Predictors of upstage and treatment strategies for stage IA lung cancers after sublobar resection for adenocarcinoma in situ and minimally invasive adenocarcinoma

BACKGROUND: Invasive adenocarcinoma intraoperatively underestimated as adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) based on frozen section (FS) is more likely to undergo insufficient resection. We aimed to investigate the predictors of upstage and treatment strategies for stage IA invasive adenocarcinoma after sublobar resection for AIS and MIA. METHODS: We identified 2,006 patients from January 2012 to December 2016 with early-stage lung adenocarcinoma who underwent sublobar resection based on FS diagnosis to guide surgical decision-making. All FS were categorized into three groups in real-time: (I) atypical adenomatous hyperplasia (AAH), (II) AIS, and (III) MIA. RESULTS: A total of 272 (13.5%, 272/2,006) cases were upstaged in the final pathology (FP) diagnosis (82 AAH to AIS, 127 AIS to MIA, and nine AIS and 54 MIA to invasive adenocarcinoma), and most upstage cases (64.3%, 175/272) were attributed to sampling error. Multivariate logistic regression showed that tumor size ≥1 cm was the only independent predictor of upstage. The upstage of 209 cases to AIS or MIA had no influence on the therapy because the extent of their resection was enough. Of the 63 cases upstaged to invasive adenocarcinoma, only 13 cases agreed to receive complementary treatment: five patients underwent complementary lobectomy, and seven patients received chemotherapy. Two invasive adenocarcinoma cases without complementary treatment experienced a local recurrence after surgery. No recurrence was observed in AAH, AIS and MIA. No patient died until December 01, 2019. CONCLUSIONS: Timely complementary treatment is encouraged in AIS/MIA upstaged to invasive adenocarcinoma based on the FP after sublobar resection to avoid local recurrence. Pathologists should be more cautious about AIS and MIA with tumor size ≥1 cm to avoid underestimation and potentially insufficient resection.