A robotic-assisted thymectomy is equivalent to a transsternal resection in large thymomas

Introduction

Although rare, thymomas remain the most common primary anterior mediastinal neoplasm (1). Surgical treatment remains the mainstay of treatment for thymomas for both the primary and recurrent tumors (1-4). For years, the standard surgical approach has been a sternotomy. Recently, several studies have demonstrated the safety and efficacy of various minimally invasive approaches, including video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS) for thymectomy.

VATS and RATS appear to be associated with decreased operative time, patient hospital length of stay (LOS), and postoperative complication rates compared to open thymectomy (OT) (5). In addition, a recent study by Raveglia et al. suggested that RATS has more favorable outcomes compared to VATS thymectomy in early Masaoka stages I and II (6). Most studies have advocated for a RATS approach for small, well encapsulated lesions and have identified tumor size >5 cm as a predictor of recurrence and poor prognosis (7,8). Nevertheless, little data exists to assess the feasibility, safety, and efficacy of RATS for large thymomas measuring ≥5 cm. This study uses a large national database to compare oncological and perioperative outcomes associated with OT versus RATS for these larger tumors. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-637/rc).

Methods

Study design and outcomes

This is a retrospective study using the National Cancer Database (NCDB) to identify all patients with thymoma from 2010–2020. The NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society that captures ~72% of all newly diagnosed cancer cases in the United States. It collects information from over 1,500 Commission on Cancer-accredited US centers and contains over 20 million patient records (9). The 2020 NCDB participant use data file was identified for inclusion using topography codes. The years 2010–2020 were selected because surgical approach data was unavailable before 2010, and the latest data available was in 2020. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

Only patients who were diagnosed with thymoma (using the histology thymoma codes 8580–8585, 858–859) and had available data on surgical approach (OT or RATS) were included. Patients were excluded if they had missing survival status, no surgical approach identified, neoadjuvant therapy, or intraoperative systemic therapy. The primary outcome of interest was overall survival (OS) between OT and RATS. Secondary outcomes included hospital LOS, 30-day readmission rate, and 30-day and 90-day mortality rates.

Statistical analysis

Patients were grouped based on surgical approach, OT versus RATS. Baseline characteristics and outcomes were identified as categorical variables and presented as frequencies and percentages and compared using Pearson’s Chi-squared test. After testing for normality, continuous variables were expressed as mean and standard deviation or median and interquartile range (IQR) and compared using t-test or Mann-Whitney U test, respectively. OS was estimated from the date of diagnosis to the last known follow-up date or death from any cause. Univariable and multivariable predictors of mortality were evaluated using Cox proportional hazards regression analysis. Differences in perioperative, postoperative, and OS between the two surgical approaches were assessed using a propensity score-matched analysis of OT versus RATS, controlling for age, race, facility type, tumor size, comorbidity index, and year of diagnosis. Patients who underwent OT and RATS were matched 1:1 based on their propensity scores using nearest-neighbor matching with a caliper at 0.2. Standardized mean difference (SMD) was used to assess the balance of matched variables between both groups, with SMD <0.1 reflecting proper balance. After propensity score matching, OS was estimated and presented using Kaplan-Meier curves. All analyses were performed using MatchIt on RStudio and IBM Statistical Package for the Social Sciences Software (version 29.0; SPSS, Inc., Chicago, IL, USA).

Results

Using the 2004–2020 NCDB database, 9,325 patients were identified with thymoma. A total of 5,644 patients were excluded due to tumor size <5 cm; 2,077 patients were excluded as they did not have an approach identified as approach data has been present only since 2010; 19 patients were excluded due to missing survival status; 281 patients were excluded because they underwent neoadjuvant therapy; 126 patients were excluded because they underwent a VATS approach (Figure S1). A total of 1,178 patients were finally included in the study analysis, of which 1,015 (86.2%) underwent an OT approach, and 163 (13.8%) underwent a RATS approach.

Baseline demographics are presented in Table 1. Patients who underwent an OT approach were younger, with a mean age of 58.16±14.36 years (P=0.049). More black patients underwent OT (19.8% versus 12.3% in the RATS approach), while more Asian patients underwent a RATS approach (14.1% versus 8.7% in the OT group; P=0.03). RATS was more likely to be performed in academic centers than OT cases (73.8% versus 61.5%; P=0.004). Also, patients who underwent the OT approach were more likely to be uninsured (5.6% versus 1.2% in the RATS group, respectively). In comparison, RATS patients were more likely to have governmental insurance than OT (48.5% versus 41.6%, respectively, P=0.03).

Pathologic outcomes are presented in Table 2. The RATS approach was more likely to have a smaller median tumor size (6.50 cm) versus the OT approach (7.50 cm, P<0.001). There was no significant difference between the two groups in the World Health Organization (WHO) histologic type. The RATS group had a significantly shorter LOS compared to the OT group (2 versus 4 days, respectively; P<0.001) (Table 3). However, there was no difference between the two groups regarding the 30-day readmission rate (5.2% in the OT group versus 2.5% in the RATS group, P=0.13). Also, there was no difference between the two groups in 30-day mortality rates (0.7% in OT versus 1.2% in the RATS approach, P=0.47) or 90-day mortality rates (1.2% in OT versus 1.2% in the RATS approach, P=0.96).

The median follow-up of the entire cohort was 85 (IQR, 66–107) months. Kaplan-Meier analysis showed no significant difference in OS, with a 5-year OS of 87% in the OT group and 90% in the RATS group (P=0.14) (Figure 1). Factors associated with decreased survival on univariable analysis were older age [hazard ratio (HR) =1.037, 95% confidence interval (CI): 1.027–1.048, P<0.001], males (HR =1.176, 95% CI: 0.923–1.499, P=0.11), higher comorbidity index, governmental insurance (HR =2.144, 95% CI: 1.671–2.752, P<0.001), community center (HR =1.223, 95% CI: 0.948–1.579, P=0.12), tumor size (HR =1.043, 95% CI: 1.004–1.084, P=0.03), WHO histologic type A (HR =1.482, 95% CI: 0.944–2.326, P=0.09), and WHO histologic type B3 (HR =1.927, 95% CI: 1.301–2.852, P=0.001). On multivariable analysis, older age (HR =1.038, 95% CI: 1.023–1.053, P<0.001), higher comorbidity index, government insurance (HR =1.456, 95% CI: 1.051–2.018, P=0.02), tumor size (HR =1.073, 95% CI: 1.033–1.124, P<0.001), and WHO histologic type B3 (HR =2.067, 95% CI: 1.366–3.128, P<0.001) remained independent predictors of decreased survival. The surgical approach was not a predictor of reduced survival (Table 4).

Figure 1 Kaplan-Meier overall survival curve of unmatched patient with thymoma who underwent open or robotic-assisted thymectomy. Percentages in parentheses are overall survival rates. OT, open thymectomy; RATS, robotic-assisted thoracoscopic surgery.

Propensity score-matched analysis

Propensity score matching was performed to create two groups of 163 patients that underwent an OT or RATS approach. These patients were matched on age, race, facility type, tumor size, comorbidity index, and year of diagnosis. All SMDs were less than 0.1 (Figure S2). There was no significant difference between the groups in terms of baseline demographics and pathologic characteristics, except patients who underwent the RATS approach had a shorter LOS (2 versus 4 days in the OT approach, P<0.001) (Table S1). The median follow-up of the matched cohort was 76 (IQR, 48–97) months. There was no significant difference in OS between the two groups. 5-year OS was 88% after OT versus 90% after a RATS approach (HR =0.721, 95% CI: 0.424–1.226, P=0.23) (Figure 2).

Figure 2 Kaplan-Meier overall survival curve of matched patient with thymoma who underwent open or robotic-assisted thymectomy. Percentages in parentheses are overall survival rates. OT, open thymectomy; RATS, robotic-assisted thoracoscopic surgery.

Discussion

In this large national retrospective study, we found that most patients underwent an OT approach for thymomas measuring ≥5 cm. Nonetheless, patients who underwent a RATS approach had similar OS, 30-day readmission rates, and mortality rates compared to those who underwent an OT approach. However, the RATS group had a shorter hospital LOS in both the unadjusted and the propensity score-matched analysis. These findings remain consistent within the literature and are further supported by single institutional and national retrospective studies demonstrating similar survival and postoperative outcomes between the standard OT approach and minimally invasive thymectomies (5,6,10) in small thymomas. Our group, as well as others, have demonstrated that in small thymomas, a RATS approach is viable and oncologically sound. We have previously reported that the RATS approach was associated with lower intraoperative blood loss, decreased duration of chest tube drainage, and shorter LOS compared to the OT approach (11). Given these data, RATS has become our first choice for early small to moderate sized thymomas.

To date, there is little supportive data for RATS in larger lesions, measuring greater than 5 cm. While there has been no consensus on what defines a large thymoma, historically, 5 cm has been chosen to define a higher risk of recurrence following surgical resection (7,8). There is some concern that RATS may be more likely to cause capsule rupture and subsequent dissemination of disease that would lead to early pleural or local recurrence. However, there is limited data to support that notion. While several studies have suggested larger thymomas were associated with worse outcomes, the ability to deliver an R0 resection is the most critical determinant in patient outcomes, especially for recurrence (7,8). In Liu et al.’s retrospective review, they reported a tumor size cutoff point of 5 cm that predicted thymoma recurrence (8). Also, a study by Okumura and colleagues showed on multivariable analysis that tumor size >5 cm, WHO histologic type, and Tumor-Node-Metastasis (TNM) pathologic stage were independent predictors of recurrence (7). They reported that tumor size was associated with completeness of the surgical resection, WHO histology type, and the pathologic stage. Although the tumor size is not considered in the Masaoka staging or the TNM staging system, Okumura et al. report an association between tumor size and TNM staging (7).

There have been small institutional reports that have suggested that VATS is viable for larger thymomas. Takeo et al. report that a VATS thymectomy in tumors larger than 5 cm was technically challenging but feasible (12). In this small retrospective review, Takeo and colleagues reported a median tumor size of 5.2 cm in all patients receiving an R0 resection. In this series, only 1/19 recurred. Marulli et al. also reported that the RATS approach had an advantage over VATS with better visibility and a better ability to discern malignant versus non-malignant tissue, which led to a more precise dissection and less manipulation of thymic and peri-thymic tissue (10).

This current study supports the notion that tumor size alone should not be the limiting factor in determining the surgical approach. Instead, the ability to offer an R0 resection remains the single most important prognostic indicator in patients’ outcomes (7,10). Ultimately, this study shows the feasibility of performing a RATS in large tumors. However, the surgeon’s clinical decision plays a role in determining if a minimally invasive approach is appropriate and will lead to a complete pathologic resection. There are limitations to this study due to its retrospective nature, such as selection bias, which we tried to address using propensity score matching analysis. Secondly, the NCDB lacks data on recurrence and disease-free survival. This database also does not delineate the postoperative complications; variables such as readmission rates and LOS were used as a proxy to assess postoperative outcomes.

Conclusions

In conclusion, RATS in large thymomas (≥5 cm) is feasible. RATS appears to be oncologically sound, with similar survival and postoperative outcomes, and is associated with a shorter hospital LOS compared to the standard OT approach.

Acknowledgments

The data used in the study are derived from a de-identified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data by the investigators.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-637/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-637/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-637/coif). B.L. receives speaker fees from AstraZeneca. N.A. received grants or contracts from AstraZeneca and Roche/Genentech, and has ownership interest in Angiocrine Bioscience, TMRW and Viewpoint Medical. J.P. has ownership interest in Angiocrine Bioscience, TMRW and Viewpoint Medical. The other 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 (as revised in 2013). This study used de-identified data from the NCDB and so IRB approval and patient consents were not required.

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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