Surveillance of thymic epithelial tumors (TETs)—a narrative review
Review Article

Surveillance of thymic epithelial tumors (TETs)—a narrative review

Giye Choe ORCID logo, Nassrene Elmadhun

Department of Thoracic Surgery, Kaiser Permanente Northern California, Oakland, CA, USA

Contributions: (I) Conception and design: G Choe; (II) Administrative support: Both authors; (III) Provision of study materials or patients: G Choe; (IV) Collection and assembly of data: Both authors; (V) Data analysis and interpretation: Both authors; (VI) Manuscript writing: Both authors; (VII) Final approval of manuscript: Both authors.

Correspondence to: Giye Choe, MD, FACS. Department of Thoracic Surgery, Kaiser Permanente Northern California, 3rd Floor, 3600 Broadway, Oakland, CA 94612, USA. Email: giye.x.choe@kp.org.

Background and Objective: Surveillance after thymic epithelial tumors (TETs) is widely recommended yet poorly studied. While this is not a situation unique to TETs, we seek to evaluate the rational of surveillance after treatment of TETs and summarize current available guidelines.

Methods: A literature review was conducted in PubMed/MEDLINE and Google Scholar databases. Articles were included if they discussed the following: (I) the epidemiology and natural history of TETs; (II) the diagnosis of recurrent TETs; (III) the treatment and outcomes of recurrent TETs; (IV) current available guidelines for surveillance or follow-up after treatment of TETs.

Key Content and Findings: TETs are rare group of neoplasms that include thymoma, thymic carcinoma and neuroendocrine neoplasms. Thymomas have excellent overall survival but can recur over longer periods of time compared to other malignancies. Thymic carcinoma and neuroendocrine neoplasms have less favorable outcomes but still have prolonged survival even at advanced stages. Moreover, recurrence tends to be asymptomatic and localized to the chest and pleura, making it amenable to local treatments such as surgery and/or radiation. As such, TETs may be positioned to benefit from surveillance but also present unique challenges regarding surveillance. There are no prospective studies addressing surveillance in TETs, but at least 5 guidelines have made recommendations that mostly recommend computed tomography (CT) of the chest in variable frequencies and durations. Most agree that the duration for thymoma surveillance should be 10 years or longer. Thymic malignancies are frequently associated with paraneoplastic syndromes which can be a symptom of recurrence, and knowledge of these disorders should be a component of surveillance.

Conclusions: Surveillance after treatment for TETs is felt to be beneficial, but there is a paucity of evidence directly studying this. Currently available guidelines do offer some direction based on expert opinion. Given the rare occurrence of TETs and recurrences after treatment, pooling of data such as the International Thymic Malignancy Interest Group (ITMIG) database to study follow up will be necessary to develop more effective surveillance strategies.

Keywords: Surveillance; thymic epithelial tumors (TETs); thymoma; thymic carcinoma; guidelines

Received: 03 April 2025; Accepted: 19 June 2025; Published online: 25 June 2025.

doi: 10.21037/med-25-20

Introduction

After completion of curative treatment, a cancer patient often asks ‘what now’? With the awareness that cancer can recur after curative treatment, there is an implicit understanding that cancer survivors should then be monitored for recurrence. This monitoring—surveillance—is by no means the entirety of a cancer survivor’s unique needs, but is an important part of survivorship care, in addition to monitoring and ameliorating symptoms related to the treatment rendered and chronic conditions (1). As cancers are detected at earlier stages, and more successful treatment strategies are developed and introduced, over 20 million cancer survivors are anticipated to live within the US alone in 2025 (2). Yet, surveillance has been poorly studied, and evidence that surveillance prolongs survival or improves quality of life are severely limited (3).

Nearly all surveillance guidelines are based on expert opinion and for thymic epithelial tumors (TETs) in particular there is a paucity of data to guide surveillance practices. There is not a single study prospectively evaluating the effectiveness of surveillance in TETs that we are aware of.

The objective of this review is to evaluate the rationale of surveillance of TETs and current available guidelines. We present this article in accordance with the Narrative Review reporting checklist (available at https://med.amegroups.com/article/view/10.21037/med-25-20/rc).

Methods

A search of literature was conducted between November 15th and December 31st, 2024, in the following databases: PubMed/MEDLINE and Google Scholar databases. A search strategy summary is included below (Table 1). Articles were reviewed and included if they described (I) the epidemiology and natural history of TETs; (II) the diagnosis of recurrent TETs; (III) the treatment and outcomes of recurrent TETs; (IV) current available guidelines for surveillance or follow-up after treatment of TETs.

Table 1

The search strategy summary

Items Specification
Date of search November 15–December 31, 2024
Databases searched PubMed/MEDLINE, Google Scholar
Search terms used “Thymoma”, “thymic carcinoma”, “thymic epithelial tumor/neoplasm”, “epidemiology”, “outcomes”, “recurrence”, “paraneoplastic syndrome”, “surveillance”, “follow up”
Timeframe No restriction on publication date of included articles
Inclusion No restriction on study type. All included articles were written in English
Selection process Selection process was independently conducted by G.C.

Surveillance of TETs

General considerations

A surveillance strategy’s success depends on (I) the testing modality’s ability to accurately diagnose a recurrence, and (II) whether a detected recurrence can be successfully treated to either improve survival or quality of life. (III) Detection of recurrence should ideally occur at a preclinical, asymptomatic phase of disease for a surveillance strategy to be useful. If recurrent disease can be treated effectively for subsequent durable disease-free interval there is potential for a positive impact of surveillance. However, patients who develop asymptomatic, gradually progressive recurrences may also be able to defer treatment for a prolonged time without adverse effect to quality of life or longevity, and aggressive surveillance studies can result in overtreatment without meaningful improvement in outcomes due to lead-time bias. Balancing these considerations is key to an effective surveillance strategy and treatment decision. Surveillance should include detection of secondary cancers and assess the long-term effects of the treatment. Finally, the surveillance strategy should take into consideration the financial, emotional and clinical burden of the surveillance imaging and subsequent follow-up. (IV) TETs are a unique group of malignancies that present unique challenges regarding surveillance but may also be positioned to benefit from surveillance (4). In this review, we aim to go over TETs surveillance and summarize currently available guidelines.

TETs after initial treatment

TETs are a rare group of neoplasms that include thymoma, thymic carcinoma and neuroendocrine neoplasms. The estimated incidence is 0.13–0.50 per 100,000 people annually (5-9). Some studies have demonstrated an increase in the incidence of TETs (8,9) which is likely due to an increase in imaging studies rather than a true increase in the incidence. There is emerging evidence that there is racial disparity in the incidence of TETs, with black and Asian/Pacific Islander people at higher risk than whites (5,9,10). However, it remains true that TETs, particularly thymomas, have excellent overall survival, with overall 5-, 10- and 15-year survival of 82–90%, 67–84%, and 57–73% respectively (8,11,12). Thymic carcinomas and thymic neuroendocrine neoplasms have less favorable outcomes, with 5-year survival of 52–46.2% (8,13). Given the relatively indolent behavior of thymomas patients also have a relatively long disease-free survival with 10-year recurrences in 14–21% of patients after surgery (14-16). Moreover, at all stages including stage IV [in both Masaoka and tumor-node-metastasis (TNM) staging], patients with TETs tend to have prolonged survival, measured in years (17). This means that while the incidence of TETs is low, the prevalence of TET survivors tends to be relatively high. Unfortunately, at present there are no published epidemiologic data available to provide the exact number of TET survivors.

Surgery is a key component to treatment and is often deployed for all stages of treatment. Perioperative systemic treatment and radiation are also deployed as needed, particularly for higher stages. Notably, recurrence of thymomas tends to be localized to the chest and pleura and can be amenable to local therapy such as surgery or radiation (14,15,18). Local treatment such as surgery has been shown to prolong survival in recurrences (14,18,19), and many recurrences are asymptomatic. Some patients undergo multiple local treatments throughout their disease course as they develop additional recurrences, usually in the pleural space. Treatment strategies should be carefully considered in a multidisciplinary fashion as overtreatment can lead to complications and increased cost, and overall diminished quality of life. Local treatments such as surgery and radiation both have challenges as repeat attempts have an increased burden on the patient (14,18), even if a disease-free state is achieved after each recurrence.

TETs can recur far out from the time of initial treatment, with documented recurrence timelines stretching past a decade (20). This raises the question of the economic cost of surveillance, but also the psychosocial burden to the patient. Psychosocial issues that adversely affect patients include depression, anxiety, post-traumatic stress disorder, difficulty returning to work, financial hardships and fear of recurrence (2). A prolonged need for active surveillance must be balanced with the patient’s needs, and physicians treating TETs must be prepared to support patients through a longer disease follow-up than many other malignancies, which usually follow survivors for 5 years (21-24).

Such unique natural history of TETs poses unique challenges for surveillance. Its indolent course requires a longer surveillance duration than most malignancies, but its tendency to recur locally with available treatment options demonstrate potential for surveillance to effect patient outcomes. Unfortunately, surveillance of TETs has not been studied in a systematic way, and there is no high-quality data currently available. It is still unclear what the ideal duration of surveillance should be in TETs.

Guidelines

Currently available guidelines from various groups are available have varied recommendations when it comes to surveillance. Despite some guidelines’ assessment that the strength of the recommendation is strong, it is our opinion that all current recommendations are made based on indirect evidence and mostly reflect consensus expert opinion, highlighting the need for further study.

Below we summarize currently available surveillance recommendations from various societies on management of TETs (Table 2) (25-29). All guidelines attempt to differentiate between TET patients who have a low risk of recurrence, vs those who have high risk disease. Thymomas, particularly World Health Organization (WHO) A, AB and B1, are thought to be indolent, whereas thymic carcinoma and thymic neuroendocrine neoplasms are found to be more aggressive and have less favorable outcomes. Liu et al. assessed additional clinical characteristics of TET patients to further delineate low vs high-risk patients and found that WHO histologic type and International Association for the Study of Lung Cancer/International Thymic Malignancy Interest Group (IASLC/ITMIG) T stage were independent indicators of recurrence (30). Patients with T1 thymomas or T2 or T3 type A, AB, and B1 thymomas fell into the low risk group, whereas those with T2 or T3 type B2 or B3 thymomas and all thymic carcinomas and neuroendocrine neoplasms were found to be high risk (recurrence of 2.7% vs. 20.1% respectively). Median time to recurrence in high-risk patients was 19 months compared to 33 months in the low-risk group. More than half of high-risk group recurrences were seen within the first 3 postoperative years, and all but 1 out of 29 were recorded within 6 years after surgery. In contrast, in the low-risk group, recurrence occurred evenly distributed over 10 years. Additionally, in high-risk patients, distant metastasis was the most common type of recurrence (40.7%). Based on these findings the authors proposed that this predictive model may assist in deciding surveillance strategies. Notably, they suggest that more thorough surveillance methods such as imaging of the abdomen and pelvis may be necessary in high-risk patients. This final suggestion has not been incorporated into any available recommendations as summarized below in Table 2 but is certainly worth considering on an individual basis.

Table 2

Summary of available guidelines for TET surveillance

Society Year Surveillance recommendation Strength of recommendation
Type of study Frequency Duration
NCCN 2025 Chest CT with contrast (MRI is an acceptable alternative in certain clinical situations) TC—every 3–6 months. Thymoma—every 6 months for 2 years, then annually Thymic carcinoma—5 years. Thymoma—10 years (duration has not been established) 2A: based on lower level evidence, there is uniform NCCN consensus that the intervention is appropriate
CACA 2023 Not specified. Physical exam Low-risk group (IASLC/ITMIG stage T1 thymoma, stage T2/T3 WHO type A/AB/B1 thymoma)—annually. High-risk group (stage T2/T3 WHO type B2/B3 thymoma, TC, TNET)—every 6 months for 3 years then annually Low-risk group—10 years. High-risk group—at least 6 years 1B: strong, with moderate evidence
ECLUNG 2023 CT chest Baseline scan at 3–4 months after resection. TNM stage I/II thymoma with R0 resection—annually for 5 years, then every 2 years thereafter. Stage III/IV thymoma, TC, R1–2 resection—every 6 months for 2 years, then annually Thymoma—10 years. TC—5 years. Low-risk group—10 years. High-risk group—until recurrence Strongly recommended
ESMO 2015 Thoracic CT scan Baseline at 3–4 months after surgery. Completely resected stage I/II thymomas*—every year for 5 years, then every 2 years. Stage III/IV thymomas, TC, R1–2 resection—every 6 months for 2 years, then annually 10–15 years V: studies without control group, case reports, expert opinions. C: insufficient evidence for efficacy or benefit does not outweigh the risk or the disadvantages, optional
ITMIG 2011 CT scan of the thorax. MRI may be useful for better visualization or to minimize cumulative radiation dose (especially in young patients). PET generally not recommended Baseline imaging 4–12 weeks postoperatively. Annually for 5 years after surgical resection, then alternating annually with a chest radiograph until year 11, followed by annual chest radiographs alone. Resected stage III or IVa thymoma*, TC, incomplete resection or other high risk neoplasms—additional CT imaging every 6 months for 3 years At least chest radiographs indefinitely Not specified

*, IASLC/ITMIG TNM staging was first proposed in 2014 and formally incorporated in the 8th edition of the UICC and the AJCC TNM staging system, published in 2016. Guidelines published prior to 2016 were based on Masaoka staging system. AJCC, American Joint Committee on Cancer; CACA, China Anti-Cancer Association; CT, computed tomography; ECLUNG, East China LUng caNcer Group; ESMO, European Society of Medical Oncology; IASLC, International Association for the Study of Lung Cancer; ITMIG, International Thymic Malignancy Interest Group; MRI, magnetic resonance imaging; NCCN, National Comprehensive Cancer Network; PET, positron emission tomography; TC, thymic carcinoma; TET, thymic epithelial tumor; TNET, thymic neuroendocrine tumor; TNM, tumor-node-metastasis; UICC, Union for International Cancer Control; WHO, World Health Organization.

Autoimmune disorders and syndromes associated with thymomas

Thymic malignancies can also be associated with autoimmune disorders. While these are commonly referred to as paraneoplastic syndromes, some such as myasthenia gravis occur without the presence of a TETs and may not be truly paraneoplastic but rather an autoimmune process related to thymic reactivation. They are numerous and wide ranging, including neuromuscular disorders (such as myasthenia gravis, Lambert-Eaton syndrome and limbic encephalitis), hematologic disorders (such as pure cell aplasia and Good Syndrome) and dermatologic conditions (such as lichen planus and pemphigus foliaceus). The most common of these is myasthenia gravis. After surgery, up to 76% of patients will have a complete or partial resolution of symptoms related to these unique disorders and up to 21% of patients will have a relapse or new autoimmune disorder after surgery. Approximately 11% of patients who undergo surgical resection of TETs will go on to have concurrent development of an autoimmune disorder associated with thymoma recurrence (31). The guidelines from China Anti-Cancer Association (CACA), East China LUng caNcer Group (ECLUNG) and European Society of Medical Oncology (ESMO) discuss the late onset of an autoimmune disorder as a possible symptom of recurrence, or even without recurrence as a feature of survivorship in this unique patient population. No guideline currently recommends routine surveillance of acetylcholine antibodies, but a knowledge of the variety of autoimmune disorders that can accompany TETs can aid intermittent history taking to facilitate surveillance (Table 3) (31). When considering the holistic needs of a TET survivor, it is important to have a low index of suspicion for these disparate manifestations, which may require additional specialized care for management. Due to the long disease course of TETs, surveillance may be performed by providers who are not specialized in oncologic care, such as primary care providers, which can make the diagnosis of recurrent TETs in the context of a new paraneoplastic syndrome challenging.

Table 3

Common paraneoplastic syndromes associated with TETs

Autoimmune disorders associated with TETs
   Myasthenia gravis
   Lambert Eaton syndrome
   Acquired neuromyotonia (Isaac’s syndrome)
   Encephalitis
   Morvan’s syndrome
   Pure red cell aplasia
   Lichen planus
   Good syndrome
   Vitiligo
   Alopecia areata
   Nephrotic syndrome
   Pemphigus foliaceus
   Lupus
   Graft-versus-host disease
   Polymyositis
   Hypogammaglobulinemia
   Intestinal pseudo-obstruction
   Myositis
   Myocarditis
   Aplastic anemia

TETs, thymic epithelial tumors.

Future directions

TET is a rare indolent disease with low rate of recurrences, making surveillance a difficult topic to study. Pooling of patient data across treating groups, such as the ITMIG database, to study follow up is critical. However, it is realistically unlikely that an adequately powered prospective randomized study of different surveillance strategies will ever be conducted. Future efforts may be directed at continued risk stratification and refinement to allow for tailored approaches to surveillance. Additional novel methods of surveillance such as liquid biopsies may be considered for study. A single center study published in 2021 demonstrated that patients with TETs had higher levels of circulating cell-free DNA (32). While this study was done in the perioperative setting and not related to surveillance, whether this could be a novel surveillance strategy to be used alone or to augment imaging studies remains to be seen. TET survivors are unique in that patients have a long disease-free survival with an overall well-preserved quality of life after treatment (33). However, TET survivors must also endure the inconvenience, cost and anxiety of surveillance for a prolonged period compared to other malignancies. Studies evaluating holistic survivorship in TETs may reveal a pathway to further develop a surveillance strategy for these patients.

Conclusions

Surveillance after treatment for malignancy is felt to be intuitively beneficial, yet there is a paucity of evidence directly studying this in cancer patients, and a rare disease such as TETs are especially understudied. However, data suggesting that TET recurrences can be treated successfully with improved outcomes lends hope that we are benefiting our patients as we follow them (8-14). TETs can be largely divided into low- vs. high-risk for recurrence, and when choosing a strategy and counseling patients, one should consider which category the patient falls into. Current recommendations mostly propose thoracic computed tomography (CT) scans on an annual basis, for at least 10 years for most thymomas and around 5 years for more aggressive disease. Over the duration of surveillance there should be a low index of suspicion for autoimmune disorder or paraneoplastic syndromes as the presenting symptom of recurrence, and any physician tasked with surveillance of TETs should have a working knowledge of the many possible entities. As we look to the future, additional risk stratification allowing tailored surveillance strategies to balance the burden of follow-up vs. the benefit is necessary. Pooled databases such as ITMIG to strengthen efforts will likely be necessary.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Malgorzata Szolkowska) for “The Series Dedicated to the 14th International Thymic Malignancy Interest Group Annual Meeting (ITMIG 2024)” published in Mediastinum. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://med.amegroups.com/article/view/10.21037/med-25-20/rc

Peer Review File: Available at https://med.amegroups.com/article/view/10.21037/med-25-20/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-25-20/coif). “The Series Dedicated to the 14th International Thymic Malignancy Interest Group Annual Meeting (ITMIG 2024)” was commissioned by the editorial office without any funding or sponsorship. The authors have no other 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.

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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doi: 10.21037/med-25-20
Cite this article as: Choe G, Elmadhun N. Surveillance of thymic epithelial tumors (TETs)—a narrative review. Mediastinum 2025;9:18.

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