Characteristics of Patients with Stage I Follicular Lymphoma (FL) Selected for Watchful Waiting (WW) in the US: Report from the National LymphoCare Study (NLCS).

The NLCS is a multi-center, disease-based, longitudinal, observational study designed to collect information on treatment regimens and outcomes for patients (pts) with newly-diagnosed FL in the US. We have previously demonstrated that demographics of enrolled patients are similar to the SEER and FLIPI databases. There remains controversy and lack of consensus regarding the appropriate initial therapy for pts with FL. Historically, randomized trials have indicated no benefit to early therapeutic intervention, and many pts were managed by a “watchful waiting” (WW), or observation, approach. More recently, studies have suggested that initial treatment of FL may influence survival, calling into question the role of WW today. The National Comprehensive Cancer Network (NCCN) guidelines identify locoregional radiotherapy (RT) as the treatment of choice for stage I and II FL pts, whereas WW is reserved for select pts where toxicity of RT outweighs potential clinical benefit. The NLCS has over 2700 pts enrolled, and, of these, 455 were managed with WW as their initial therapy as of 1/31/07. This analysis focuses on the 134 stage I FL pts (29.3% of all stage I pts) in the NLCS database who were initially managed with WW, and examined their baseline characteristics as possible predisposing factors to a WW approach. The cohort of WW pts includes pts meeting both of the following criteria:

1. initially reported to be managed by WW by the investigator, and

2. were not administered treatment within 3 months of diagnosis.

Age distribution was 6.0% <45 yr, 20.9% 45–59 yr, 39.6% 60–74 yr, and 33.6% 75+ yr. Low grade disease predominated (82.8% grades 1–2, 10.4% grade 3, 6.7% unknown/mixed grade). Nearly all pts had good (83.5%) or intermediate (15.5%) FLIPI score, and 97.5% had ECOG PS <2. B symptoms were present in 7.5%, and LDH was elevated in 6.0%. Interestingly, 75% of these pts had both good FLIPI score and PS 0. 61.7% pts of patients with a good FLIPI score were ≥60 yr at diagnosis, and 70.2% pts with PS 0 were ≥60 yr at diagnosis. Multivariate logistic regression comparing the stage I pts who were managed with WW vs. active treatment suggests older age (odds ratio [OR] = 1.025 for one-year increase), lower grade (OR=0.612 for one-unit increase), and lower PS (OR=0.485 for one-unit increase) are significantly associated with WW. FLIPI and B symptoms were not identified as significant predictors in the multivariate model. In conclusion, although therapies have recently demonstrated benefits in several endpoints, WW continues to be utilized relatively frequently in the US. Stage I pts who were initially managed by WW tended to have at last one of the following characteristics: older age, lower disease grade, good PS, or FLIPI score. This group is of particular interest, given that RT as an alternative active therapeutic modality has the potential for long term progression-free survival. The design of the NLCS with comprehensive data collection and long-term follow-up will enable this unique, large pt cohort to be followed through the natural history of this indolent disease.