MSEC is not very rare in clinical practice, but because of the poor prognosis of patients, it is often not paid enough attention [1-3]. Theliterature contains only a few case reports. Its low incidence and concealment make it difficult for clinicians to determine appropriate treatment strategies and prognosis.
The mechanism by which esophageal cancer metastasizes to the axial skeleton is presumed to be related to the cancer’s anatomical characteristics [6,7]. The esophageal vein merges into the azygos vein and hemiazygous vein. The azygos vein and hemiazygous vein are extensively connected to the intercostal and vertebral vein systems, and the spinal venous system is lacking. The blood flow in this venous system is slow and when the pressure in the thoracic and abdominal cavity is increased, the tumor embolus in the thoracic and abdominal cavity can enter the vertebral venous system directly without passing through the lung and liver, allowing it to transfer to the vertebrae and to colonize and proliferate to form a metastatic tumor. In addition, the esophagus is adjacent to the thoracic vertebrae allowing easy transfer of cancer cells. Our research also shows that these metastases are more frequent in the thoracic spine, which supports this hypothesis.
It has been reported that the peak time of bone metastasis of esophageal cancer is within one year after the primary lesion resection, and the incidence rate decreases after one year [4,5,8,9]. About half of the cases have multiple lesions [1-3]. Goodner et al reported 100 patients with bone metastases from esophageal cancer . The survival time of patients with a single bone metastasis was about 3.1 months, and the survival time of patients with multiple bone metastases was about 1.5 months . In this study, there were cases with four single lesions, accounting for 66.7%, and two cases with multiple lesions, accounting for 33.3%. No metastasis to other organs was seen in the four patients with single spinal lesions. After active surgical treatment, both the patients’ quality of life and the prognosis were significantly improved. In the literature, the longest survival time was reported to be up to 12 months [1-3]. Studies have shown that isolated, single-site bone metastases that are not accompanied by metastases to other organs can survive for up to 12 months after active treatment, with a good prognosis [1-3,11]. This shows that surgical treatment is an effective method to improve the quality of life and prolong the survival of MSEC patients.
For MSEC patients with severe pain or neurological deficits, surgery is the fastest and most effective treatment option [12,13]. Due to the poor prognosis of MSEC, the main surgical methods in this study include two cases that underwent open surgery and four cases that underwent percutaneous vertebroplasty. We found that esophageal cancer spinal metastases have heavy blood flow during the operation, which is consistent with its imaging features. They usually show osteolytic changes, may be associated with vertebral compression fractures, and are not accompanied by paravertebral soft tissue masses, so percutaneous vertebroplasty with bone cement to reconstruct spinal stability may have potential advantages for improving the quality of life of patients. The main symptom of spinal metastasis is back pain, which requires analgesic and hormonal symptomatic treatment. The results are often short-lived and ineffective. Traditional surgical procedures are highly invasive in nature and the surgery itself brings more complications [1-3,12-15]. In contrast, bone cement has the potential to inhibit tumor growth and percutaneous vertebroplasty is a potentially powerful tool for the treatment of esophageal cancer spinal metastases.
Life expectancy is an important factor in deciding whether to treat surgically [12-15]. In general, if the life expectancy is between three and six months, non-surgical treatment is usually recommended. The scoring systems proposed by Tokuhashi and Tomita emphasize the importance of the primary tumor type for prognostic assessment to distinguish surgical indications for patients with different scores [16,17]. However, the revised Tokuhashi score and Tomita score are not completely applicable to all possible situations of a specific tumor, creating potential difficulties for clinicians in making correct clinical decisions. There are certain inaccuracies in the spine tumor scoring systems currently used with the result that the clinical decision for surgery cannot rely solely on a particular scoring system. Other factors must also be considered, including how to perform a reasonable evaluationofspinal metastasis from a specific malignant tumor.
Adjuvant therapies for MSEC include palliative radiotherapy, chemotherapy, and bisphosphonate [12-19]. The purpose is to control local lesions, reduce pain, prevent fractures, and improve quality of life. Bone pain is the most prominent clinical symptom in these patients. Because squamous cell carcinoma is highly sensitive to radiotherapy, local palliative radiotherapy results in rapid relief of bone pain, with good effects and few adverse reactions [18,19]. Radiotherapy is well tolerated bya majority of patientsand is still an important treatment to control bone pain. The National Comprehensive Cancer Network guidelines recommend functional status scores for patients with esophageal cancer who cannot tolerate surgery. Only patients with a KPS score of ≥60 points and/or an Eastern Cancer Cooperative Group score of ≤2 points are given chemotherapy; in other cases, only the best supportive treatmentis used . After radiotherapy and chemotherapy, the patient’s tumor load is reduced, the pain is relieved, and the improvement of psychological and physiological conditions can benefit the patient’s survival [18-20]. In our study, three patients received postoperative combined radiotherapy and chemotherapy after esophageal cancer surgery, one patient received only radiotherapy, one patient received chemotherapy combined with Nimotuzumab, and one patient declined further adjuvant therapy.
Bisphosphonate is the first-line treatment for most patients with osteoporosis and is effective for reducing the risk of fractures in the spine, pelvis and other non-spinal bones. All six patients in this study received bisphosphonate therapy. However, the exact efficacy of bisphosphonate therapy in MSEC patients is not clear due to the limited number of cases and the lack of detailed clinical observations.
Patients with bone metastases have a significantly increased risk of skeletal-related events (SREs), and the occurrence of SRE is significantly related to a reduction in patient survival time . Clinically, SREs such as pathological fractures and spinal cord compression caused by spinal metastasis, pain, cauda equina syndrome, and paraplegia seriously affect the quality of life in these patients. Additional problems such as pneumonia, deep vein thrombosis, pulmonary embolism, and pressure ulcers caused by long-term bed rest may greatly shorten the survival time of patients [1-3,22,23]. Our results also show that pathological fractures and spinal cord compression can affect the prognosis of MSEC patients. Complete paralysis or incomplete paralysis before spinal surgery often indicates a poor prognosis.
This study nevertheless has several limitations. Firstly, the number of cases is too small for more accurate and detailed statistical analysis to assess prognostic factors. Secondly, this study is a single-center retrospective analysis. The accuracy and practicability would need to be tested by a larger sample of data. It is the goal of this institution and other medical institutions to practice, continue to improve, and to offer accurate guidance for future clinical work. In addition, only esophageal cancer patients with spinal metastasis who had received spinal surgery within a 10 year period at a single center were included in this study, and patients with MSEC who had received only non-surgical treatment were not included, which could cause a certain selective bias in the conclusions. Despite the inclusion of only six MSEC cases this case study constitutes the first clinical series reported on MSEC, and is based on a retrospective analysis of more than 1,000 patients underwent spine surgery in a single center in the past 10 years. This specific focus on the comprehensive treatment and prognosis of MSEC will help improve the clinical management of this disease, help reduce the rate of perioperative complications and maximize the survival time of these patients.