grade malignancy, lymph node involvement, and others. The following factors had a significant negative impact on recurrence-free survival: thrombosis level I (HR = 2.86; 95 % CI: 1.15–7.10; p = 0.0236), thrombosis level II (HR = 3.82; 95 % CI: 1.06–13.80; p = 0.0406), tumor size (HR = 1.59; 95 % CI: 1.17–2.17; p = 0.0031), ISUP grade (HR = 1.43; 95 % CI: 1.00–2.04; p = 0.0472), tumor morphology – light cell carcinoma (HR = 3.94; 95 % CI: 1.25–12.47; p = 0.0195).

Despite the high-risk ratio in the univariate analysis for lymph node involvement (HR = 24.80), in the multifactorial model, this parameter did not reach statistical significance (p = 0.355), which may be due to the small number of patients with positive lymph nodes (n = 18) and a decrease in sample power.

Further analysis of the research results obtained is aimed at correlating the data with retrospective studies described in the scientific literature and discussing their clinical and prognostic significance.

The results confirm the oncological equivalence of laparoscopic and laparotomy approaches when performing nephrectomy with thromboectomy in patients with RCC complicated by grade 0–II venous thrombosis. The absence of statistically significant differences in survival between the groups (p = 0.5892) is consistent with the data presented in the works of V.A. Atduev et al., who also noted no deterioration in prognosis when using minimally invasive technologies in carefully selected patients [9].

Studies by S. Bahadoram et al. (2022) and U. Capitanio, P. Montorsi (2019) emphasize the trend toward expanding the indications for laparoscopy in oncological urology, which is due not only to a reduction in intraoperative trauma and the frequency of complications, but also to comparable oncological outcomes when oncological principles of intervention are followed [1; 5]. Our study also confirmed the high prognostic significance of metastatic involvement of regional lymph nodes, with an HR = 24.80 (p <  0.0001), which corresponds to the data obtained by M.I. Davydov et al. (2014) L. Bukavina et al. (2022), according to which the presence of N1 status is associated with an unfavorable prognosis and requires more aggressive postoperative management [10; 15]. It has been established that grade II thrombosis according to the Mayo classification significantly reduces recurrence-free survival (HR = 7.79; p <  0.0001). The degree of invasion into the main vessels is an independent negative prognostic factor, especially when the thrombus extends above the renal vein junction [19]. The presented results confirm the current provisions of clinical guidelines and systematic reviews on the acceptability of laparoscopic access in RCC with 0–II level thrombosis in carefully selected patients.

Conclusions

The data obtained indicate that laparoscopic access is comparable in effectiveness to laparotomy in terms of cancer control and can be considered as an alternative method of surgical intervention while complying with oncological principles. The key prognostic factors determining recurrence-free survival remain the morphological characteristics of the tumor, the presence of thrombosis, and metastatic lymph node involvement. However, the limitations of this study must be taken into account, including its retrospective nature, the limited number of cases with grade II thrombosis, and the possible influence of comorbidities, particularly obesity and hypertension, on the prognosis. Further multicenter prospective studies with larger cohorts and stratification by morphological subtypes of RCC are needed.

About the authors

M. K. Mirzabekov

A.M. Granov Russian Research Center for Radiology and Surgical Technologies

Author for correspondence.
Email: Musabek.mirzabekoff@yandex.ru
ORCID iD: 0009-0003-8365-7672
SPIN-code: 5892-4003

Postgraduate Student of the Department of Radiology, Surgery and Oncology

Russian Federation, Saint Petersburg

O. A. Bogomolov

A.M. Granov Russian Research Center for Radiology and Surgical Technologies

Email: Musabek.mirzabekoff@yandex.ru
ORCID iD: 0000-0002-5860-9076
SPIN-code: 6554-4775

PhD (Medicine), Associate Professor of the Department of Radiology, Surgery and Oncology, Chief Researcher

Russian Federation, Saint Petersburg

M. I. Shkolnik

A.M. Granov Russian Research Center for Radiology and Surgical Technologies

Email: Musabek.mirzabekoff@yandex.ru
ORCID iD: 0000-0003-0589-7999
SPIN-code: 4743-9236

DSc (Medicine), Associate Professor, Professor of the Department of Radiology, Surgery and Oncology, Chief Researcher

Russian Federation, Saint Petersburg

N. V. Trukhacheva

Altai State Medical University

Email: Musabek.mirzabekoff@yandex.ru
ORCID iD: 0000-0002-7894-4779
SPIN-code: 3515-5231

PhD (Pedagogy), Associate Professor of the Department of Physics and IT

Russian Federation, Barnaul

N. D. Tikhonsky

Altai State Medical University

Email: Musabek.mirzabekoff@yandex.ru
ORCID iD: 0000-0001-7525-277X
SPIN-code: 4983-2377

Lecturer of the Department of Physics and IT

Russian Federation, Barnaul

References

Supplementary files