Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial
Jp. Neoptolemos et al., Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial, ANN SURG, 234(6), 2001, pp. 758-768
Objective To assess the influence of resection margins on survival for pati
ents with resected pancreatic cancer treated within the context of the adju
vant European Study Group for Pancreatic Cancer-1 (ESPAC-1) study.
Summary Background Data Pancreatic cancer is associated with a poor long-te
rm survival rate of only 10% to 15% after resection. Patients with positive
microscopic resection margins (R1) have a worse survival, but it is not kn
own how they fare in adjuvant studies.
Methods ESPAC-1, the largest randomized adjuvant study of resectable pancre
atic cancer ever performed, set out to look at the roles of chemoradiation
and chemotherapy. Randomization was stratified prospectively by resection m
argin statu
Results Of 541 patients with a median follow-up of 10 months, 101 (19%) had
R1 resections. Resection margin status was confirmed as an influential pro
gnostic factor, with a median survival of 10.9 months for R1 versus 16.9 mo
nths months for patients with R0 margins. Resection margin status remained
an independent factor in a Cox proportional hazards model only in the absen
ce of tumor grade and nodal status, There was a survival benefit for chemot
herapy but not chemoradiation, irrespective of R0/R1 status. The median sur
vival was 19.7 months with chemotherapy versus 14.0 months without. For pat
ients with R0 margins, chemotherapy produced longer survival compared with
to no chemotherapy, This difference was less apparent for the smaller subgr
oup of R1 patients, but there was no significant heterogeneity between the
R0 and R1 groups.
Conclusions Resection margin-positive pancreatic tumors represent a biologi
cally more aggressive cancer; these patients benefit from resection and adj
uvant chemotherapy but not chemoradiation. The magnitude of benefit for che
motherapy treatment is reduced for patients with R1 margins versus those wi
th R0 margins. Patients with R1 tumors should be included in future trials
of adjuvant treatments and randomization and analysis should be stratified
by this significant prognostic factor.