Salvage surgery after failed chemoradiotherapy in squamous cell carcinoma of the esophagus

doi:10.1016/j.ejso.2008.02.014

European Journal of Surgical Oncology (EJSO)

Volume 35, Issue 3, March 2009, Pages 289-294

https://doi.org/10.1016/j.ejso.2008.02.014 Get rights and content

Abstract

Aims

To investigate the survival benefit and preoperative risk factors for hospital mortality of salvage surgery in esophageal cancer patients who had locoregional residual/recurrent tumor after definitive chemoradiotherapy.

Methods

We retrospectively reviewed the esophageal cancer patients who presented at our hospital from 1997 to 2004. Forty-seven patients who had squamous cell cancer and developed locoregional recurrent/persistent disease after primary definitive chemoradiotherapy were elected. Twenty-seven of them received salvage esophagectomy (group 1) and the other 20 underwent non-operative treatment only (group 2). In order to assess the surgery-related mobility and mortality in group 1, 191 patients who received neoadjuvant chemoradiotherapy followed by operation during the same time period were also enrolled (group 3).

Results

The 5-year overall survival of group 1 patients was 25.4%. In contrast, all of the patients in the group 2 died within 16.7 months. The difference was statistically significant (p = 0.0029). In comparison with group 3, group 1 patients had significantly more surgery-related complications and hospital mortality. In univariate analysis for preoperative risk factors, a low albumin or hemoglobulin level was associated with high hospital mortality in group 1 (p = 0.004 and 0.003, respectively). After multivariate analysis, only the low albumin level remained borderline significance. As for disease specific survival after salvage surgery, R0 resection was the only independent prognosticator (p = 0.049).

Conclusion

Salvage surgery provides survival benefit in esophageal cancer patients with locoregional persistent or recurrent disease after primary definitive chemoradiotherapy. Preoperative albumin and hemoglobulin levels are associated with hospital mortality and may aid in selecting suitable patient for salvage surgery.

Introduction

Current strategies for treating primary locoregional-advanced esophageal cancer consisted of radical surgery, definitive chemoradiotherapy, or neoadjuvant chemoradiotherapy followed by operation.1, 2 Among them, definitive chemoradiotherapy had less treatment-related mortality and an similar overall survival rate, especially for patients with squamous cell carcinoma.2, 3 But patients who had chemoradiotherapy also tend to develop residual or recurrent disease, which often poses difficulty in clinical management.2, 3

Treatments for the residual/recurrent disease at the locoregional sites include salvage surgery or chemotherapy. However, many clinicians opposed the use of salvage surgery due to serious post-operation mobility and mortality. And only a few reports with regard to this issue are available in literature.4, 5, 6 Most importantly, although the reported overall survival for patients receiving salvage surgery is better than those receiving non-surgery treatments, the improved survival in the salvage group may be due to bias in patient selection among different studies and needs further validation. Besides, no investigator has studied the preoperative prognostic factors for outcome after salvage surgery, which can enable better patient selection beforehand and thus avoid unnecessary surgery.

In this context, we conducted this retrospective study with 2 aims. One is to compare the survivals of esophageal cancer patients who received salvage surgery or non-surgery therapy due to locoregional residual/recurrent tumor. The other is to investigate the preoperative prognostic factor for salvage surgery.

Section snippets

Patient population

The clinical data of primary esophageal cancer patients with the histology of squamous cell carcinoma treated in our hospital from 1995 to 2004 were reviewed. A total of 84 patients received definitive chemoradiotherapy and 47 of them had locoregional residual/recurrence tumor. The detail of definitive chemoradiotherapy is showed in the following section. Histological biopsy to prove recurrent/residual tumor was done in all feasible cases. For the other patients, the diagnosis of recurrent or

Characteristics and survivals for patients receiving salvage surgery or non-surgery treatment

Table 1 showed the demographic data of group 1 and group 2 patients. No significant difference exists between characteristics of these 2 groups. In group 1, the pathological result of salvage surgery was T1–2N0 (defined as early stage) in nine patients (37%) and T1–4N1 or T3–4N0 (advanced stage) in another 15 (52%). Three patients achieved pathologic complete remission (pCR).

All of the patients in the group 2 died within 16.7 months due to cancer or cancer-related complication. For group 1, with

Survival benefit of salvage esophagectomy

Definitive chemoradiotherapy is considered a standard treatment for locally advanced esophageal cancer. Despite of long-term survival of 15–20%1, 2, 3 after such treatment, locoregional recurrence is not uncommon and occurs in around 40–60% of patients.1, 2, 3 Prognosis after locoregional recurrence is dismal and all patients will die in one year without treatment.⁷ Treatment options for recurrent or persistent disease after definitive chemoradiotherapy are limited. Further radiotherapy is

Conclusions

Salvage surgery provides survival benefit for esophageal cancer patients with locoregional recurrent disease but may lead to serious surgery-related complication and hospital mortality. Preoperative albumin and hemoglobulin levels are important risk factors for hospital mortality and may aid in selecting suitable patient for salvage surgery.

Conflict of interest

We hereby declare that there is no potential or actual personal, financial or political interest related to this article.

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Cited by (69)

Salvage Esophagectomy
2021, Surgical Clinics of North America
A meta-analysis on salvage surgery as a potentially curative procedure in patients with isolated local recurrent or persistent esophageal cancer after chemoradiotherapy
2019, European Journal of Surgical Oncology
Isolated local recurrent or persistent esophageal cancer (EC) after curative intended definitive (dCRT) or neoadjuvant chemoradiotherapy (nCRT) with initially omitted surgery, is a potential indication for salvage surgery. We aimed to evaluate safety and efficacy of salvage surgery in these patients.
A systematic literature search following PRISMA guidelines was performed using databases of PubMed/Medline. All included studies were performed in patients with persistent or recurrent EC after initial treatment with dCRT or nCRT, between 2007 and 2017. Survival analysis was performed with an inverse-variance weighting method.
Of the 278 identified studies, 28 were eligible, including a total of 1076 patients. Postoperative complications after salvage esophagectomy were significantly more common among patients with isolated persistent than in those with locoregional recurrent EC, including respiratory (36.6% versus 22.7%; difference in proportion 10.9 with 95% confidence interval (CI) [3.1; 18.7]) and cardiovascular complications (10.4% versus 4.5%; difference in proportion 5.9 with 95% CI [1.5; 10.2]). The pooled estimated 30- and 90-day mortality was 2.6% [1.6; 3.6] and 8.0% [6.3; 9.8], respectively. The pooled estimated 3-year and 5-year overall survival (OS) were 39.0% (95% CI: [35.8; 42.2]) and 19.4% [95% CI:16.5; 22.4], respectively. Patients with isolated persistent or recurrent EC after initial CRT had similar 5-year OS (14.0% versus 19.7%, difference in proportion −5.7, 95% CI [-13.7; 2.3]).
Salvage surgery is a potentially curative procedure in patients with locally recurrent or persistent esophageal cancer and can be performed safely after definitive or neoadjuvant chemoradiotherapy when surgery was initially omitted.
Does timing of esophagectomy following neoadjuvant chemoradiation affect outcomes? A meta-analysis
2018, International Journal of Surgery
Citation Excerpt :
This observation can possibly be caused by dense fibrosis after prolonged waiting time that makes it dangerous to perform mediastinal dissection [34]. It may also be due to the selection bias, because more patients with poor general condition who need an extended recovery period after nCRT were represented in the longer interval group [35,36]. These patients cause high peri-operative mortality rate.
The optimal timing of esophagectomy after neoadjuvant chemoradiation treatment (nCRT) remains unclear. Here, a meta-analysis was conducted to determine whether prolonged interval between nCRT and surgery can affect the outcomes in esophageal cancer.
The databases PubMed, Embase, Web of Science, and Cochrane were systematically searched for studies reporting the outcomes in esophageal cancer according to the length of interval between nCRT and surgery. The primary outcome was rate of pathologic complete response (pCR), and the secondary outcomes included R0 resection rate, incidence of anastomotic leak, postoperative mortality, and two or five-year overall survival (OS). The intervals were classified into dichotomous (≤7–8 weeks and >7–8 weeks) for the pooled analysis, and a combined relative risk (RR) was calculated.
A total of 13 studies involving 15,086 patients were analyzed. The overall results indicated that an interval longer than 7–8 weeks between the end of nCRT and the surgery was significantly associated with an improved pCR rate (RR, 1.13; 95% confidence interval [CI], 1.05–1.21; P = 0.001). However, it was related to a higher 30-day surgical mortality (RR, 1.51; 95% CI, 1.19–1.92; P = 0.0006). The subgroup analyses only detected a significant association of the extended interval with pCR and the surgical mortality rate in adenocarcinoma patients. Moreover, an increased time interval resulted in a lower 2-year (RR, 0.94; 95% CI, 0.90–0.98; P = 0.002) and 5-year OS (RR, 0.88; 95% CI, 0.82–0.95; P = 0.0009). No association with R0 resection rate or anastomotic complication resulting from delayed resection was detected.
Although increasing the time interval from nCRT to esophagectomy was associated with significantly higher pathologic complete response rates in esophageal cancer, delaying the surgery might be disadvantageous for the long-term survival.
Esophageal brachytherapy: Institut Gustave Roussy's experience
2020, Brachytherapy
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In this clinical situation, prognosis is particularly poor because median survival is about 6 months and therapeutic options are limited (5,29–32). Surgery, when possible, provides admittedly a gain in OS but is associated with frequent severe complications, for example, anastomotic leaks, respiratory decompensations, and a high rate of perioperative mortality ranging in the literature from 7.5% to 22% (33–36). About 60% of local relapses after radiochemotherapy will occur in the initial planning target volume (37), which makes any EBRT reirradiation delicate.
Esophageal cancer is characterized by its propension to local evolution, which conditions prognosis and quality of life. Brachytherapy may be a therapeutic option for all stages of esophageal cancer.
This retrospective unicentric study included all consecutive patients treated for an esophageal high-dose-rate brachytherapy in our institution from 1992 to 2018.
Ninety patients were included. They were treated in four distinct indications: exclusive (7 patients), boost after external beam radiotherapy (41), reirradiation (36), or palliative aim (6). Most frequently prescribed schemes were 3 × 5 Gy (boost) or 6 × 5 Gy (exclusive treatment and reirradiation) at applicator's surface or at 5 mm. At the end of follow-up, 50% of patients had presented with local recurrence. Seventeen percent of patients had a metastatic relapse. Median overall survival was 15 months in the whole cohort: 22 months in the boost setting, 25 months for exclusive brachytherapy, 15 months for reirradiation, and only 2 months for palliative treatment. Tumor length at brachytherapy, brachytherapy dose, and interfraction response were significantly associated to overall survival. 40% of patients presented with grade 2+ toxicity, mostly esophagitis, including three toxic deaths.
Although local control outcomes are still poor, one must remember that patients are unfit for any curative therapeutic option and that palliative chemotherapy offers mediocre results. The most promising setting probably is reirradiation because brachytherapy offers a remarkable dose gradient allowing best organ at risk sparing, with an encouraging rate of long survivors (19% at 2 years). Esophageal brachytherapy deserves to be further investigated because some patients, even unfit, may benefit from it, with acceptable toxicity.
Clinical Impact of the Charlson Comorbidity Index on the Efficacy of Salvage Photodynamic Therapy Using Talaporfin Sodium for Esophageal Cancer
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Treatment Outcomes and Risk Factors for Incomplete Treatment after Definitive Chemoradiotherapy for Non-Resectable or Metastatic Esophageal Cancer
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Salvage surgery after failed chemoradiotherapy in squamous cell carcinoma of the esophagus

Abstract

Aims

Methods

Results

Conclusion

Introduction

Section snippets

Patient population

Characteristics and survivals for patients receiving salvage surgery or non-surgery treatment

Survival benefit of salvage esophagectomy

Conclusions

Conflict of interest

J Thorac Cardiovasc Surg

Am J Surg

Am J Surg

Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102

J Clin Oncol

Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus

J Clin Oncol

INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy

J Clin Oncol

Factors affecting the prognosis of patients with esophageal cancer undergoing salvage surgery after definitive chemoradiotherapy

J Surg Oncol