Clinical efficacy of robot-assisted thymectomy for large thymomas: a dual analysis of national and single-institution data

Introduction

A thymectomy ranks among the most performed surgeries on the anterior mediastinum, addressing both benign and malignant diseases (1). Complete resection stands as the most crucial prognostic factor for thymoma treatment, and median sternotomy has been considered the conventional approach (2-4). However, since the first report of a robot-assisted thymectomy (RAT) for a 3 cm-sized Masaoka stage I thymoma in 2001 (5), the application of RAT has continuously expanded according to the accumulation of surgeons’ experiences and the evolution of robotic technology (6-10). Although RAT techniques are widely used for thymomas smaller than 4 cm, their use in larger tumors, especially those over 4 cm, remains controversial (11-14). The reluctance to perform RAT for large-sized thymomas stems from several factors: the limited camera field of view obstructed by the mass in the narrow anterior mediastinal space, the challenges in manipulating the robot arms due to restricted working space, concerns about incomplete resection due to potential invasion of adjacent organs, and the risk of damaging nearby structures, including the phrenic nerves, innominate vein, lungs, pericardium, heart, and its major blood vessels. Furthermore, there is apprehension that the lack of tactile feedback associated with robotic surgery might lead to tumor capsule rupture, potentially causing tumor cell spillage, thus compromising R0 resection and increasing the chance of pleural recurrence (15). However, it is also true that these limitations are being overcome in centers with extensive experience in robotic thoracic surgery (7-9).

This study compares the peri-operative and long-term oncological outcomes between open thymectomy (OT) and RAT for large thymomas by analyzing the large-scale National Cancer Database (NCDB; https://www.facs.org/quality-programs/cancer-programs/national-cancer-database/) and our single institution’s database. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-714/rc).

Methods

Data source and study cohort

This retrospective cohort study utilized data from the NCDB and a single-institution dataset to evaluate the perioperative and oncologic outcomes of RAT compared to OT for thymomas larger than 4 cm. The NCDB, a hospital-based cancer registry that aggregates data from over 1,500 United States facilities, provided a broad, nationally representative patient population for the study. The single-institution dataset, spanning from 2008 to 2023, offered detailed clinical data from a high-volume academic center. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The single-institution analysis was approved by Institutional Review Board (IRB) of Northwestern University (No. STU00206649), with informed consent waived due to the retrospective nature of the study.

Patient selection and inclusion criteria

From the NCDB, patients with thymomas exceeding 4 cm who underwent either RAT or OT between 2010 and 2017 were identified. Inclusion criteria required patients to have complete demographic and tumor information, with survival data available for at least one-year post surgery. Patients who underwent a thoracoscopic approach were excluded to allow for a focused comparison of the efficacy between RAT and OT (Figure 1). Within our institution’s dataset, patients with thymomas larger than 5 cm were selected for balanced representation of both RAT and OT groups, as patients with 4–5 cm tumors disproportionately underwent RAT. This selection criterion enabled us to conduct a more focused analysis of large thymomas in our institutional data.

Figure 1 Flowchart illustrating the process of selecting study subjects.

Patient demographic and clinical characteristics

Patient demographic data, including age, gender, and comorbidity indices, were extracted from both datasets. Tumor characteristics included size, Masaoka staging, and resection margin status (R0 vs. R1/R2). Socioeconomic data, such as insurance type (Medicaid/uninsured vs. private/Medicare) and racial classification (White, Black, Asian, others), were analyzed to investigate disparities in surgical approach. The NCDB categorized patients based on facility type (academic or nonacademic) and recorded each institution’s annual thymectomy surgical volume.

Surgical approach classification

The surgical approach was categorized as RAT or OT. In the NCDB cohort, all patients who underwent robotic thymectomy or whose robotic procedures were converted to open resections were classified under RAT. In the single-institution dataset, RAT was performed using a robotic

platform with the da Vinci Surgical System, while OT was performed through a median sternotomy approach. All surgical cases aimed for complete tumor resection (R0), and cases where residual tumor was observed were classified as R1 or R2 resections.

Propensity score matching (PSM) and cohort formation

To mitigate selection bias in the NCDB cohort, we used PSM based on the likelihood of undergoing RAT versus OT (Table S1). Covariates included in the propensity model were patient age, sex, race, comorbidity index (Charlson-Deyo), facility type, surgical volume, insurance status, year of diagnosis, and resection margin status. A caliper of 0.2 standard deviations of the logit of the propensity score was applied for Nearest-neighbor matching without replacement. A balanced cohort of 500 patients (250 RAT and 250 OT) was achieved, with standardized mean differences (SMDs) of covariates within acceptable limits (<10%) for all matched variables. In our institutional cohort, cases were analyzed in an unmatched design due to the limited sample size, focusing on descriptive comparisons.

Outcome measures

Perioperative outcomes

Primary perioperative outcomes included postoperative complication rates, hospital length of stay (LOS), 30- or 90-day mortality rate, and unplanned 30-day readmission rates. Postoperative complications and LOS were exclusively extracted from the institutional database.

Oncologic outcomes

Oncologic outcomes were measured in terms of overall survival (OS) and recurrence-free survival (RFS). OS was defined as the duration from surgery to death from any cause or last follow-up. RFS, available only in the institutional dataset, was defined as the time from surgery to the first documented recurrence. Survival estimates were calculated using Kaplan-Meier survival curves and compared between RAT and OT groups using the log-rank test.

Statistical analyses

All statistical analyses were performed using Stata MP Version 17 (StataCorp, College Station, TX, USA). Statistical significance was set at a two-tailed P value of <0.05 for all tests.

Descriptive statistics and bivariable analysis

Descriptive statistics were calculated to characterize patient demographics, tumor features, and clinical outcomes by surgical approach. Categorical variables were compared using Chi-square (χ²) tests, and continuous variables were assessed for normality. Mann-Whitney U and Kruskal-Wallis tests were used for non-normally distributed variables.

Survival analysis

Kaplan-Meier survival estimates were generated for both OS and RFS, with log-rank tests used to assess statistical significance between RAT and OT groups in the matched NCDB cohort. Cox proportional hazards models were developed to adjust for potential confounders, with hazard ratios (HRs) and 95% confidence intervals (CIs) reported. Unadjusted models were applied to the institutional dataset due to the sample size limitations and absence of matching.

Trend analysis of RAT utilization

To assess trends in the adoption of RAT, cases from both cohorts were stratified by year of surgery. The percentage of RAT cases was calculated for each year, and changes in the utilization of RAT over time were analyzed. In our institution’s dataset, the proportion of RAT cases rose significantly over time, suggesting increased surgeon experience and comfort with robotic techniques for large thymomas.

Socioeconomic and racial disparity analysis

The NCDB dataset enabled analysis of socioeconomic and racial disparities in access to RAT. Disparities were examined by comparing RAT utilization rates among different racial groups and insurance types. Logistic regression models were employed to evaluate the odds of receiving RAT versus OT, controlling for patient demographics, clinical characteristics, and facility factors.

Results

Patient demographics and clinical characteristics

NCDB cohort

A total of 1,592 patients with thymomas larger than 4 cm were identified in the NCDB, comprising 259 patients (16.3%) who underwent RAT and 1,333 patients (83.7%) treated with OT. Baseline demographic and clinical characteristics are summarized in Table 1. Both groups were similar in age (median: RAT 63 years, OT 62 years) and gender distribution, with 51.6% of patients in the cohort being female. However, significant differences emerged in racial and socioeconomic profiles. The RAT group had a higher proportion of White patients (66.8% vs. 62.3% for OT), whereas the OT group showed a statistically significantly higher proportion of African American patients (18.7% vs. 10.8% for RAT, P=0.03). A higher percentage of uninsured or Medicaid patients underwent OT (14.5% vs. 7.3% for RAT, P=0.002). Tumor size also varied, with larger tumors (>6 cm) more frequently treated with OT (68.5% vs. 45.6% for RAT, P<0.001).

Single-institution cohort

From 2008 to 2023, our institution treated 43 patients with thymomas larger than 5 cm, including 21 patients who underwent RAT and 22 treated with OT. The mean age of patients was similar between groups (RAT: 60.8±12.3 years, OT: 60.0±14.4 years), and both groups had comparable distributions of Masaoka stages I to IVA. Unlike the NCDB cohort, the single-institution dataset allowed for the assessment of additional clinical variables such as body mass index and specific comorbid conditions like myasthenia gravis (present in 28.6% of RAT cases vs. 4.5% in OT cases, P=0.04). Tumor characteristics, including average size (RAT: 7.3±2.3 cm vs. OT: 7.9±2.6 cm, P=0.42), were also comparable across groups (Table 2).

Perioperative outcomes

NCDB cohort analysis

In the NCDB cohort, perioperative outcomes, including unplanned 30-day readmission, 30- and 90-day mortality, were assessed between RAT and OT groups (Table 1). The 30- and 90-day mortality rates were comparable between the two groups (P=0.69 and P=0.97, respectively). However, there was a trend toward lower 30-day readmission rates in the RAT group (1.5%) compared to the OT group (3.9%), although this difference did not reach statistical significance (P=0.06). To validate these findings with greater control over patient characteristics and clinical follow-up, we transitioned to analyzing our single-institution dataset. This dataset allowed for more detailed perioperative assessments, particularly regarding specific postoperative complications and trends in RAT utilization over time.

Single-institution analysis

In the single-institution cohort, RAT demonstrated superior perioperative outcomes, with significantly lower postoperative complication rates (4.8% vs. 31.8%, P=0.02) and a shorter LOS (2.1±2.3 vs. 4.3±2.3 days, P=0.003) compared to OT. These findings suggest that RAT offers a perioperative advantage consistent with previous studies highlighting the minimally invasive benefits of RAT.

Oncologic outcomes

NCDB cohort: OS

In the PSM cohort (n=500; 250 RAT and 250 OT), the subgroup analysis by tumor size indicated that RAT patients with tumors between 4-5 cm experienced improved survival compared to OT (adjusted HR =0.32, 95% CI: 0.11–0.88), while no OS advantage was observed for patients with tumors larger than 5 cm (Table 3). These results suggest that RAT offers similar long-term survival to OT, even for large thymomas, although further studies with extended follow-up may be necessary to confirm this observation.

Single-institution cohort: OS and RFS

In our single-institution cohort, OS and RFS were analyzed, with a median follow-up of 21.1 months for the RAT group and 67.8 months for the OT group. Both RAT and OT groups showed a comparable R0 rate, with 100% for RAT and 95.5% for OT (P=0.51). There was one recurrence (4.8%) in the RAT and three recurrences (13.6%) in the OT group (P=0.61). Kaplan-Meier survival curves for OS and RFS demonstrated no significant difference between the two groups (Figure 2). The single-institution cohort provided a more nuanced perspective on recurrence and long-term survival, reinforcing the NCDB findings that RAT does not compromise oncologic outcomes for large thymomas.

Figure 2 Recurrence-free and overall survival after robot-assisted vs. open thymectomy: single institution data.

Trends in utilization of RAT for large thymomas

Between 2008 and 2017, only five robotic surgeries were performed on thymomas larger than 5 cm in our institution. However, this number increased to 16 in the past 6 years, marking a 3.2-fold rise. Concurrently, the proportion of OT declined significantly over time, dropping from 69% during the first third of the study period (2008–2012) to 16% in recent years (Figure 3). This trend aligns with the evolution of robotic technology and increased surgeon experience, which may contribute to better outcomes and broader acceptance of RAT for larger thymomas.

Figure 3 The changes in the ratio of robotic surgery for >5 cm sized thymomas over time in our institution.

Socioeconomic and racial disparities in RAT access

An analysis of the NCDB cohort revealed notable disparities in access to RAT based on socioeconomic and racial factors. The proportion of African American patients was significantly higher in the OT group compared to the RAT group (18.7% vs. 10.8%; P=0.03) and patients with Medicaid or no insurance were more likely to undergo OT than RAT (14.5% vs. 7.3%, P=0.002) (Table 1). Logistic regression analysis confirmed these disparities, with African American race (OR =0.57, 95% CI: 0.34–0.93) and Medicaid/uninsured status (OR =0.53, 95% CI: 0.30–0.95) independently associated with lower odds of receiving RAT.

Discussion

The prevailing view that large thymomas should be managed with open surgery is based on the challenges posed by these tumors, particularly in the confined and delicate anterior mediastinum (12,15,16). However, advances in minimally invasive surgery, particularly RAT, have transformed this paradigm, allowing for enhanced precision and visualization, even in complex cases. Our study set out to determine the feasibility and efficacy of RAT compared to OT in patients with large thymomas. Through analysis of nationwide NCDB data, we found that RAT for thymomas larger than 4 cm demonstrated comparable R0 rates and survival outcomes compared to the conventional transsternal approach. Moreover, in a retrospective analysis of a single institution’s data, RAT for tumors larger than 5 cm maintained mid-term oncologic efficacy and resulted in fewer postoperative complications and shorter hospital stays. These insights underscore the potential of RAT as an effective alternative to OT for large thymomas.

Previous studies on large thymomas have similarly shown that RAT is safe, offers faster recovery, and has comparable R0 rates to OT. Kneuertz et al. (17) compared RAT and OT for thymomas larger than 4 cm using PSM in their single institutional analysis. Their results showed that RAT was associated with lower blood loss, shorter hospital stays, and similar postoperative complication rates without compromising R0 rates. Jiang et al. (8) also reported on the safety and efficacy of RAT in patients with thymomas larger than 6 cm. Their findings showed that, compared to OT, RAT had a shorter operation time, less blood loss, no difference in R0 rates, concomitant resections, and postoperative complication rates but higher in-hospital costs. Despite these promising short-term outcomes, long-term follow-up is still needed to fully assess the oncologic efficacy of RAT in the treatment of large thymomas.

Our trend analysis showed a steady increase in the utilization of RAT for large thymomas, particularly within our institution, where RAT adoption for tumors >5 cm increased from 31% during 2008–2012 to 84% during 2018–2023. This shift reflects growing confidence in robotic techniques and the accumulation of surgical expertise with the Da Vinci system, which has proven instrumental in overcoming the visual and operational challenges associated with large thymomas. As robotic systems continue to evolve and surgeons gain more experience, we anticipate that RAT will increasingly become the standard of care for large thymomas in well-equipped centers. This trend aligns with other studies indicating that centers with high robotic surgery volumes often report superior outcomes, suggesting that surgeon experience and case volume are crucial to maximizing the benefits of RAT (18-20).

Socioeconomic and racial factors appear to be key determinants of the type of surgical approach the patient receives, according to the NCDB analysis. A higher proportion of African American patients and patients with no insurance or Medicaid tended to receive an open surgical approach, while patients with insurance and the white population received a minimally invasive RAT approach. Similar trends were noted in other surgical specialties as well. Logan et al. (21) used the NCDB to investigate disparities in the utilization of the robot platform for patients who underwent radical prostatectomy. Similarly to our study, the study found that Black and Hispanic patients received robotic-assisted radical prostatectomy (RARP) at lower rates and that patients on Medicaid/uninsurance were less likely to undergo RARP. The authors pointed out that these disparities could affect perioperative outcomes in prostate cancer surgery. The rapid development of health technology has primarily originated from urban, well-funded, high-volume centers. These centers have led the swift transition from open surgery to minimally invasive surgical techniques. Notably, the use of robotic thoracic surgery has increased exponentially (22). However, patients residing in impoverished, rural areas continue to have limited access to robotic surgery (23). Several systemic factors may contribute to this gap, including unequal distribution of high-resource hospitals, geographic limitations, lack of insurance coverage, and potential implicit bias in surgical decision-making. To address these disparities, efforts should focus on expanding access to robotic technology through strategic allocation of resources, surgical training programs in underserved areas, and implementation of institutional protocols that promote equitable patient selection. Furthermore, ongoing monitoring of demographic data in national databases such as the NCDB can help identify trends and guide policy interventions aimed at minimizing procedural inequity.

Given the rarity of large thymomas, our study has the strength of gathering a large cohort of patients from various academic and community centers. This enabled subgroup analyses based on tumor size stratification and PSM, making the findings applicable to a wider range of medical settings. Additionally, our single-institution data analysis allowed us to more comprehensively address the NCDB’s shortcomings in perioperative outcomes. However, there are some limitations. First, the retrospective design of this study introduces potential selection bias. Second, the NCDB does not include information on specific robotic surgical approaches (e.g., lateral vs. subxiphoid), concomitant procedures, or postoperative complications. Each robotic approach has distinct advantages and limitations. The lateral approach allows for easy visualization of anatomical structures, but it provides limited access to the contralateral phrenic nerve and the distal left brachiocephalic vein. In contrast, the subxiphoid approach offers excellent exposure to the anterior mediastinum, although maneuverability near the lower thymic pole may be compromised (24). Although all robotic thymectomies in our single-institution cohort were performed using the lateral thoracic approach, the NCDB does not distinguish between these techniques. Therefore, further studies are warranted to determine the optimal surgical approach, particularly in the management of large thymomas. Another limitation is the lack of detailed tumor location data (e.g., left vs. right, cranial vs. caudal) in the NCDB, which prevents evaluation of how tumor position within the thymus may affect surgical complexity, operative time, or conversion risk. Although no conversions to open surgery were observed in our institutional series based on a review of operative reports, we did not conduct a formal analysis of operative time relative to tumor location. As robotic thymectomy is increasingly utilized for large thymomas, further investigation into the influence of tumor location on surgical outcomes would be a valuable area for future research. Third, the follow-up period for our institutional data is relatively short (RAT, 21.1 months vs. OT, 67.8 months), limiting our ability to accurately report on RFS or OS. Recurrence and survival analyses should be interpreted with caution due to the imbalance in follow-up duration. Fourth, the NCDB lacks direct clinical staging information. Although we initially considered reconstructing staging using surrogate variables (e.g., tumor extension and invasion status), variability in data quality and completeness across institutions limited the reliability of this approach. To address this limitation, we referenced detailed staging data from our institution cohort, which provides a more granular clinical context and supports the rationale for using tumor size as a surrogate marker in the national dataset analysis. Fifth, this study was based on NCDB data available up to 2017, which reflects outcomes during the early adoption phase of robotic thoracic surgery, largely coinciding with the da Vinci Si platform. At the time of data extraction, more recent datasets such as the 2022 public use file were not yet available. We acknowledge that our findings represent a historical perspective rather than the current landscape of thymoma resection. Future studies incorporating updated data will be necessary to evaluate the impact of newer robotic platforms and accumulated surgical experience on clinical outcomes. Finally, there was a significant difference between the R0 rates shown in the NCDB (RAT: 68.3% and OT: 66.0%) and those in our institutional data (RAT: 100% and OT: 95.5%). Yang et al. (25) also reported relatively low R0 rates for >4 cm sized thymomas in their study using the NCDB, with video-assisted thoracic surgery/RAT at 70.8% and OT at 71.5%. The low R0 rates observed in the NCDB likely reflect heterogeneity in data submission across institutions and variations in intraoperative margin assessment protocols. At our institution, intraoperative frozen section analysis is routinely performed in all cases where close resection margins are a concern, which may explain the higher R0 rates observed in our dataset. Unfortunately, the NCDB does not provide data on margin assessment techniques or the use of adjuvant therapy. We need more clues to explain whether this discrepancy is due to inaccuracies in margin status, inconsistencies in some measurement factors, or the actual experience of the surgeons.

Conclusions

RAT is associated with reduced postoperative complications and shorter hospital stays, while maintaining comparable or improved survival rates compared to OT, even in patients with large thymomas. This study supports using robotic techniques for large thymomas in well-selected patients. However, to draw more definitive conclusions, large-scale prospective studies are needed.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-714/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-714/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-714/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-714/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The single-institution analysis was approved by Institutional Review Board (IRB) of Northwestern University (No. STU00206649), with informed consent waived due to the retrospective nature of the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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