Abstract
Study Design
A multicenter retrospective cohort study using prospectively collected data.
Objectives
Radiotherapy (RT) is the standard treatment for spinal metastases; however, the optimal timing of RT in patients requiring surgery remains unclear. This study compared the clinical outcomes of palliative surgery according to RT timing.
Methods
Among 413 patients screened across 35 centers, 146 patients with spinal metastases limited to the spine who underwent palliative surgery were included. Patients were classified into three groups based on RT timing: preoperative RT, postoperative RT, and no RT. Short-term outcomes were compared among the three groups.
Results
Of the 146 patients (preoperative RT: n = 42; postoperative RT: n = 59; no RT: n = 45), baseline characteristics and postoperative functional outcomes were comparable between the postoperative RT and no RT groups. Preoperative opioid use was significantly more frequent in the preoperative RT group. Postoperative complications were more common in the preoperative RT group. Functional outcomes improved in all groups; however, greater improvements in pain and numbness were observed in the nonpreoperative RT group than in the preoperative RT group, with a significant difference noted in numbness improvement.
Conclusions
Postoperative recovery after palliative surgery was largely comparable among the three groups. Although greater improvements in pain and numbness were observed in patients who did not receive preoperative RT, the clinical impact of preoperative RT in patients with mechanical instability remains uncertain. Postoperative wound complications were more frequent in the preoperative RT group, but these findings should be interpreted with cautiously given the limited number of events.
Keywords: spine metastasis, preoperative radiation therapy, clinical outcomes, complications, preoperative opioid administration
Introduction
Recent advances in cancer treatment have contributed to increased life expectancy; however, the incidence rates of bone and spinal cord metastases have increased.1-3 The spine is the most common location for bone metastasis. Approximately 50% of cases of spinal metastases require some treatment, such as chemotherapy or radiotherapy (RT), and 5-10% require surgical intervention. 4 RT improves the complete response rate for pain in patients with painful spinal metastases. 5 Spinal stereotactic ablative RT is an effective treatment option for well-selected patients with spinal metastases, as it achieves high local tumor control rates with moderate side effect rates. 6 Surgical therapy has also been reported to improve pain and health-related quality of life and may even improve survival by maintaining the ability to walk.7-9 Moreover, combination therapy with palliative surgery and RT after surgery for symptomatic spinal metastases is more effective.10-12 The incidence rates of wound complications such as surgical site infection (SSI) and wound dehiscence have been reported as complications of combined surgery and RT, especially before surgery.13-15 On the other hand, if spinal surgery is performed first, metallic spinal instrumentation can disturb RT beams, thus leading to changes in distribution. 16
In palliative surgery for patients with only spinal metastases, it is unclear how a history of RT affects clinical outcomes. This study aimed to compare the complications and clinical outcomes of palliative surgery between patients with only spinal metastasis who did and who did not receive preoperative RT.
Materials and Methods
Study Design and Population
This multicenter cohort study was conducted between October 2018 and March 2022. Patients who were scheduled for surgical treatment of metastatic spinal tumors, those aged ≥20 years, and those who provided consent to participate were included. Those aged <20 years and those with difficulty completing the questionnaire were excluded. Patients who consented to this study and underwent surgical treatment for metastatic spinal tumors were included. A total of 413 patients from 35 facilities were included, and 146 patients with only spinal metastases who underwent palliative surgery were included in the study. The exclusion criteria were as follows: metastases outside the spine, total en bloc spondylectomy, balloon kyphoplasty, or a Spinal Instability Neoplastic Score (SINS) ≤ 6 (Figure 1). We compared postoperative outcomes and complications among patients who received RT before surgery (preoperative RT), after surgery (postoperative RT), or without RT (no RT) for the surgical treatment of spinal metastases. Although the data were prospectively collected in a multicenter registry, treatment decisions—including the timing of radiotherapy—were made at the discretion of the treating physicians at each institution. Therefore, this study is considered a retrospective analysis of prospectively collected data.
Figure 1.
Flowchart of patient selection. This multicenter study, conducted between 2018 and 2021, enrolled 413 patients from 35 institutions who underwent surgery for spinal metastases. Exclusion criteria included metastases outside the spine, total en bloc spondylectomy, balloon kyphoplasty, and spinal instability neoplastic Score ≤6. A total of 146 patients who underwent palliative surgery for spinal metastases were included in the analysis. Patients were first categorized into three groups based on the timing of radiotherapy: Preoperative RT (n = 42), Postoperative RT (n = 59), and No RT (n = 45)
Ethical Considerations
Ethical approval for this registry study was obtained from the institutional review boards of all the participating centers. Informed written consent was obtained from all participants prior to enrollment to ensure compliance with ethical guidelines and to ensure the integrity of the research process. For patients who were unable to provide consent because of incapacity, written informed consent was obtained from their legal representative. This study was conducted in accordance with the ethical standards of the 1964 Declaration of Helsinki.
Assessment
The following patient characteristics were assessed: age, sex, surgical procedure, revised Tokuhashi score, 17 Tomita score, 18 SINS, 19 Epidural Spinal Cord Compression (ESCC) scale score, 20 Charlson Comorbidity Index, 21 pre- or postoperative chemotherapy, pre- or postoperative opioid use, amount of radiation, emergency operation time, blood loss, intraoperative and postoperative complications, and wound-related complications, including surgical site infection (SSI). Patients’ ADLs and QOL were evaluated using the Eastern Cooperative Oncology Group (ECOG) performance status (PS), the Barthel Index, and the EuroQol 5 Dimensions 5-level (EQ-5D-5 L), which includes the face scale and the visual analog scale (VAS), at one and six months post-operatively. Pain and numbness were assessed using VAS and face scale-based patient-reported measures. While these scales are inherently subjective, they are widely accepted and validated tools for evaluating pain and numbness intensity in clinical spine research. There was no standardized protocol dictating the timing or sequence of chemotherapy, radiotherapy, surgery, or analgesic use across the participating centers. Treatment decisions were made at the discretion of the treating spine surgeons and multidisciplinary teams, reflecting institutional practice patterns and individual patient status.
Grouping and Baseline Matching
Patients were first classified into three groups according to the timing of radiotherapy: preoperative RT, postoperative RT, and no RT. The primary analyses were performed using this three-group comparison. In addition, to explore potential baseline differences between patients who received preoperative RT and those who did not (postoperative RT + no RT), a propensity score–matched analysis was conducted. Propensity scores were estimated using logistic regression including age, sex, and preoperative opioid use as covariates. Patients were matched at a 1:1 ratio using a nearest-neighbor matching algorithm with a caliper width of 0.2 standard deviations of the logit of the propensity score.
Given the heterogeneity of clinical decision-making in this registry-based study, the propensity score analyses were conducted for exploratory purposes only and were not used as the primary basis for interpretation. Accordingly, the results of the propensity score–matched analyses are presented in the Supplemental Material.
Statistical Analysis
Continuous variables are presented as the median (interquartile range 25-75% quartile), and categorical variables are presented as frequencies and percentages. The Wilcoxon rank-sum test and Fisher’s exact test were used to calculate the P values as indices of the differences in patient characteristics between those with and without preoperative RT. For comparisons among the three groups (preoperative RT, postoperative RT, and no RT), continuous variables were analyzed using the Kruskal–Wallis test, and categorical variables were analyzed using the chi-square test. P values less than 0.05 were considered to indicate statistical significance. Kaplan–Meier survival analysis was conducted to compare overall survival among the preoperative RT group, the postoperative RT group and the no RT group. The log-rank test was used to assess statistical significance. The software used for the statistical analyses was JMP (version 18.0; SAS Institute, NC, USA).
Results
Patient Characteristics
The median age was 69.0 years, with 92 males. The preoperative RT group comprised 42 patients, the postoperative RT group 59, and the no-RT group 45. Baseline characteristics of each group are presented in Tables 1 and 2. The Preoperative RT group showed significantly higher rates of pre- and postoperative opioid administration (P < 0.001). Postoperative Chemotherapy was More Frequently administered in both the postoperative RT and No RT groups (P < 0.05) (Table 1). In this three-group comparison, baseline demographic characteristics were generally comparable; however, significant differences were observed in the Revised Tokuhashi score and the Charlson Comorbidity Index (Table 1) Since the Postoperative RT and No RT groups showed comparable baseline characteristics and postoperative outcomes, they were combined into a single Non-Preoperative RT group (n = 104). A subsequent two-group comparison was then performed between the Preoperative RT group (n = 42) and the Non Preoperative RT group.
Table 1.
Demographic Characteristics Among the Pre-RT, Post-RT, and No-RT Groups
| Variables | Preoperative radiotherapy group, n (%) (N = 42) | Postoperative radiotherapy group, n (%) (N = 59) | No radiotherapy group, n (%) (N = 45) | P Value |
|---|---|---|---|---|
| Age | 67.5 (56.8-75.3) | 71.0 (64.0-74.0) | 69.0 (59.0-74.0) | 0.43 |
| Male | 29 (69.1) | 37 (62.7) | 26 (57.8) | 0.55 |
| Breast Ca | 4 (9.5) | 8 (13.6) | 5 (11.1) | 0.82 |
| Lung Ca | 7 (16.7) | 12 (20.3) | 13 (28.9) | 0.36 |
| Prostate Ca | 3 (7.1) | 2 (3.4) | 2 (4.4) | 0.68 |
| Hematologic malignancies | 1 (2.4) | 3 (5.1) | 6 (13.3) | 0.10 |
| ESCC 0 | 0 (0) | 3 (5.1) | 0 (0) | 0.09 |
| ESCC 1a-c | 6 (14.3) | 18 (30.5) | 6 (13.3) | |
| ESCC 2 | 14 (33.3) | 18 (30.5) | 19 (42.2) | |
| ESCC 3 | 19 (45.2) | 20 (33.9) | 20 (44.4) | |
| Height (cm) | 165.0 (156.8-169.6) | 162.0 (155.0-167.0) | 160.1 (151.0-169.3) | 0.35 |
| Weight (kg) | 57.4 (49.5-66.3) | 57.0 (49.8-65.0) | 56.4 (48.9-65.5) | 0.99 |
| Frankel A | 1 (2.4) | 2 (3.4) | 2 (4.4) | 0.45 |
| Frankel B | 1 (2.4) | 1 (1.7) | 3 (6.7) | |
| Frankel C | 11 (26.2) | 18 (30.5) | 17 (37.8) | |
| Frankel D | 17 (40.5) | 16 (27.1) | 8 (17.8) | |
| Frankel E | 12 (28.6) | 22 (37.3) | 15 (33.3) | |
| Preoperative chemotherapy | 21 (50) | 16 (27.1) | 15 (33.3) | 0.06 |
| Postoperative chemotherapy | 15 (35.7) | 35(59.3) | 26 (57.8) | <0.05 |
| Postoperative radiation | 14 (33.3) | 59 (100.0) | 0 (0) | <0.0001 |
| Preoperative opioid use | 29 (69.1) | 15 (25.4) | 11 (24.4) | <0.0001 |
| Postoperative opioid use | 28 (66.7) | 22 (37.9) | 14 (31.1) | <0.005 |
| Tomita score | 6 (4-7) | 5 (3-7) | 5 (3-7) | 0.18 |
| Revised Tokuhashi score | 8 (7-10.3) | 9 (7-12) | 8 (5.5-10) | <0.05 |
| SINS | 11 (9.8-13) | 11 (9-12) | 11 (9-13) | 0.29 |
| Spinal metastasis = 1 | 14 (33.3) | 21 (35.6) | 11 (24.4) | 0.46 |
| Charlson comorbidity index | 6 (6-7) | 7 (6-8) | 6 (6-7) | <0.05 |
Notes. ESCC: Epidural Spinal Cord Compression, SINS: Spinal Instability Neoplastic Score.
Median (25% quartile–75% quartile) N (%).
Kruskal–Wallis test.
Chi-square test.
Table 2.
Surgical Details and Complications Among the Pre-RT, Post-RT, and No-RT Groups
| Variables | Preoperative radiotherapy group, n (%) (N = 42) | Postoperative radiotherapy group, n (%) (N = 59) | No radiotherapy group, n (%) (N = 45) | P Value |
|---|---|---|---|---|
| Emergency | 18 (42.9) | 26 (44.1) | 24 (53.3) | 0.55 |
| Operation time, (min) | 173.0 (115.0-240.0) | 180.0 (145.0-232.0) | 201.0 (143.5-240.5) | 0.57 |
| Blood loss, (g) | 165.0 (65.3-436.3) | 220.0 (100.0-380.0) | 212.5 (96.3-450.0) | 0.64 |
| Posterior stabilization with decompression | 24 (57.1) | 42 (71.2) | 33 (73.3) | 0.21 |
| Minimally invasive stabilization without decompresion | 12 (28.6) | 6 (10.2) | 4 (8.9) | <0.05 |
| Open posterior stabilization without decompression | 6 (14.3) | 11 (18.6) | 8 (17.8) | 0.84 |
| Intraoperative complications | 1 (2.4) | 6 (10.2) | 1 (2.2) | 0.12 |
| Intraoperative dura tear | 1 (2.4) | 4 (6.8) | 0 (0) | 0.15 |
| Perioperative complications | 6 (14.3) | 11 (18.6) | 5 (11.1) | 0.56 |
| Perioperative wound-related complications | 2 (4.8) | 2 (3.4) | 0 (0) | 0.37 |
| Postoperative complications | 10 (23.8) | 7 (11.9) | 3 (6.7) | 0.08 |
| Postoperative wound related complications | 4 (9.5) | 1 (1.7) | 0 (0) | <0.05 |
| Postoperative worsening of neurological symptoms | 5 (11.9) | 3 (5.1) | 1 (2.2) | 0.16 |
Notes: Postoperative complications (within 6 months after the operation).
Multivariate logistic regression analyses revealed that preoperative opioid use was a significant factor associated with receiving preoperative RT. The results of the propensity score–matched analyses are presented in the Supplemental Material. In the matched cohort (37 pairs), the baseline characteristics were well balanced between the preoperative RT group and the non–preoperative RT group (Supplemental Table 1). The preoperative RT group received a median radiation dose of 30 Gy.
Surgical Outcomes and Complications
The surgical details and complication rates of the three groups are summarized in Table 2. The operation time, blood loss, and proportion of emergency procedures did not significantly differ among the three groups.
The use of minimally invasive posterior stabilization without decompression was significantly more common in the preoperative RT group than in the other groups (P < 0.05). In contrast, open posterior stabilization without decompression was distributed equally across the three groups.
With respect to complications, the incidence rates of intraoperative and perioperative complications were comparable. However, the rate of wound-related complications was significantly greater in the preoperative RT group (9.5% vs 1.7% vs 0%, P < 0.05) (Table 2).
Functional and Quality of Life Outcomes, VAS and Face Scale
Preoperative functional scores (Barthel Index, EQ5D-5 L, VAS, and Face Scale) were comparable among the three groups. At 1 and 6 months post-surgery, no significant differences were observed in the Barthel Index or EQ5D-5 L scores (Tables 3, and 4). However, pain-related improvement was greater in the postoperative RT group and non-RT group. Notably, the change in the face scale score was also greater in the postoperative RT group and non-RT group (ΔFace scale score of 6 M: 0 vs −4 vs −3, P < 0.01) (Table 4). At 6 months, compared with the postoperative RT (−40 mm) and non-RT (−38.5 mm) groups, the preoperative RT group exhibited a greater improvement in the VAS pain score (median change: −10 mm) (P = 0.08) (Table 4). After PS matching, the ΔVAS and ΔFace Scale scores were significantly greater in the nonpreoperative RT group (Supplemental Table 2).
Table 3.
Comparison of Postoperative Outcomes Among the Pre-RT, Post-RT, and No-RT Groups
| Preoperative radiotherapy group (N = 42) | Postoperative radiotherapy group (N = 59) | No radiotherapy group (N = 45) | P Value | |
|---|---|---|---|---|
| Barthel index | ||||
| Pre | 65 (50-82.5) | 60 (46.3-88.8) | 50.0 (30.0-85.0) | 0.75 |
| 1 M post-operation | 85 (61.3-100) | 87.5 (68.8-100) | 80.0 (55.0-100) | 0.88 |
| 6 M post-operation | 95 (67.5-100) | 100 (76.3-100) | 100 (88.8-100) | 0.42 |
| EQ5D-5 L | ||||
| Pre | 0.25 (0.13-0.47) | 0.26 (0.12-0.46) | 0.21 (0.10-0.64) | 0.80 |
| 1 M post-operation | 0.47 (0.33-0.71) | 0.62 (0.38-0.75) | 0.54 (0.33-0.71) | 0.51 |
| 6 M post-operation | 0.65 (0.42-0.81) | 0.68 (0.47-0.83) | 0.68 (0.58-0.88) | 0.59 |
| VAS | ||||
| Pre | 50 (22.3-80.8) | 70 (50.0-85.0) | 70 (48.0-82.5) | 0.20 |
| 1 M post-operation | 27.5 (4.3-50) | 27.5 (10-47) | 23.0 (12.3-41.3) | 0.99 |
| 6 M post-operation | 15 (0-49.5) | 20 (5-40) | 15.5 (0-47.5) | 0.89 |
| Face scale | ||||
| Pre | 6 (4-8) | 6 (4-8) | 8 (4-8) | 0.17 |
| 1 M post-operation | 2 (2-4) | 2 (2-4) | 4 (2-4) | 0.41 |
| 6 M post-operation | 4 (2-6) | 3 (2-4) | 2 (0-4) | 0.24 |
Notes: Pre: preoperative values; 1 M post-operative: values at 1 month; 6 M post-operative: values at 6 months.
Table 4.
Changes in Patient-Reported Outcomes Among the Pre-RT, Post-RT, and No-RT Groups (Δ Values)
| Preoperative radiotherapy group (N = 42) | Postoperative radiotherapy group (N = 59) | No radiotherapy group (N = 45) | P Value | |
|---|---|---|---|---|
| ΔBarthel index | ||||
| 1 M | 15 (0-33.8) | 15 (0-32.5) | 12.5 (0-30) | 0.96 |
| 6 M | 10 (−5-40) | 12.5 (0-38.8) | 15 (0-50) | 0.55 |
| ΔEQ5D-5 L | ||||
| 1 M | 0.19 (0.05-0.37) | 0.23 (0.04-0.42) | 0.18 (0.07-0.31) | 0.69 |
| 6 M | 0.22 (0.03-0.48) | 0.25 (0.05-0.50) | 0.34 (−0.03-0.62) | 0.80 |
| ΔVAS | ||||
| 1 M | −20 (−44-0) | −31.5 (−53 to −13) | −40 (−60 to −4.5) | 0.14 |
| 6 M | −10 (−48-25.5) | −40 (−60 to −15.5) | −38.5 (−60 to −18.3) | 0.08 |
| ΔFace scale | ||||
| 1 M | −2 (−4-0) | −2 (−4-0) | −4 (−6-0) | 0.55 |
| 6 M | 0 (−2.5-2.5) | −4 (−6 to −0.5) | −3 (−6 to −2) | <0.01 |
Notes: 1 M: values at 1 month post-operatively, 6 M: values at 6 months post-operatively.
Survival Outcomes
With respect to palliative surgery, preoperative RT did not affect postoperative survival (Figure 2).
Figure 2.
Kaplan–Meier survival curves after surgery for preoperative RT group (n = 42), postoperative RT group (n = 59), and No RT group (n = 45). The log-rank test revealed no significant difference in overall survival among the three groups (P = 0.31). The numbers at risk at baseline and at follow-up time points (91, 183, 274, and 365 days) are shown below each survival curve
Discussion
This multicenter study investigated the impact of a history of RT on the clinical outcomes of palliative surgery in patients with only spinal metastases. This is the first multicenter, cohort study to analyze the clinical outcomes and complications of this population while controlling for confounding factors, such as extraspinal metastases. We found that preoperative RT was associated with less improvement in postoperative pain and a trend toward more wound-related complications, despite similar functional recovery and overall survival.
Effect of Radiotherapy on Metastasis
RT is effective for pain relief in patients with metastatic spinal tumors22,23 and for tumor control. 24 An RT dose of approximately 25 Gy is safe, with minimal negative effects on quality of life and a high probability of tumor control. 25 In this study, approximately 30 Gy was used for irradiation. In the group that received preoperative RT, a greater proportion of patients used opioids preoperatively and continued to use opioids postoperatively. In contrast, postoperative chemotherapy and postoperative RT were significantly more common in the nonpreoperative RT group. This finding was considered because the cancer had already been diagnosed and treated by other departments prior to surgery. The higher incidence of postoperative chemotherapy and RT in the nonpreoperative RT group may be partly explained by the fact that the diagnosis was made at the time of surgery.
Surgery and Radiotherapy
Compared with RT alone, surgical intervention results in superior neurological outcomes in patients with malignant spinal cord compression. 26 The combination of surgery and radiation is important for neurological preservation. 27 Posterior spinal fusion with decompression effectively relieves pain and improves neurological function in patients with spinal metastases. 28 In this study, 69% of the patients underwent posterior decompression and stabilization surgery.
Surgery was indicated for patients with rapid neurological decline or spinal instability, regardless of tumor radiosensitivity. In high-grade, symptomatic patients, especially those with radioresistant tumors, surgery followed by radiation is superior to radiation alone.29-32 Notably, our study population consisted exclusively of patients with a SINS ≥7, reflecting significant mechanical instability. While upfront RT may be appropriate for patients with stable, intralesional metastases, surgical stabilization was indicated in all the patients included in this cohort because of structural compromise. In patients with spinal metastases causing epidural spinal cord compression, upfront surgical decompression and stabilization are often recommended to prevent neurological deterioration due to post-RT swelling, especially in radiosensitive tumors. 33 This has been reflected in our cohort, where surgical intervention was performed in all patients, although the timing of radiotherapy relative to surgery varied depending on institutional protocols and clinical presentation. Accordingly, surgery was performed in all patients, and those treated with radiation alone were excluded.
For radiosensitive tumors (eg, myeloma, breast, prostate), RT alone is effective, particularly in patients without severe neurological symptoms or instability. For radioresistant tumors, combination therapy (surgery plus radiation) is preferred.31,34 In low-grade or asymptomatic cases, RT is typically the primary treatment, regardless of radiosensitivity. Surgery is reserved for patients with progression or instability.32,34 In this study, there was no significant difference in cancer type distribution among the three groups. The absence of a difference in postoperative blood loss among the three groups may also be attributed to the lack of significant variation in cancer type. In patients who required palliative surgery, as in this study, significant improvements were observed in the Barthel index, EQ-5D-5 L score, VAS score, and face scale score at both 1 month and 6 months post-surgery compared with the preoperative values, with no significant differences among the three groups. The significantly lower degree of pain improvement in the preoperative RT group than in the nonpreoperative RT group may be attributed to the fact that pain had already improved because of the RT itself, potentially reducing the additional pain relief effect achieved by surgery. In other words, preoperative RT may alleviate pain before surgery, but it may also limit the extent of further symptom improvement achievable through surgical intervention alone.
Complications of Radiotherapy
Previous reports35,36 suggest that spinal radiation may cause epidural fibrosis, tissue fragility, and adhesions, thereby increasing the degree of technical difficulty of surgery,15,37 potentially predisposing patients to incidental durotomy during malignant spinal tumor surgery. 38 In the present study, there was no significant difference in the incidence of intraoperative dural injury between the two groups. This may be attributed to the palliative nature of decompression and the reduced impact of prior RT.
However, previous studies reported a significantly greater incidence of wound-related complications in patients who received preoperative RT, 13 and a similar trend was observed in the present study. Postoperative wound-related complications were more common in the preoperative RT group, which is consistent with the findings of previous reports. Although the Pre-RT group received more frequent preoperative chemotherapy, these treatments were routinely suspended before surgery. Moreover, preoperative inflammatory marker levels, such as WBC and neutrophil counts, did not significantly differ across groups (Supplemental Table 3), suggesting that baseline immune status was comparable and unlikely to explain the higher wound complication rate in the Pre-RT group. Although preoperative inflammatory marker levels, including white blood cell and neutrophil counts, were comparable among the three groups, this does not exclude the potential impact of radiotherapy on local tissue conditions. Preoperative radiation may impair wound healing through local soft tissue damage, reduced vascularity, and radiation-induced fibrosis, which are not reflected in systemic inflammatory markers. These local effects may predispose patients to wound-related complications, even in the absence of systemic immune suppression.
In the present study, advances in minimally invasive surgical techniques and perioperative management may have mitigated the impact of radiotherapy-related complications that have been reported in previous studies. 39 Indeed, the proportion of minimally invasive procedures without decompression was significantly greater in the preoperative RT group. Nevertheless, postoperative wound-related complications were more frequently observed in this group, whereas intraoperative complication rates were comparable between groups. These findings suggest that the adverse effects of preoperative radiotherapy on wound healing may not be fully offset by reduced surgical invasiveness alone, likely reflecting persistent radiation-induced local tissue changes.
Our cohort also showed a higher rate of preoperative opioid use in the preoperative RT group, suggesting more severe pain or disease burden at presentation. This finding is consistent with prior reports indicating that higher opioid requirements are associated with poorer overall survival. 40 However, in the present study, no significant differences in overall survival were observed among the three radiotherapy timing groups. This discrepancy may be partly explained by the fact that our cohort was limited to patients who underwent surgical treatment for spinal metastases, in whom surgical intervention may have mitigated the prognostic impact of pain-related factors, as well as by the complex, multifactorial clinical decision-making that influenced treatment selection.
Moreover, a recent propensity score-matched study of total en bloc spondylectomy for previously irradiated spinal metastases reported higher complication and local recurrence rates in irradiated patients, despite matched baseline characteristics. 15 While the surgical invasiveness and treatment goals differ from those in our study, both investigations highlight that prior irradiation can adversely affect surgical outcomes. Our multicenter design provides complementary evidence that even in a palliative setting, preoperative RT may influence postoperative recovery—particularly pain improvement—although its impact on complication rates may be attenuated with contemporary techniques.
Strengths and Limitations
However, several limitations should be acknowledged. First, although the cohort size was sufficient for group comparison, the number of patients in the preoperative RT group was relatively small, potentially limiting the statistical power. Second, owing to the observational nature of the study, the influence of unmeasured confounding variables cannot be excluded. Third, the modality, dose, fractionation, and timing of radiotherapy were not standardized across institutions and were inconsistently recorded, making it impossible to evaluate these parameters as controlled variables. This heterogeneity, inherent to the multicenter design, may have introduced treatment variability. Fourth, in this study, we did not evaluate the interval between RT and surgery, although the optimal interval between RT and surgery is considered two weeks (minimum of seven days). 14 Fifth, the proportion of minimally invasive stabilization procedures without decompression was greater in the preoperative RT group, representing a potential confounding factor; therefore, the observed intergroup differences cannot be attributed solely to the timing of radiotherapy. However, our previous multicenter study 41 demonstrated that, among patients who primarily presented with spinal instability and pain, the addition of decompression to posterior stabilization did not lead to significantly greater postoperative neurological improvement within 6 months. Finally, differences in postoperative chemotherapy among the groups may have influenced the short-term outcomes, and the follow-up period was limited to 6 months. Long-term tumor control and late complications beyond this interval were not assessed.
The primary strength of this study lies in its multicenter design and strict inclusion criteria, which focus solely on patients with spinal metastasis and mechanical instability (SINS ≥7). This homogeneity enhances the internal validity of our findings and allows for a clearer interpretation of treatment effects. Prospective data collection and the use of multiple validated outcome measures—including functional, quality-of-life, and neurological scales—further strengthen the reliability of the findings. Although our primary analyses included a limited number of covariates, additional exploratory analyses incorporating a broader range of clinical factors yielded consistent results, supporting the robustness of our conclusions
Conclusion
The overall clinical outcomes, including pain relief and functional improvement, were comparable regardless of RT history. Although the degree of improvement in pain and numbness was lower in the preoperative radiation group, these findings should be interpreted with caution. In patients with mechanical instability requiring surgery, the impact of preoperative radiotherapy on postoperative symptom improvement remains uncertain, and further studies are needed to clarify its clinical significance. In addition, postoperative wound complications were more frequently observed in the preoperative RT group; however, given the limited number of events, these findings should be interpreted with caution.
Supplemental Material
Supplemental Material for Clinical Outcomes of Patients Who Underwent Palliative Surgery for Spinal Metastases With and Without a History of Radiation: A Multicenter Registry Study in Global Spine Journal.
Acknowledgments
We would like to thank Dr Kazuhide Inage for administrative assistance. We express our gratitude to Dr Katsumi Harimaya, Dr Hideki Murakami, Dr Yasuchika Aoki, Dr Seiji Okada, and Dr Kei Ando for their efforts in managing the Japan Association of Spine Surgeons with Ambition (JASA). Additionally, we thank all JASA members for their contributions to data collection. We recognize the assistance of ChatGPT-4o, an AI language model developed by OpenAI, in editing and proofreading the English content of this manuscript. However, the final version of the paper and full responsibility for its content remain solely with the human authors.
Author Contributions: I.K., H. T., and N. T. led the drafting of this manuscript in collaboration with other authors. I.K., H. T., H. S., and H. Sa. Participated in the data analysis. Y.S., A.S., H.Ter., T.S., K.K., Y.K., M.I., M.P., Y.T., T.F., K.M., E.S., H.I., A.K., T.I., H.M., H.N., S.W., K.A., N.Ta., K.N., H.Saw., K.Ma., M.F., H.Su., H.F., T.O., T.Hi., B.O., K.Ko., K.U., H.M., S.T., K.H., C.I., D.Y., A.H., S.S., Y.G., M.M., K.W., T.N., T.K., H.Nak., N.N., S.K., S.I., K.Wat., G.I. and T.Fu. Contributed to the collection of the clinical data. All the authors have read and approved the final manuscript.
Funding: The authors received no financial support for the research, authorship, and/or publication of this article.
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Supplemental Material: Supplemental material for this article is available online.
ORCID iDs
Hiroyuki Tominaga https://orcid.org/0000-0001-8701-2343
Hidetomi Terai https://orcid.org/0000-0001-9183-3363
Masayuki Ishihara https://orcid.org/0000-0001-6062-6767
Kousei Miura https://orcid.org/0000-0001-7826-184X
Hirokazu Inoue https://orcid.org/0000-0001-8420-6724
Atsushi Kimura https://orcid.org/0000-0003-4948-1792
Hideaki Nakajima https://orcid.org/0000-0001-8260-7401
Koji Akeda https://orcid.org/0000-0001-9468-9387
Hidenori Suzuki https://orcid.org/0000-0002-3156-0591
Takashi Hirai https://orcid.org/0000-0001-6200-0100
Ko Hashimoto https://orcid.org/0000-0002-9644-054X
Takashi Kaito https://orcid.org/0000-0003-4882-2997
Hiroaki Nakashima https://orcid.org/0000-0002-0039-9678
Narihito Nagoshi https://orcid.org/0000-0001-8267-5789
Shiro Imagama https://orcid.org/0000-0002-6951-8575
Gen Inoue https://orcid.org/0000-0001-6500-9004
Takeo Furuya https://orcid.org/0000-0002-5378-940X
Ethical Considerations
Ethical approval for this prospective registry study was initiated by the Japan Association of Spine Surgeons with Ambition and obtained from the Institutional Review Board of Kagoshima University (approval no: 180080).
Consent to Participate
Written informed consent was obtained from all the participants, and the study was conducted in accordance with the Declaration of Helsinki.
Consent for Publication
Not applicable, as this study does not contain any person’s identifiable data.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.*
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplemental Material for Clinical Outcomes of Patients Who Underwent Palliative Surgery for Spinal Metastases With and Without a History of Radiation: A Multicenter Registry Study in Global Spine Journal.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.*