title: Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial.
abstract: BACKGROUND
  Neither chemotherapy with a single-alkylating agent nor aggressive combination chemotherapy cures advanced stage low-grade non-Hodgkin lymphomas, even when combined with radiotherapy. Our aim was to compare administration of immediate chlorambucil treatment with a policy of delaying chlorambucil until clinical progression necessitated its use, in asymptomatic patients with advanced-stage, low-grade non-Hodgkin lymphoma.
  
  
  METHODS
  309 patients with asymptomatic, advanced-stage, low-grade non-Hodgkin lymphomas were recruited from 44 UK centres between Feb 1, 1981, and July 31, 1990. 158 patients were randomised to receive immediate systemic therapy with oral chlorambucil 10 mg per day continuously. The remaining 151 were randomised to an initial policy of observation, with systemic therapy delayed until disease progression. In both groups, local radiotherapy to symptomatic nodes was allowed.
  
  
  RESULTS
  Median length of follow-up was 16 years. Overall survival or cause-specific survival did not differ between the two groups (median overall survival for oral chlorambucil 5.9 [range 0-17.8] years and for observation 6.7 [0.5-18.9] years, p=0.84; median cause-specific survival 9 [0-17.8] years and 9.1 [0.67-18.9] years, respectively p=0.44). In a multivariate analysis, age younger than 60 years, erythrocyte sedimentation rate (ESR) 20 mm/h or less, and stage III disease, conferred significant advantages in both overall survival (p<0.0001, 0.03, and 0.03, respectively) and cause-specific survival (p=0.002, 0.008, and 0.001, respectively). In the observation group, at 10 years' follow-up, 19 patients were alive and had not received chemotherapy. The actuarial chance of not needing chemotherapy (non-lymphoma deaths censored) at 10 years was 19% (40% if older than 70 years).
  
  
  CONCLUSIONS
  An initial policy of watchful waiting in patients with asymptomatic, advanced stage low-grade non-Hodgkin lymphoma is appropriate, especially in patients older than age 70 years.
authors.affiliation: British National Lymphoma Investigation, CRC and UCL Cancer Trials Centre, London NW1 2DA, UK. kirit.ardeshna@uclh.org
authors.forename: K M
authors.initials: KM
authors.lastname: Ardeshna
authors.forename: P
authors.initials: P
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Norton
authors.forename: B W
authors.initials: BW
authors.lastname: Hancock
authors.forename: P J
authors.initials: PJ
authors.lastname: Hoskin
authors.forename: K A
authors.initials: KA
authors.lastname: MacLennan
authors.forename: R E
authors.initials: RE
authors.lastname: Marcus
authors.forename: A
authors.initials: A
authors.lastname: Jelliffe
authors.forename: G
authors.initials: G
authors.lastname: Vaughan
authors.lastname: Hudson
authors.forename: D C
authors.initials: DC
authors.lastname: Linch
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D002423:Cause of Death; D002699:Chlorambucil / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil