Challenges for real‐time intraoperative diagnosis of high risk histology in lung adenocarcinoma: A necessity for sublobar resection

Abstract

Recently, the incidence of small, peripheral lung adenocarcinoma has been increasing as lung cancer screening with radiologic examination is more widely performed. Tumor size is one of the determinants of the prognostic outcome in clinically node‐negative lung adenocarcinoma. Sublobar resection has been proposed as one of the minimally invasive surgical options for small‐sized adenocarcinomas. Despite the lack of robust clinical trial evidence, sublobar resection has become more popular, especially in developed countries where less extensive surgery may be of benefit in a population where the age of the elderly is growing. However, high risk histologic features such as micropapillary subtype and tumor spread through air space (STAS) have been associated with a significantly higher risk of local recurrence after sublobar resection, but not after lobectomy. Surgical decision‐making based on frozen section diagnosis of high risk histologic features may be useful to prevent local control failure after sublobar resection. At the present time, there is little evidence to demonstrate the diagnostic accuracy of identifying high risk histologic features on frozen section. One study has so far demonstrated that diagnostic accuracy of identifying STAS is higher than that of identifying the micropapillary subtype. Additionally, the presence of STAS has been found to be more strongly associated with local recurrence in patients who had undergone sublobar resection. Although further investigation is required for validation of this finding, STAS diagnosis on frozen section may shed further light on intraoperative surgical decision‐making during sublobar resection. To this end, we review the recently published data on the intraoperative identification of high risk features.

Surgery without preoperative histological confirmation of lung cancer: what is the current clinical practice?

“…Conversely, an upfront segmentectomy is technically more challenging than wedge resection, and is associated with higher surgical morbidity (29,30) and mortality (31), exposing the patient to unnecessary surgical trauma and risks in the case of an ultimately benign diagnosis. Moreover, several adenocarcinoma subtypes [such as micropapillary adenocarcinoma (31)] and tumors with high-risk histologic features [such as "tumor spread through air space" (16)] are known to have an inferior prognosis after sublobar resection (15,16,32), and lobectomy is therefore recommended. However, when a preoperative diagnosis is not available, the indispensable intraoperative FS examination has been associated with a diagnostic accuracy of only 68-85% in identifying predominant histologic subtype (25,33).…”

“…However, when a preoperative diagnosis is not available, the indispensable intraoperative FS examination has been associated with a diagnostic accuracy of only 68-85% in identifying predominant histologic subtype (25,33). Additionally, various studies have documented low sensitivity for FS in diagnosing high-risk morphology, often caused by sampling error largely affected by tumor heterogeneity (16,34). Consequently, errors in intraoperative FS examination are factual and well reported (28,33), and could potentially have significant negative clinical impact (15).…”

“…Moreover, with a rising trend of utilizing sublobar resections to treat smallsized early-stage lung cancer (14), accurate pathological classification beforehand will become increasingly important. After all, high-risk histological subtypes such as solid or micropapillary adenocarcinoma are associated with local recurrence in patients who have undergone limited resections when compared to lobectomy (15), and the diagnostic accuracy of intraoperative FS on these high-risk histologic features is still debatable (16).…”

Deep Learning Analysis of CT Images Reveals High-Grade Pathological Features to Predict Survival in Lung Adenocarcinoma

“…However, although we know that the prognosis is worse with the high-grade pattern, it is difficult to know in advance the existence of a high-grade pattern before surgery. In addition, surgical decision-making based on frozen sections of highgrade histologic patterns has little evidence to prove diagnostic accuracy, which can be problematic when considering sub-lobar resection [25]. In this respect, our DL model is meaningful because it noninvasively predicts high-grade histologic patterns using CT scans prior to obtaining pathologic specimens.…”

Predicting the Clinical Outcome of Lung Adenocarcinoma Using a Novel Gene Pair Signature Related to RNA-Binding Protein

“…Overall, patients with larger inoperable tumors or early metastases usually have a poorer prognosis and reduced survival. For earlier, more localized lung adenocarcinoma lesions, surgery has been the preferred option with excellent results [3]. In inoperable patients, a puncture biopsy of the lesion, genetic testing, and immunohistochemical testing are usually performed clinically to determine whether molecular targeted therapy or immunotherapy can be used properly [4].…”