Maria Cattoni1,2, Eric Vallières1, Lisa M Brown3, Amir A Sarkeshik3, Stefano Margaritora4, Alessandra Siciliani4, Pier Luigi Filosso5, Francesco Guerrera5, Andrea Imperatori2, Nicola Rotolo2, Farhood Farjah6, Grace Wandell6, Kimberly Costas7, Catherine Mann1, Michal Hubka8, Stephen Kaplan8, Alexander S Farivar1, Ralph W Aye1, Brian E Louie9. 1. Division of Thoracic Surgery, Swedish Cancer Institute, 1101 Madison Street, Suite 900, Seattle, WA, 98105, USA. 2. Center for Thoracic Surgery, Department of Medicine and Surgery, University of Insubria, Ospedale di Circolo, 9 Via Guicciardini, 21100, Varese, Italy. 3. Section of General Thoracic Surgery, Department of Surgery, UC Davis Health, 2221 Stockton Boulevard, Room 2115, Sacramento, CA, 95817, USA. 4. Unit of Thoracic Surgery, Catholic University 'Sacred Heart', 1 Largo Francesco Vito, 00168, Rome, Italy. 5. Department of Thoracic Surgery, San Giovanni Battista Hospital, 3 Via Genova, 10126, Turin, Italy. 6. Division of Cardiothoracic Surgery, University of Washington Medical Center, 1959 NE Pacific Street, 3rd Floor, Seattle, WA, 98195, USA. 7. Division of Thoracic Surgery, Providence Regional Medical Center, 1330 Rockefeller Avenue, Suite 400, Everett, WA, 98201, USA. 8. Division of Thoracic Surgery, Virginia Mason Hospital & Seattle Medical Center, 1100 9th Avenue, Seattle, WA, 98101, USA. 9. Division of Thoracic Surgery, Swedish Cancer Institute, 1101 Madison Street, Suite 900, Seattle, WA, 98105, USA. brian.louie@swedish.org.
Abstract
BACKGROUND: Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies. METHODS: We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage. RESULTS: Median follow-up was 47 (95%CI 41-79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3-70.9) and 47.4% (95%CI 32.3-61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01-1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and >3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6-93.6) and 38.2% (95%CI 20.6-55.6) (p < 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1-78.8) and 54.2% (95%CI 32.6-71.6) (p = 0.31), respectively. CONCLUSIONS: A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors >3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC >3 cm, even in the absence of nodal involvement.
BACKGROUND: Minimal knowledge exists regarding the outcome, prognosis and optimal treatment strategy for patients with pulmonary large cell neuroendocrine carcinomas (LCNEC) due to their rarity. We aimed to identify factors affecting survival and recurrence after resection to inform current treatment strategies. METHODS: We retrospectively reviewed 72 patients who had undergone a curative resection for LCNEC in 8 centers between 2000 and 2015. Univariable and multivariable analyses were performed to identify the factors influencing recurrence, disease-specific survival and overall survival. These included age, gender, previous malignancy, ECOG performance status, symptoms at diagnosis, extent of resection, extent of lymphadenectomy, additional chemo- and/or radiotherapy, tumor location, tumor size, pT, pleural invasion, pN and pStage. RESULTS: Median follow-up was 47 (95%CI 41-79) months; 5-year disease-specific and overall survival rates were 57.6% (95%CI 41.3-70.9) and 47.4% (95%CI 32.3-61.1). There were 22 systemic recurrences and 12 loco-regional recurrences. Tumor size was an independent prognostic factor for systemic recurrence [HR: 1.20 (95%CI 1.01-1.41); p = 0.03] with a threshold value of 3 cm (AUC = 0.71). For tumors ≤3 cm and >3 cm, 5-year freedom from systemic recurrence was 79.2% (95%CI 43.6-93.6) and 38.2% (95%CI 20.6-55.6) (p < 0.001) and 5-year disease-specific survival was 60.7% (95%CI 35.1-78.8) and 54.2% (95%CI 32.6-71.6) (p = 0.31), respectively. CONCLUSIONS: A large proportion of patients with surgically resected LCNEC will develop systemic recurrence after resection. Patients with tumors >3 cm have a significantly higher rate of systemic recurrence suggesting that adjuvant chemotherapy should be considered after complete resection of LCNEC >3 cm, even in the absence of nodal involvement.
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