Poster # 18, abstract # 4530Long term results of a phase III study investigating chemoradiation with and

without surgery in locally advanced squamous cell carcinoma of the esophagusM. Stahl, H. Wilke, N. Lehmann, M. Stuschke on behalf of the German Oesophageal Cancer Study Group

AbstractBackground: In 2005 we reported on a multicenter randomized trial comparing chemoradiotherapy followed by surgery vs. definitive chemoradiation in LA-SCC of the esophagus (Stahl M., JCO 23:2310, 2005). The data showed equivalence for both arms regarding 2- and 3-year survival, but survival curves seemed to diverge after 2 years. By now, long term results are available at a median follow-up of 10.1years. Methods: After randomization both arms started with induction chemotherapy (3 cycles of 5-FU/leucovorin/etoposid/ cisplatin). Afterwards, patients in arm A received concomitant chemoradiotherapy (40 Gy) followed by transthoracic esophagectomy and patients in arm B were treated with definitive chemoradiation (>60 Gy) without surgery. Regular follow-up was planned for up to five years after the end of treatment. Data of pts. surviving 5 years were colleted by a survey in 11/07. Results: Survival data were available in 169 out of 172 randomized patients. 17/86 pts. (19.8%) and 11/86 pts. (12.8%) were alive in arm A and B, respectively. Overall survival at 5 and 10 years (intention to treat) was 27.9% and 19.2% in Arm A, and it reached 17.0% and 12.2% in arm B. P-value for noninferiority was 0.06 (noninferiority margin: HR arm A vs. B > 0.67). In an as treated analysis (excluding cross-over) the survival rates at 5 / 10 years were 28.0%/19.8% and 17.0%/12.9% in arms A and B, respectively. Eight patients in Arm A, but none in arm B died unrelated to tumor or treatment. Thus, disease specific 10-year survival was 24.8% vs. 12.2% (logrank p = 0.14). Cox regression analysis proved clinical response to induction chemotherapy to be an independent prognostic factor for long term survival (HR responder vs. non-responder 0.30, 95%CI 0.19-0.48). Conclusions: Our mature results show no clear survival difference between operative and conservative treatment of patients with LA-SCC of the esophagus. Independent of treatment modality, clinical response to induction chemotherapy may be a valuable surrogate for predicting prognosis.

Participating Centers• Essen (KEM, AKK, University,EKH)• Düsseldorf (University)• Tübingen (University)• Marburg (University)• Duisburg (St.J., Städt.)• Trier (KB)• Berlin (RRK)• Göttingen (University)• Mönchengladbach (Franz.)

Eligibility Criteria• SCC of the intrathoracic esophagus• Stage T3-4 N0-1 M0 according to CT und EUS• Medically fit for surgery, PS 0-1• Age up to 70 years• Written informed consent

StrataCenter, Gender, Weight loss (up to vs. > 10%),

Complete EUS, Tumorstage

Endpoints• Primary endpoint- 2-year-survival (Noninferiority 35+/-15%)• Secondary endpoints- Rate of R0-Resection- Rate of PCR- Postoperative Mortality- Local tumor control

Results at Surgery• Surgery 62 patients• Resection 55 / 62 (89%)• R0 51 / 62 (82%)

ypT0 N0 M0 18 / 51 (35%)ypT1-3 N0 M0 17 / 51 (33%)ypT1-3 N1 M0 9 / 51 (18%)ypT1-3 N0-1 M1 7 / 51 (14%)

Surgical Procedures• Exploration 7 /62• Resection 55/62

(89%)TTE 49/55 (89%)THE 4/55Other 1/55Unknown 1/55

Mortality at CTX CRTX Surgery

Arm A 2/86(2.2%) 0 7/57(12.3%) Arm B 2/85(2.3%) 0 0/5

All 4/171(2.3%) 0 7/62(11.3%)

Treatment failure

Arm A Arm B

Any failure 31/56 (55%) 57/83 (69%)

Locoregional 14/31 (45%) 41/57 (72%)Distant (only) 16/31 (52%) 14/57 (25%)Unknown 1/31 ( 3%) 2/57 ( 3%)

Overall Survival5-YSR 27.9% vs 17.0%Calc. 10-YSR 19.2% vs 12.2%p=0.36, HR 1.15 (0.82-1.61)

Survival for responders5-YSR 56.5% vs 37.0%Calc.10-YSR 41.1% vs 31.8% p=0.48, HR 1.30 (0.62-2.75)

Conclusions• Long term survival possible with and without surgery in high risk patients with SCC• No clear advantage by adding surgery to chemoradiation• Clinical tumor response to induction chemotherapy prognostic according to Cox regression analysis

Recruitment

Pts. eligiblen = 184

Pts. randomisedn = 172

Allocated An = 86

Allocated Bn = 86

Cox Regression Analysis (survival)Item HR (95%CI) p-valueResponse to CTX 0.30 (0.19-0.48) <.001Treatment arm 1.19 (0.80-1.76) 0.39Gender 1.06 (0.65-1.73) 0.82Weight loss 1.19 (0.76-1.85) 0.45Complete EUS 0.91 (0.61-1.35) 0.64