Introduction
Metastatic epidural spinal cord compression (MESCC) is a serious complication resulting from spinal metastases. Annually, approximately 80,000 new MESCC cases arise in the USA, constituting around 2–3% of cancer patients [ 1 , 2 ]. With its propensity for neurological compromise, MESCC can precipitate motor and sensory paralysis. Particularly for those with severe MESCC who have lost ambulatory function, the resultant diminished quality of life and complications from prolonged bed rest may reduce willingness and tolerance to anti-tumor drugs, and curtail life expectancy. Thus, prompt diagnosis and intervention for these severe cases are imperative.
Previous studies have advocated for emergent surgery within 24–48 h post-acute spinal cord injury to optimize neurological recuperation [ 3 , 4 ]. However, in MESCC patients, the intricate evaluation of metastatic lesions and primary disease necessitates a systematic preoperative assessment, consuming valuable time. Consequently, a considerable portion of patients present having been paralyzed for more than 48 h, or even several weeks, upon admission, often surpassing the optimal surgical window as outlined in existing literature. We did not find previous articles and guidelines reporting the neurological results of surgery for these patients. Consequently, determining the surgical intervention for severe MESCC cases paralyzed for over 48 h poses a challenging dilemma, with outcomes remaining uncertain.
In the current study, our objective is to investigate the surgical outcomes of non-ambulatory MESCC patients and analyze the factors influencing neurological recovery. Through this analysis, we endeavor to furnish an feasible framework for the management of such patients.
Materials and methods
Patient recruitment
This is a retrospective study. We hypothesize that, unlike in cases of trauma and degenerative disorders where delayed decompression surgery often leads to poor outcomes, delayed decompression surgery for MESCC-induced paralysis yields relatively favorable results.
All consecutive patients with MESCC who were non-ambulatory preoperatively and underwent decompressive surgery in our hospital between 2012 and 2020 were retrospectively reviewed.
The inclusion criteria were: (1) severe neurological deficit (Frankel A, B, or C) caused by MESCC; (2) an expected survival time of more than three months according to the Tomita or Tokuhashi prognosing score systems; and (3) postoperative pathology confirming spinal metastasis. The exclusion criteria were: (1) MESCC patients who did not undergo decompressive surgery; and (2) postoperative pathological examinations confirming a primary tumor or infectious disease.
Medical management and surgical techniques
All paralyzed patients received steroids and mannitol upon admission. Urgent imaging examinations, including computed tomography (CT) and magnetic resonance imaging (MRI), were conducted to find spinal cord compression in the thoracic or lumbar spine. Once cord compression was confirmed, emergency surgery was performed. However, those patients with limited life expectancy (less than three months), severe comorbidities contraindicating surgery, or widespread systemic involvement, were excluded for surgery.
All patients underwent decompressive surgery combined with screw-rod fixation. For cases where the vertebral body was invaded or a pathological fracture was present, anterior decompression and lesion resecting was performed through a transpedicular approach. A complete circumeferential decompression was then achieved, involving the removal of the lamina, facet joints, pedicles, and tumor tissue within the vertebral body. After tumor removal, the cavity within the vertebral body was filled with bone cement to restore stability (Fig. 1 ). The bone cement was manually formed into small spheres about the size of soybeans and inserted into the cavity, where it was compacted, rather than using the conventional method of injection through a cannula. In cases where the tumor involvement was limited to less than one-third to one-fourth of the vertebral body, we opted not to use bone cement (Fig. 2 ). Postoperatively, steroids and mannitol were continued for three days, along with anti-infection, thromboprophylaxis, and rehabilitation therapy.
Data collection
The primary outcome of this study is neurological recovery. Patients’ demographic profile, primay malignancy history (including tumor pathologies, treatment, and metastasis status), surgical information and complications, neurological function, pain, and ambulatory status were collected in the study. Patients’ Karnofsky Performance Scores (KPS) were assessed, with scores indicating poor (10–40), medium (50–70), and good (80–100) status. Neurological function and pain were evaluated using Frankel grades and the Visual Analogue Scale (VAS), respectively. Data were collected preoperatively, postoperatively, and at the final follow-up, defined as either the end of life or December 2022. Additionally, survival time and status were recorded. The study received approval from our Institutional Review Board, and written consent was obtained from all participants.
Radiographic assessment
The Epidural Spinal Cord Compression (ESCC) scale and Spinal Instability Neoplastic Score (SINS) were assessed based on imaging manifestions. The hardness of the intraspinal tumors was assessed using the mean Hounsfield unit values, which were obtained by examining the compressed mass in the spinal cord on magnified transverse sections of the CT scan (0.3 mm slice thickness).
Both ESCC and SINS were calculated independently by two physicians, and the average results were utilized for analysis. Data collection and score calculation were facilitated through a digital imaging and communications in medicine (DICOM) network and a GE computer workstation using the GE Healthcare-Centricity RIS CE V3.0/PACS software program.
Statistical analysis
Statistical analysis was performed using SPSS Statistics (Version 20.0, Armonk, NY: IBM Corp.). Continuous variables were expressed as the mean ± standard deviation or median (range), as appropriate, and comparisons were made using Student’s t-test or the Mann-Whitney U test. Categorical variables were presented as frequencies, and Pearson’s χ² test was used for group comparisons. The Kaplan-Meier method was employed to calculate and analyze postoperative survival time. Univariate logistic regression was employed to evaluate the relationship between different clinical factors and neurological recovery, with odds ratios (OR) and 95% confidence intervals (CI) calculated for each factor. Significant factors were subsequently analyzed in a multivariate logistic regression model. Statistical significance was defined as a P-value of < 0.05.
Results
Demographics and baseline data
45 patients with MESCC treated with decompressive surgery were involved in this study, in which 37 patients were successfully followed up and the other 8 cases (17.8%) were lost. Totally, the cohort included 24 males and 13 females, with an average age of 55.2 ± 12.1 years (range 21 to 78 years). The median follow-up period was 41 months (ranging from 28 to 107 months). The median preoperative paralysis time was 9 days, ranged from 2 to 35 days (Table 1 ). 33 patients had symptoms of locoregional pain, most of which were moderate or severe (Table 2 ). All participants had lost ambulatory function prior to the operation, including 7 cases classified as Frankel A, 14 as Frankel B, and 16 as Frankel C. 31 patients exhibited varying degrees of sphincter dysfunction, with 25 requiring catheterization. Preoperative KPS were poor in 30 cases (81.1%), moderate in 7 cases (18.9%), ranged 20 to 50 scores (Table 2 ).
Table 1
Demographics, clinical characteristics and imaging findings ( n = 37)
*Others include multiple myeloma, esophagus, colon, liver, rectum, thyroid, melanoma, stomach, cervix, pleural mesothelioma and pheochromocytoma SD stands for standard devication; CT, computed tomography
| Characteristic | Values |
| Gender, n (%) | |
| Male | 24 (64.9) |
| Female | 13 (35.1) |
| Age (years), mean ± SD | 55.2 ± 12.1 |
| Tumor pathologies, n (%) | |
| Lung | 13 (35.1) |
| Prostate | 5 (13.5) |
| Kidney | 3 (8.1) |
| Breast | 2 (5.4) |
| Other* | 15 (40.5) |
| Levels of vertebral metastasis, n (%) | |
| Solitary | 20 (54.1) |
| Multiple | 17 (45.9) |
| Tomita score, median (range) | 6 (4, 9) |
| Tokuhashi score, median (range) | 5 (2, 12) |
| Preoperative paralysis days, median (range) | 9 (1, 35) |
| Epidural spinal cord compression grade, n (%) | |
| 1a | 0 (0) |
| 1b | 0 (0) |
| 1c | 1 (2.7) |
| 2 | 19 (51.4) |
| 3 | 17 (45.9) |
| Spinal instability neoplastic scores, n (%) | |
| 0–6 | 5 (13.5) |
| 7–12 | 27 (73.0) |
| 13–18 | 5 (13.5) |
| CT values of tumor (Hounsfiled Unit), mean ± SD | 64.0 ± 11.0 |
| Intraoperative blood loss (ml), mean ± SD | 817.6 ± 720.6 |
| Operative time (min), mean ± SD | 196.9 ± 72.6 |
| Postoperative Adjuvant therapy, n(%) | |
| Radiotherapy | 15 (40.5) |
| Chemotherapy or Targeted therapy | 23 (62.2) |
Table 2
Comparison of preoperative and postoperative symptoms and neurological status
*Statistically different at P < 0.05, using Pearson’s chi-square test
| Preoperative | Postoperative | P values | |
| Visual analog scores, n (%) | |||
| No pain (0 score) | 5 (13.1) | 12 (32.4) | 0.001 * |
| Mild (1–3 scores) | 9 (23.7) | 13 (35.1) | |
| Moderate (4–6 scores) | 12 (32.4) | 10 (27.0) | |
| Severe (7–10 scores) | 11 (29.7) | 2 (5.4) | |
| Karnofsky performance scores, n (%) | |||
| Poor (10–40 points) | 30 (81.1) | 4 (10.8) | < 0.001 * |
| Moderate (50–70 points) | 7 (18.9) | 16 (43.2) | |
| Good (80–100 points) | 0 (0) | 17 (45.9) | |
| Frankel grades, n (%) | |||
| Frankel A | 7(18.9) | 1 (2.7) | < 0.001 * |
| Frankel B | 14 (37.8) | 3 (8.1) | |
| Frankel C | 16 (43.2) | 11 (29.7) | |
| Frankel D | 0 (0) | 6 (16.2) | |
| Frankel E | 0 (0) | 16 (43.2) | |
| Ambulatory ability, n (%) | |||
| Yes | 0 (0) | 20 (54.1) | < 0.001 * |
| No | 37 (100) | 17 (45.9) |
Tumor characteristics
Most patients were solitary metastasis (54.1%, Table 1 ), and thoracic vertebra metastasis were most common (94.6%). The most common primary origins of the spinal metastasis were lung cancer (13 cases, 35.1%), followed by prostate cancer (5 cases) and renal cancer (3 cases). The median Tomita score was 6 (range 4 to 9 scores) while the median Tokuhashi score was 5 (range 2 to 12 scores). 5 patients had signs of spinal instability (SINS score 13–18), 27 cases were potential instability (SINS score 7–12) and 5 were stable (SINS score 0–7). The ESCC scale was Grade 3 in 17 patients (45.9%), Grade 2 in 19 patients (51.4%) and Grade 1c in one patient (2.7%). The mean CT value of intraspinal tumors were 64.0 ± 11.0 Hu (range 43.6 to 94.8 Hu). 7 cases (18.9%) were subjected to complete 360˚ circular compression while 30 cases (81.1%) were incompletely compressed (Table 1 ).
Surgical information and complications
All patients underwent extensive neurological decompression accompanied with instrumental fixation. Reconstruction of vertebral column with bone cement was achieved when required (Fig. 1 ). The mean intraoperative blood loss was 817.6 ± 720.6 ml (range: 100 to 3000 ml), and the average surgical duration was 196.9 ± 72.6 min (range: 57 to 361 min) (Table 1 ). Postoperatively, 15 cases (40.5%) received radiotherapy, and 23 cases (62.2%) were treated with anti-tumor medication.
Complications were observed in 13 cases (35.1%) after the operation. These included two cases of pulmonary dysfunction (one with hydrothorax and one with respiratory failure), one case of arrhythmia (supraventricular tachycardia), and one case of intermuscular vein thrombosis in the calf. Two cases experienced infective fever, and one case had cerebrospinal fluid leakage. Additionally, six cases presented with severe anemia and electrolyte disturbances.
Surgical outcomes
The postoperative VAS scores of 30 cases (81.1%) were lower than preoperative ( P = 0.001, Table 2 ). Postoperative KPS scores were poor only in 4 cases (10.8%), moderate in 16 cases (43.2%) and good in 17 cases (45.9%), which were significantly improved compared with preoperative ( P < 0.001). For bladder dysfunction, 17 patients (68.0%, 17/25) regained spontaneous urination, while 8 patients still required long-term catheterization.
Frankel grades were also significantly improved after surgery ( P < 0.001) and no cases became worse (Table 2 ). 30 patients (81.1%) had improved by at least one Frankel grade after surgery while 7 patients (18.9%) remained at preoperative neurological function (Fig. 3 ). 22 patients (59.5%) regained ambulatory ability after operation (Fig. 4 ), which were recovered in a mean time of 2.1 ± 1.5 months (range 0.75 to 7 months). Compared to their preoperative status, 28.6% (2 out of 7) of Frankel A subgroup, 57.1% (8 out of 14) of Frankel B, and 75.0% (12 out of 16) of Frankel C regained ambulatory ability (Fig. 5 ). We analyzed the relationship between some patients clincal factors and postoperative neurological recovery, and did not find any significant factors (Table 3 ).
Table 3
Univariate logistic analysis of potential factors influencing neurological function improvement
| Odds ratio | 95% confidential interval | P values | |
| Age, years | 0.998 | 0.932–1.070 | 0.958 |
| Gender (female/male) | 0.321 | 0.059–1.739 | 0.188 |
| Preoperative Karnofsky performance score | 0.979 | 0.887–1.079 | 0.664 |
| Preoperative Frankel grades | 1.540 | 0.475–4.995 | 0.472 |
| Epidural spinal cord compression grades | 1.827 | 0.401–8.315 | 0.436 |
| Paralysis period before surgery, days | 1.134 | 0.961–1.338 | 0.138 |
| Anti-tumor drugs | 2.667 | 0.498–14.285 | 0.252 |
| Radiotherapy | 5.250 | 0.562–49.080 | 0.146 |
Survival outcomes
The median follow-up period was 90.0 months, ranging from 17 to 107 months. By the end of this study, 10 patients (27.0%) were still alive, while 27 patients (73.0%) had passed away. The median survival was 19 months. The survival rates at 3, 6, 12, 24, and 36 months postoperatively were 89.2%, 78.4%, 58.9%, 40.3%, and 29.4%, respectively (Fig. 6 ).
Discussion
In MESCC cases where patients have lost the ability to walk, timely decompressive surgery is particularly critical [ 5 , 6 ]. However, due to the intricate nature of MESCC and the necessary time for preoperative evaluation, surgeons frequently face challenges in making surgical decisions within the recommended timeframe of 24–48 h, as indicated in previous literature [ 1 , 7 , 8 ]. Currently, the duration from symptom onset to surgery is approximately 14 days [ 2 , 9 ]. The question of whether patients can still benefit from surgery performed more than 48 h after the onset of paralysis remains unanswered. In our study, we continuously recruited and followed 37 patients with MESCC who underwent decompressive surgery more than 48 h after paralysis. These findings underscore the significance of surgical treatment for these patients, even beyond the recommended time window for surgery.
The increasing prevalence of spinal metastases is attributed to the growing population of cancer patients, despite the advancements in cancer treatment. Spinal metastases, characterized by severe pain and paralysis due to skeletal-related events, can greatly impact daily activities and quality of life, presenting unique challenges compared to other forms of bone metastases. MESCC is a significant complication affecting approximately 10% of all spinal metastases [ 10 ]. In addition to causing potential permanent disability and a decline in overall quality of life, this complication often imposes treatment constraints. Some anticancer therapies and radiation options may become infeasible, consequently affecting life expectancy [ 11 ]. The treatment of MESCC, especially when considering surgical interventions, poses intricate challenges due to the complexity of spinal anatomy, a variety of tumor pathologies, and the absence of uniform, widely accepted management guidelines. Especially, in severe cases where patients with MESCC experience a loss of ambulation for over 48 h, the value and benefits of surgical decompression remain uncertain.
Patchell et al. reported that patients with MESCC who had been completely paraplegic for less than 48 h experienced favorable outcomes with decompressive surgery [ 5 ]. However, for patients with paralysis lasting longer than 48 h, the results have been controversial and remains an open question. Similar to our study, Li et al. also reported that for those whose treatment is delayed for more than 48 h from the onset of symptoms, surgery within one week is still beneficial [ 12 ]. However, in the study presented by Meyer et al., it was suggested that surgery should be performed within 16 h of admission, and there was no significant impact when surgery was performed later than 24 h after admission [ 7 ]. In another study performed by Fehlings et al., it was also suggested that positive surgical results were only seen in those who underwent decompressive treatment within 24 h [ 13 ].
Significant progress has been made in surgical techniques enhancing outcomes for patients with MESCC. Separation surgery followed by stereotactic body radiotherapy has been proven effective in achieving local control of spinal metastases, in addition to significant improvements in neurological function and quality of life [ 5 , 14 – 16 ]. Separation surgery aims to achieve thorough spinal cord decompression with appropriate tumor debulking. By creating a 2–3 mm separation between the tumor and the spinal cord for subsequent radiotherapy, this approach has shown promise in reducing local recurrence rates and improving patient outcomes [ 17 , 18 ]. In a prospective study involving 111 patients conducted by Barzilai et al., the 6- and 12-month cumulative incidence rates for local recurrence were found to be 2.1% and 4.3%, respectively, while rates for death were 25.6% and 42.1%, respectively [ 19 ]. Our case series have also shown positive results, with over half of patients regaining the ability to walk within three months post-surgery (Table 2 ).
Many factors play a role in the recovery of neurological function in patients with MESCC. Early surgical intervention following proper evaluation is considered a crucial factor in achieving favorable outcomes [ 7 , 20 ]. It is recommended that surgery be performed as soon as possible after completing preoperative assessments and ruling out any surgical contraindications. A study by Younsi et al. reported on a group of 28 MESCC patients who underwent early decompressive surgery within 24 h of admission. In this study, neurological function improved in 17 patients (63%), and seven patients (26%) regained the ability to walk following surgery [ 21 ]. Additionally, a systematic review has shown that fewer vertebral metastases and visceral organs involvement are associated with longer survival periods and improved ambulation recovery in MESCC patients [ 22 ]. In addition, we found that patients with more severe preoperative neurological impairment have a lower likelihood of regaining the ability to walk (Fig. 5 ).
This study’s limitations include its retrospective design and a relatively small sample size. Future prospective multicenter investigations and randomized controlled studies will be needed to identify the best treatment approach for MESCC patients.
Conclusions
This study found that, despite the delayed surgical intervention, a significant proportion of patients regained ambulatory function and exhibited neurological improvements for MESCC patients with severe neurological deficits. Specifically, 59.5% of the patients were able to walk postoperatively, with notable recoveries observed across different Frankel grades. The study underscores the potential benefits of decompressive surgery even beyond the conventionally recommended 24–48 h window for surgical intervention.
Acknowledgements
We extend our sincere gratitude to the members of our institutional multidisciplinary treatment team focused on spinal tumors. We deeply appreciate the collaborative efforts of our colleagues from the departments of breast surgery, pathology, oncology chemotherapy, and radiotherapy. Their invaluable contributions were pivotal in the thoughtful development and execution of treatment strategies, as well as in the preparation of this article.
Author contributions
P. Hu and Y, Li played instrumental roles in the study’s conception and design, patient review, clinical data collection and processing, and manuscript drafting. S. Zhai, S. Yang and F. Liu took charge of data collation and conducted the statistical analysis. H. Zhou, and Xiao Liu undertook the patients’ follow-up and data curation. F. Wei, in addition to designing the study, patient selection, and data processing, provided overall supervision for the research endeavor. X. Liu and Z. Liu took on supervisory roles in data collection and processing.
Funding
This study was supported by the institutional research fund (Peking University Third Hospital; grant number: BYSYZD2022023, P. Hu; Y73504-10, F. Wei). The fund provider has no influence on the design of the study and data collection, analysis, and interpretation of data and in the preparation of the manuscript.
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethics approval and consent to participate
The study was approved by the institutional ethics committee of Peking University Third Hospital (approval number: M2023797), and performed in accordance with the ethical standards of the Declaration of Helsinki (1964) and its subsequent amendments. All patients signed the informed consent to participate.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Yan Li and Panpan Hu shared the first authorship.
References
1. Cole JS, Patchell RA. Metastatic epidural spinal cord compression. Lancet Neurol. 2008;7(5):459–66.
2. Husain ZA, Sahgal A, Chang EL, et al. Modern approaches to the management of metastatic epidural spinal cord compression. CNS Oncol. 2017;6(3):231–41.
3. Badhiwala JH, Wilson JR, Witiw CD, et al. The influence of timing of surgical decompression for acute spinal cord injury: a pooled analysis of individual patient data. Lancet Neurol. 2021;20(2):117–26.
4. George G, Jeba J, Ramkumar R, et al. Palliative radiotherapy for non-small cell lung cancer: a Cochrane systematic review. Cochrane Database Syst Rev. 2015;2015(5):CD006716.26337716
5. Patchell RA, Tibbs PA, Regine WF, et al. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005;366(9486):643–8.
6. Choi D, Crockard A, Bunger C, et al. Review of metastatic spine tumour classification and indications for surgery: the consensus statement of the global spine Tumour Study Group. Eur Spine J. 2010;19(2):215–22.
7. Meyer HS, Wagner A, Raufer A, et al. Surgery in acute metastatic spinal cord compression: timing and functional outcome. Cancers (Basel). 2022;14(9):2249.
8. Fan Y, Zhou X, Wang H, et al. The timing of surgical intervention in the treatment of complete motor paralysis in patients with spinal metastasis. Eur Spine J. 2016;25(12):4060–6.
9. Husband DJ. Malignant spinal cord compression: prospective study of delays in referral and treatment. BMJ. 1998;317(7150):18–21.
10. Spratt DE, Beeler WH, de Moraes FY et al. (2017) An integrated multidisciplinary algorithm for the management of spinal metastases: an International Spine Oncology Consortium report. Lancet Oncol. 2017;18(12):e720-e730.
11. Morimoto T, Toda Y, Hakozaki M, et al. A new era in the management of spinal metastasis. Front Oncol. 2024;14:1374915.
12. Parker SL, Godil SS, Shau DN, et al. Assessment of the minimum clinically important difference in pain, disability, and quality of life after anterior cervical discectomy and fusion: clinical article. J Neurosurg Spine. 2013;18(2):154–60.
13. Fehlings MG, Vaccaro A, Wilson JR et al. (2012) Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PLoS One. 2012;7(2):e32037.
14. Laufer I, Iorgulescu JB, Chapman T, et al. Local disease control for spinal metastases following separation surgery and adjuvant hypofractionated or high-dose single-fraction stereotactic radiosurgery: outcome analysis in 186 patients. J Neurosurg Spine. 2013;18(3):207–14.
15. Sciubba DM, Pennington Z, Colman MW, et al. Spinal metastases 2021: a review of the current state of the art and future directions. Spine J. 2021;21(9):1414–29.
16. Rothrock R, Pennington Z, Ehresman J, et al. Hybrid therapy for spinal metastases. Neurosurg Clin N Am. 2020;31(2):191–200.
17. Gong Y, Hu J, Jiang L et al. (2021) What predicts the prognosis of spinal metastases in separation surgery procedures. World Neurosurg. 2021;146:e714-e723.
18. Moussazadeh N, Laufer I, Yamada Y, et al. Separation surgery for spinal metastases: effect of spinal radiosurgery on surgical treatment goals. Cancer Control. 2014;21(2):168–74.
19. Barzilai O, Amato MK, McLaughlin L, et al. Hybrid surgery-radiosurgery therapy for metastatic epidural spinal cord compression: a prospective evaluation using patient-reported outcomes. Neuro-Oncol Pract. 2018;5(2):104–13.
20. Laufer I, Zuckerman SL, Bird JE et al. (2016) Predicting neurologic recovery after surgery in patients with deficits secondary to MESCC: systematic review. Spine (Phila Pa 1976). 2016;41(Suppl 20):S224-S230.
21. Younsi A, Riemann L, Ishak B, et al. Feasibility of salvage decompressive surgery for pending paralysis due to metastatic spinal cord compression. Clin Neurol Neurosurg. 2021;202:106509.
22. Hsieh MK, Bowles DR, Canseco JA et al. (2020) Is open surgery for metastatic spinal cord compression secondary to lung cancer really beneficial? A systematic review. World Neurosurg. 2020;144:e253-e263.
Associated Data
Data Availability Statement
No datasets were generated or analysed during the current study.