Esophageal Cancer Trials

Pre-op Chemoradiation vs Surgery Alone

Walsh et al. (NEJM 1996) [2]

  • Prospective, randomized study of pre-operative chemo (5-FU/CDDP) radiation (40Gy/15 fxs) followed by esophagectomy vs. surgery alone for ACA of the esophagus.


  • 113 patients enrolled (58 chemo/XRT and 55 surgery alone).


Treatment Med survival 1-yr OS 2-yr OS 3-yr OS
ChemoRT/Surgery 16 months 52% 37% 32%
Surgery 11months 44% 26% 6%
p-value P=0.01 P=0.01
  • Median F/U 10 months.
  • There was a 6% mortality rate.
  • 13 pts (25%) in the CMT group had a pCR at the time of surgery.
  • Criticized for poor survival in surgery arm

Bosset et al. NEJM 1997; 337:161-167.

  • Prospective, randomized study of chemoradiation followed by surgery vs. surgery alone for SCCA of the esophagus.
    • chemo (Cisplatinum wekly)
    • radiation (split course 37 Gy in 3.7 Gy daily fractions)


  • 282 evaluable patients (139 received surgery alone and 143 CMT)


  • Median F/U 55.2 months.
  • Overall survival advantage for chemoradiation
  • Criticized for poor RT

Predictors of decreased survival.

  • Weight loss > 5% body weight
  • tumor located within 25 cm of the mandibular arch
  • and N1 disease
Treatment # patients Post-op mortality 3-yr DFS
ChemoRT/Surgery 143 16.7% 39%
Surgery 139 5% 37%
p-value 0.78

Urba et al.

  • Recent. Prospective randomized single institution study comparing surgery vs chemo RT surgery RT @ 45 Gy @ 1.5 Gy BID with concurrent chemo (Cis plat/5FU)


  • 16% vs 30% 3-OS (.15)
  • Trend toward survival benefit toward combined modality

Meta-analysis (Urschel) [1]

  • Survival odds ratio of .66 at 3 years in favor of patient receiving preoperative therapy.

Definitive Chemoradiation vs Radiation

Herskovic et al. RTOG 8501 NEJM 1992;326:1593-8 (update 6 /96 and in JAMA 1999).

  • Prospective, randomized trial of SCCA of thoracic esophagus
  • definitive radiation 64 Gy vs.
  • 50Gy/25 fx concurrent with chemoradiation (5-FU 1000mg/m2 and CDDP 75mg/m2 weeks 1,5,8,11)


  • 5-yr F/U. 5 yr survival 26% vs 0%
  • Combined modality treatment (CMT) better than radiation alone.
  • Even with 64 Gy, radiation alone had a very high 52% failure in the radiation field.
Treatment Med survival Local Relapse
64 Gy 9.3 mos 64%
50 Gy + CT 14.1 mos 43%

Surgery vs Post-op Radiation

Zieren et al. World J surg 1995;19:444-9.

  • Prospective randomized study of 68 patients with SCC randomized to treatment with surgery +/- XRT. No difference in OS.

Teniere Surg Gyn Obstet 1991[3]

  • epidermoid carcinoma of the middle third or the lower third of the esophagus.


  • curative esophageal resection and post-operative 45 to 55 Grays was delivered in the mediastinal, right and left supraclavicular areas and also to the celiac area when celiac lymph node invasion was present.


  • group N0 had significantly higher survival compared to (groups N+1 and N+2).
  • No difference in OS.
  • RT significantly reduced local recurrences

Pre-op Chemotherapy vs Surgery

Magic Trial (N Engl J Med. 2006;355:11–20, 76–77)

  • MAGIC trial used a chemotherapy regimen consisting of epirubicin, cisplatin, and fluorouracil (ECF), administered for 3 cycles preoperatively and 3 cycles postoperatively.
  • 5-year survival was 36% in the group that received chemotherapy compared with 23% in the group treated with surgery alone.

Medical Research Council Oesophageal Cancer working Party

  • Neoadjuvant chemotherapy improves 2-OS by 9%


  • 802 Resectable

Treatment and Results

Treatment 2-OS
5FU + Cis-P + Surg 43%
Surgery Alone 34%
p-value < .01
  • Meta-analysis showed improvement with adjuvant chemotherapy
1. Urschel JD, Vasan H: A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgeyr alone for resectable esophagus cancer. Am J Surg 185:538-543, 2003.
2. Walsh TN, Noonan N, Hollywood D, et al: A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 335:462-467, 1997.
3. Teniere P, Hay JM, Fingerhut A, Fagniez PL. Postoperative radiation therapy does not increase survival after curative resection for squamous cell carcinoma of the middle and lower esophagus as shown by a multicenter controlled trial. French University Association for Surgical Research. Surg Gynecol Obstet. 1991 Aug;173(2):123-30. PMID: 1925862
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