Analysis of the tumor length and other prognosis factors in pT1-2 node-negative esophageal squamous cell carcinoma in a Chinese population

Before 1987, the American Joint Committee on Cancer (AJCC) staging system used tumor length to predict patient prognosis [1]; however, the current TNM staging system, first published in 2009, did not take tumor length into account [2]. In the current AJCC staging system for esophageal tumors, stage depends on the depth of the tumor (T classification), lymph-node (LN) involvement (N classification), and distant metastasis (M classification).

Recent publications have suggested that pathologic esophageal tumor length is directly correlated with long-term survival [3–6]; however, most of these data originated in western countries, and the cancer type was predominantly adenocarcinoma.

The aim of this study is to evaluate the value of tumor length and other prognostic factors in predicting the behavior of early-stage esophageal squamous cell carcinoma (SCC) without LN involvement, and the outcome after definitive surgery for such cases, in a Chinese population.

We assessed patients who had undergone surgical resection for esophageal cancer between January 2002 and December 2008 in Zhejiang Cancer Hospital. The total number of patients was 1,325, of whom 431 had received a pathological diagnosis of T1-2; 199 of these had LN metastasis, and were excluded. Of the 232 patients without LN metastasis, 13 did not have microscopically tumor-free margin (R0), and a further 18 either had fewer than 12 dissected LNs or had a cancer type other than SCC, and these were also excluded, leaving 201 patients for analysis.

All of the 201 patients with complete tumor resection had pathologically confirmed SCC. The tumor length was measured immediately after resection. Preoperative evaluation and staging investigations included a complete medical history and physical examination, complete blood count and serum biochemistry tests, and scans (for example, computed tomography (CT) of the thorax, ultrasonography of the upper abdomen, magnetic resonance imaging of the brain, total body bone scan, and fluorodeoxyglucosepositron emission tomography).

To our knowledge, this is one of the largest studies to evaluate the value of tumor length in predicting patient prognosis for resectable early-stage esophageal SCC. We found that pathologic esophageal tumor length was associated with long-term survival in esophageal SCC. Our results suggest that tumor length might be a valuable prognostic factor and might help to identify a high-risk group of patients after surgery for early-stage esophageal SCC.

According to the guidelines of the National Comprehensive Cancer Network, systemic chemotherapy is not recommended for esophageal carcinoma of pT1-2 without LN metastases; observation after complete tumor resection is the recommended approach. However, the 5-year survival rate for some patients, thus it could be useful to assess possible risk factors in addition to tumor depth and grade. In other cancers, such as lung and breast cancers, tumor size is an important prognostic factor for predicting long-term survival, where as only tumor depth and grade are considered prognostic factors in the p-TNM staging for esophageal carcinoma [7].Eloubeidi et al. [4] proposed a revised TNM classification for esophageal carcinoma to include tumor length. Other authors have also indicated the importance of tumor length for prognosis; however, most of these data were based on western populations, with the tumor type being predominantly adenocarcinoma [8–10].

In our study, we attempted to eliminate any influence of LN metastases by focusing only on the pathologic esophageal tumor length. In addition, we selected only patients who had undergone esophagectomy with complete tumor R0 resection achieved; any cases withoutR0 resection was excluded. Our study clearly demonstrates that tumor length is an independent predictor of long-term survival, and association of tumor length with survival was consistent regardless of whether length was analyzed as a continuous or categoric variable (Figure 1, Figure 2). In addition, this effect was present even when the other standard staging prognostic factors (pTNM) were taken into account.

The question of how many LNs should be dissected has been a point of debate in previous studies [11–13]. Greenstein et al. [14]. and Yang et al. [15] recommended 18 as the minimum number of resectable LNs, whereas Peyre et al. [16] recommended a minimum of 23 regional LNs, and Schwarz and Smith recommended at least 30 LNs be removed for an adequate lymphadenectomy [17]. However, most previous studies were included patients with locally advanced cancers. The LN dissection number was not clear in early-stage esophageal carcinoma. We did not find any survival difference when using 18 LNs as a cut-off point in our data.

As noted by other authors, Tumor depth also correlated with long-term outcome in patients with different pT disease stages, as reported previously by other authors [9, 11]. The overall 5-year survival rates for pT1 and T2 were 76.2% and 67.4%, respectively in this study. Similarly, level of differentiation (well/moderately versus poorly/not) was also a strong prognosis factor in our study (P = 0.04).

Our study has several limitations. It was a retrospective study with all the limitations that accompany such a study. In addition, because the study used data from a single institution but with different pathologists and different surgeons, there may have been a lack of uniformity in measurement methods. The LN dissection number was also not consistent, and we also excluded patients who had a dissected LN number of less than 12, which may have influenced our analysis. Thus, carefully designed prospective studies are needed to confirm the role of tumor length in guiding esophageal SCC treatment.

In summary, our study suggests that esophageal tumor length in early-stage esophageal SCC without LN involvement could be a useful prognostic factor to help identify high-risk patients with esophageal cancer before surgical resection. We found that esophageal tumor length was a significant independent predictor of long-term survival. We consider that it should be incorporated in the current esophageal cancer staging system to better predict the long-term survival of patients with esophageal cancer.