Importance of the field: Primary central nervous system lymphomas (PCNSL) are rare but potentially curable tumours. The overall outcome for PCNSL patients is unsatisfactory and several therapeutic questions remain open. Modest progress in outcome reflects difficulties in conducting randomized trials and scarce molecular and biological knowledge.
Areas covered in this review: This review describes conventional and investigational treatments for PCNSL and focuses on the main questions for future clinical trials. PubMed and the authors' own files were utilized for references search. The terms 'PCNSL', 'primary AND CNS lymphoma', and 'CNS AND lymphoma' were used for PubMed queries. All papers published in English before November 2009 were considered.
What the reader will gain: This review illustrates how the paradigm for PCNSL treatment changed during the 1990s from radiotherapy alone to the establishment of high-dose methotrexate-cytarabine combination as standard approach. We present promising data from Phase II studies and discuss questions for randomized trials. Finally, we offer a 5-year scenario for the management of PCNSL.
Take-home message: The methotrexate-cytarabine combination should currently be considered as the reference treatment for PCNSL. Well-designed randomized trials and biological studies deriving from the use of novel technologies will be crucial to further improve outcome in these patients.