Watchful waiting—initial patient characteristics of TSOG 102

Detecting ground-glass opacities (GGOs) has become increasingly common, and the optimal management of these lesions has yet to be determined. As such, there is a growing interest in scientific studies that compare active surveillance to immediate intervention in such cases.

In the initial evaluation of the Thoracic Surgical Oncology Group 102 (TSOG 102) prospective registry, Huang et al. hypothesized that active surveillance is a safe and feasible management option for patients with multiple GGOs. Enrollment consisted of patients with ≥2 GGOs (<50% solid, ≤3 cm), followed prospectively with computed tomography scans every 6–12 months. Target accrual was met after 5 years, with 337 patients, 23 institutions, and 1,467 GGOs included. Most of the patient population included former (70%) and current smokers (9%), more than half of the participants had a prior history of lung cancer (51%), and the majority were already under active surveillance at the time of study entry (86%). The GGO lesions are measured and tracked over time, and the incidence of lung cancer diagnosis, lung cancer progression, and lung cancer-related death while under surveillance is determined. The group found active surveillance was an acceptable option among patients and physicians, and enrollment was feasible. Additionally, preliminary data from this study has shown that no patients under surveillance have died of lung cancer in the 5 years since the trial’s opening. The group will longitudinally assess the safety endpoints and long-term outcomes, including lung cancer-specific survival (LCCS) and overall survival (OS) rates over a 5-year follow-up period. This study highlights the prevalence of these lesions and raises critical questions regarding safe management strategies (1).

A strength of this study lies in the diversity of institutions enrolling in the registry—the sample size of 337 patients is represented by 23 distinct institutions. The median age of participants was 70 years old, and the patient population was predominantly comprised of former and active smokers—a patient population that was older and more predisposed to lung malignancies than other studies with similar objectives, reflecting real-world populations who would be receiving active surveillance of lung GGOs. Previous studies looking at the progression of GGOs are retrospective, and the patient populations were younger, consisted of an increased proportion of never-smokers, and had a more significant number of patients with no prior history of lung cancer (2-4). Compared to these previous studies, TSOG 102 has a design that more accurately represents modern practices and prospectively tracks patients and outcomes, thus increasing the generalizability of their findings. Additionally, the more considerable prevalence of aging individuals and those with extensive smoking histories included in this study made the lack of lung cancer-related deaths over the 5-year accrual period much more supportive of active surveillance as an effective management strategy. However, caution must be given to the number of included patients already receiving active surveillance, as this could introduce selection bias into the study’s results and skew outcomes.

Given the nature of a watchful waiting treatment strategy, the implications of potential patient harm and ethical concerns could be raised. While active surveillance holds the potential as a safe management option, providers may argue that the “watchful waiting” approach is an approach of “no treatment”. However, this study appropriately highlights that the active surveillance approach more accurately identifies specific patients and lesions that require further intervention without undue harm of overtreatment. Most GGOs, once resected, are found to be nonmalignant lesions or low-grade malignancies with an indolent nature and excellent prognosis. Given the indolent nature of these lesions, resection, and radiation are potentially aggressive with the potential of little to no therapeutic benefit. To this end, special consideration much be given to include the presence of GGOs in the post-COVID-era, as studies have shown subsequent long-term pneumonia after COVID infection where the presence of GGOs reached 86% (5).

The decision to include patients with prior histories of lung cancer poses another critical question. Due to the larger population of aging individuals, smokers, and patients with histories of lung cancer, is it acceptable to watchfully wait in a population that is at higher risk of harboring malignancy? Halpenny et al. conducted a study looking at the prevalence of subsequent lung cancer in patients with a history of a prior lung malignancy. They found that smokers with a previous history of malignancy were at higher risk for the development of subsequent lung cancer (6). However, the TSOG 102 researchers have identified this gap and have appropriately addressed this concern by including these patients who more accurately modeled real-life practice and allowed for shorter accrual. As preliminary data demonstrates, patients are regularly followed with imaging every 6–12 months and undergo further intervention should the GGOs grow by >50% or when the consolidation-to-tumor ratio is >0.50—an appropriate criterion for advancing intervention. These preliminary data could be groundbreaking for the future of lung lesion management. Active surveillance can potentially decrease the overtreatment of GGOs and reduce patients’ emotional and financial burdens that often accompany intervention. Additionally, the prospective nature of this study allows for the observation and tracking of the growth velocities of GGOs, introducing the potential for future research involving predictive models of GGO growth and prognosis. While this study demonstrates promising preliminary results, much of the supportive data lies in the study’s endpoints and long-term outcomes that have yet to be reported. As we await the study’s endpoints and long-term outcomes, clinicians could consider extending the surveillance period past 5 years as lung lesions have the potential to grow outside this period.

The detection of GGOs in modern medicine continues to rise, along with the growing need for a safe and effective management strategy. Huang et al. conducted a thorough, well-designed study that accurately models modern clinical practice, addresses patient safety, and collects long-term outcomes. We eagerly await the results of the study’s endpoints; for now, the preliminary data support active surveillance as a safe and feasible option for managing multiple GGOs.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Current Challenges in Thoracic Surgery. The article has undergone external peer review.

Peer Review File: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-4/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-4/coif). B.C.G. was a K12 scholar from January 22 to December 24 with a focus on learning how to develop clinical trials in thoracic malignancies. This manuscript pertains to a clinical trial dealing with lung cancer surveillance. There is no overlap in B.C.G.’s particular research focus while a K12 scholar. The other author has 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.

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/.

References

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