Long-term results of PRRT in advanced bronchopulmonary carcinoid

Purpose: Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumours (NET) has been explored for almost two decades, but there are still few trials that have exclusively investigated well-differentiated and moderately differentiated NET arising from the respiratory tree. Thus, the aim of this study was to explore the outcome in patients affected by bronchopulmonary carcinoid (BPC) following PRRT. Methods: We retrospectively analysed 114 patients with advanced stage BPC consecutively treated with PRRT at the European Institute of Oncology, Milan, from 1997 to 2012 and followed until October 2014. The objective responses, overall survival (OS) and progression-free survival (PFS) were rated, and three different PRRT protocols (⁹⁰Y-DOTATOC vs. ¹⁷⁷Lu-DOTATATE vs. ⁹⁰Y-DOTATOC + ¹⁷⁷Lu-DOTATATE) were compared with regard to their efficacy and tolerability. Results: The median OS (evaluated in 94 of the 114 patients) was 58.8 months. The median PFS was 28.0 months. The ¹⁷⁷Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4 %). Morphological responses (partial responses + minor responses) were obtained in 26.5 % of the cohort and were associated with longer OS and PFS. The ⁹⁰Y-DOTATOC + ¹⁷⁷Lu-DOTATATE protocol provided the highest response rate (38.1 %). Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival. No severe (grade 3/4) serum creatinine increase was observed. Patients treated with ⁹⁰Y-DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity. Conclusion: In a large cohort of patients with advanced BPC treated in a “real-world” scenario and followed up for a median of 45.1 months (range 2 – 191 months), PRRT proved to be promising in prolonging survival and delaying disease progression. Despite the potential selection biases, considering the risk-benefit ratio, ¹⁷⁷Lu-DOTATATE monotherapy seems the best option for PRRT. Our results indicate that the use of PRRT in earlier stages of the disease could provide a more favorable outcome.