Surgery has been the treatment of choice for localized esophageal cancer. However the prognosis of the patients with SCCE treated by surgery alone is still poor. The locally invasive nature of the disease and anatomic limitations are both the major obstacles for a curative resection. In unselected patient cohorts, the 5-year survival rates for potentially resectable patients are low as 10-15% [
1,
7,
8]. A number of studies have investigated whether preoperative chemotherapy followed by surgery leads to an improvement in cure rates, but the individual reports have been conflicting.
In early studies using different chemotherapy regimens with or without radiotherapy preoperatively, the rate of resectability was found as 35-86% [4,8-12]. Also the rate of pathologic response in those studies was ranging between 0 and 10% and median survivals were between 10 and 18 months. Cisplatinum and 5-FU combination with different schedules has been the most widely used regimen preoperatively. In this small group of patients with locally advanced disease (stage III), we achieved a 60% complete resection rate. However, early mortality rate following the surgical procedure was 20%, which is highly unfavorable when compared to the previous reports [8-16]. It might be due to the preoperative chemotherapy that caused very frequent side effects being mainly the grade 3-4 myelosuppression. Although the higher response rate achieved in the current study, lack of the pathological response following chemotherapy is another unfavorable result. Further cycles of chemotherapy would possibly result in pathological responses. However, the complete pathological response rates seen in nonrandomized trials reported so far are ranging between 0 and 10% [17,18].
In the vast majority of the previous studies no survival advantage has been reported with the use of neoadjuvant chemotherapy. In a randomized trial studying the efficacy of 3 cycles of preoperative cisplatin and 5-FU combination chemotherapy and 2 additional cycles of the same regimen after surgery, no survival advantage over surgery alone arm has been reported (14.9 months v.s. 16.1 months) [19]. However, The Medical Research Council Esophageal Cancer Working Party has reported a slight survival advantage in the patients administering 2 cycles of preoperative cisplatin and 5-FU combination compared to surgery alone group (16.8 v.s. 13.3 months, respectively) [20]). In the current study, we observed a median survival of 17 months, which is comparable to those achieved in previous both randomized and nonrandomized trials. However, it could be noticed from the previous reports that, there is a trend of increased survival rates in the subgroup of patients achieving pathological complete response [21-23].
Recently, results of some phase II and randomized neoadjuvant chemoradiotherapy trials have raised the hopes for increasing the survival in SCCE, although some of them failed to show survival benefit [14-16,24,25]. In Nygaard study [14], the comparison between the chemoradiation plus surgery arm with the surgery-alone arm showed a statistically insignificant improvement in 3-year diseasefree survival from 9% to17% (p=0.03). In the same study, the rate of curative resection was lower than compared with similar studies. In the Michigan University study, median survival was approximately 17 months in both arms; 3-year survival was compared in the chemoradiation plus surgery arm (32% v.s. 15%) but of borderline statistical significance. The rate of loco regional recurrence was 19% for the chemoradiation plus surgery arm v.s. 39% for the surgery-alone arm (p=0.039) (24). Also the use of the combination of new drugs is reported to yield better results in terms of response and survival [21,26]. However, along with the non-clear survival benefit, the increased morbidity of the surgery following chemoradiotherapy seems to be an important limitation for this multimodal therapeutic approach.
The question of which therapeutic approach yields the best survival benefit in patients with potentially resectable stage III SCCE remains unanswered. Although the majority of the previous reports show a minor benefit from the preoperative chemoradiotherapy in patients with locally advanced SCCE, the interpretation of the results of those trials are challenging. To clarify the role of neoadjuvant treatment, either chemotherapy or chemoradiotherapy, in the treatment of patients with potentially resectable SCCE, further studies are needed.
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