Minimal access versus open spinal surgery in treating painful spine metastasis: a systematic review

Study design The study design of this paper is a systematic review of literature published in the recent 10 years. Objective It is the objective of this paper to compare the clinical efficacy and safety of minimal access (MIS) spinal surgery and open spinal surgery for treating painful spine metastasis. Methods Two research questions below were determined through a consensus among a panel of spine experts. A systematic review of literature on spinal surgery was conducted by searching PubMed with a combination of keywords including “metastatic”, “metastasis”, “metastases”, “spinal”, and “spine”. Independent reviewers selected the articles for analysis after screening the titles, abstracts, and full texts, then extracted data and graded the quality of each paper according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Specific clinical questions were as follows: In patients with spine metastatic disease, what is the impact of different surgical approaches (MIS versus open) on pain relief and functional outcome? In patients with metastatic disease, what is the impact of different surgical approaches (MIS versus open) on local recurrence, survive rate, and complication? Results A total of 1,076 abstracts were identified using various keywords. 5 prospective (level II) and 12 retrospective articles (level III) were eligible for inclusion, involving a total of 979 cases of spine metastasis. There were 345 cases in 8 studies regarding the clinical evaluation of MIS spinal surgery and 634 cases in 9 studies regarding the clinical evaluation of open spinal surgery for spine metastasis. Conclusion Both open spinal surgery and MIS seem to achieve the improvement of pain and neurological dysfunction through decompression and stabilization for patients with spine metastasis, but open surgery may involve more major complications with a trend of lower survival rates and higher recurrence rates compared to MIS.


Introduction
About 10% of cancer patients develop metastases in the spine [1]. The most common site of metastasis in the spine is the thoracic spine (50% to 60% of all metastases), followed by the lumbar (30% to 35%) and cervical spines (10% to 15%) [2][3][4]. Vertebral metastasis is one of the most serious life-threatening diseases [5]. About one third of patients with spinal metastases become symptomatic, which means intractable pain, neurological deficits, and/or biomechanical instability requiring surgical treatment [3,6].
These nonsurgical methods, such as chemotherapy, radiotherapy, and hormonal therapy, were commonly used for the management of vertebral metastatic disease, which have been proven to be effective in halting the osteolytic process and reversing the neurological compromise [7]. However, these modalities are unable to provide stability to an instable spinal column and also unable to be expected to relieve pain and spinal cord compression. In these cases, surgery is the best method for the resolution of intractable pain, neurological compromise, and overt or impending spinal instability in patients with spinal metastases. The primary goal of the surgery is to improve patients' quality of life by providing pain relief, maintaining or improving neurological function, and restoring the structural integrity of the spinal column [8].
Stabilization of the spine is often necessary as extensive lesions may cause spinal instability by erosion of the normal bony structures. The most efficacious therapy for restoring spinal instability is reconstructive surgical intervention. Unfortunately, lots of patients are not considered as candidates for conventional surgery intervention due to neoplasm-associated comorbidities such as malnourishment and a weak immune system that make amounts of surgical procedures unfeasible [9]. However, these patients can be managed with vertebral augmentation, since it can provide some degree of restabilization [10].
Vertebroplasty or kyphoplasty, which involves the percutaneous injection of polymethyl methacrylate (PMMA) bone cement into a collapsed vertebral body, is a currently available minimally invasive spine surgery for palliative treatment. Poor surgical candidates with disabling pain secondary to a pathologic thoracic or lumbar vertebral body fracture without epidural compression are ideal candidates for these procedures [11]. The two procedures have been shown to relieve pain effectively to improve the quality of life, and they can be used as effective palliative treatment even for patients whose general condition is quite poor, with decreased pain, less blood loss, and shorter hospital stays [12]. On the other hand, their putative benefits with regard to spinal stability and neurological function, as well as their risks affecting their overall survival, have not yet been adequately documented by clinical studies because of limitations such as insufficient spinal cord decompression and stabilizing the vertebral column.
Despite numerous reports on open spinal surgery in treating painful spine metastasis, there exist no randomized controlled comparisons of clinical efficacy and safety between open and minimal access (MIS) procedures. In addition, due to the heterogeneity of study designs, inconsistent reporting of complications, and the use of different grading scales for pain and functional outcomes, it was not possible to perform a meta-analysis using the prospective and retrospective studies. Therefore, we endeavored to perform a quantitative systematic review of the current literature published in the recent 10 years to evaluate the clinical efficacy between MIS and open spinal surgery in patients with spinal metastases. A secondary aim was to compare complication rates between MIS and open spinal surgery.

Materials and methods
Two clinically relevant questions below were determined through a consensus among a panel of spine oncology experts (the Spine Oncology Study Group), and a systematic review of related literature published in the recent 10 years was conducted using PubMed. Specific clinical questions were as follows:

Search criteria
We used the search terms that included "spin*", "metasta*", and "surg*" to searched literature from PubMed. The following terms would be contained: "metastatic", "metastasis", "metastases", "spinal", "spine", "surgery", and "surgical". Criteria for possible inclusion are as follows: 1) articles published in the recent 10 years, 2) all articles in English or with an English translation, 3) articles with 20 or more subjects, 4) adult age group (18 years and older), 5) articles describing surgical treatment of spinal metastatic cancer, and 6) articles evaluating the alterations of pain and neurologic function postoperatively. Exclusion criteria include the following: 1) primary tumors, 2) intradural tumors, 3) pediatric age group, 4) articles with fewer than 20 subjects, and 5) articles with nonhomogeneous pathology (e.g., trauma and primary tumors in the same series).
Studies were reviewed using a standardized data collection form. The type of study (prospective or retrospective) was noted. Data including surgery technique, the total number of patients, and the type of tumors were totally collected. The methods of pre-and postoperative clinical evaluations with respect to pain and functional outcome were also recorded. All temporary and permanent complications were collected, including major and minor complications. To avoid duplicate records of patients' data, each group or institution was limited to one study in the systematic review. Some authors were contacted directly to clarify certain aspects of their studies.
The quality of evidence for each article was evaluated as high, moderate, low, or very low. The results of the systematic review and ratings of the evidence for each article were determined by a multidisciplinary, international group of spine oncology surgeons, oncologists, and methodologists (Spine Oncology Study Group). The group then went through a consensus-based decisionmaking process using a modified Delphi technique to arrive at treatment recommendations related to the key clinical questions. This process and the strength of the recommendation were based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method [13,14]. These articles were evaluated independently by the authors according to the GRADE criteria.

Result
A total of 1,076 abstracts were identified using various keywords. All abstracts were screened, and 1,013 articles were excluded as obviously unrelated. The full texts of 63 papers were screened and 17 papers were identified to meet the inclusion criteria, including 5 prospective (level II) [15][16][17][18][19] (Table 1). In one study, the primary cancer was breast cancer, whereas in other studies were a mixed group such as lung cancer, prostate cancer, and colon cancer.
Among these articles regarding open spinal surgery, three studies were performed with several kinds of approaches such as posterior, anterior, and combined approach  to remove tumors in spines. Studies regarding MIS spinal surgery were performed primarily with vertebroplasty whereas two studies [22,17] were performed with kyphoplasty. Pain alleviation was crucially important for the therapy of spine metastases to improve quality of life in patients. A visual analog scale was available for each study to evaluate the effect of pain relief in patients with spine metastases. In all, one study did not display the visual analog scale (VAS) score in detail [26], and prospective studies had especially detailed pre-and postoperative VAS score. It was found that both MIS and open spinal surgery were efficient in pain alleviation, and most of the studies reported statistically significant improvement ( Table 2).Given the high rates of pain alleviation, the results suggest that both MIS and open spinal surgery are efficacious in respect to pain alleviation through decompression and stabilization.
Each study assessed postoperative neurologic function, and multiple methods for evaluating neurologic function were included, such as the Eastern Cooperative Oncology Group performance scale, the Oswestry Disability Index, the Frankel scale, the Karnofsky scale and American Spinal Injury Association grades, the Short Form 36 Physical Function, the Japanese Orthopaedic Association Score, and the Karnofsky performance scores. The neurologic function was not assessed in two studies (Farrokhi et al. [15] and Tseng et al. [23]) regarding MIS surgery. Only nine studies provided pre-and postoperative neurologic function score, and neurologic function was statistically significantly improved (Table 3). Other studies without detailed data also showed that MIS and open spinal surgery were successful in improving physical function.
It is reported that decreased complication rates are considered to be one of the advantages of MIS spinal surgery. This was confirmed by the evidences we provided in this systematic review. There are no major complications for MIS spinal surgery except in two studies [20,23], whereas six studies regarding open spinal surgery reported major complications with a trend of lower survive rates and higher recurrence rates (Table 4).

Discussion
For most of the patients with spinal metastasis, the treatment is largely palliative and aims to achieve relief of pain and regain function, thus improving the quality of the life of the patients. Because of the immunocompromised

Conclusions
In conclusion, we performed the systematic review based on literature published in the recent 10 years to possibly compare clinical efficiency and complication rate between open and MIS spinal surgery for spine metastasis and found that both open spinal surgery and MIS seem to achieve the improvement of pain and neurological dysfunction through decompression and stabilization, but open surgery may involve more major complications with a trend of lower survival rates and higher recurrence rates compared to MIS. However, it is necessary to perform a controlled study to compare the clinical efficiency between the two procedures for spine metastasis in the future.

Competing interests
The authors declare that they have no competing interests.  NA not available.