HOME > Articles >

Korean J Gastroenterol  <  Volume 83(3); 2024 <  Articles

Korean J Gastroenterol 2024; 83(3): 102-110  https://doi.org/10.4166/kjg.2023.100
Comparison of the Clinical Outcomes of Esophagectomy and Concurrent Chemoradiotherapy in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma
Myung Hun Lee, Moo In Park , Ju Won Lee, Kyoungwon Jung, Jae Hyun Kim, Sung Eun Kim, Won Moon, Seun Ja Park
Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
Correspondence to: Moo In Park, Department of Internal Medicine, Kosin University College of Medicine, 262 Gamcheon-ro, Seo-gu, Busan 49267, Korea. Tel: +82-51-990-5205, Fax: +82-51-990-5055, E-mail: gimipark2003@naver.com, ORCID: https://orcid.org/0000-0003-2071-6957
Received: August 17, 2023; Revised: February 12, 2024; Accepted: February 13, 2024; Published online: March 25, 2024.
© The Korean Journal of Gastroenterology. All rights reserved.

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims: The efficacy of concurrent chemoradiotherapy (CCRT) or esophagectomy for locally advanced esophageal squamous cell carcinoma (ESCC) is unclear. This study compared the survival and recurrence of patients with locally advanced ESCC after definitive CCRT and surgery.
Methods: A retrospective study was conducted on patients with locally advanced ESCC who underwent CCRT or esophagectomy at Kosin University Gospel Hospital from January 2010 to December 2016. The patients’ baseline characteristics, pathology, recurrence rate, and three-year/five-year overall survival were obtained
Results: This study evaluated ESCC patients with cT1-T2, N+ or cT3-T4, or N, who were treated by definitive CCRT (n=14) or esophagectomy (n=32). No significant difference was noted between the two groups, except for the location of the cancer and performance state. The respective three- and five-year overall survival rates were 30.8% and 23.1% in the CCRT group and 40.2% and 22.5% in the esophagectomy group (p=0.685). In the CCRT group, three patients (21.4%) had a complete response, and two (66.7%) had a recurrence. In the esophagectomy group, an R0 resection was achieved in 28 (87.5%) patients, and a recurrence occurred in 18 (64.3%). The median disease-free survival in the CCRT and esophagectomy groups was 14 and 17 months, respectively (p=0.882).
Conclusions: These results showed no significant difference in survival between the definitive CCRT and surgery as the initial treatment. Nevertheless, larger prospective studies will be needed because of the retrospective nature and small number of patients in this study.
Keywords: Esophageal squamous cell carcinoma; Chemoradiotherapy; Esophagectomy
INTRODUCTION

1. Core tip

This retrospective study evaluated the clinical outcomes of definitive concurrent chemoradiotherapy (CCRT) and surgery in patients with locally advanced esophageal squamous cell carcinoma (ESCC). The five-year overall survival rates in the CCRT and esophagectomy groups were 23.1% and 22.5%, respectively (p=0.685). Multivariate analysis revealed chronic obstruction pulmonary disease as the only factor affecting survival in both groups (relative risk: 3.5, p=0.025). Definitive CCRT and surgery may be equally effective as initial treatments for locally advanced ESCC. Nevertheless, a large, well-designed, prospective randomized clinical trial will be needed to draw a definite conclusion.

Esophageal cancer is generally discovered at an advanced stage and has a poor prognosis/Only 20% are a localized disease; 31% are regional, and 39% are distantly metastatic at diagnosis.1 Moreover, the five-year survival rate for esophageal cancer is only 19%, which is the fourth lowest rate after pancreatic cancer (8%), hepatobiliary cancer (18%), and lung cancer (18%).1 Locally advanced esophageal squamous cell carcinoma (ESCC) is defined as stage IIb to IIIb, including tumors invading the regional lymph nodes or local structures. For resectable local esophageal cancer, surgical treatment is the mainstay of treatment, but the response rate is not as satisfactory as other solid tumors.2

The 2017 National Comprehensive Cancer Network (NCCN) guidelines3 recommended neoadjuvant concurrent chemoradiotherapy (nCCRT), concurrent chemoradiotherapy (CCRT) alone, or esophagectomy for cT1-T4aN0-N+ ESCC, whereas the 2019 NCCN4 prioritized esophagectomy for cT1b-cT2 N0 ESCC while recommending nCCRT or CCRT alone for cT1-T2N+ or cT3-T4N0 ESCC.

Randomized studies on the treatment of locally advanced ESCC revealed inconsistent results for CCRT (alone, nCCRT, adjuvant therapy) and surgical treatment, and the need for surgery after nCCRT is still unclear.2,5-8 Nevertheless, according to the 2019 NCCN guidelines, surgery alone is no longer recommended as an initial treatment for locally advanced ESCC.4 Therefore, this study compared the survival and recurrence rates of different initial treatments on locally advanced ESCC to provide significant data that can improve the guidelines for treating locally advanced ESCC.

SUBJECTS AND METHODS

1. Patients

From January 2010 to December 2016, a retrospective study was conducted on patients who received CCRT alone or esophagectomy as the initial treatment after being pathologically diagnosed with esophageal cancer at Kosin University Gospel Hospital. Chest and abdominal computed tomography (CT) and F-fluorodeoxyglucose (FDG) positron emission tomography (PET) were taken, and the clinical stage was determined based on the eighth edition of the American Joint Committee on Cancer (AJCC) staging manual.9,10 Of all qualified patients, only patients with locally advanced esophageal cancer (cT1-T2N+ or cT3-T4N0) and histological squamous cell carcinoma were studied. The patient’s clinical characteristics, pathologic data, and survival-related clinical outcomes were reviewed retrospectively using the electronic medical records. The authors’ Institutional Review Board approved the study. All procedures were conducted in accordance with the ethical standards of the Declaration of Helsinki (IRB No.: KUGH 2020-01-024).

2. Treatment method

1) Concurrent chemoradiotherapy alone

Thirteen out of 14 patients who received CCRT infused with 5-Fluorouracil (1,000 mg/m2/day, days 1–5, continuously intravenous) and cisplatin (75 mg/m2/day, day 1, for six hours, intravenous) every four weeks with concurrent radiotherapy to a dose of 50.4 Gy in 28 fractions or 68.8 Gy in 38 fractions. The other patient received radiotherapy with a dose of 50.4 Gy, and took Vinorelbine (50 mg/m2/day, day 1) and cisplatin (35 mg/m2/day, day 1) every two weeks.

2) Esophagectomy

The study was conducted on 32 patients who underwent an Ivor Lewis esophagectomy, including nine patients with surgery alone and 23 patients with postoperative adjuvant therapy. Sixteen patients received adjuvant Vinorelbine (50 mg/m2/day, day 1) and cisplatin (35 mg/m2/day, day 1) concurrent chemotherapy every two weeks. Two patients received adjuvant CCRT with the same adjuvant chemotherapy regimen plus CCRT. Two patients received adjuvant CCRT with 5-FU (1,000 mg/m2/day, days 1–5, continuously intravenous) and cisplatin (75 mg/m2/day, day 1, for six hours, intravenous) plus radiotherapy to a dose of 50.4 Gy in 28 fractions. Three patients received adjuvant radiotherapy with 50.4 Gy in 28 fractions.

3. Treatment response

Based on the World Health Organization (WHO) criteria, the treatment responses were evaluated as complete remission, partial remission, stable disease, and progressive disease using imaging studies, such as esophagography, chest and abdominal CT, and esophagogastroduodenoscopy. The definitions of each category are as follows: complete remission indicates the disappearance of all lesions; partial remission signifies ≥50% decrease in lesions; stable disease means <50% decrease or <25% increase in lesions; progressive disease indicates ≥25% increase or appearance of new lesions.11

The patients were followed up for concurrent radiotherapy every eight weeks after starting the treatment, while they were followed up for esophagectomy every two to three months after surgery. After completing the treatment, for asymptomatic patients, the follow-up was performed every three months up to the first two years and every six months thereafter. The patients were observed until the last follow-up visit or death. The survival period was calculated from the date of diagnosis until the time of death. The disease-free survival periods in the CCRT-alone group with complete remission and the esophagectomy group with a histopathologically confirmed R0 resection ranged from the completion of radiotherapy to recurrence and the day of surgery to recurrence, respectively.

4. Statistical analysis

Kaplan–Meier survival analysis was used to estimate the survival rates, and the survival distributions were compared using the Wilcoxon signed-rank test. Cox proportional hazards regression models were used to analyze the factors affecting the survival rate, and a p-value <0.05 was considered significant. An independent samples t-test was performed to compare the patients’ ages in each group. On the other hand, a chi-square test was carried out to compare sex, Eastern Cooperative Oncology Group (ECOG) performance scales, tumor location, tissue pathology diagnosis, and clinical stage in each group. All data were analyzed using IBM SPSS version 25.0 (IBM Co., Armonk, NY, USA).

RESULTS

1. Clinical characteristics of the patients

From January 1, 2010, to December 31, 2016, 14 and 32 patients received CCRT alone and underwent esophagectomy, respectively, among 433 patients who were pathologically diagnosed with esophageal cancer at Kosin University Gospel Hospital. Of the 433 patients, 74 patients were excluded due to early or more advanced clinical stage cancer (50 cases with cT1-2N0 and 24 cases with distant metastases), diagnosis of concurrent cancer (two cases), transfer- out during the treatment or treatment refusal (eight cases), histologically confirmed adenocarcinoma (two cases), and diagnosis of gastrointestinal stromal tumors (one case). Finally, the study included only 46 patients (43 males and three females) who met the clinical stage (five cases with cT1-T2N+, 41 cases with cT3-T4anyN), including 14 patients with CCRT alone, and 32 patients with esophagectomy as the initial treatment (Fig. 1).

Figure 1. Diagram depicting the flow of patients in the study. CTx, chemotherapy; RTx, radiation therapy; CCRT, concurrent chemoradiation therapy; SQCC, squamous cell carcinoma; ADC, adenocarcinoma; CR, complete remission; PR, partial remission; PD, progressive disease.

The mean age of the 46 patients was 62 years, and the median follow-up period was 20 months. Table 1 lists the general characteristics of the patients. The mean age of the CCRT alone group (14 patients) and surgery group (32 patients) was 68 and 62 years, respectively. The CCRT alone patients were all male, while the surgery group consisted of 29 males and three females. The ECOG performance scale and location of the tumor were significantly different between the two groups; an ECOG performance score of 0 was observed in 75% of the surgery group and 42.9% of the CCRT alone group, and the cancer was detected in the upper part of the esophagus in 35.7% of the CCRT alone group and 3.1% of the surgery group. No statistically significant differences in age, sex, tumor grade, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, and clinical stage were observed between the two groups (Table 2).

Table 1 . Patients and Pretreatment Tumor Characteristics

CharacteristicValue
Age62 (40–82)
SexMale43 (93.5)
Female3 (6.5)
GroupCCRT14 (30.4)
Esophagectomy32 (69.6)
DifferntiationUnknown3 (6.5)
WD15 (32.6)
MD20 (43.5)
PD8 (17.4)
ECOG performance030 (65.2)
114 (30.4)
22 (4.3)
DMNo5 (10.9)
Yes41 (89.1)
HTNNo39 (84.8)
Yes7 (15.2)
COPDNo42 (91.3)
Yes4 (8.7)
Clinical stageStage 00
Stage I3 (6.5)
Stage II20 (43.5)
Stage III21 (45.7)
Stage IVA2 (4.3)
Stage IVB0
LocationUpper6 (13.0)
Middle23 (50.0)
Lower17 (37.0)

Values are presented as median (range) or number of patients (%).

CCRT, concurrent chemoradiotherapy; WD, well differentiated; MD, moderately differentiated, PD, poorly differentiated; ECOG, Eastern Cooperative Oncology Group; DM, diabetes mellitus; HTN, hypertension; COPD, chronic obstructive pulmonary disease.


Table 2 . Clinical Characteristics of Patients and Overall Survival Rate

CharacteristicCCRTSurgeryp-value
Median (range) or number or months%Median (range) or number or months%
Age68 (43–82)62 (40–80)0.317
SexMale141002990.6
Female0039.4
Tumor length (just surgery group)4 (1.3–10.2 cm)
DifferentiationUnknown214.313.10.743
WD428.61134.4
MD642.91443.8
PD214.3618.8
ECOG performance0642.924750.018
1–2857.1825
DMNo1178.63093.80.256
Yes321.426.3
HTNNo1392.92681.30.118
Yes17.1618.8
COPDNo1178.63196.30.162
Yes321.413.1
Clinical stageStage 0–II642.91753.10.857
Stage III7501443.8
Stage IVA-B17.113.1
LocationUpper535.713.10.027
Middle535.71856.3
Lower428.61337.5
Median survival2325
Overall survival rate1 yr61.565.6
2 yr46.253.1
3 yr30.840.2
5 yr23.122.5

CCRT, concurrent chemoradiotherapy; WD, well differentiated; MD, moderately differentiated, PD, poorly differentiated; ECOG, Eastern Cooperative Oncology Group; DM, diabetes mellitus; HTN, hypertension; COPD, chronic obstructive pulmonary disease.



2. Survival rates and prognostic factors

For the whole cohort, the median survival was 25 months, and the three- and five-year survival rates were 29.6% and 22.6%, respectively (Fig. 2A). For the CCRT alone group, the median survival, three- and five-year survival rates were 23 months, 30.8%, and 23.1%, respectively. For the surgery group, the median survival, three- and five-year survival rates were 25 months, 40.2%, and 22.5%, respectively. Based on the Wilcoxon signed-rank test, there were no statistically significant differences in the survival rates between the two groups (p=0.685) (Fig. 2B).

Figure 2. Kaplan–Meier survival curves for the overall survival (A) in all patients, overall survival (B), and disease-free survival (C) according to the treatment modality (concurrent chemoradiotherapy and surgery).

3. Treatment response and recurrence rates

In the CCRT alone group, the cancer showed complete remission in three patients (21.4%), recurrence in two patients (66.7%), partial remission in 10 patients, and progression in one patient. Surgery was not performed in the 10 patients who showed partial remission because of treatment refusal (four cases), the tumor located in the cervical esophagus (two cases), and the underlying conditions that placed patients in a high-risk surgical group (four cases). In the esophagectomy group, an R0 resection was achieved in 28 patients (87.5%), but the tumor recurred in 18 (64.3%) (Table 3). The median disease-free survival of the CCRT alone and esophagectomy groups was 14 and 17 months, respectively; there was no significant difference between the two groups based on the Wilcoxon signed-rank test (p=0.882) (Fig. 2C).

Table 3 . Tumor Response and Frequency of Recurrence

CCRTSurgeryp-value
Number%Number%
Complete remission or R0 resection321.42887.50.882
RecurrenceNo133.31035.7
Yes266.71864.3
Recurrence locationLocal150422.2
Remote1501477.8

CCRT, concurrent chemoradiotherapy.



4. Cause of death and major complications

During the follow-up period, 24 patients (75%) died from various causes, including cancer progression (20 cases), postoperative pneumonia (two cases; 30 and 60 days after surgery), the appearance of a new lesion (one case, bladder cancer 63 months after surgery), and unknown cause (one case) in the esophagectomy group. Of these, two patients (postoperative pneumonia) were related to treatment, which accounted for 6%. Among the CCRT-only group, 10 patients (71.4%) died from cancer progression in the CCRT-alone group, and two patients (14.3%) presented with major complications; one patient presented with grade 3 neutropenia (680/L), while another patient developed a tracheoesophageal fistula after 10 fractions of radiation therapy.

DISCUSSION

This retrospective study compared the treatment outcomes of CCRT-alone and esophagectomy in patients with local advanced ESCC. The five-year survival rates for the CCRT alone and the esophagectomy groups were 23.1% and 22.5%, respectively, indicating no significant difference in survival between the two groups. In previous studies, the standard treatment of locally advanced esophageal cancer was unclear because of the inconsistent findings regarding the treatment outcomes of CCRT (alone, neoadjuvant therapy, and adjuvant therapy) and surgery.5-8

Only a few studies comparing CCRT alone and the surgical treatment for the initial treatment of locally advanced esophageal cancer, most of which are retrospective studies,12 and only a few randomized controlled trials have been performed.13,14 Chan and Wong12 conducted a retrospective study to compare the treatment outcomes of CCRT alone and surgery alone (82 patients vs. 81 patients) as an initial treatment for patients with localized esophageal cancer. Based on this study, there was no significant difference in the disease-free and overall survival between the two groups: the five-year disease-free survival of CCRT alone group (5-FU + mitomycin C ± leucovorin, 50–60 Gy) and surgery alone group was 23% and 21%, respectively; the five-year survival was 25% and 23%, respectively.12 In detail, adenocarcinoma (17%) and squamous cell carcinoma (83%) cases were involved. Based on the AJCC-TNM staging manual (1983), the CCRT alone group was composed of 8% of Stage I (T1N0/xM0), 59% of Stage II (T2N0/xM0), and 30% of Stage III (T3anyNM0/anyTN1M0). The surgery alone group comprised 28% of Stage I, 56% of Stage II, and 16% of Stage III.12 The mentioned study was different from this study in terms of the inclusion of adenocarcinoma, chemotherapy regimen, and subject’s cancer stage, but the findings were not significantly different from the present study. According to an RCT for resectable esophageal cancer conducted by Teoh et al.,13 the five-year survival of 36 patients with CCRT alone (5-FU + cisplatin, 50–60 Gy) and 45 patients with surgery was 50% and 29%, respectively, resulting in no significant difference between the two groups (p=0.147).13 Compared to Teoh et al., who included only patients under 75 years of age and 77.3% of cT3, the present study revealed lower survival, possibly due to the inclusion of higher-risk groups, such as elderly patients aged 82 years and older and 89% of cT3.

The 2019 NCCN guidelines recommend surgery on resectable residual lesions without metastatic lesions after the CCRT.4 Previous studies on the clinical implications of additional surgical treatment after CCRT reported superior or equivalent outcomes to those who did not undergo additional surgical treatment.6,7,15,16 Bedenne et al.7 conducted an RCT (FFCD 9102 trial) on patients with resectable ESCC (T3N0-1M0). The two-year survival of 129 patients who underwent CCRT (5-FU + cisplatin, 46 Gy) with additional surgery and 130 patients who did not undergo additional surgery but received CCRT (5-FU + cisplatin, 20 Gy) with radiation treatment was 34% and 40%, respectively, showing that additional surgery was not favorable for survival (unadjusted hazard ratio [HR]=0.90, p=0.49; adjusted HR=0.88, p=0.44). On the other hand, the two-year locoregional control of the two groups was 66.4% and 57.0%, respectively, which was higher in the CCRT with surgery group.7 Vincent et al.15 conducted an additional study on patients who did not respond to CCRT during Vincent’s FFCD 9120 trial. According to this study, 111 non-randomized patients who did not respond to CCRT were further divided into the additional surgery group (77 patients), and the CCRT alone group, and the study compared the median survival of the two groups. The median survival was longer in the surgery group (17.0 months) than in the CCRT alone group (5.5 months) (HR=0.39 [0.25–0.61]; p<0.0001).15 Other studies support these findings. Stahl et al.6 conducted a phase three prospective randomized study on the treatment of locally advanced ESCC. The study compared the two-year and progressive-free survival between 86 patients with additional surgery after CCRT and 86 patients with CCRT alone. As a result, the two-year survival was similar in the two groups (log-rank test for equivalence, p<0.05). Nevertheless, the two-year progressive-free survival was longer in the additional surgery group (64.3%) than the CCRT alone group (40.7%).6 According to a retrospective study conducted on 298 patients with locally advanced ESCC,16 the relative risk of death between the CCRT with additional surgery group and CCRT alone group was 0.56, suggesting that there was a decreased risk among the patients given CCRT with additional surgery. If the four patients initially excluded from the study had been included, 14 patients showed partial remission. Of them, 10 patients (71.4%) were unable to undergo surgery due to inoperable states (six cases) and treatment refusal (four cases). The two-year survival rates for the surgical and non-surgical groups were 50% and 25%, respectively, but the small number of patients did not reach statistical significance. In actual clinical practice, pursuing additional surgery on the patients was difficult. Even if the two-year survival of the surgical group was higher, the outcome may vary depending on the patient’s preoperative condition.

The treatment-related mortality in this study was two deaths from postoperative complications, which accounted for 6% of the surgery group. Among the CCRT-only group, two patients (14.3%) presented with major complications; one patient presented with grade 3 neutropenia (680/L), while another patient developed a tracheoesophageal fistula after 10 fractions of radiation therapy. Previous studies on complications of CCRT and surgical treatment showed that the surgery group had a higher mortality rate for treatment-related mortality, but no direct comparison between the two groups was made.5,17-19 Schieman et al.17, who analyzed 1552 cases of esophagectomy, reported that perioperative mortality occurred in 45 cases (3.0%), which included anastomosis and gastrointestinal necrosis (40%) and pulmonary complications (40%), such as aspiration, pneumonia, and acute respiratory distress syndrome. Of the patients, Ivor Lewis esophagectomy was performed on 853 cases with a 3.17% (27 cases) mortality rate.17 In addition, a study conducted on 229 patients who performed esophagectomy as a treatment for esophageal cancer18 reported that 6.1% of 229 patients with ESCC died within postoperative days 30.

The CCRT-related mortality tends to vary according to the study. Burmeister et al.5 conducted a randomized controlled study comparing 128 patients treated with esophagectomy and 128 with neoadjuvant chemotherapy plus esophagectomy. They reported no chemotherapy-related deaths in the neoadjuvant chemotherapy group. A retrospective study by Ren et al.19 compared the treatment outcomes of CCRT according to different radiation doses in 380 patients with ESCC. They reported that one of 190 patients treated with 50.4–54 Gy (0.6%) died from treatment-related acute radiation pneumonia, while 13 patients (7.9%) developed grade three or above bone marrow suppression. For 190 patients treated with 60 Gy, three patients (2.3%) died of bone marrow suppression-induced infection, and 15 patients (8%) developed grade three or above bone marrow suppression19. In contrast, a previous study reported that nCCRT increases the postoperative mortality. A study comparing the postoperative mortality rate of 59 ESCC patients who underwent surgery after CCRT and 553 ESCC patients who underwent surgery before CCRT reported a higher hospital mortality rate in the nCCRT group (8% vs. 2%).20 The treatment complication could be related to the quality of life after treatment. Chen et al.21 compared the quality of life according to the treatment method using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in 105 patients with ESCC. As a result, the surgery and CCRT groups at stages I–II showed β of 8 and −10, respectively, indicating a higher quality of life in the surgery group. In contrast, no patient in the surgery group had stages III or IV.

A summary of the present study and previous studies showed that the surgery-related treatment mortality was approximately 3 to 6%, which was higher than CCRT-related treatment mortality. Nevertheless, no study has directly compared the treatment-related mortality between the two groups. As a result, it is unclear if surgery and CCRT are safer and better for patients with ESCC because surgical treatment performed after CCRT may increase the mortality rate, and the surgery group at low stage of cancer showed better quality of life.

In the present study, lymph node metastasis tended to relate more to the pathological stage than the clinical stage (Fig. 3). Consistent with these findings, Yamada et al.22 studied the diagnostic value of FDG PET/CT for lymph node metastasis of 258 patients with ESCC. They reported a sensitivity and specificity of 28.8% and 97.8%, respectively. In addition, the false positives were rare; most false negatives were lymph nodes less than 7 mm.22 Thus, an imaging study, such as thoracic FDG PET/CT, may not be sufficient to determine lymph node metastasis in patients with ESCC.22 Considering the results of this study, the pathological stage of cancer may be identified when the patient undergoes surgery as an initial treatment and can be useful for the prognostic assessment and establishing a treatment plan.

Figure 3. Comparison of clinical with pathological lymph nodal staging.

This study had some limitations. First, this was a retrospective study including only a small number of patients. Although the medical records were carefully reviewed to provide accurate data regarding treatment outcomes and complications, there may be missing data compared to prospective studies. Second, the study only included the treatment outcome from a single institution for seven years. This result cannot reflect the treatment outcomes of all institutions because the treatment outcomes may vary according to the institution. Third, the treatment outcome was compared with the updated NCCN guidelines for locally advanced esophageal cancer (Nov. 2019). This study compared the outcomes of the treatments performed before the guidelines were updated. Therefore, the study included patients who received postoperative adjuvant chemotherapy no longer recommended under the updated guidelines, which might have affected the study results.

In conclusion, there was no significant difference in survival between the CCRT and surgery as an initial treatment for patients with locally advanced esophageal cancer. Even if the patient plans to undergo surgery after CCRT, the surgery may not proceed if the patient becomes inoperable or refuses treatment. Moreover, there is no clear evidence that additional surgery can improve the survival in patients who received CCRT. Therefore, in an actual clinical setting, it may be difficult to completely exclude esophagectomy for the initial treatment of locally advanced ESCC, as recommended by the 2019 NCCN guidelines. After diagnosis, the treatment plan should be established by considering the patient’s condition, the presence or absence of chronic underlying diseases, and multidisciplinary care. A large-scale prospective randomized controlled trial of early treatment of locally advanced esophageal cancer is recommended to suggest a better treatment option for patients with esophageal squamous cell cancer.

Financial support

None.

Conflict of interest

None.

References
  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7-30.
    Pubmed CrossRef
  2. Rahma OE, Greten TF, Duffy A. Locally advanced cancer of the esophagus, current treatment strategies, and future directions. Front Oncol 2012;2:52.
    Pubmed KoreaMed CrossRef
  3. NCCN guidelines version 4. 2017. Esophageal and Esophagogastric Junction cancers. [Internet]. Fort Washington: National Comprehensive Cancer Network; [cited 2017 Oct 13]. Available from: http://www.nccn.org.
  4. NCCN guidelines version 3. 2019. Esophageal and Esophagogastric Junction cancers. [Internet]. Fort Washington: National Comprehensive Cancer Network; [cited 2019 Nov 18]. Available from: http://www.nccn.org.
  5. Burmeister BH, Smithers BM, Gebski V, et al. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol 2005;6:659-668.
    Pubmed CrossRef
  6. Stahl M, Stuschke M, Lehmann N, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 2005;23:2310-2317.
    Pubmed CrossRef
  7. Bedenne L, Michel P, Bouché O, Milan C, Mariette C, Conroy T, et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 2007;25:1160-1168.
    Pubmed CrossRef
  8. Shapiro J, van Lanschot JJB, Hulshof MCCM, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 2015;16:1090-1098.
    Pubmed CrossRef
  9. Rice TW, Patil DT, Blackstone EH. 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice. Ann Cardiothorac Surg 2017;6:119-130.
    Pubmed KoreaMed CrossRef
  10. Wang WP, He SL, Yang YS, Chen LQ. Strategies of nodal staging of the TNM system for esophageal cancer. Ann Transl Med 2018;6:77.
    Pubmed KoreaMed CrossRef
  11. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981;47:207-214.
    Pubmed CrossRef
  12. Chan A, Wong A. Is combined chemotherapy and radiation therapy equally effective as surgical resection in localized esophageal carcinoma? Int J Radiat Oncol Biol Phys 1999;45:265-270.
    Pubmed CrossRef
  13. Teoh AY, Chiu PW, Yeung WK, Liu SY, Wong SK, Ng EK. Long-term survival outcomes after definitive chemoradiation versus surgery in patients with resectable squamous carcinoma of the esophagus: results from a randomized controlled trial. Ann Oncol 2013;24:165-171.
    Pubmed CrossRef
  14. Xu C, Lin SH. esophageal cancer: comparative effectiveness of treatment options. Comparative effectiveness Research 2016;6:1-12.
    CrossRef
  15. Vincent J, Mariette C, Pezet D, et al. Early surgery for failure after chemoradiation in operable thoracic oesophageal cancer. Analysis of the non-randomised patients in FFCD 9102 phase III trial: Chemoradiation followed by surgery versus chemoradiation alone. Eur J Cancer 2015;51:1683-1693.
    Pubmed CrossRef
  16. Chen CY, Li CC, Chien CR. Neoadjuvant vs definitive concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma patients. World J Surg Oncol 2018;16:141.
    Pubmed KoreaMed CrossRef
  17. Schieman C, Wigle DA, Deschamps C, et al. Patterns of operative mortality following esophagectomy. Dis Esophagus 2012;25:645-651.
    Pubmed CrossRef
  18. Gockel I, Exner C, Junginger T. Morbidity and mortality after esophagectomy for esophageal carcinoma: a risk analysis. World J Surg Oncol 2005;3:37.
    Pubmed KoreaMed CrossRef
  19. Ren X, Wang L, Han C, Ren L. Retrospective analysis of safety profile of high-dose concurrent chemoradiotherapy for patients with oesophageal squamous cell carcinoma. Radiother Oncol 2018;129:293-299.
    Pubmed CrossRef
  20. Tachimori Y, Kanamori N, Uemura N, Hokamura N, Igaki H, Kato H. Salvage esophagectomy after high-dose chemoradiotherapy for esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg 2009;137:49-54.
    Pubmed CrossRef
  21. Chen CY, Hsieh VC, Chang CH, et al. Impacts of treatments on the quality of life among esophageal squamous cell carcinoma patients. Dis Esophagus 2017;30:1-8.
    CrossRef
  22. Yamada H, Hosokawa M, Itoh K, et al. Diagnostic value of 18F-FDG PET/CT for lymph node metastasis of esophageal squamous cell carcinoma. Surg Today 2014;44:1258-1265.
    Pubmed CrossRef


This Article


Author ORCID Information

Stats or Metrics
  • View: 196
  • Download: 108

Services

Social Network Service

e-submission

Archives

Official Journal of

Indexed/Covered by

  • esci
  • scopus
  • thomson reuters
  • koreamed
  • crossref
  • google
  • synepse
  • kofst
  • DOAJ
  • ORCID