Abstract

Background:Follicular lymphoma (FL) is a heterogenous malignancy, reflected, in part, by the highly variable clinical course. Major advances over the past decades in diagnosis, classification, and management—especially the introduction of rituximab—have significantly contributed to improved survival among patients with FL. At present, however, population‐based studies that comprehensively assessed the contribution of these advances on survival according to disease stage are scarce.Aims:The aim of this nationwide population‐based study was to assess trends in primary therapy and survival among patients with FL in the Netherlands during a 28‐year period.Methods:We selected all adult (≥18 years) FL patients diagnosed between 1989–2016 from the nationwide Netherlands Cancer Registry (NCR), with survival follow‐up till January 1, 2018. Data on primary therapy—i.e. no anti‐neoplastic therapy, treatment with a chemotherapeutic backbone (CT), radiotherapy (RT) only, and other/unknown therapy—started within one year after diagnosis were available in the NCR. Information on the use of rituximab was available for patients diagnosed from 2007. We calculated relative survival (RS) and the relative excess risk of mortality up to five years after diagnosis to estimate disease‐specific survival. All analyses were performed separately for stages I‐II (i.e. limited stage; n = 4,350; median age, 63 years) and stages III‐IV (i.e. advanced stage; n = 7,658; median age, 61 years) disease, and stratified by calendar period (1989–1995, 1996–2002, 2003–2008, and 2009–2016) and age (18–60, 61–70, and >70 years). The periods were selected based on the availability of rituximab in the Netherlands, which was introduced in the Netherlands in 2003Results:In limited‐stage FL the use of CT decreased with each calendar period, following an increased proportion of patients that did not receive anti‐neoplastic therapy within one year after diagnosis (Fig 1A). Throughout the entire study period, around one‐third of patients across the three age groups received RT alone (Fig 1A). Trends in therapy among patients with advanced‐stage FL followed patterns akin to limited‐stage FL. However, in advanced‐stage FL, RT only was rarely applied, whereas CT was commonly applied (Fig 1A). During 2007–2016, ≥95% of the CT‐treated patients in the three age groups across both stages received rituximab.Five‐year RS improved significantly over time across the three age groups and both stage groups (Fig 1B‐C). Overall, when adjusted for age, sex, and year of follow‐up, patients with limited‐ and advanced‐stage FL diagnosed in 2009–2016 had 49% and 61% lower excess mortality, as compared with patients diagnosed in 1996–2002, respectively (P < .05). The survival improvement was generally greater among patients with advanced‐stage FL and patients aged >70 years. Of note, 5‐year RS was ∼90% among patients with limited‐stage FL diagnosed in 2009–2016. This was independent of age.Summary/Conclusion:In summary, in this nationwide population‐based study, survival among patients with FL improved considerably over time, particularly among patients with advanced‐stage FL and older age groups. Most notably, patients with limited‐stage FL diagnosed in 2009–2016 rarely experience excess mortality within five years after diagnosis. Collectively, the improvements in survival may be accounted for by changes and advances in therapy over time 3/4 particularly the introduction of rituximab in 2003 3/4 and improvements in supportive care, staging techniques, and risk‐adapted therapy.image

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