Abstract
Objectives
To summarize the epidemiological characteristics of patients following surgery for spinal metastases retrospectively and make a univariate analysis to identify independent variables that could affect the operation decision making.
Methods
This was a multicenter retrospective review of patients with spinal metastasis who were treated with surgery from 1 January 2007 to 31 July 2019. Basic clinical data were analyzed retrospectively by univariate analysis to identify independent variables that could affect the decision of operation modalities, including gender, age, spinal metastatic site, Frankel score, Karnofsky performance score (KPS), spinal instability neoplastic score (SINS), visual analogue scale (VAS), Tokuhashi score, urinary and fecal incontinence, spinal pathological fracture, primary tumor, extraspinal metastasis, visceral metastasis, and bone lesion (osteolytic, osteoblastic or mixed).
Results
A total of 580 patients including 332 males and 248 females were enrolled in the study with an average age of 58.26 years old (range, 13–86 years old). The most common spinal metastatic level was the thoracic vertebra (190 [32.76%]), followed by the lumbar vertebra (146 [25.17%]), cervical vertebra (47 [8.10%]), and sacral vertebra (35 [6.03%]). Metastases involving more than two sites of the cervical, thoracic, lumbar, and sacral vertebrae arose in 162 (27.93%) patients. For primary tumor, there were 198 (34.14%) cases of lung cancer, 41 (7.07%) cases of kidney cancer, 39 (6.72%) cases of breast cancer, 38 (6.55%) cases of gastrointestinal cancer, 35 (6.03%) cases of lymphoma and myeloma, 25 (4.31%) cases of prostate cancer, 24 (4.14%) cases of liver cancer, 23 (3.97%) cases of mesenchymal tissue sarcoma, 20 (3.45%) cases of thyroid cancer, and 84 (14.48%) cases were tumor with unknown origin. Sixty‐three (10.86%) patients received minimally invasive surgery, 460 (79.31%) patients received palliative surgery, and the remaining 57 (9.83%) received tumor resection. According to the univariate analysis, the KPS score, SINS score, VAS score, Tokuhashi score, urinary and fecal incontinence, spinal pathological fracture, and bone lesion (osteolytic, osteoblastic or mixed) were independent and favorable factors affecting the surgery modalities.
Conclusions
Surgical treatment for spinal metastases was mainly to relieve pain, rebuild spinal stability, improve nerve function, control local tumors, and improve the quality of life of patients. For middle‐aged and elderly patients with good general conditions, severe pain, spinal pathological fracture, spine instability and without urinary and fecal incontinence, early surgical treatment should be actively carried out.
Keywords: Epidemiological study characteristics, Spinal metastases, Surgical treatment, Univariate analysis
Introduction
Spinal metastases are the most common type of bone metastases with a prevalence of 30%–70% in cancer patients and 5%–10% metastases may be associated with epidural spinal cord compression (ESCC) leading to impaired mobility, neurologic deficits, and decreased quality of life1, 2, 3, 4.
In order to relieve pain, improve nerve function, control local tumors, and improve quality of life for patients, surgery is more and more widely performed, including minimally invasive surgery, palliative surgery, or radical surgery. In turn, the majority of studies report a significant clinical effect for carefully selected spinal metastatic patients5, 6, 7. Flavio Tancioni et al.8 reported 25 consecutive patients with a diagnosis of ESCC from solid primary tumors. These patients were treated with minimally invasive surgery, with 96% clinical remission of pain and 88% improvement of neurological deficit after 2 weeks. Masuda et al.9 assessed the surgical outcomes of 44 patients treated with posterior decompression and stabilization and reported that the Frankel score and Eastern Cooperative Oncology Group performance status (ECOG‐PS) improved in all patients after surgery. Boriani et al.10 also applied total en‐bloc spondylectomy for 165 patients, and reported that all patients had neurologic deficits improvement and the local recurrences recorded were just 15.28% after 25 years.
However, there still remains some problems when treating spinal metastasis with surgery. Complications must be considered after surgery, such as intra‐operation bleeding, spinal cord injury, and hematoma11, 12. Furthermore, the purposes for spinal metastasis treatment are usually different from visceral metastases, which makes the treatment concept, preoperative evaluation, and treatment strategy of spinal metastasis become irregular and arbitrary13, 14. At the same time as the rapid development of immuno‐therapy, endocrine therapy, radiotherapy, and chemotherapy (especially targeted therapy), a multidisciplinary combined therapy of spinal metastasis has become a trend15, 16, 17. Therefore, indications and contraindications for spinal metastasis surgery treatment should be clearly understood.
Accordingly, a multicenter retrospective study was performed with the aim of: (i) summarizing the epidemiological characteristics of patients following surgery for spinal metastases; (ii) making a subgroup analysis to identify independent and favorable factors which could affect the surgery selection; and (iii) helping clinicians make a more appropriate surgery decision for patients with spinal metastasis.
Patients and Methods
Participants
This was a multicenter retrospective review of patients with spinal metastasis who were treated with surgery from 1 January 2007 to 31 July 2019. All patients met the following inclusion criteria: (i) patients diagnosed with spinal metastasis precisely by clinical imaging examination (CT, MRI, ECT or PET‐CT) or pathological examination; (ii) patients with hematological malignancy spinal metastasis, including lymphoma and myeloma; (iii) patients who were treated by surgical intervention; and (iv) patients whose observation indicators below could be retrospectively analyzed.
Exclusion criteria for this review were: (i) patients with impaired spinal cord function due to other diseases, such as primary spinal tumors, spinal tuberculosis, or spinal degenerative diseases; (ii) outpatients; (iii) patients with another spinal surgery aside from the metastatic tumor; and (iv) patients undergoing biopsies as the only surgical intervention.
Operation Category
Operations applied for patients were mainly divided into minimally invasive surgery and aggressive surgery based on the operation invasiveness.
Minimally invasive surgery was defined as techniques which had lower associated soft tissue damage and shorter hospital lengths of stay, including percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP).
For aggressive surgery, palliative surgery was applied for the purpose of improving impaired mobility, neurologic function, and quality of life, but the tumor was not resected completely. Posterior laminectomy decompression and subtotal corpectomy (combing with vertebroplasty and microwave ablation or not) were included.
For the purpose of removing the tumor completely, radical surgery was performed for patients, including total or piecemeal vertebrectomy, piecemeal or total en‐bloc spondylectomy.
Observation Indicators
Indicators were collected including gender, age, primary malignancy type, spinal metastatic level, spinal pathological fracture, urinary and fecal incontinence, extraspinal metastasis, visceral metastasis, bone lesion, Frankel score, Karnofsky performance score (KPS), visual analogue scale (VAS), spinal instability neoplastic score (SINS), and Tokuhashi score.
Primary malignancy type was defined as the origin of spinal metastatic tumor, such as lung cancer, breast cancer, and kidney cancer, among others.
Spinal metastatic level was defined as the location where the metastatic tumor existed. Based on the anatomical structure of the spine, it was divided into the cervical vertebra, thoracic vertebra, lumbar vertebra, sacral vertebra, and trans‐segmental metastasis.
Spinal pathological fracture was defined as vertebral body or appendix fractured due to the tumors based on examinations with X‐rays, CT, or MRI.
Extraspinal metastasis was defined as patients with bone metastasis other than that occurring in the spine (such as rib, femur, tibia, fibula).
Bone lesion was identified based on the function of osteoblasts and osteoclasts, including osteolytic, osteoblastic, and mixed, through examinations with X‐rays or CT.
Frankel score classification provided an assessment of spinal cord function, which was divided into five grades of A, B, C, D, and E based on the degree of spinal cord injury. Grade A meant complete neurological injury with no motor and sensory function, Grade B meant preserved sensation only, Grade C meant preserved nonfunctional motor, Grade D meant preserved functional motor, and Grade E meant normal motor and sensory function18.
KPS score was used to assess the functional status of patients. From 0 to 100, patients with no symptoms were scored at 100, patients who died were scored at 0. Generally speaking, KPS score above 80 was considered to be self‐care level, 50–70 was considered into half self‐care level, and 50 was considered patients needing help from others19.
VAS score was a measure of pain intensity and it was a continuous scale comprised of a horizontal (called horizontal visual analog scale) or vertical (called vertical visual analog scale) scale. For pain intensity, the scores could be from 0–10, which was determined by measuring the distance (mm) on the 10 cm line between the “no pain” anchor and the patient's mark20.
SINS score was applied for assessing the spinal instability. It contained the lesion location, mechanical pain, bone lesion, radiographic spinal alignment, vertebral body collapse, and posterolateral involvement. The total score was 18 (1–6 meant stable, 7–12 meant potentially stable, and 13–18 meant unstable)21. Tokuhashi score was a prognostic evaluation of patients which was based on KPS score, numbers of extraspinal metastasis, numbers of vertebra bodies, visceral metastasis, primary malignancy type, and spinal cord palsy. The score was from zero to 15, usually divided into 0–8 with overall survival less than 6 months, 9–11 with overall survival between 6 and 12 months, and 12–15 with overall survival more than 12 months22.
Statistical Analysis
Measurement data (age, intra‐operation bleeding, and operation time) were expressed as their mean, with the minimum and maximum values compared with the t‐test. Counting data (gender, primary tumor, and neurological assessment etc.) were compared using the χ2‐test. All statistical analyses were performed using IBM SPSS Statistics 22.0, and a two‐tailed P < 0.05 was considered significant difference statistically.
Results
Cohort Characteristics
As shown in Table 1, a total of 332 male and 248 female patients were enrolled in the study with an average age of 58.26 years old (range, 13–86 years old), an average intra‐operation bleeding of 1334.98 mL (range, 5–9000 mL), and an average operation time of 216.31 min (range, 60–680 min).
Table 1.
Characteristics of the studied cohort (n = 580)
| Lung cancer | Kidney cancer | Breast cancer | Prostate cancer | Thyroid cancer | Liver cancer | Colorectal cancer | Gastric cancer | Myeloma and lymphoma | Mesenchymal tissue sarcoma | |
|---|---|---|---|---|---|---|---|---|---|---|
| Gender | ||||||||||
| Male | 120 | 35 | 0 | 25 | 5 | 20 | 10 | 15 | 19 | 9 |
| Female | 78 | 6 | 39 | 0 | 15 | 4 | 11 | 2 | 16 | 14 |
| Age (year) | ||||||||||
| ≤44 | 24 | 3 | 10 | 0 | 0 | 2 | 1 | 1 | 2 | 8 |
| 45–59 | 79 | 13 | 18 | 4 | 10 | 9 | 11 | 6 | 11 | 6 |
| 60–74 | 89 | 21 | 10 | 15 | 8 | 13 | 8 | 8 | 22 | 9 |
| 75–89 | 6 | 4 | 1 | 6 | 2 | 0 | 1 | 2 | 0 | 0 |
| Spinal metastatic site | ||||||||||
| Cervical vertebra | ||||||||||
| Single segment | 14 | 5 | 0 | 2 | 1 | 4 | 0 | 0 | 0 | 1 |
| Multiple segment | 5 | 0 | 2 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Thoracic vertebra | ||||||||||
| Single segment | 30 | 9 | 9 | 4 | 3 | 3 | 5 | 5 | 8 | 5 |
| Multiple segment | 25 | 8 | 7 | 7 | 4 | 4 | 3 | 3 | 5 | 5 |
| Lumbar vertebra | ||||||||||
| Single segment | 39 | 6 | 5 | 2 | 6 | 3 | 6 | 2 | 9 | 6 |
| Multiple segment | 16 | 2 | 2 | 1 | 0 | 1 | 1 | 0 | 5 | 2 |
| Sacral vertebra | 8 | 1 | 0 | 3 | 1 | 3 | 3 | 1 | 0 | 3 |
| Trans‐segmental metastasis | 61 | 10 | 14 | 6 | 4 | 5 | 3 | 6 | 8 | 1 |
| Extraspinal metastasis | ||||||||||
| Yes | 96 | 17 | 14 | 14 | 8 | 9 | 7 | 7 | 14 | 6 |
| No | 102 | 24 | 25 | 11 | 12 | 15 | 14 | 10 | 21 | 17 |
| Visceral metastasis | ||||||||||
| Yes | 31 | 6 | 3 | 2 | 5 | 6 | 9 | 2 | 0 | 5 |
| No | 167 | 35 | 36 | 23 | 15 | 18 | 12 | 15 | 35 | 18 |
| Spinal pathological fracture | ||||||||||
| Yes | 69 | 15 | 21 | 9 | 6 | 8 | 8 | 5 | 20 | 9 |
| No | 129 | 26 | 18 | 16 | 14 | 16 | 13 | 12 | 15 | 14 |
| Bone lesion | ||||||||||
| Osteolytic | 67 | 15 | 11 | 8 | 5 | 7 | 4 | 8 | 24 | 9 |
| Osteoblastic | 5 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Mixed | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Unknown | 125 | 26 | 28 | 15 | 15 | 17 | 17 | 9 | 11 | 13 |
| Unknown origin | Reproductive system tumors | Esophageal cancer | Bladder cancer | Pancreas cancer | Others | Totally (n) | |
|---|---|---|---|---|---|---|---|
| Gender | |||||||
| Male | 48 | 2 | 7 | 3 | 5 | 9 | 332 |
| Female | 36 | 10 | 2 | 3 | 0 | 12 | 248 |
| Age (year) | |||||||
| ≤44 | 8 | 2 | 0 | 1 | 1 | 7 | 70 |
| 45–59 | 27 | 7 | 2 | 2 | 2 | 10 | 217 |
| 60–74 | 38 | 3 | 7 | 3 | 2 | 3 | 259 |
| 75–89 | 11 | 0 | 0 | 0 | 0 | 1 | 34 |
| Spinal metastatic site | |||||||
| Cervical vertebra | |||||||
| Single segment | 4 | 0 | 1 | 0 | 0 | 1 | 33 |
| Multiple segment | 2 | 0 | 0 | 0 | 0 | 0 | 14 |
| Thoracic vertebra | |||||||
| Single segment | 7 | 2 | 3 | 1 | 3 | 2 | 99 |
| Multiple segment | 14 | 0 | 1 | 1 | 1 | 6 | 91 |
| Lumbar vertebra | |||||||
| Single segment | 16 | 3 | 1 | 2 | 0 | 5 | 111 |
| Multiple segment | 7 | 0 | 0 | 0 | 0 | 0 | 35 |
| Sacral vertebra | 8 | 2 | 0 | 1 | 0 | 3 | 35 |
| Trans‐segmental metastasis | 26 | 5 | 3 | 1 | 1 | 4 | 162 |
| Extraspinal metastasis | |||||||
| Yes | 32 | 3 | 2 | 2 | 0 | 5 | 237 |
| No | 52 | 9 | 7 | 4 | 5 | 16 | 344 |
| Visceral Metastasis | |||||||
| Yes | 11 | 0 | 2 | 0 | 2 | 6 | 90 |
| No | 73 | 12 | 7 | 6 | 3 | 15 | 490 |
| Spinal pathological fracture | |||||||
| Yes | 29 | 3 | 3 | 2 | 2 | 3 | 212 |
| No | 55 | 9 | 6 | 4 | 3 | 18 | 368 |
| Bone lesion | |||||||
| Osteolytic | 23 | 3 | 4 | 3 | 2 | 2 | 195 |
| Osteoblastic | 2 | 0 | 0 | 0 | 0 | 0 | 8 |
| Mixed | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Unknown | 59 | 9 | 5 | 3 | 3 | 19 | 374 |
The most common spinal metastatic level was the thoracic vertebra (190 [32.76%]), followed by the lumbar vertebra (146 [25.17%]), cervical vertebra (47 [8.10%]), and sacral vertebra (35 [6.03%]). Metastases involving more than two sites of the cervical, thoracic, lumbar, and sacral vertebrae arose in 162(27.93%) patients. Among these patients, only one single segment metastasis was presented in 270 (46.55%) patients and two or more segment metastases were presented in 310 (53.45%) patients (Fig. 1).
Figure 1.
Spinal metastatic level among the 580 patients. The most common spinal metastatic site was the thoracic vertebra (190 [32.76%]), followed by the lumbar vertebra (146 [25.17%]), cervical vertebra (47 [8.10%]), sacral vertebra (35 [6.03%]) and trans‐segmental metastasis (162 [27.93%]). Only one single segment metastasis was presented in 247 (42.59%) and two or more segment metastasis was in 333 (57.41%).
For primary tumors, there were 198 (34.14%) cases of lung cancer, 41 (7.07%) cases of kidney cancer, 39 (6.72%) cases of breast cancer, 38 (6.55%) cases of gastrointestinal cancer, 35 (6.03%) cases of lymphoma and myeloma, 25 (4.31%) cases of prostate cancer, 24 (4.14%) cases of liver cancer, 23 (3.97%) cases of mesenchymal tissue sarcoma, 20 (3.45%) cases of thyroid cancer, and 84 (14.48%) cases were with unknown origin of tumor (Fig. 2).
Figure 2.
Distribution of the primary tumors in 580 patients with spinal metastasis treated with surgery. Lung cancer was the most one in 198(34.14%) cases. Kidney cancer, breast cancer, gastrointestinal cancer, lymphoma, and myeloma did not show significant difference. Prostate cancer, liver cancer and mesenchymal tissue sarcoma were nearly at the same. 84 (14.48%) cases were with unknown origin of tumor but with clear pathological examinations.
Four hundred and seventy one (81.21%) patients presented unbearable pain with an average VAS score of 7.12 (range, 0–9). As for neurological impairment, 90 (15.52%) patients presented paralysis including Frankel A in 27 patients, Frankel B in 13 and Frankel C in 50 patients. Furthermore, 485 (83.62%) patients presented spinal instability and the average SINS score of 8.02 (range, 7–18). More details were presented in Fig. 3.
Figure 3.
Distribution of Tokuhashi score, SINS score, VAS score, Frankel score and KPS score in 580 patients treated with surgery. Tokuhashi score more than nine was shown in 488 (84.14%) patients; 485 (83.62%) patients presented spinal instability with SINS score more than 7; 471 (81.21%) patients presented pain with VAS score more four. As for neurological impairment, 90 (15.52%) patients presented paralysis.
Operation Category and Univariate Analysis
In this cohort study, 63 (10.86%) patients received minimally invasive surgery (including 58 PVP and five PKP). Four hundred and sixty (79.31%) patients received palliative surgery (including 290 posterior laminectomy, 155 subtotal corpectomy, 15 subtotal corpectomy combined with microwave ablation and vertebroplasty) and 57 (9.83%) patients received radical surgery (including 36 total vertebrectomy and 21 total en‐bloc spondylectomy). The results of univariate analysis were shown in Table 2, with KPS score, SINS score, VAS score, Tokuhashi score, urinary and fecal incontinence, spinal pathological fracture, and bone lesion (osteolytic, osteoblastic or mixed) being independent and favorable factors affecting the surgery treatment.
Table 2.
Univariate analysis to identify independent variables that could affect the operation modality (P < 0.05 was identified with significant difference; n = number)
| Minimally invasive surgery n = 63 (10.86%) | Palliative surgery n = 460 (79.31%) | Radical surgery n = 57 (9.83%) | P value | |
|---|---|---|---|---|
| Gender | ||||
| Male | 36 | 258 | 36 | |
| Female | 27 | 202 | 21 | P = 0.120 |
| Age (year) | ||||
| ≤44 | 6 | 59 | 3 | |
| 45–59 | 21 | 167 | 31 | |
| 60–74 | 32 | 203 | 23 | |
| 75–89 | 4 | 31 | 0 | P = 0.059 |
| Spinal metastatic site | ||||
| Cervical vertebra | 0 | 42 | 5 | |
| Thoracic vertebra | 17 | 152 | 21 | |
| Lumbar vertebra | 16 | 122 | 8 | |
| Sacral vertebra | 3 | 28 | 4 | |
| Trans‐segmental metastasis | 27 | 116 | 19 | P = 0.078 |
| Frankel score | ||||
| A–C | 3 | 75 | 12 | |
| D | 33 | 195 | 29 | |
| E | 27 | 190 | 16 | P = 0.067 |
| KPS score | ||||
| 10–40 | 0 | 30 | 3 | |
| 50–70 | 21 | 209 | 34 | |
| 80–100 | 42 | 221 | 20 | P = 0.017 |
| SINS score | ||||
| 1–6 | 8 | 84 | 3 | |
| 7–12 | 42 | 327 | 24 | |
| 13–18 | 13 | 49 | 30 | P < 0.001 |
| VAS score | ||||
| 0–3 | 6 | 93 | 10 | |
| 4–6 | 26 | 223 | 36 | |
| 7–10 | 31 | 144 | 11 | P = 0.009 |
| Tokuhashi score | ||||
| 0–8 | 15 | 72 | 5 | |
| 9–11 | 31 | 221 | 20 | |
| 12–15 | 17 | 167 | 32 | P = 0.021 |
| Urinary and fecal incontinence | ||||
| Yes | 0 | 58 | 6 | |
| No | 63 | 402 | 51 | P = 0.028 |
| Primary tumor | ||||
| Slow growth | 16 | 113 | 12 | |
| Moderate growth | 23 | 182 | 18 | |
| Rapid growth | 24 | 165 | 27 | P = 0.335 |
| Extraspinal metastasis | ||||
| Yes | 30 | 185 | 22 | |
| No | 33 | 275 | 35 | P = 0.385 |
| Visceral metastasis | ||||
| Yes | 0 | 70 | 9 | |
| No | 54 | 390 | 48 | P = 0.971 |
| Spinal pathological fracture | ||||
| Yes | 35 | 155 | 22 | |
| No | 28 | 305 | 35 | P = 0.002 |
| Bone lesion | ||||
| Osteolytic | 31 | 153 | 8 | |
| Osteoblastic | 0 | 8 | 1 | |
| Mixed | 1 | 2 | 0 | |
| Unknown | 31 | 297 | 48 | P < 0.001 |
KPS Score
The KPS score was divided into three groups (10–40, 50–70, 80–100) (P = 0.017). For group 10–40, no patients received minimally invasive surgery, 30 (5.17%) patients received palliative surgery, and three (0.52%) patients received radical surgery. For group 50–70, 21 (3.62%) patients received minimally invasive surgery, 209 (36.03%) patients received palliative surgery, and 34 (5.86%) patients received radical surgery. For group 80–100, 42 (7.24%) patients received minimally invasive surgery, 221 (38.10%) patients received palliative surgery, and 20 (3.45%) patients received radical surgery.
SINS Score
Three groups (1–6, 7–12, 13–18) (P < 0.001) were included for the SINS score. For group 1–6, eight (1.38%) patients received minimally invasive surgery, 84 (14.48%) patients received palliative surgery and three (0.52%) patients received radical surgery. For group 7–12, 42 (7.24%) patients received minimally invasive surgery, 327 (56.38%) patients received palliative surgery, and 24 (4.14%) patients received radical surgery. For group 13–18, 13 (2.24%) patients received minimally invasive surgery, 49 (8.45%) patients received palliative surgery, and 30 (5.17%) patients received radical surgery.
VAS Score
The VAS score was divided into three groups (0–3, 4–6, 7–10) (P = 0.009). For group 0‐3, six (1.03%) patients received minimally invasive surgery, 93 (64.58%) patients received palliative surgery, and 10 (1.72%) patients received radical surgery. For group 7–12, 26 (4.48%) patients received minimally invasive surgery, 223 (38.45%) patients received palliative surgery, and 36 (6.21%) patients received radical surgery. For group 13–18, 31 (5.34%) patients received minimally invasive surgery, 144 (24.8%) patients received palliative surgery, and 11 (1.90%) patients received radical surgery.
Tokuhashi Score
The Tokuhashi score was divided into three groups (0–8, 9–11, 12–15) (P = 0.021). For group 0–8, 15 (2.59%) patients received minimally invasive surgery, 72 (12.41%) patients received palliative surgery, and five (0.86%) patients received radical surgery. For group 9–11, 31 (5.34%) patients received minimally invasive surgery, 221 (38.10%) patients received palliative surgery, and 20 (3.45%) patients received radical surgery. For group 12–15, 17 (2.93%) patients received minimally invasive surgery, 167 (28.79%) patients received palliative surgery, and 32 (5.52%) patients received radical surgery.
Urinary and Fecal Incontinence
Among these 580 patients, 64 (11.03%) patients presented urinary and fecal incontinence including 58 (10.00%) patients receiving palliative surgery and six (1.03%) patients receiving radical surgery. The remaining 516 (88.97%) patients were with no urinary and fecal incontinence, 63 (10.86%) patients received minimally invasive surgery, 402 (69.31%) patients received palliative surgery, and 51 (8.79%) patients received radical surgery. The difference was significant among groups (P = 0.028).
Spinal Pathological Fracture
Two hundred and twelve (36.55%) patients presented spinal pathological fracture, and among these patients 35 (6.03%) patients received minimally invasive surgery, 155 (26.72%) patients received palliative surgery, and 22 (3.79%) patients received radical surgery. And while spinal pathological fracture did not occur in 368 (63.45%) patients, 28 (4.83%) patients received minimally invasive surgery, 305 (52.59%) patients received palliative surgery, and 35 (6.03%) patients received radical surgery. The difference was significant among groups (P = 0.002).
Bone Lesion (Osteolytic, Osteoblastic, or Mixed)
Totally, 192 (33.10%) patients presented with osteolytic lesions through imaging examinations and received surgery treatment. Thirty‐one (5.34%) patients received minimally invasive surgery, 153 (26.38%) patients received palliative surgery, and eight (1.38%) patients received radical surgery. For patients with osteoblastic lesions, only eight (1.38%) patients received palliative surgery and one (0.17%) patient received radical surgery. For patients with mixed lesions, just one (0.17%) patient received minimally invasive surgery and two (0.34%) patients received palliative surgery. The difference was significant among groups (P < 0.001).
Discussion
Spinal metastases are the most common type of bone metastasis with a prevalence of 30%–70% in cancer patients; 5%–10% of metastases may be associated with ESCC leading to impaired mobility, neurologic deficits, and decreased quality of life. However, there is still no consensus regarding the best treatment modality for these lesions. In this multicenter study, a total of 580 patients with an average age of 58.26 years (range, 13–86 years old) were enrolled in the study to summarize and analyze the epidemiological characteristics and independent variables affecting surgical modalities for spinal metastases.
Among these 580 patients, the epidemiological characteristics were analyzed. Three hundred and thirty two male and 248 female patients were enrolled with a ratio of 1.34:1, and most patients were at middle or elderly age between 45 years and 74 years. For primary lesion, the most common were lung cancer, followed by kidney cancer, breast cancer, gastrointestinal cancer, lymphoma and myeloma, prostate cancer, mesenchymal tissue sarcoma, and thyroid cancer. Especially, lung cancer was the top one leading to spinal metastasis either in males or females, which was different from data published abroad (prostate cancer in males and breast cancer in females). It may be due to the regional and cultural differences23. The most common spinal metastatic site was the thoracic vertebra (190 [32.76%]), followed by the lumbar vertebra (146 [25.17%]), and metastases involving more than two sites of the cervical, thoracic, lumbar, and sacral vertebrae arose in 162 (27.93%) patients, that was the same as in the report by Bollen et al.24.
As shown in Table 2, the KPS score, SINS score, VAS score, Tokuhashi score, urinary and fecal incontinence, spinal pathological fracture, and occurrence of bone lesion (osteolytic, osteoblastic or mixed) were independent and favorable factors affecting the surgery modalities. It could be determined that patients who received minimally invasive surgery preferentially should have a good general condition, the KPS score was more than 70 without urinary and fecal incontinence and visceral metastasis. Spinal metastatic sites showed no significant difference, but subgroup of vertebral body metastasis and appendix metastasis was not analyzed. However, some investigators pointed out that the minimally invasive surgery should be carefully selected for patients with vertebral body posterior wall and pedicle involvement25, so further analyses were needed to determine minimally invasive surgery indications for different spinal metastatic sites.
Unlike primary spinal tumors, the goal of surgery for spinal metastases is not cure but an overwhelming improvement of symptoms.26, 27, 28, 29 That is to say, surgeons must consider the patients’ overall health, as well as the imaging examination of the vertebral metastases. In this study, 460 (79.31%) patients received palliative surgery including 290 posterior laminectomy, 155 subtotal corpectomy, and 15 subtotal corpectomy combined with microwave ablation and vertebroplasty. Most of them presented severe pain and spinal instability but the general conditions were good with KPS score more than 60 and Frankel score in D and E. The revised Tokuhashi score have suggested that surgery only be considered in patients with a life expectancy of more than 6 months30, 31, meaning that patients, especially those with aggressive primary tumor metastasis, are ineligible for surgical symptom palliation29, 32. However, in this multicenter case series, lung cancer was the most common metastasis, as seen in 198 patients. Rapid development of radiotherapy and chemotherapy, especially targeted therapy, may help to improve patients’ life expectancy.
Radical surgery was also performed for spinal metastasis, but the complex anatomical structure of the spine made the operation very difficult and bleeding occurs frequently during the operation. Therefore, indications and contraindications should be strictly clear. The indications for spinal metastatic tumor resection are generally as follows: single‐level metastatic tumors of thoracic and lumbar vertebra with well‐controlled primary lesions susceptible to chemotherapy or targeted therapy; without vital visceral metastasis; patients with longer life expectancy; no more than two adjacent segment lesions; Tokuhashi score at a range of 12~1522, 33, 34. Only 57 (9.83%) patients who received tumor resection containing 36 total vertebrectomy and 21 total en‐bloc spondylectomy were enrolled in this retrospective study, most of them were met with the indications above. In addition, univariate analysis identified that patients with spinal pathological fracture and spinal instability (SINS score at a range of 13–18) could also be treated with tumor resection which should be considered for indications.
The limitations of this retrospective study include: lack of non‐surgical patients enrolled as control group; spinal metastatic sites are just on the basis of cervical vertebra, thoracic vertebra, lumbar vertebra, sacral vertebra, and trans‐segmental metastasis, however, another subgroup containing vertebral body and appendix should also be considered; and surgery modalities are not divided into the subgroup of operation combining with or without radiotherapy, chemotherapy and targeted therapy.
Conclusions
Surgical treatment for spinal metastases is mainly to relieve pain, rebuild spinal stability, improve nerve function, control local tumors, and improve the quality of life of patients. With the rapid development of radiotherapy, chemotherapy (especially targeted therapy), immunotherapy and endocrine therapy, the level of surgical treatment of spinal metastases has been greatly improved. For middle‐aged and elderly patients with good general conditions, severe pain, spinal pathological fracture, spine instability and without urinary and fecal incontinence, early surgical treatment should be actively carried out.
Acknowledgments
The authors are grateful for support from the Library of Tianjin Medical University. We would also like to thank the friends who gave us help in the creation and revision of the article.
Disclosure: This research did not receive any specific grants from funding agencies in the public, commercial, or not‐for‐profit sectors.
Declaration: All authors listed meet the authorship criteria according to the latest guidelines of the International Committee of Medical Journal Editors, and all authors are in agreement with the manuscript.
Contributor Information
Guo‐chuan Zhang, Email: anewing@sohu.com.
Yong‐cheng Hu, Email: yongchenghu@126.com.
References
- 1. Barzilai O, Laufer I, Yamada Y, et al Integrating evidence‐based medicine for treatment of spinal metastases into a decision framework: neurologic, oncologic, mechanicals stability, and systemic disease. J Clin Oncol, 2017, 35: 2419–2427. [DOI] [PubMed] [Google Scholar]
- 2. Barzilai O, McLaughlin L, Amato MK, et al Predictors of quality of life improvement after surgery for metastatic tumors of the spine: prospective cohort study. Spine J, 2018, 18: 1109–1115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Moussazadeh N, Laufer I, Yamada Y, Bilsky MH. Separation surgery for spinal metastases: effect of spinal radiosurgery on surgical treatment goals. Cancer Control, 2014, 21: 168–174. [DOI] [PubMed] [Google Scholar]
- 4. Witham TF, Khavkin YA, Gallia GL, Wolinsky JP, Gokaslan ZL. Surgery insight: current management of epidural spinal cord compression from metastatic spine disease. Nat Clin Pract Neurol, 2006, 2: 87–94. [DOI] [PubMed] [Google Scholar]
- 5. Yao A, Sarkiss CA, Ladner TR, Jenkins AL 3rd. Contemporary spinal oncology treatment paradigms and outcomes for metastatic tumors to the spine: a systematic review of breast, prostate, renal, and lung metastases. J Clin Neurosci, 2017, 41: 11–23. [DOI] [PubMed] [Google Scholar]
- 6. Lau D, Chou D. Posterior thoracic corpectomy with cage reconstruction for metastatic spinal tumors: comparing the mini‐open approach to the open approach. J Neurosurg Spine, 2015, 23: 217–227. [DOI] [PubMed] [Google Scholar]
- 7. Daniel JW, Veiga JC. Prognostic parameters and spinal metastases: a research study. PLoS One, 2014, 9: e109579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Tancioni F, Navarria P, Pessina F, et al Early surgical experience with minimally invasive percutaneous approach for patients with metastatic epidural spinal cord compression (MESCC) to poor prognoses. Ann Surg Oncol, 2012, 19: 294–300. [DOI] [PubMed] [Google Scholar]
- 9. Masuda K, Ebata K, Yasuhara Y, Enomoto A, Saito T. Outcomes and prognosis of neurological decompression and stabilization for spinal metastasis: is assessment with the spinal instability neoplastic score useful for predicting surgical results. Asian Spine J, 2018, 12: 846–853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Boriani S, Gasbarrini A, Bandiera S, Ghermandi R, Lador R. En bloc resections in the spine‐the experience of 220 cases over 25 years. World Neurosurg, 2017, 98: 217–229. [DOI] [PubMed] [Google Scholar]
- 11. Mesfin A, EI Dafrawy MH, Jain A, Hassanzadeh H, Kebaish KM. Total en bloc spondylectomy for primary and metastatic spine tumor. Orthopedics, 2015, 38: e995–e1000. [DOI] [PubMed] [Google Scholar]
- 12. Salame K, Regev G, Keynan O, Lidar Z. Total en bloc spondylectomy for vertebral tumors. Isr Med Assoc J, 2015, 17: 37–41. [PubMed] [Google Scholar]
- 13. Bollen L, Wibmer C, Van der Linden YM, et al Predictive value of six prognostic scoring systems for spinal bone metastases: an analysis based on 1379 patients. Spine (Phila Pa 1976), 2016, 41: E155–E162. [DOI] [PubMed] [Google Scholar]
- 14. Wibmer C, Leithner A, Hofmann G, et al Survival analysis of 254 patients after manifestation of spinal metastases: evaluation of seven preoperative scoring systems. Spine (Phila Pa 1976), 2011, 36: 1977–1986. [DOI] [PubMed] [Google Scholar]
- 15. 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: 643–648. [DOI] [PubMed] [Google Scholar]
- 16. Park S, Kim KH, Rhee WJ, Lee J, Cho Y, Koom WS. Treatment outcome of radiation therapy and concurrent targeted molecular therapy in spinal metastasis from renal cell carcinoma. Radiat Oncol J, 2016, 34: 128–134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Cazzato RL, Garnon J, Caudrelier J, Rao PP, Koch G, Gangi A. Percutaneous radiofrequency ablation of painful spinal metastasis: a systematic literature assessment of analgesia and safety. Int J Hyperthermia, 2018, 34: 1272–1281. [DOI] [PubMed] [Google Scholar]
- 18. van Middendorp JJ, Goss B, Urquhart S, Atresh S, Williams RP, Schuetz M. Diagnosis and prognosis of traumatic spinal cord injury. Global Spine J, 2011, 1: 1–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Terret C, Albrand G, Moncenix G, Droz JP. Karnofsky performance scale (KPS) or physical performance test (PPT)? That is the question. Crit Rev Oncol Hematol, 2011, 77: 142–147. [DOI] [PubMed] [Google Scholar]
- 20. Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: visual analog scale for pain (VAS pain), numeric rating scale for pain (NRS pain), McGill pain questionnaire (MPQ), short‐form McGill pain questionnaire (SF‐MPQ), chronic pain grade scale (CPGS), short form‐36 bodily pain scale (SF‐36 BPS), and measure of intermittent and constant osteoarthritis pain (ICOAP). Arthritis Care Res (Hoboken), 2011, 63: S240–S252. [DOI] [PubMed] [Google Scholar]
- 21. Fisher CG, DiPaola CP, Ryken TC, et al A novel classification system for spinal instability in neoplastic disease: an evidence‐based approach and expert consensus from the Spine Oncology Study Group. Spine (Phila Pa 1976), 2010, 35: E1221–E1229. [DOI] [PubMed] [Google Scholar]
- 22. Tokuhashi Y, Matsuzaki H, Oda H, Oshima M, Ryu J. A revised scoring system for preoperative evaluation of metastatic spine tumor prognosis. Spine (Phila Pa 1976), 2005, 30: 2186–2191. [DOI] [PubMed] [Google Scholar]
- 23. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet‐Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65: 87–108. [DOI] [PubMed] [Google Scholar]
- 24. Bollen L, van der Linden YM, Pondaag W, et al Prognostic factors associated with survival in patients with symptomatic spinal bone metastases: a retrospective cohort study of 1,043 patients. Neuro Oncol, 2014, 16: 991–998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Goetz MP, Callstrom MR, Charboneau JW, et al Percutaneous image guided radiofrequency ablation of painful metastases involving bone: a multicenter study. J Clin Oncol, 2004, 22: 300–306. [DOI] [PubMed] [Google Scholar]
- 26. Yang SB, Cho W, Chang U. Analysis of prognostic factors relating to postoperative survival in spinal metastases. J Korean Neurosurg Soc, 2012, 51: 127–134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Sohn S, Kim J, Chung CK, et al A nationwide epidemiological study of newly diagnosed spine metastasis in the adult Korean population. Spine J, 2016, 16: 937–945. [DOI] [PubMed] [Google Scholar]
- 28. Vanek P, Bradac O, Trebicky F, Saur K, de Lacy P, Benes V. Influence of the preoperative neurological status on survival after the surgical treatment of symptomatic spinal metastases with spinal cord compression. Spine (Phila Pa 1976), 2015, 40: 1824–1830. [DOI] [PubMed] [Google Scholar]
- 29. Pennington Z, Ahmed AK, Molina CA, Ehresman J, Laufer I, Sciubba DM. Minimally invasive versus conventional spine surgery for vertebral metastases: a systematic review of the evidence. Ann Transl Med, 2018, 6: 103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Kaloostian PE, Yurter A, Zadnik PL, Sciubba DM, Gokaslan ZL. Current paradigms for metastatic spinal disease: an evidence‐based review. Ann Surg Oncol, 2014, 21: 248–262. [DOI] [PubMed] [Google Scholar]
- 31. Zadnik PL, Hwang L, Ju DG, et al Prolonged survival following aggressive treatment for metastatic breast cancer in the spine. Clin Exp Metastasis, 2014, 31: 47–55. [DOI] [PubMed] [Google Scholar]
- 32. Goodwin CR, Sankey EW, Liu A, et al A systematic review of clinical outcomes for patients diagnosed with skin cancer spinal metastases. J Neurosurg Spine, 2015, 24: 837–849. [DOI] [PubMed] [Google Scholar]
- 33. Murakami H, Kawahara N, Demura S, Kato S, Yoshioka K, Tomita K. Total en bloc spondylectomy for lung cancer metastasis to the spine. J Neurosurg Spine, 2010, 13: 414–417. [DOI] [PubMed] [Google Scholar]
- 34. Oka S, Matsumiya H, Shinohara S, et al Total or partial vertebrectomy for lung cancer invading the spine. Ann Med Surg (Lond), 2016, 12: 1–4. [DOI] [PMC free article] [PubMed] [Google Scholar]