Postoperative chemotherapy vs chemoradiotherapy for thoracic esophageal cancer: a prospective randomized clinical trial.
BACKGROUND
Neither postoperative radiotherapy nor chemotherapy alone provided a survival benefit after curative esophagectomy for esophageal squamous carcinoma.


METHODS
Of 103 consecutive patients who underwent potentially curative esophagectomy for esophageal squamous carcinoma, 45 patients with advanced cancers without preoperative adjuvant treatments were prospectively randomized to two groups; postoperative chemotherapy alone (Group A, n=23) and postoperative radio/chemotherapy (Group B, n=22). In Group A, cisplatin (CDDP) (50 mg/m(2)) was given by intravenous infusion on days 1 and 15, and 5-fluorouracil (5-FU) (300 mg/m(2)) was given daily by continuous intravenous infusion for 5 weeks. In Group B, in addition to the same chemotherapeutic regimen of Group A, 50 Gy of radiotherapy was given to the mediastinum over 5 weeks. The immunohistochemical staining of tumoral p53 and microvessel density was undertaken to correlate to the radio/chemosensitivity.


RESULTS
There were no significant differences in the clinicopathologic characteristics between the two groups. The median dose of 5-FU and CDDP administered were not significantly different between the two groups. The mean (SD) dose of radiotherapy in Group B was 42+10 Gy. The 1-, 3- and 5-year survival rates in Group A were 100, 63 and 38% and those in Group B were 80, 58 and 50%, respectively (P=0.97). In each group, four patients succumbed to locoregional recurrences. Tumoral p53 was immunohistochemically negative in 43% in Group A and 77% in Group B (P=0.03), indicating that many patients in Group B might be potentially sensitive to radiochemotherapy. The 3- and 5-year survival rates (75 and 64%) of patients with p53 negative expression (n=18) were significantly (P=0.03) better than those with p53 positive expression (n=27, 44 and 26%). The long-term survival was better for patients with p53 negative tumours than those with p53 positive tumours in Group B (P=0.06 by long-rank test, P<0.05 by Generalized-Wilcoxon test). However, the long-term survival was not different between the patients who had p53 negative and positive tumours in Group A (P=0.19). These data suggest that there were no survival advantage for patients receiving radiotherapy in Group B, instead p53 negative tumours appeared to have a favorable prognosis.


CONCLUSIONS
Postoperative radiotherapy administered concurrently with chemotherapy does not provide a survival benefit compared with chemotherapy alone. Tumoral p53 expression has a predictive value for survival in patients treated with postoperative radio/chemotherapy.
Tachibana
M
M
Department of Digestive and General Surgery, Shimane Medical University, Enya-cho 89-1, Izumo 693-8501, Shimane, Japan. nigeka35@shimane-med.ac.jp
Yoshimura
H
H
Kinugasa
S
S
Shibakita
M
M
Dhar
D K
DK
Ueda
S
S
Fujii
T
T
Nagasue
N
N
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000098:blood supply / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D011184:Postoperative Period; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D016019:Survival Analysis; D013909:Thorax; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin; D005472:Fluorouracil