Development of an evaluation and treatment strategy for olfactory neuroblastoma: a review of evidence from large-scale studies, including population-based and multicenter studies, and meta-analyses.

Olfactory neuroblastoma is a rare sinonasal malignancy arising from the olfactory epithelium that is characterized by skull base involvement and a modest natural history. Because of its rarity and long course, identification of independent prognostic factors is dependent on multivariate analysis of large, long-term data. In this review, we outline evidence for the evaluation and treatment of olfactory neuroblastoma obtained from recent large-scale population-based studies, meta-analyses and multicenter studies. Hyams grade is currently the only pathological grade system for olfactory neuroblastoma. The modified Kadish staging and Dulguerov classification are available for clinical staging. The results of large-scale studies have confirmed Hyams, the modified Kadish and Dulguerov as independent prognostic factors. Surgery followed by radiotherapy provides the best overall survival and recurrence-free survival for resectable disease. The question of whether postoperative radiotherapy should be administered for all cases or only for those at risk of recurrence remains unanswered. Exclusively endoscopic resection is indicated for modified Kadish A/B cases without any increase in the risk of death or recurrence, and is also indicated for modified Kadish C cases if a negative surgical margin is ensured. For more advanced cases, such as those with extensive brain infiltration, the open approach is indicated. Elective nodal irradiation prevents late nodal recurrence of N0 patients. Chemotherapy has failed to show a benefit in survival or disease control. Current needs for olfactory neuroblastoma include the development and validation of refined staging systems suitable for current practice; expansion of indications for endoscopic surgery; less invasive surgery; definitive radiotherapy and novel systemic therapy.