Single anesthetic pathways for the diagnosis, staging, and treatment of lung cancer: a narrative review

Introduction

Lung cancer remains the leading cause of malignancy-related deaths worldwide (1,2). Prompt recognition and timely treatment ultimately decrease mortality (3). Primary lung cancer has one of the longest median times from diagnosis to first treatment at 35 days, with older age, black race, and seeking care at academic hospitals all identified as risk factors for delays (4). Specifically, delays in care greater than 8 weeks are associated with higher rates of upstaging, increased 30-day mortality, and decreased median survival (5).

Currently, a significant lag time exists between detection and treatment (average times range from 46–56 days). The traditional, stepwise treatment algorithm involves image-guided biopsy, followed by review of histopathology, discussion with a multidisciplinary tumor board, preoperative optimization (including but not limited to positron emission tomography (PET) and computed tomography (CT), pulmonary function testing, staging bronchoscopy and/or mediastinoscopy, and finally surgical resection (6). Single anesthetic event (SAE) pathways have been developed to integrate advanced diagnostic bronchoscopy, rapid on-site evaluation (ROSE) or frozen-section pathologic diagnosis, and immediate surgical resection in one single anesthetic procedure. SAE has been shown to decrease time from biopsy to intervention by an average of 36 days (7).

There are several key knowledge gaps in the current evidence on SAE for lung cancer—including absent patient selection criteria guidelines, no established procedural workflow, and unaddressed safety/efficacy concerns with high initial benign resection rates. Rather than high-quality systematic reviews, meta-analyses, or randomized trials, most of the current SAE literature is retrospective in nature or originates from single centers. This paper aims to summarize the existing data regarding SAE for lung cancer, delineate current indications and candidacy for such protocols, provide impactful workflow pearls, and comment on potential pitfalls. Our paper is also the first narrative review to combine all available literature across multiple databases and synthesize SAE data. We present this article in accordance with the Narrative Review reporting checklist (available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-37/rc).

Methods

Studies from January 2021 to January 2026 in PubMed, Google Scholar, Cochrane Library, and Elsevier’s ScienceDirect databases were included for this narrative review. Studies that did not utilize SAE protocols or that were not written in English were excluded. Examples of MeSH search terms included “Intraoperative Diagnosis” and “Combined Modality Therapy”. Other search terms included “single anesthetic lung”, “robot assisted lung”, “single anesthetic event”, “robotic bronchoscopy”, and “Ion robot”. All articles utilized were reviewed by the authors and independently verified for data and relevance to the review topic. Please see Table 1 for additional details. No relevant papers describing SAEs were identified in the Cochrane Library database using the same search terminology.

Overview of the existing data

SAE pathways started gaining popularity in 2021, where Ross et al. were among the first to publish a small series of ten patients who underwent robotic bronchoscopy and subsequent same anesthetic resection without any noted complication (8). This same group published the largest study cohort undergoing SAE the following year, in which 52 patients underwent robotic bronchoscopy followed by robotic resection (9). Although ROSE confirmed malignancy in 42 patients [34 non-small cell lung cancer (NSCLC), 1 small-cell lung cancer, 7 non-lung cancer primary metastasis], final pathology revealed benign disease in 10 patients (granuloma/hamartoma)—raising an important question about the added morbidity of SAE surgical resection for those who would have otherwise been found to have benign nodules if they progressed along the traditional pathway.

In their retrospective study of 36 patients at a single institution, Palleiko et al. considered all patients with clinical stage I or IIA disease and excluded those with nodules highly concerning for small cell lung cancer, multiple nodules, pure ground glass opacities, or suspicious nodes (10). Compared to robotic lobectomies alone, their “Robotic One Anesthetic Diagnosis and Treatment” (ROADAT) group added 73 minutes on average per operation (P=0.003). When compared to controls, total cost for ROADAT was lower ($26,668 vs. $29,882, P=0.03) while hospital length of stay was the same (3 days, P=0.17). Other studies report shorter hospitalization with SAE pathways in patients with non-small cell lung carcinoma (3.6 vs. 6.2 days). Moreover, Weiser et al. found no difference in complications (air leak, pneumonia, atrial fibrillation) when comparing their single-anesthetic group to controls with similar pre-operative forced expiratory volume in 1 second (FEV1) (100% vs. 83%, P=0.71) or DLCO (83% vs. 96%, P=0.12) (11). SAE pathways have proven to be safe and efficient for patients and hospital systems alike, with another study reporting no mortality and only three complications of prolonged air leaks (>5 days) out of 41 participants (12).

Proponents for SAE such as Patel et al. highlight the fact that initiation of the traditional treatment pathway does not always immediately yield a tissue diagnosis (13). In fact, older American studies have shown patients undergo an average of 1.7 biopsies with 46% of lung cancer patients requiring two or more biopsies or occasional invasive wedge resections to achieve a final diagnosis (14). However, this Intuitive-funded observational study was limited in that it only assessed patient data from IBM MarketScan claims between the years of 2013 through 2015 and therefore may not be generalizable. Despite having an increased morbidity, diagnostic wedge resections were associated with high benign resection rates of up to 23–28% based on data from the National Lung Cancer Screening and NELSON trials (15-18). In contrast, the United Kingdom Lung Cancer Screening Trial reported a much lower benign resection rate of 10% (19). There appears to be a great degree of variability in this data, as certain authors report benign resection rates as low as 2.1–9%—albeit in much lower-powered studies (20-22). Others cite figures that fall in the middle of these data, such as Manyak’s 12%, Archer’s 12.8%, and El Alam’s 15% benign resection rates respectively (23-25). Interestingly, although Grogan et al. reported a 23% benign resection rate, they underscore that surgical intervention led to a new diagnosis in 69% of cases and treatment course changes such as medication initiation and/or new specialist consultation in 68% of cases (26). This paper argues that not all benign resections are harmful, as the authors noted no difference in intraoperative, in-hospital, or 30-day mortality compared to malignant resections.

Rocco et al. compared single-anesthetic bronchoscopy and resection to the previous established gold standard of diagnostic wedge resection and reported a significantly lower benign resection rate of 7.6% in the SAE group without differences in overall complication rates or 90-day readmissions (27). Perez et al. also achieved a similar 7.6% benign resection rate in their SAE arm, though the 23% of non-diagnostic biopsies suggest that there may be a steep learning curve for mastering robotic-assisted bronchoscopy (RAB) technologies (28). In fact, Bott et al. suggest that it takes at least 25 biopsies for a proceduralist to become facile with RAB (29). Furthermore, Brownlee et al. highlight that benign resection rates sharply decline with surgeon case volume, with an initial rate of 25% decreasing to just 5% for their last 20 cases (12). Likewise, Soukiasian et al. saw improvement in their benign resection rate over four years from 23.1% to almost 0%, owing to increased surgeon comfort with abstaining from surgical resection in benign diagnoses based on frozen section (30). Data from certain specialized centers suggest that SAE may therefore be able to spare patients from the morbidity of anatomic lung resections performed for diagnostic purposes.

Besides expediting treatment and minimizing multiple exposures to anesthesia, SAE also has significant financial advantages to both patients and hospital systems. For example, Na et al. found that lung cancer operations following surgical biopsy were associated with less cost (USD 12,669 vs. USD 14,403) than those after percutaneous needle biopsy first (31). Other previously cited studies report lower total cost ($70,591 vs. $81,025, P=0.004) and similar rates of complications when comparing SAE patients to controls (11). Several authors also project that SAE pathways can yield decreased rates of psychological distress among lung cancer patients, among whom >40% report baseline symptoms of depression and/or anxiety (32). We hypothesize that SAE may also help mitigate the health-related stigma associated with lung cancer, which has been linked to poorer quality of life outcomes in this vulnerable patient population (33). Additionally, robot-assisted bronchoscopy is a reliable diagnostic tool with a 96.2% rate of lesion localization, comparable yield to CT-guided biopsy, and lower incidence of pneumothorax or hemorrhage (34). Other benefits of modern advanced diagnostic bronchoscopy include multimodal localization and sampling techniques and the versatility of targeting multiple synchronous lung nodules and performing simultaneous mediastinal nodal staging in a single procedural setting (35).

Disadvantages of SAE include its requirement for resource-heavy environments due to needing thoracic surgeons, interventional pulmonologists, fluoroscopy, and advanced bronchoscopy (ADB) technology on standby. The need for onsite pathologists and ROSE may also hinder early adoption for SAE, especially given that agreement between pathologists for NSCLC varies from 67–89% (6). Alternatives to ROSE or frozen section analysis include novel fluorescein-free confocal laser endomicroscopy systems, which are being used by some Chinese centers to decrease time delays and improve diagnostic accuracy for traumatic biopsy samples (36). Additionally, existing SAE pathways typically fail to expand on the role of metastatic work-up [e.g., brain magnetic resonance imaging (MRI) or PET-CT] or how to approach the possibility of upstaging prior to beginning resection.

Before the advent of RAB, other established modalities including electromagnetic navigational bronchoscopy (ENB) and cone-beam CT (CBCT)-guided navigational bronchoscopy were thoroughly studied. A Dutch group led by Kops et al. demonstrated that CBCT can be a cost-effective alternative to conventional CT-guided transthoracic needle biopsy (37). The NAVIGATE trial used the superDimension electromagnetic system (Medtronic, Minneapolis, Minnesota) to achieve a 73% diagnostic yield with low complication rates including: 2.9% pneumothorax requiring intervention or admission, 1.5% bronchopulmonary hemorrhage, 0.7% respiratory failure (38). Of note, most of these cases also utilized adjuncts such as fluoroscopy (91%) and radial endobronchial ultrasound (rEBUS) (57%). The same technological platform was utilized by several studies in Folch’s systematic review and meta-analysis, showing that ENB achieved sufficient sample size for ancillary testing in 90.9% of patients (I²=80.7%) with low risk of pneumothorax (39). Folch et al. remark that the applicability of their findings are limited due to the use of a single ENB system (superDimension) and high degree of heterogeneity between included studies.

Low et al. performed direct comparisons between RAB and ENB in their retrospective study, suggesting that RAB had similar diagnostic yield compared to ENB with low rates of pneumothorax (40). Others like Kheir et al. suggest that a hybrid approach of use of CBCT augments diagnostic yield and decreases procedure time in ENB-guided peripheral lung biopsies (41). Soon after, Abdelghani et al. showed that a hybrid approach of RAB plus CBCT led to better navigational success and diagnostic yield when compared to ENB plus CBCT despite smaller median nodule size for the robotic arm (42).

Several large trials such as PRECISION-1, BENEFIT, and PRECIsE ultimately confirmed the role of robotic-assisted bronchoscopy for nodule diagnosis and for mediastinal staging (43-45). Similarly, the RELIANT single-center, cluster-randomized trial proved that RAB was not inferior to ENB (using Medtronic’s ILLUMISITE platform) for sampling peripheral pulmonary lesions (46).

Indications and candidacy for single anesthetic pathway

The widespread utilization of CT scans and implementation of national lung cancer screening has increased the detection of lung nodules in the United States (15,47). While there are no definitive guidelines, an effective SAE program should accomplish the following: (I) minimize diagnostic procedures; (II) avoid unnecessary surgeries; (III) reduce time to definitive therapies; and (IV) decrease unnecessary operational costs. Maximizing the value of SAE depends on proper patient selection and effective coordination of expert resources (Figure 1).

Figure 1 Single anesthesia pathway for bronchoscopic diagnosis and surgical resection of malignant peripheral pulmonary nodule. cEBUS, convex-probe endobronchial ultrasound; PPN, peripheral pulmonary nodule; ROSE, rapid on-site evaluation.

The first step in the single-anesthetic pathway is identifying a lung nodule with an intermediate-high risk for primary lung cancer (~50–70%) that is suitable for curative surgery, namely a reasonable suspicion for an early-stage tumor in an operable patient. Utilizing an SAE approach for nodules outside this range is likely to result in inefficient mobilization of resources and/or unnecessary procedures. Fleischner Society Guidelines and Lung-RADS (Lung CT Screening Reporting and Data System) from the American College of Radiology are two commonly used tools for the evaluation of lung nodules discovered incidentally or within the context of lung cancer screening, respectively (48,49). In addition, the American Association of Thoracic Surgeons (AATS) submitted an expert consensus statement for the management of subsolid lung nodules (50). While a full description is beyond the scope of this paper, these documents guide the initial evaluation of such patients and are most helpful in excluding SAE candidates. For example, lung nodules less than 6 mm in size are almost never in a high enough risk category to justify an SAE approach, regardless of patient profile.

Effective risk stratification is accomplished by incorporating patient and nodule characteristics. Tobacco smoking remains the most important clinical risk factor for primary lung cancer. Others include older age, chronic lung disease (e.g., chronic obstructive pulmonary disease), a cancer history (either personal or family), and certain occupational exposures (51). Nodule features consistently shown to predict lung malignancy include a larger size (e.g., >8 mm), presence of spiculated or irregular borders, upper lobe location, and part-solid attenuation (52-54). For part-solid nodules, risk of malignancy also increases as the size of the solid component increases and with associated internal air bronchograms or pleural or vascular changes (50). Fluorodeoxyglucose (FDG)-avidity on PET/CT scan, particularly high standardized uptake values (SUVs), also suggest cancer. However, in endemic fungal regions the specificity of PET scan is lower and should be interpreted within the clinical context (55,56). These patients may be ideal SAE candidates, as distinguishing focal endemic fungal disease from primary lung cancer is often difficult based on imaging and noninvasive tests alone (57,58). Finally, a nodule larger than 3 cm (lung mass) or one that grows over time or demonstrates a solidifying component on serial imaging is very suspicious for malignancy. Such patients without evidence of metastatic disease (e.g., lymph nodes) should be considered for direct surgical resection.

Multiple validated lung nodule risk calculators can facilitate stratification (59). These include but are not limited to the Brock University Calculator, NPS-BIMC (Bayesian Inference Malignancy Calculator), the Solitary Pulmonary Nodule Malignancy Risk (Mayo Clinic Model), and the Herder Model, which incorporates PET scan. Each risk calculator has relative advantages and can be used independently or within a broader risk stratification scheme, such as with emerging biomarkers of various types (60). Regardless, pulmonologist or thoracic surgeon input remains the cornerstone of assessing pre-test malignancy risk. The clinical judgement of a lung nodule expert has been shown to compare favorably to several mathematical models (61). At our institution, we exclude patients with imaging concerning for locally-advanced disease or patients with suspicion for nodal or distant metastasis.

Once an intermediate-high risk nodule is identified, the patient is assessed for surgical candidacy. Lung cancers at the lung nodule stage (≤3 cm) overall carry a relatively low risk for mediastinal and other metastases, especially in the absence of thoracic lymphadenopathy. Unnecessary staging practices should be minimized to enhance the efficiency of the therapeutic algorithm. The physiologic work-up and evaluation prior to lung resection is well-described in the literature. Preoperative lung function testing should be performed in all cases. Patients with at least FEV1 >60% predicted and diffusing capacity for carbon monoxide (DLCO) >60% predicted have a low perioperative mortality risk. Patients with predicted postoperative FEV1 (ppoFEV1) >800 mL or ppoFEV1 >40% predicted and predicted postoperative DLCO (ppoDLCO) >40% predicted are considered acceptable for major lung resection. Adjunct testing including cardiopulmonary testing, stair climbing, or shuttle walk can be considered in select patients. Cardiovascular testing [e.g., obtaining a baseline electrocardiogram (EKG) and/or echocardiogram] is also routinely performed for perioperative risk stratification. The Eastern Cooperative Oncology Group (ECOG) score can also be utilized to evaluate functional status, with an ECOG score >1 being correlated with increased risk of postoperative pulmonary complications (62).

Absolute contraindications to surgical resection include presences of distant metastases at the time of diagnosis, new cardiac conditions requiring coronary intervention (e.g., coronary artery bypass graft, valve replacement, percutaneous coronary intervention), or untreated pulmonary comorbidities such as emphysema, interstitial disease, or pulmonary hypertension. Relative contraindications include local invasion into mediastinal structures, chest wall involvement, dense pleural adhesions, advanced age (>80 years old), and poor nutritional status. Scoring systems such as the modified Thoracic Relative Cardiac Risk Index (ThRCRI) have been validated for use in identifying patients who may benefit from additional cardiac evaluation pre-operatively (63). For patients with ppoFEV1 or ppoDLCO <30% or positive high-risk cardiac evaluation, Cardiopulmonary Exercise Testing is often pursued yielding objective maximal oxygen consumption data in terms of VO2max results. VO2max <10 mL/kg/min is yet another relative contraindication to surgery (64). Patients who are at a prohibitive risk for surgery will undergo conventional tissue sampling via minimally-invasive techniques and thereafter be managed based on the biopsy results. In addition, any thoracic lymphadenopathy, unexplained pleural or pericardial effusion, suspicious abdominal or bony lesions, or focal neurologic signs should prompt case-specific staging evaluation and SAE should be deferred until advanced disease is excluded.

Once a clinically appropriate SAE candidate is identified, an informed discussion with the patient regarding workflow, advantages, and risks of both the SAE and traditional stepwise pathway is mandatory. This helps ensure the recommended clinical algorithm aligns with patient goals and values. For example, while many patients prefer the efficiency of the combined diagnosis and cure approach, others may need the psychological or emotional space to process a definitive diagnosis before deciding on therapy. A collaborative multidisciplinary environment in which the patient meets with multiple providers (e.g., pulmonologist, thoracic surgeon, radiation oncologist, etc.) simultaneously during a single clinic visit or over a short period of time may provide clarity, enhance comfort, and assist in clinical decision-making.

Workflow pearls

See Figure 1 for an illustration of our operational workflow.

An advanced bronchoscopist, thoracic surgeon, pathologist, and anesthesiologist are all essential components of planning a single anesthesia procedure. Consequently, poor coordination among these service lines could represent a significant potential obstacle to a successful SAE program. For example, aligning advanced bronchoscopist and thoracic surgeon operating schedules can be challenging, particularly for busy programs with a small number of these providers. While most operating rooms (ORs) have consistent access to frozen section pathology services, advanced bronchoscopists frequently obtain needle aspiration samples for on-site cytologic evaluation (ROSE). This may require additional coordination with cytopathology staff, particularly in the absence of an automated on-site or virtual (tele) evaluation system. Additional obstacles include inconsistent access to the OR, strained cytopathologist availability, or limited resources after normal operating hours. Collectively deciding on and reserving dedicated days in a month for SAE cases can minimize scheduling conflicts and manage expectations among the stakeholder services. Finally, additional testing, such as a pre-anesthesia evaluation, is performed prior to day of surgery and may either be mandatory or at the discretion of the provider, depending on an individual health system’s protocol. Establishing protocolized physiologic work-up pathways may help streamline the pre-operative process.

Patient preparation on the day of the procedure proceeds in routine pre-operative fashion, with a few exceptions. A recent CT scan of the chest is required to guide the ADB portion of the SAE procedure. In our practice, unless a very recent study is available, we prefer obtaining a CT chest on the day of surgery to maximize anatomic fidelity and ensure no significant changes from prior CT scans have occurred (e.g., new lesions, pleural effusion, etc.), thus minimizing potential for CT-to-body divergence (CTBD) (65). Assuming an on-site CT scanner is available, these can be performed once the patient arrives in the preoperative area of the hospital. The scan is typically a thin-cut (<1 mm), end inspiratory hold exam performed without IV contrast. Using a laptop computer in the procedure area, the target lung nodule is then mapped and labeled for bronchoscopic navigation. All patients are seen by the anesthesia team for discussion of perioperative and post-operative pain control. Patients and their families are reminded that the post-operative clinical course (same day discharge home vs. lung resection and hospitalization) will be dictated by intraoperative findings.

The OR is an important consideration for a SAE procedure. The OR should be large enough to house all the appropriate equipment, including the anesthesia unit, operative bed/table, ADB components, and the Intuitive Da Vinci Robotic Surgical System (Sunnyvale, CA, USA) for planned lung resection after bronchoscopy. The OR should also be able to accommodate intraoperative movements of several pieces of equipment (e.g., changes in bed position, ROSE components) and a relatively large number of healthcare personnel. Since the initial portion of SAE is ADB, the bed should first be positioned to optimize bronchoscopy logistics (Figure 2). All modern advanced peripheral bronchoscopies are performed with at least two-dimensional (2D) fluoroscopy, and the bed should be thus compatible. A special radiolucent bed may be required with the use of other advanced intraoperative imaging modalities, such as CBCT technology. Bed positioning should factor use and movements of adjunct technology (fluoroscopy or CBCT), intraoperative cytopathology services, and anesthesia equipment and tubing.

Figure 2 Standard operating room layout during single anesthetic event. This image is published with the participants’ consent.

Anesthetic considerations are important to the success of SAE. The ADB portion will leverage various techniques and ventilation protocols to help minimize intraprocedural atelectasis and CTBD, thus optimizing lesion targeting. These include rapid intubation with a large bore endotracheal tube (8.5 mm or larger), timely recruitment maneuvers, situation-specific positive end-expiratory pressure (PEEP) and/or tidal volume settings, extended breath holds and, in selected cases, lateral or prone patient positioning (66-69). The transition to lung resection will require airway revision to double-lumen intubation and adjustment of the ventilation protocol. Consequently, effective pre- and intra-procedural communication and planning with the anesthesia team is essential to procedure outcome. Depending on the practice type (e.g., academic vs. private/community), establishing protocols or a core SAE anesthesia group may enhance SAE efficiency and patient safety by minimizing practice variability between rotating anesthesia teams.

The ADB portion of the procedure follows a standard workflow and approach previously well-described in the literature (70,71). At our institution, we use robotic-assisted bronchoscopy (Ion Endoluminal System, Intuitive Inc., Sunnyvale, CA, USA) integrated with three-dimensional/mobile cone beam CT technology (Siemens Healthineers Cios Spin mobile imaging, Erlangen, Germany) to localize and sample the target nodule. We aggressively incorporate extended-length breath holds during the cone-beam CT spin and lesion targeting phases of the procedure to not only maximize diagnostic yield but also to minimize motion artifacts, enhance image clarity, minimize CTBD, and confirm tool-in-lesion (Figure 3). For practices without intraoperative advanced imaging such as augmented fluoroscopy or CBCT, the combination of 2D fluoroscopy and rEBUS is also effective in lesion targeting (72).

Figure 3 Cone-beam CT with transbronchial needle confirmation in subsolid nodule. CT, computed tomography.

Nodule sampling and on-site cytohistologic assessment is a critical component of the SAE, as the results will dictate whether the patient will proceed to immediate surgery or be discharged home. The goal is to secure as specific an intraoperative diagnosis as possible (malignancy vs. a specific non-malignant result). The ideal sampling approach within the SAE context is unknown and will depend on a multitude of factors, including local bronchoscopist preference, the presence and type of on-site cytopathology services, and the comfort of a human cytopathologist to make a definitive intraoperative diagnosis. While transbronchial needle aspiration (TBNA) with ROSE is a common approach, we diversify our sampling to maximize intraoperative diagnostic yield. Two or three alternating 21-gauge TBNAs and 1.1 mm cryoprobe biopsies are taken and assessed on-site as cytologic and touch-preparations, respectively (73,74). An additional 2–3 generous cryobiopsies are sent for frozen section evaluation (Figure 4). This latter approach is used exclusively if an on-site cytopathologist is unavailable. A specific diagnosis from any of the above is considered adequate for decision-making.

Figure 4 ROSE cytopathology in operating room. Note da Vinci Xi Robotic Surgical System in background. This image is published with the participants’ consent. ROSE, rapid on-site evaluation.

Intraoperative results are reviewed for consensus among the bronchoscopist, thoracic surgeon, and cytopathologist. A specific non-malignant result, such as hamartoma, granuloma, or fungal organisms, is satisfactorily diagnostic, assuming pathologist certainty and consistency with the clinical presentation. In such cases, additional samples are obtained by bronchoscopy and sent for relevant testing (e.g., culture and polymerase chain reaction for suspected infection). The procedure is then concluded and the patient discharged home after recovery from anesthesia.

Most other cases will proceed with immediate lung resection. A malignant diagnosis, especially one consistent with a primary lung cancer, is the most straightforward result. Inconclusive findings include nonspecific inflammation, necrosis, and cytologic atypia. Unless there is a compelling clinical suggestion of infection, these patients should also proceed with wedge resection for better pathologic characterization. In particular, up to two-thirds of nodules yielding atypical cells on bronchoscopic biopsy will ultimately prove malignant (75). Recovery of benign bronchial cells, normal lung parenchyma or blood represents non-lesional material and suggests inadequate sampling. These patients should also move forward with immediate diagnostic wedge resection.

For cases in which a wedge or segmentectomy is planned, such as for small sub-solid malignant nodules or those diagnostically inconclusive on bronchoscopic evaluation, intraoperative fiducial or dye marking is pursued to facilitate localization of the nodule. At our institution we utilize a 1:1:2 mixture of 5 mg/mL methylene blue, 2.5 mg/mL indocyanine green and 2 mL of autologous blood, respectively. The mixture is primed into a 21 or 23G TBNA needle and under advanced bronchoscopic imaging guidance ~1 mL is injected into the peripheral nodule, extending to the subpleural area (Figure 5). Finally, if indicated, mediastinal staging is performed using convex-probe endobronchial ultrasound (cEBUS), according to National Comprehensive Cancer Network (NCCN) guidelines (76). If intraoperative cEBUS-ROSE confirms malignant mediastinal lymph node involvement, SAE is deferred, the procedure is concluded, and the patient is referred for therapy per NCCN guidelines. For patients without mediastinal metastases, immediate lung resection is pursued.

Figure 5 Intraoperative image of ICG dye-marking visualization utilizing Firefly fluorescence imaging in the da Vinci Robotic Surgical System. ICG, indocyanine green.

The patient’s single-lumen endotracheal tube is exchanged for a double-lumen endotracheal tube. Standard robotic anatomic lung resection along with thoracic lymphadenectomy is then performed for definitive treatment of the patient’s lung cancer. Bronchoscopic marking prior to surgical intervention improves the ability to perform sublobar resections especially for nodules that would be unable to be visualized or palpated using the Robotic platform (19). Need for adjuvant therapy is dictated by final surgical pathology.

Limitations and future directions

This paper has certain limitations. Most studies regarding SAE do not provide comprehensive details regarding patient demographics (e.g., smoking status), comorbidities, or pre-operative pulmonary function testing. Importantly, low predicted postoperative FEV1 would preclude certain patients from surgical resection due to unacceptably high rates of morbidity and mortality. Additionally, most published authors are based in the U.S. and are therefore not capturing international data or data from low-resource nations. We hope to see future studies analyze short-term and long-term recurrence data and perform survival comparisons comparing the “traditional” management pathway to SAE.

Currently, no established guidelines exist for SAE patient selection. In the published literature, Patel et al. reported selecting patients with clinical stage I to II NSCLC, whereas Wolf et al. reported only selecting for stage I NSCLC as determined by pre-operative PET-CT (7,35). Palleiko et al. recommend excluding clinical stage IIIA or higher and nodules with pure ground glass features (as minimally invasive biopsies of these lesions have relatively low sensitivity) (10). Future studies may analyze the use of American Society of Anesthesiologists (ASA) physical status class or ECOG functional status to exclude higher-risk patients from undergoing prolonged anesthesia.

Unfortunately, no direct cost-analyses exist in the current literature to comment on individual cost drivers such as robotic disposables versus hospital bed days. We theorize that additional procedures and/or hospital days associated with pre-operative diagnosis in non-SAE groups leads to increased costs when compared to SAE. The aforementioned ROADAT study does note, however, that OR times are longer for SAE procedures. Future studies need to be done directly comparing SAE arms to established controls to truly prove cost-savings.

Conclusions

SAE for the diagnosis and treatment of clinical stage I–II lung cancer is a novel option for providers and patients alike. SAE has been suggested to be safe and cost-effective in multiple initial retrospective and single-centered studies. Although initial reports showed comparable benign resection rates to the previous gold standard of diagnostic wedge resection, we demonstrate that these can be lowered with increased SAE familiarity and increased case volumes. SAE has been shown to decrease time from biopsy to intervention by an average of 36 days for acceptable surgical candidates with intermediate to high-risk lung nodules. SAE has been associated with decreased cost, similar hospital length of stay, and equivalent complication rates when compared to conventional treatment pathways. Disadvantages of SAE include its requirement for resource-heavy environments due to needing multidisciplinary specialists on standby and access to robotic technologies. In order to succeed, SAE requires an updated CT chest scan as well as excellent coordination between advanced bronchoscopists, thoracic surgeons, pathologists, and anesthesiologists.

Acknowledgments

We would like to thank our pathology team and respiratory therapy staff for helping to make the advanced diagnostic bronchoscopy portion of the SAE program a success.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Taryne A. Imai) for the series “Revolutionizing Lung Cancer Care with Technological Advancements” published in Current Challenges in Thoracic Surgery. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-37/rc

Peer Review File: Available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-37/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ccts.amegroups.com/article/view/10.21037/ccts-25-37/coif). The series “Revolutionizing Lung Cancer Care with Technological Advancements” was commissioned by the editorial office without any funding or sponsorship. A.A.C. reports consulting fees and speaker payments from Intuitive Surgical, Inc. 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. All images are published with the patient’s/participants’ consent.

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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