Patterns of disease recurrence in relation to the extent of lymph node sampling in patients with resected lung carcinoid: A population-based study

In patients (pts) with resected pulmonary carcinoids, recurrence of disease may occur up to 10 years after surgery, but the exact incidence remains unknown. Locoregional lymph node (LN) involvement predicts poor prognosis. We evaluated recurrence-free interval (RFI) patterns in relation to the extent of surgical LN sampling. By combining the Netherlands pathology and cancer registries, all pts with surgically resected pulmonary carcinoids, diagnosed between 2003-2012 were included. Tumour node metastasis (TNM) staging was updated to TNM8 by screening of complete pathology reports. Extent of surgical LN dissection was scored for 1) number of LN, 2) location (hilar/mediastinal) and 3) complete according European Society of Thoracic Surgeons (ESTS) guidelines. Last follow-up was until 02-2019. RFI was defined as time to recurrence and evaluated using Kaplan Meier and multivariate Cox regression analysis. In total 662 pts were included of which 22,1% had an atypical carcinoid, 76% had a pTNM stage IA/IB, 17% stage IIA/B and 7% stage IIIA/B. pN1 was observed in 8.8% and pN2 in 3.6%. An anatomical resection was performed in 88% and 7% had incomplete surgical resection margin (R1/R2). Median follow-up was 87 (95% confidence interval (CI) 84-91) months. Recurrence occurred in 10.0%; liver (50%) and locoregional (45%). Median time to distant and locoregional recurrence was 51 (95% CI 37-65) and 45 (95% CI 23 – 67) months, respectively. Poor prognostic factors were atypical carcinoid, pN1/2 and R1/R2 resection (p<0.05). In 546 pts extended data on LN dissection was available; at least one N2 LN was examined in 44%, six LN including one N1 and N2 in 20% and according to ESTS in 7%. In pts with cN0 (n=477), 5.9% had pN1 and 2.5% had pN2 disease; no difference in locoregional recurrence was observed when ≥1 vs. 0 N2 LN were sampled. In resected pulmonary carcinoid, recurrence of disease is not uncommon and our data show that long-time follow-up is required. Recurrence occurs significantly more, but not exclusively, in pts with atypical carcinoid and/or LN involvement. Systemic mediastinal LN sampling is rarely performed, but is recommended as it provides important prognostic information.