In this retrospective study, we investigated the factors affecting survival in operated patients with ESCC. We observed better survival in patients treated with nCRT and worse survival duration as the pathological stage increased.
In ESCC, esophageal obstruction due to tumor causes progressive dysphagia, often accompanied by weight loss. Dysphagia generally occurs when the esophageal lumen diameter is <13 mm, indicating advanced disease [17]. In this study, dysphagia and obstruction were observed in 95% and 16.4% of the patients, respectively. In ESCC, although the main risk factors remain unclear, malnutrition, low vegetable and fruit intake, and hot beverage consumption are believed may play a role in the pathogenesis [5].
There is no obvious gender difference in regions where ESCC is endemic. However, it is more prevalent in men in low-incidence countries [18]. In this study, the female-to-male ratio was almost two-folds because it was conducted in a high-incidence region for ESCC. Low vegetable and fruit intake and some traditional nutritional habits in our region were quite common, such as salty cheese and hot tea consumption. Furthermore, of the patients included here, 30% were active smokers. A review from our country that included 31 studies between 1988 and 2010 suggested that the frequency of smoking ranged from 27.5% to 63.8% in males and 8.4%–27.8% in females [19]. In this study, the lower rate of smoking resulted from the high female-to-male ratio.
A study conducted by Javle et al. that included 172 patients with esophageal cancer, 74 of whom were ESCC, reported that tumor stage and surgery independently affected survival [20]. Suzuki et al. conducted a study on patients with ESCC and reported that stage independently affected survival [21]. Similarly, in this study, a higher stage significantly decreased survival and mortality rate in pathological stage III patients was nearly 5-folds higher than those in stage I.
In RTOG 85-01 study, Al Sarraf et al. compared RT to definitive nCRT in 123 locally advanced patients with esophageal cancer. mOS was 14.1 months in nCRT arm vs. 9.3 months in RT arm. Furthermore, another 69 patients were treated with CRT and the OS rate was 17.2 months, similar to the previous outcomes [22]. In another study that randomized 172 locally advanced patients with esophageal cancer to induction chemotherapy, followed by nCRT plus surgery or definitive CRT, no significant survival difference between the groups was observed during the median 6-years follow-up. The 2-year locoregional control rate was found to be better in the surgery arm [23]. In the meta-analyses of studies comparing nCRT vs. surgery alone, nCRT was found to be superior [24-26].
In the meta-analysis that included 14 randomized studies conducted by Jin et al., it was observed that local control rates and survival rates with nCRT were better than surgery alone [24]. Likewise, in the meta-analysis of 9 randomized studies conducted by Urschel et al., it was observed that both 3-year survival and local control rates were better in the nCRT arm than surgery alone [25]. A study conducted by Munch et al. including 95 patients with ESCC compared nCRT with surgery or definitive CRT and found that a higher rate of local tumor control was observed in patients treated with nCRT than in patients treated with definitive CRT. There was at least a trend towards an improved OS and PFS in patients undergoing nCRT [27]. In this study, 75 patients were operated without nCRT, while 35 patients were operated without nCRT. OS was significantly longer in patients operated after nCRT. The 5-year survival rate was 84.4% in those operated after nCRT and 59.5% in patients who underwent direct surgery. In addition, administration of nCRT before surgery decreased the mortality by 68.5%.
There are limited studies in the literature that investigated the effect of pathological response after nCRT on survival only in ESCC. The results of the histological subtypes (ESCC and EAC) of esophageal cancer were given together in previous studies. In the study conducted by Takeda et al., pCR after nCRT in esophageal cancer significantly improved survival. Of 134 patients included in the study, only 94 were ESCC [28]. Likewise, in the study conducted by Gua et al. including 122 patients, only 43 patients were ESCC and found that the degree of tumor regression correlated with survival. The authors argued that tumor regression grade can be used to predict the long-term survival of esophageal cancer patients [29]. In this study, however, survival was significantly prolonged as the tumor response improved. At a median follow-up of 35 months, no recurrence or death was observed in any patient with pCR.
Unlike other studies, this study only included patients with ESCC and presented real-life data. In addition, only operated patients were included to ensure homogeneity. However, this study was designed retrospectively and as a single center. Furthermore, this study was conducted in a region where esophageal cancer is endemic, thus we were unable to determine how this could affect the results of the study.
In conclusion, administration of nCRT and early clinical stage in patients with ESCC were found to be the most important factors affecting survival in this study. It was observed that survival was prolonged as the tumor response improved in those who were operated after nCRT. We suggest that nCRT should be administered before surgery, especially in locally advanced ESCC. In addition, we believe that nCRT response can be used as a good parameter for survival. These results should be supported by prospective clinical studies.