Natural History of Localized and Locally Advanced Atypical Lung Carcinoids after Complete Resection: A Joined French-Italian Retrospective Multicenter Study

Abstract

Background: The natural history and the best modality of follow-up of atypical lung carcinoids (AC) remain ill defined. The aim of this study was to analyze recurrence-free survival (RFS) after complete resection (R0) of stage I-III pulmonary AC. Secondary objectives were prognostic parameters, the location of recurrences, and the modality of follow-up. Methods: A retrospective review of 540 charts of AC patients treated between 1998 and 2008 at 10 French and Italian centers with experience in lung neuroendocrine tumor management was undertaken. The exclusion criteria were MEN1-related tumor, history of another cancer, referral after tumor relapse, and being lost to follow-up. A central pathological review was performed in each country. Results: Sixty-two patients were included. After a median follow-up time of 91 months (mean 85, range 6-165), 35% of the patients experienced recurrence: 16% were regional recurrences and 19% were distant metastases. Median RFS was not reached. The 1-, 3-, and 5-year RFS rate was 90, 79, and 68%, respectively. In univariate analysis, lymph node involvement (p = 0.0001), stage (p = 0.0001), mitotic count (p = 0.004), and type of surgery (p = 0.043) were significantly associated with RFS. In multivariate analysis, lymph node involvement was significantly associated with RFS (HR 95% CI: 0.000-0.151; p = 0.004). During follow-up, somatostatin receptor scintigraphy, fibroscopy, and abdominal examination results were available for 22, 12, and 25 patients, respectively. The median time interval for imaging follow-up was 10 months. Conclusions: After complete resection of AC, recurrences were observed mostly within the first 5 years of follow-up, within bronchi, mediastinal nodes, the liver, and bones. In R0 patients, lymph node involvement could help to stratify follow-up intervals. Suboptimal imaging is evidenced.

Lung and thymic carcinoids: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆

“…org/10.1016/j.annonc.2021.01.003). 4,5,9,21,45,[48][49][50][51] Although Ki-67 index is considered a promising prognostic marker by the whole author panel, its technique of evaluation and the most accurate thresholds remain a matter of debate; moreover, no definitive validation of its added value to WHO and pTNM classifications has been provided so far in large series of LCs. 18,28,45,52,53 At the metastatic stage, WHO classification, performance status, CgA levels, tumour burden and somatostatin receptor imaging (SRI) uptake, as well as tumour growth slope and the functioning syndrome, should be taken into account for adequate risk assessment [IV, B].…”

“…4,5,55,56 In ACs, but also in N-positive TCs, lobectomy is reported as superior to segmentectomy in terms of OS in some, but not all. 5,7,8,18,51,54,55,57,58 Bronchoplastic procedures (e.g. sleeve resections) are preferred for suitable centrally located tumours, with the aim of avoiding pneumonectomy [IV B].…”

Lung Carcinoids: Long-Term Surgical Results and the Lack of Prognostic Value of Somatostatin Receptors and Other Novel Immunohistochemical Markers

“…High tumour proliferation is also associated with shorter survival, but the current grading system’s cut-off used for gastrointestinal NENs between G1 and 2 (Ki-67 > 3%) fails to reliably predict the disease outcome in terms of OS [6]. Other reported prognostic factors include TNM stage, primary tumour size and nodal metastases [3, 7, 8]. …”

“…On the other hand, the prognosis for patients with ACs is worse and the disease has a more aggressive course, with 5-year survival rates ranging from 56 to 87%. This implies that adjuvant therapy may have a role in selected cases [4, 8]. Nevertheless, locoregional recurrence and/or metastases may develop late in the disease course in patients with LCs, and thus a minimum 10- to 15-year surveillance after surgery has generally been recommended [10].…”

Pneumonectomy in bronchial carcinoid tumors

“…TCs have an excellent prognosis after a complete resection: 5-year survival rates may vary between 87% to 100% and 10-year survival rates between 87% and 80%, according to the different clinical series (8)(9)(10)(11). ACs have a poorer 5 and 10-year survival rates, ranging between 95% and 40% (5-year) and 56% to 35% (10-year) (12)(13)(14)(15).…”