Can histopathologic assessment of circumferential margin after preoperative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for 3-year disease-free survival?

Int J Radiat Oncol Biol Phys. 2005 Nov 1;63(3):745-52. doi: 10.1016/j.ijrobp.2005.03.003.


Purpose: This study set out to determine the impact of a positive circumferential resection margin (CRM) (R1-R2) and pathologic downstaging on local recurrence and survival in patients with borderline resectable or unresectable rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy (CRT).

Methods and materials: A total of 150 patients with locally advanced rectal cancer were treated with long-course neoadjuvant CRT using low-dose folinic acid and 5-fluorouracil. CRT was followed 6-12 weeks later by surgical excision. The CRM rate and incidence, site, and pattern of local and systemic recurrences were recorded. The median follow-up was 25 months.

Results: The overall median survival was 37 months, with a 5-year overall survival rate of 34%. Of the 150 patients, 122 underwent curative resection; 12% had a complete pathologic response, and downstaging to pT1-T2 occurred in an additional 16%. A negative CRM (R0) was achieved in 65% overall (98 of 150). Local recurrence occurred in 10% of those with R0 resection and 62% of those with R1-R2 resections. Distant metastases occurred in 29% of those with R0 resections and 75% of those with R1-R2 resections. The 3-year disease-free and 3-year overall survival rate was 9% and 25% and 52% and 64%, respectively, for patients with and without a histologically positive CRM.

Conclusion: After 5-fluorouracil-based CRT, a positive CRM predicted for a high risk of subsequent local recurrence and a 3-year disease-free survival rate of only 9%. For this reason, the CRM should be considered a major prognostic factor and should be validated in future trials as an early alternative clinical endpoint.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Fluorouracil / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Mitomycin / therapeutic use
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Neoplasm, Residual
  • Radiotherapy Dosage
  • Rectal Neoplasms / mortality
  • Rectal Neoplasms / pathology*
  • Rectal Neoplasms / therapy*
  • Survival Rate


  • Antimetabolites, Antineoplastic
  • Mitomycin
  • Leucovorin
  • Fluorouracil