Retrospective case series.
To investigate the oncological outcomes, including distant relapse, after
Although EBS has been reported to be locally curative and extend survival in select patients with spinal metastases, detailed reports regarding the control of distant relapse after EBS are lacking.
We conducted a retrospective review of 18 consecutive patients (median age at EBS, 62 years; range, 40–77 years) who underwent EBS for spinal metastases between 1991 and 2015. The primary cancer sites included the kidney (n=7), thyroid (n=4), liver (n=3), and other locations (n=4). Survival rates were estimated using the Kaplan–Meier method, and groups were compared using the log-rank method.
The median operative time and intraoperative blood loss were 767.5 minutes and 2,375 g, respectively. Twelve patients (66.7%) experienced perioperative complications. Five patients (27.8%) experienced local recurrence of the tumor at a median of 12.5 months after EBS, four of which had a positive resection margin status. Thirteen patients (72.2%) experienced distant relapse at a median of 21 months after EBS. The estimated median survival period after distant relapse was 20 months (95% confidence interval, 0.71–39.29 months). No association was found between resection margin status and distant relapse. Overall, the 2-year, 5-year, and 10-year survival rates after EBS were 72.2%, 48.8%, and 27.1%, respectively. Importantly, the era in which EBS was performed did not impact the oncological outcomes.
Our results suggest that EBS by itself, even if margin-free, cannot prevent further dissemination, which occurred in >70% of patients at a median of 21 months after EBS. These results should be considered and conveyed to patients for clinical decision-making.
Spinal metastases can cause bony compromise and tumor invasion into the epidural space, progressing to axial pain and neurologic deficits. These symptoms negatively affect the quality of life (QOL) and life expectancy of patients with cancer [
The ethics committee of the Niigata University Graduate School of Medical and Dental Sciences approved this study (approval no., 2017-0103). A retrospective review of all 18 consecutive patients who underwent EBS for spinal metastasis between 1991 and 2015 at Niigata University Medical and Dental Hospital, Niigata, Japan was performed. No patients were lost to follow-up. The surgical indicators for spinal metastases requiring EBS were as follows: (1) a solitary metastasis existing on the spine or a spinal metastasis with radically resectable skip lesions; (2) a tumor involving less than three consecutive vertebral levels; (3) no evidence of tumors at the primary cancer site; (4) no other metastases, or if present, metastases are stable and controllable; and (5) the patient was in good general condition (Eastern Cooperative Oncology Group performance status score ≤3). Oncologists made all decisions about adjuvant chemotherapy and radiation therapy prior to and after EBS.
In the present series, three approaches for EBS were utilized: a single posterior approach, a combined anterior and posterior approach, or a simultaneous anterior and posterior approach. EBS through the single posterior approach was performed as described by Tomita et al. [
Patients were placed in the prone position, and the posterior procedure was performed. After performing both a laminectomy at the tumor-free site and pediculotomies, dissection on the lateral aspect of the vertebrae for the non-dominant side of the tumor was performed. Posterior reconstruction involved a pedicle screw system with dual rods positioned at least two vertebral levels above and below the lesion. The simultaneous anterior and posterior procedure was either performed on the same day as the posterior procedure or 2–3 weeks after the first surgery. To begin, the patient was placed in a lateral decubitus position, with the tumor-dominant side facing upward. After a standard transpleural and/or retroperitoneal approach performed through an oblique thoracolumbar skin incision re-opened the posterior wound, a 360° dissection around the tumor vertebrae was made, and discectomy or osteotomy was performed using a T-saw. Finally, the tumor vertebra was removed in an
All resected specimens were analyzed histologically to determine the surgical margin status [
All patients were followed-up with radiological examinations (X-ray, computed tomography, and/or magnetic resonance imaging), which evaluated changes in the treated segments and lesions in other sites. Local recurrence was defined as recurrence in the area where EBS was performed or in an adjacent area contiguous to the EBS area. Distant relapse was defined as a new occurrence of metastasis in an area other than the EBS or surrounding areas. The distant relapse-free period was defined as the duration between EBS and the first occurrence of distant metastasis after EBS.
Statistical analyses were performed using IBM SPSS Statistics for Windows ver. 21.0 (IBM Corp., Armonk, NY, USA). Survival rates were estimated using the Kaplan–Meier method, and group differences were evaluated using the log-rank method. For categorical variables, group differences were evaluated using the chi-square or Fisher’s exact tests. In all analyses, a
The demographics of the patients are shown in
Two patients (cases 8 and 14) had skip lesions in the spinous process and laminae of the upper thoracic spine (
In 12 patients (66.7%), 18 perioperative complications occurred. Four patients (22.2%) underwent revision surgery for perioperative complications (surgical site infection in three patients and neurological deficits due to misplaced pedicle screws in one patient). Among the three patients with postoperative neurological deficits, neurological function was partially recovered after revision surgery in one patient (case 6) and fully recovered without revision in two patients (cases 8 and 13).
Five patients (27.8%) required revision surgeries because of the mechanical failure of spinal instrumentation, including rod breakage due to pseudarthrosis (n=4), and fractures in the uppermost (n=1) or lowermost (n=1) instrumented vertebra. All patients had improved or preserved Frankel grade after EBS. Sixteen patients (88.9%) could walk independently after EBS, and two patients required walking aids (cane, n=1; walker, n=1).
In total, 10 patients had negative margins, and eight patients had positive margins (
Five patients (27.8%) experienced a local recurrence. Of these, four patients had positive margins of the resected lesion, and one patient had a negative margin with a thin (<1 mm) tumor-free layer. The incidence of local tumor recurrence was higher for patients with positive margins (4/8 patients, 50%) compared to those with negative margins (1/10 patients, 10%). However, this difference did not reach statistical significance (
In the five patients without a new occurrence of distant relapse, the tumor origin was the kidney in three patients, liver in one patient, and thymoma in one patient. The distant relapse-free 1-year, 2-year, 3-year, and 5-year survival rates after EBS were 72.2%, 50%, 38.9%, and 29.2%, respectively (
Finally, because EBS was performed from 1991 to 2015, the year in which EBS was performed was evaluated in relation to oncological outcomes. There were no significant differences according to the year EBS was performed (median [interquartile range]) between the positive (2005 [2004–2012]) and negative (2008.5 [2002.5–2013]) resection margin groups (
EBS remains one of the most challenging and technically demanding procedures for spine surgeons. In the present study, the median operative time was 12.8 hours, and the median blood loss was 2.4 L, which are comparable to the values reported in previous studies [
Previous studies have reported that intralesional resections and EBS with contaminated margins will have a negative effect on local recurrence [
In the present series, 72.2% of patients experienced newly formed distant metastases occurring after EBS. Cloyd et al. [
The limitations of the current study include its retrospective design, small sample size, and the inclusion of heterogeneous primary cancer sites. Because patients with spinal metastases requiring EBS are uncommon, future studies should involve prospective, multicenter collaborations. Moreover, although the era in which EBS was performed did not impact the surgical and oncological outcomes in this study, the 25-year span of the study was sufficiently long for cancer treatment to advance during the study period. Therefore, it should be noted that the outcomes in this study represent the minimum expected outcomes, given the present state of cancer treatment. In the future, the outcomes for EBS could be improved.
In conclusion, margin-free EBS is effective for the local control of spinal metastases. However, EBS by itself, even if margin-free, cannot completely prevent further dissemination. The present results regarding distant relapses after EBS will assist spinal surgeons in the clinical decision-making process and should be conveyed to patients and their families to help in treatment choices.
No potential conflict of interest relevant to this article was reported.
The authors wish to thank the physicians in the Niigata Spine Group who contributed to the treatment of this series of patients.
Masayuki Ohashi wrote and prepared the manuscript. Masayuki Ohashi, Kei Watanabe, Toru Hirano, Kazuhiro Hasegawa, Keiichi Katsumi, Hirokazu Shoji, and Tatsuki Mizouchi contributed to the conception and design of this study, data acquisition, and analysis and interpretation of the data. Takao Homma and Naoto Endo contributed to the study design, analysis and interpretation of data, and supervision. All authors have read, reviewed, and approved the article.
Distant relapse-free survival curves. (A) Distant relapse-free survival in 18 patients who underwent
Survival curve after distant relapse in 13 patients who experienced distant relapses after
Overall survival after
Patient demographics
Case | Age (yr) | Sex | Primary cancer site | Level | Tomita classification | Metastasis to vital organ | Metastasis to extraspinal bone | Frankel grade | Tokuhashi score |
---|---|---|---|---|---|---|---|---|---|
1 | 55 | F | Breast | T6 | 2 | No | No | E | 13 |
2 | 40 | F | Thyroid | T12 | 5 | No | No | D | 14 |
3 | 53 | M | Kidney | T10, 11 | 6 | No | No | C | 9 |
4 | 45 | F | Salivary gland | T7 | 5 | Lung | No | D | 10 |
5 | 54 | M | Kidney | T6 | 5 | No | No | D | 12 |
6 | 73 | M | Kidney | T10 | 6 | No | No | D | 12 |
7 | 73 | M | Kidney | L3 | 6 | Lung | No | D | 10 |
8 | 77 | M | Liver | T4, 8, 9, 10 | 7 | No | No | E | 9 |
9 | 70 | M | Kidney | L1 | 6 | No | No | C | 10 |
10 | 68 | M | Kidney | T9 | 4 | No | No | E | 11 |
11 | 62 | M | Liver | T12 | 4 | No | No | E | 11 |
12 | 62 | F | Thyroid | L3 | 6 | No | No | D | 14 |
13 | 60 | M | Thyroid | L5 | 4 | No | Ilium | C | 11 |
14 | 65 | F | Pulmonary epithelioid hemangioendothelioma | T2, 12, L1 | 7 | No | Ilium, femur | D | 7 |
15 | 65 | F | Thymoma | T12 | 5 | No | No | D | 10 |
16 | 47 | M | Liver | T12 | 1 | No | No | D | 9 |
17 | 59 | F | Kidney | T11, 12 | 5 | No | No | E | 13 |
18 | 62 | F | Thyroid | L2 | 5 | No | No | D | 14 |
F, female; M, male.
Surgical procedures and results
Case | Date of EBS (yr) | Approach | Resected area |
Time (min) | Intraoperative blood loss (g) | Adjuvant therapy | Perioperative complications |
Frankel grade |
|
---|---|---|---|---|---|---|---|---|---|
Intraoperative | Postoperative | ||||||||
1 | 1991 | C-AP | T6 | 715 | 4,300 | None | None | Pneumonia | E |
2 | 1995 | C-AP | T12 | 680 | 2,625 | C+RAI | None | None | E |
3 | 2001 | C-AP | T9, 10, 11 | 1,073 | 3,478 | None | None | Paralytic ileus | D |
4 | 2001 | P | T (6), 7, (8) | 1,067 | 410 | R | None | Pneumonia | D |
5 | 2004 | C-AP | T6, (7) | 713 | 1,744 | None | None | None | E |
6 | 2004 | S-AP | T10, (11) | 1,015 | 18,070 | None | None | ND, UTI | D |
7 | 2005 | S-AP | L3 | 922 | 3,891 | C | None | None | E |
8 | 2007 | S-AP | T8, 9, 10 | 1,110 | 2,125 | C | None | ND, SSI | E |
9 | 2008 | S-AP | (T12), L1 | 834 | 8,245 | C | Durotomy | SSI | D |
10 | 2009 | S-AP | T9 | 627 | 1,670 | C | None | None | E |
11 | 2010 | S-AP | T12 | 755 | 1,235 | None | None | None | E |
12 | 2011 | S-AP | L (2), 3, (4) | 632 | 7,512 | RAI | Durotomy | None | E |
13 | 2012 | S-AP | L5 | 881 | 3,215 | R | Vena cava tear | ND, DVT | E |
14 | 2013 | S-AP | T12, L1 | 780 | 1,715 | None | Durotomy | None | D |
15 | 2013 | S-AP | T12 | 609 | 1,790 | None | Durotomy | None | E |
16 | 2014 | P | T12 | 447 | 1,180 | None | None | None | E |
17 | 2014 | S-AP | T11, 12 | 783 | 330 | C | None | SSI | E |
18 | 2015 | S-AP | L (1), 2 | 712 | 3,245 | None | Aorta and vena cava tear | SSI | D |
EBS,
Parentheses indicate resections coupled with part of adjacent vertebrae.
Frankel grade indicates the highest grade after EBS.
Oncological outcomes after EBS
Case | Surgical margin | Local recurrence |
Distant relapse after EBS |
Prognosis | Follow-up (mo) | ||||
---|---|---|---|---|---|---|---|---|---|
Yes/no | Duration after EBS (mo) | Treatment | Region | Duration after EBS (mo) | Treatment | ||||
1 | - | No | Bone | 15 | C | DOD | 24 | ||
2 | - | No | Neck | 228 | R | AWD | 266 | ||
3 | + | No | Bone | 28 | S+R | DOD | 48 | ||
4 | - | No | Bone, choroid plexus, eye | 1 | BSC | DOD | 9 | ||
5 | + | Yes | 46 | S+R | Bone | 46 | C+R | DOD | 72 |
6 | + | No | None | DOC | 80 | ||||
7 | + | Yes | 13 | R | None | DOD | 39 | ||
8 | - | No | None | NED | 120 | ||||
9 | - | No | Lung, bone, lymph nodes | 7 | BSC | DOD | 10 | ||
10 | - | No | Bone, lung, kidney, pancreas | 36 | C+R | DOD | 97 | ||
11 | - | Yes | 6 | S+R+C | Lung, lymph nodes | 6 | S+C | DOD | 14 |
12 | + | No | Bone | 18 | R | AWD | 72 | ||
13 | + | Yes | 53 | BSC | Lung, bone, thyroid | 7 | S+C+RAI+R | DOD | 55 |
14 | + | No | Bone | 6 | BSC | DOD | 20 | ||
15 | + | Yes | 12 | S | None | AWD | 42 | ||
16 | - | No | Bone | 18 | S | AWD | 36 | ||
17 | - | No | None | NED | 36 | ||||
18 | - | No | Lung | 21 | RAI | AWD | 24 |
EBS,