7527 Background: Initial treatment strategies in FL include observation (obs), rituximab (R), chemotherapy ± R, and XRT. A recent study suggests initial therapy may impact FL survival (JCO 23:8447). NLCS is the first prospective observational study in the US designed to assess FL presentation, prognosis, treatment, and clinical outcomes. We describe initial therapeutic strategy in NLCS FL pts. Methods: FL pts diagnosed within 6 months with no prior lymphomas were recruited in this ongoing study. Data collected includes histology, stage, therapy, response, relapse and death. There is no specified treatment regimen. Results: From 3/04 to 11/05 1493 pts enrolled at 237 sites in the United States. Demographics have been initially reported at ASH 2005 (Blood 106:293a) and are comparable to SEER. Initial therapeutic strategy was: obs, 19%; R-monotherapy, 13%; chemo+R, 51%; XRT, 5%; chemo only, 4%. Chemo+R regimens were: R-CHOP, 59%; R-CVP, 19%; R-fludarabine based,11%; other, 11%. Choice to initiate therapy was associated with FLIPI, stage, and grade (p < 0.0001). Significant regional differences (p < 0.0001) were noted: obs was used in 13% of pts in Southeast and 31% in Northeast (NE); fludarabine-based R-chemo was used in 18% of pts in Southwest and only 3% in NE. Academic sites were more likely than community sites to treat pts on clinical trials (12% vs 4%). In pts treated with R or chemo+R, a higher FLIPI was not associated with decision to utilize chemotherapy. 26% of initially observed pts have switched to active therapy after a median of 2.8 months on obs since diagnosis; this was associated with baseline grade (III>II>I), but not stage or FLIPI. Conclusions: Diverse regimens are used for initial management of FL in the United States. Few pts are treated on clinical trials. Significant differences among regions and between center types suggest physician preference may drive initial therapy. Studies such as NLCS are needed to better understand the impact of initial therapy on short- and long-term outcomes. [Table: see text]