First-line chemotherapy improves the resection rate and long-term survival of locally advanced (T4, any N, M0) squamous cell carcinoma of the thoracic esophagus: final report on 163 consecutive patients with 5-year follow-up

Abstract

Objective: The objective of this prospective, nonrandomized study was to evaluate the immediate and long-term results of first-line chemotherapy and possible surgery in locally advanced, presumably T4 squamous cell esophageal cancer.

Summary background data: Locally advanced esophageal cancer is rarely operable and has a dismal prognosis. For this reason, neoadjuvant cytoreductive treatments are more and more frequently used with the aim of downstaging the tumor, increasing the resection rate, and possibly improving survival.

Methods: From January 1983 to December 1991, 163 consecutive patients with a presumedly T4 squamous cell carcinoma of the thoracic esophagus (group A) received on average 2.5 cycles (range, 1-6) of first-line chemotherapy with cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per day, in continuous infusion from day 1 through day 5). Chemotherapy was followed by surgery when adequate downstaging of the tumor was obtained.

Results: Chemotherapy toxicity was WHO grade 0 to 2 in 80% of cases, but 3 toxic deaths (1.9%) occurred. Restaging suggested a downstaging of the tumor in 101 of 163 patients (62%), but only 85 patients (52%) underwent resection surgery; it was complete or R0 in 52 (32%) and incomplete or R1-2 in 33. Overall postoperative mortality was 11.7% (10 of 85), morbidity 41% (35 of 85). Complete pathologic response was documented in 6 patients, and significant downstaging to pStage I, IIA, or IIB occurred in 25 more patients. The overall 5-year survival was 11 % (median, 11 months). After resection surgery, the 5-year survival was 20% (median, 16 months); none of the nonresponders survived 4 years after palliative treatments without resection (median survival, 5 months). The 5-year survival rate of the 52 patients undergoing an R0 resection was 29% (median, 23 months). Stratifying patients according to the R, pT, pN, and pStage classifications, the survival curves were comparable to the corresponding data obtained in the 587 group B patients with "potentially resectable" esophageal cancer who underwent surgery alone during the same period. Furthermore, the results were improved in comparison with 136 previous or subsequent patients with a locally advanced tumor who did not undergo neoadjuvant treatments (group C). In these patients, the R0 resection rate was 7%, and the overall 5-year survival was 3% (median, 5 months).

Conclusion: Although nonrandomized, these results suggest that in locally advanced esophageal carcinoma, first-line chemotherapy increases the resection rate and improves the overall long-term survival. In responding patients who undergo R0 resection surgery, the prognosis depends on the final pathologic stage and not on the initial pretreatment stage.