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. Author manuscript; available in PMC: 2020 Oct 15.
Published in final edited form as: J Thorac Oncol. 2016 Jan;11(1):30–38. doi: 10.1016/j.jtho.2015.08.004

Minimally invasive versus open thymectomy for thymic malignancies: systematic review and meta-analysis

Adam J Friedant 1, Elizabeth A Handorf 1, Stacey Su 1, Walter J Scott 1
PMCID: PMC7560956  NIHMSID: NIHMS1634604  PMID: 26762737

Abstract

Introduction:

Complete resection is the standard of care for treatment of thymic malignancies. The use of minimally invasive surgery remains controversial.

Methods:

We searched online databases and identified studies from 1995 to 2014 comparing minimally invasive (MIS) to open thymectomy for thymic malignancies. Study endpoints included operative blood loss, operative time, respiratory complications, cardiac complications, length of stay (LOS), R0 resection, and recurrence. We summarized outcomes across studies using random-effects meta-analysis to account for study heterogeneity. We calculated odds ratios (OR) for binary outcomes and standardized mean differences for continuous outcomes. We calculated incidence rate ratios (IRR) for the number of recurrences, accounting for total person-time observed in each study.

Results:

Of 516 potential references, 30 studies with a total of 2038 patients met the inclusion criteria. Masaoka stage I-II comprised 94.89% of MIS patients and 78.62% of open patients. Mean tumor size was 4.09 cm (MIS) and 4.80 (open). 32 of 1355 MIS cases were converted to open. MIS patients had significantly less blood loss, but no significant difference in operating time, respiratory complications, cardiac complications, or overall complications. LOS was shorter for MIS patients. Analyzing Masaoka I - II patients only, there was no difference in R0 resection rate or overall recurrence rate. There was one postoperative death in the open group.

Conclusions:

The results of this unadjusted meta-analysis of published reports comparing MIS to open thymectomy suggest that MIS thymectomy is safe and can achieve similar oncologic outcomes to open thymectomy in selected patients with thymic malignancy.

Introduction:

Thymic malignancies (thymomas and thymic carcinomas) are rare cancers whose etiologies and risk factors are not well understood.1–13 Complete (R0) surgical resection is the standard of care for thymic malignancies, but the safest, most effective method of resection is controversial.7,9,13–26 Minimally invasive surgery, including robotic-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS), is a newer alternative to open approaches like median sternotomy and thoracotomy. Many surgeons are reluctant to adopt minimally invasive approaches because they are concerned that these techniques may be associated with increased manipulation of the tumor with a corresponding risk of capsular disruption, tumor seeding of the pleura, incomplete resection, and increased risk of local recurrence.

Current research suggests that minimally invasive thymectomy for early-stage thymic malignancies may be correlated with shorter length of hospital stay (LOS) and lower intraoperative blood loss in comparison to open thymectomy.27–34 The literature suggests that minimally invasive surgery may be as effective as, or better than open thymectomy in treating small, early-stage thymic malignancies.25,26,32,33,35,36 Further, studies have shown comparable survival data and oncologic outcomes between the two procedures.30,37,38 However, these claims are limited by small sample size and lack of long-term follow-up comparisons between minimally invasive and open thymectomy patients. Additionally, fewer studies focus on thymectomy performed for thymic malignancies as opposed to including thymectomy performed for myasthenia gravis.7,8,12,16,19,21,33,36,38–40

The purpose of this meta-analysis was to compare perioperative and long-term outcome variables between MIS and open thymectomy for thymic malignancies using the current body of literature in order to determine if MIS thymectomy is as safe as oncologically effective as open surgery.

Materials and Methods:

Search Strategy

A thorough literature review was performed using the following online databases: PubMed, Science Direct, Oxford Journals, Springer, Sage Journals, and Ovid. References and related PubMed citations for retrieved articles were also reviewed for potential inclusion in our meta-analysis. The search period lasted from May 2014 to September 2014, and we used appropriate free text terms including “thymoma”, “thymectomy”, “minimally invasive thymoma”, “minimally invasive thymectomy”, and “minimally invasive thymic carcinoma” in our search.

Study Selection

All studies included in our meta-analysis of thymectomy for thymic malignancies were published in English. Studies were analyzed if they detailed a comparison between any type of MIS thymectomy and any type of open thymectomy for thymoma and/or thymic carcinoma. Not all studies were included in the analyses for each endpoint. Studies with only one arm were included in the evaluation for demographics (age and gender), tumor characteristics (stage and size), and open conversion rate.

Any studies indicating minimally invasive and/or open thymectomy for other benign conditions alone (myasthenia gravis, thymolipomas) or non-thymic malignancies alone (germ cell tumors lymphoma, lung cancer) were excluded.

Data Extraction

One investigator independently reviewed each included article under the guidance of two faculty members from the same center. Study endpoints included some or all of the following: age (years), gender, mean blood loss (mL), open conversion rate, R0 resection rate, mean operative time (minutes), mean tumor size (cm), respiratory complication rate, cardiac complication rate, overall complication rate, LOS (days), perioperative mortality, mean follow-up time (months), and locoregional recurrence.

Statistical Analysis

The Methodological Index for Non-Randomized Studies (MINORS) was applied to all of the included studies, and then to comparative studies only, to determine quality.41 Outcomes were summarized across studies using random-effects meta-analysis to account for study heterogeneity. We calculated odds ratios (OR) for binary outcomes and standardized mean differences for continuous outcomes. Incidence rate ratios (IRR) were calculated for the number of recurrences, accounting for total person-time observed in each study.

Results:

We identified 516 references through the search criteria stated above. 30 studies, with publication dates ranging from 1995 to 2014, contained pertinent perioperative and long-term outcome information regarding one or both modalities of thymectomy for thymic malignancy. All included articles were nonrandomized and retrospective. MINORS criteria was applied to all 30 studies, with a mean of 9.87, and then to the 16 comparative studies exclusively, with a mean of 17.93.

Demographics were calculated using the subset of 16 comparative studies. Mean tumor size was 4.09 cm (range 3.23–5.76 cm) for MIS and 4.80 cm (range 3.76–7.47 cm) for open procedures. Of the 16 comparative studies, 7 studies examined Masaoka I-II patients only. For the other 9 comparative studies, 80.49% (N=82) of MIS patients and 66% (N=164) of open patients were either Masaoka stage I or II. In all 16 comparative studies, 94.89% (N=841) of MIS patients and 78.62% (N=870) of open patients were Masaoka stage I or II. The mean age was 52.34 years (range 47–63.1 years) for MIS patients and 52.72 years (range 47–65.4 years) for open patients. 48.52% (range 35.29%−63.64%) of MIS patients and 47.14% (range 16.67%−61.11%) of open patients were male 32 of 1355 (2.36%) MIS cases were converted to open, as shown in Figure 1. We found mean blood loss to be significantly less in MIS patients than open patients (226 vs. 169 mL, std diff = −0.78, 95% CI −0.97 – 0.57, p < 0.01), as shown in Figure 2. There was no significant difference between MIS patients and open patients in operative time (164.92 vs. 147.18 min, std diff = 0.13, 95% CI −0.28 – 0.54, p = 0.53), as shown in Figure 3. LOS was shorter for MIS patients (8d MIS vs. 9d open, std diff = −0.88, 95% CI −1.52 – −0.24, p < 0.01), as shown in Figure 4. There was no significant difference in respiratory complications (13 MIS vs. 38 open, OR = 0.79, 95% CI 0.29 – 2.16, p= 0.64), as shown in Figure 5. There was also no difference in cardiac complications (7 MIS vs. 21 open, OR = 0.73, 95% CI 0.28 – 1.92, p = 0.52), as shown in Figure 6. Finally, there was no significant difference between MIS patients and open patients in the overall complication rate (32 MIS vs. 63 open, OR = 0.90, 95% CI 0.41 – 1.93, p = 0.78), as shown in Figure 7.

Figure 1.

Figure 1.

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MIS vs. open thymectomy, open conversion

Figure 2.

Figure 2.

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MIS vs. open thymectomy, blood loss (mL)

Figure 3.

Figure 3.

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MIS vs. open thymectomy, operative time (min)

Figure 4.

Figure 4.

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MIS vs. open thymectomy, LOS (days)

Figure 5.

Figure 5.

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MIS vs. open thymectomy, respiratory complications

Figure 6.

Figure 6.

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MIS vs. open thymectomy, cardiac complications

Figure 7.

Figure 7.

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MIS vs. open thymectomy, all complications

Additionally, there was no significant difference in R0 resection rate (OR = 0.82, 95% CI 0.38 – 1.73, p = 0.60), as shown in Figure 8. There was no significant difference in locoregional recurrence (IRR = 1.57, 95% CI 0.47 – 5.26, p = 0.46), as shown in Figure 9. In the subset of Masaoka I-II patients, there was no difference in R0 resection rate (N = 711, 97.36% vs. 97.25%, OR = 0.98, 95% CI 0.23 – 4.14, p = 0.88) or locoregional recurrence rate (N = 234, 2.86% vs. 2.91%, IRR = 2.10, 95% CI 0.39 – 11.25, p = 0.39), as shown in Figures 10 and 11.

Figure 8.

Figure 8.

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MIS vs. open thymectomy, R0 resections

Figure 9.

Figure 9.

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MIS vs. open thymectomy, locoregional recurrences

Figure 10.

Figure 10.

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MIS vs. open thymectomy, Masaoka I/II subset, R0 resections

Figure 11.

Figure 11.

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MIS vs. open thymectomy, Masaoka I/II subset, locoregional recurrences

Discussion:

Minimally invasive surgical (MIS) techniques have become more widely adopted in some areas of thoracic surgery as the results of clinical series of patients with lung and esophageal cancers have become more mature. However, many surgeons remain reluctant to adopt MIS techniques for the treatment of patients with thymic malignancies for several reasons. Perhaps most commonly, critics have stated MIS could lead to incomplete resection or tumor seeding and therefore to increased local recurrence rates and decreased overall survival. We systematically identified and evaluated the existing data comparing the clinical outcomes of MIS thymectomy to open thymectomy using the techniques of meta-analysis. Because there are few long-term survival data available and since complete resection is an important determinant of recurrence-free survival in patients with thymic malignancy,12,14 we focused on complete resection rates and limited local recurrence data as surrogate oncologic outcome measures.

We found that there was no statistical difference in R0 resections overall in either the MIS or open groups, although the trend favored the MIS patients. The only statistically significant clinical outcomes that we observed were decreased blood loss and shorter hospital LOS, both favoring the minimally invasive group. We observed no differences in operating time or complications between the two groups. Because patients with larger tumors would more likely be assigned to undergo open surgery, we separately evaluated patients who were clinically staged by the investigators of the various trials as Masaoka I and II and found no difference in R0 resection rate in this smaller subset of patients. Data on local recurrence was mentioned in only a few of the published reports of patients with clinical early stage tumors. Based on these limited data, we observed no difference between the two groups regarding local recurrence rates.

Our meta-analysis is limited by the inclusion of only nonrandomized, retrospective studies. We found no randomized or prospective studies that met out criteria in our literature review. Furthermore, there is a paucity of long-term follow up data for patients who have undergone thymectomy for thymic malignancies. Our analysis was constrained by the inability to perform propensity matching because of small aggregate sample size and difficulty in obtaining individual patient information from the included studies. These factors led to increased heterogeneity within the analysis.

We were unable to identify factors from this analysis that would help surgeons to select appropriate patients for minimally invasive as opposed to open thymectomy approaches. Certainly, if initial attempts at MIS resection are deemed by the surgeon to be unlikely to lead to a complete resection or to violate any other principles of oncologic surgery, then conversion to open thymectomy surgery should be performed. Interestingly, conversion to open surgery was reported in only 2.4% of cases in our review suggesting that, given similar rates of R0 resection, most of the surgeons had appropriately selected patients for MIS thymectomy. Based on the findings of this meta-analysis, we conclude that for selected patients minimally invasive thymectomy is safe and can achieve rates of complete (R0) resection comparable to that of open thymectomy operations. Data on long-term cancer-specific outcomes awaits the mature results of longitudinal studies and international efforts such as the International Thymic Malignancy Interest Group (ITMIG) database.

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