Peer-Review ReportComparison of the Therapeutic Efficacy of Surgery with or without Adjuvant Radiotherapy versus Radiotherapy Alone for Metastatic Spinal Cord Compression: A Meta-Analysis
Introduction
Spinal metastases represent the most common malignancy of the spine (3), with an incidence that is 20 times higher than primary spinal tumors. Nearly half of all solid tumors are likely to metastasize to bone, and the spine is the most commonly targeted site for such metastasis (11). The incidence of metastatic spinal cord compression (MSCC) has increased over the years, likely as a result of longer survival of patients with cancer secondary to improved treatments for primary tumors and metastases (15). For patients with spinal metastasis, metastatic spinal cord compression is a catastrophic complication that can lead to pain, fractures, severe neurologic dysfunction, and impaired quality of life 6, 9, 26. Life expectancy for most patients with MSCC is usually limited to a few months but can vary from a few weeks to several years 16, 28.
At the present time, there are 3 major options for the management of spinal metastasis and MSCC: chemotherapy, radiotherapy (RT), and surgery. The main aim of treatment is to achieve maximal improvement of the patient's quality of life. Although pain relief and preservation of function are the primary aims of therapeutic intervention, the choice of treatment modality needs to be tailored to the expected survival. Surgical intervention has several advantages, including the immediate alleviation of pain, improvement or preservation of neural function, and restoration of the integrity of the spinal structure. However, resection of a spinal metastatic tumor is a palliative treatment only because it is very difficult to achieve disease-free survival. The decision to perform surgery in patients with MSCC requires additional considerations, including previous diagnosis of cancer or remote cancer, unstable spine or bony cord compression, inability to receive further irradiation, radioresistant tumor, and solitary metastasis (1).
Clinical studies and therapeutic guidelines have suggested that surgery could be considered for patients with a life expectancy of >6 months, concurrent with the following conditions: 1) progressive neural impairment induced by vertebral body collapse, with satisfactory recovery not achieved by decompression treatment; 2) severe pain not responsive to conservative treatment, which may be due to instability of the spine or erosion and compression of the surrounding tissues, spinal nerve, cord, and cauda equina by the tumor; 3) spinal instability secondary to destruction of the spine or associated structures or pathologic fracture, which results in the loss of all or part of the spine's supportive function; and 4) metastatic tumor limited to a single vertebra or multiple adjacent vertebrae. In addition, pathologic diagnosis is required.
Major surgical treatment of spinal metastases in patients with MSCC generally is not indicated if the patient is expected to survive <3 months (25). For these patients, a single-fraction RT schedule is recommended because several studies have reported that single-fraction and multiple-fraction RT provide similar levels of palliation for painful bone metastases 4, 7, 10, 20, 23. The decision-making process regarding selection of the treatment option should include consideration of the benefits and complications of each treatment modality, based on the results of valid clinical studies that were not biased by selection.
External RT has been found to have similar therapeutic effects as surgery 17, 18, 19. Consequently, RT is considered by many clinicians as a primary therapeutic option for patients with spinal metastasis and MSCC, especially for patients with solitary metastases and an absence of spinal instability or neurologic impairment. One potential advantage of RT is that studies of surgical intervention for spinal metastases have reported complication rates of 20%–30%, whereas serious complications related to palliative RT have not been reported.
RT alone without surgery seems to be the most common and appropriate treatment for MSCC. However, a randomized trial suggested that decompressive spinal surgery followed by RT has beneficial effects with regard to functional outcome and survival (14). Other investigators also suggested that surgery in combination with adjuvant RT may be superior to RT alone for the treatment of spinal metastases 8, 21. However, high-quality clinical evidence in support of this view is lacking, necessitating a more systematic analysis of the available published data. For this purpose, we undertook a meta-analysis to compare surgery with or without adjuvant RT versus RT alone with regard to their effects on several major indicators of therapeutic outcome (survival, motor function, and complications) in patients with MSCC.
Section snippets
Search Strategy
The databases of MEDLINE, EMBASE, and the Cochrane Library were systematically searched to identify articles, published between 1980 and the current year (inclusive), that evaluated the use of surgery (with or without adjuvant RT) and RT alone for the treatment of patients with spinal metastasis and MSCC. The following search terms were used: “spinal metastasis,” “metastatic spinal cord compression,” “spinal cord compression,” “radiotherapy,” “radio-chemotherapy,” “surgery,” and “survival.”
Search Results
After a systematic search in the selected databases, 348 studies were identified. Another 42 articles were found via other sources. After a careful review of the title and key words of each study, 272 articles that did not meet the inclusion criteria were excluded. With regard to the remaining 26 publications, 20 of them were discarded because of time overlapping, single-arm design, no MSCC, no available data, and other reasons (Figure 1). Finally, 6 studies 5, 12, 14, 18, 27, 28 were included
Discussion
The present meta-analysis was designed to compare the benefits of surgery (with or without adjuvant RT) with the benefits of RT alone in patients with MSCC. Compared with RT alone, treatment of MSCC with surgery (with or without RT) was associated with improved ambulation and pain control and increase in 1-year survival, but no difference in regain of walking ability, short-term survival, and extended hospital stay. However, although sensitivity analysis revealed that ambulation, pain relief,
Conclusions
The present meta-analysis demonstrated that compared with RT alone, treatment of MSCC with surgery (with or without adjuvant RT) was associated with improved ambulation and pain relief and increase in 1-year survival, with no differences in regain of walking ability, longer hospital stays, and significantly higher incidence of complications. However, these findings should be carefully considered because of a paucity of data and well-designed randomized controlled trials. Further large-scale
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Conflict of interest statement: This work was supported by the Public Welfare Research Project of the Science and Technology Department in Zhejiang Province (Grant No. 2011C23086).