How to select a treatment method for patients with potentially unstable metastatic vertebrae (spinal instability neoplastic score 7–12): a systematic review

Search strategy

We conducted a systematic literature search following the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines [15]. A PRISMA flow diagram illustrating the study identification, screening, eligibility, and inclusion process is presented in Fig. 1, which also details the search strings used. The literature search was conducted in April 2025, encompassing studies published up to and including 2024 across multiple databases: PubMed (2.365 results), Scopus (1,874 results), and Embase (2,268 results). A broad search strategy was employed to ensure comprehensive coverage of relevant literature.

Fig. 1

Search strategy: PubMed and Embase: (Metastatic OR Neoplastic) AND (Spinal OR Spine) AND (Instability OR SINS OR Fractures, Compression) AND (Spinal fusion OR Surgery OR radiotherapy). Scopus: ((metastatic OR neoplastic) AND (spinal OR spine) AND (instability OR sins OR fracture) AND (fusion OR surgery OR radiotherapy)). SINS, spinal instability neoplastic score.

After removing duplicates, studies were screened based on the following predefined inclusion criteria: (1) original research articles; (2) English-language full-text availability; (3) patients with spinal metastases and SINSs of 7–12; (4) evaluation of clinical outcomes following surgery and/or radiotherapy. Potentially relevant articles identified through title and abstract screening underwent full-text review. Studies meeting the inclusion criteria were included in the analysis.

The included studies were categorized into two groups. Group A comprised A-class literature comparing the effects of surgery and radiotherapy for patients with SINSs of 7–12. Group B comprised B-class literature that evaluated the effects of either surgery or radiotherapy for patients with SINSs of 7–12, including those who were examined as part of a subgroup analysis.

Quality assessment

The Effective Public Health Practice Project (EPHPP) tool was used to standardize quality assessment of included studies, evaluating selection bias, study design, confounders, blinding, data collection methods, and withdrawals/dropouts [16,17]. Individual components were graded as “weak,” “moderate,” or “strong” based on reference articles [16,17], focusing on studies analyzing treatment effects for the SINS 7–12 group. Global ratings were assigned as follows: strong (no weak rating), moderate (one weak rating), and weak (more than one weak rating). The review protocol, including review questions, search strategy, inclusion criteria, and risk of bias assessment, was established prior to conducting the review.

A-class literature results

The A-class literature provided the best evidence, as these studies compared surgery and radiation or a combination thereof for the SINS 7–12 group.

Dial et al. [19] conducted a retrospective study of 211 patients with SINSs of 7–12, comparing outcomes of EBRT alone (n=128), surgery+EBRT (S+E, n=57), or cement augmentation+EBRT (K+E, n=27). The study found significant differences in length of survival (LOS): 430 days in the S+E group, 169 days in the K+E group, and 121 days in the EBRT alone group (p<0.001). Ambulation retention at death was highest in the K+E group (92%), followed by the S+E group (91%) and the EBRT group (77%; p<0.01). Additionally, revision treatment rates at the same spinal level differed significantly: 17.5% for the S+E group, 7.7% for the K+E group, and 20.3% for the EBRT alone group (p<0.04). The study concluded that combining surgical management with radiation therapy improved LOS, ambulation retention, and reduced revision treatment rates compared to radiation therapy alone, supporting surgical intervention alongside radiation for patients with SINSs of 7–12.

Versteeg et al. [14] conducted an international prospective, multicenter study of 200 patients with metastatic spinal tumors and SINSs of 7–12, comparing surgery±radiation (n=136) to radiation alone (n=84). After 12 weeks, surgically treated patients showed a 3.0-point decrease in the Numeric Rating Scale (NRS) pain score (p<0.001) and a 12.7-point increase in the health-related quality of life (HRQOL) (Spine Oncology Study Group Outcomes Questionnaire 2.0 [SOSGOQ2.0] score, p<0.001). Patients treated with radiotherapy alone showed a 1.4-point decrease in NRS pain score (p=0.046) and a non-significant 6.2-point increase in SOSGOQ2.0 score (p<0.331) at 12 weeks. Notably, surgically treated patients maintained significant improvements in pain and HRQOL at 52-week follow-up, whereas radiotherapy-alone patients did not. These findings also favor surgery alone or in combination with radiotherapy for the SINS 7–12 group.

Vargas et al. [20] conducted a retrospective review of 162 patients with metastatic spinal tumors (SINSs of 7–12), comparing surgical treatment (n=63) to radiation alone (SBRT or EBRT, n=99). They measured Karnofsky Performance Scale (KPS) scores and Eastern Cooperative Oncology Group Performance Status (ECOG) pre- and post-treatment, with mean follow-up times of 1.9 years for the surgical cohort and 2 years for the radiation cohort. After accounting for covariates, the average post-treatment change in KPS scores in the surgical cohort and radiation cohort was 7.46±17.3 and −2±13.6, respectively (p=0.045). KPS scores improved in 60.3% of surgical patients and 32.3% of radiation patients. However, there were no significant differences in the ECOG scores. The study’s subanalysis of the radiation group found no difference in fracture rates between SBRT and EBRT. However, 21.2% of patients treated with radiation developed vertebral compression fractures (VCFs) at the treated level. The researchers concluded that surgical intervention for patients with SINSs of 7–12 resulted in improved KPS scores compared to radiation alone, indicating that radiation alone can lead to VCFs.

B-class literature results

The B-class literature results are summarized in Table 2, with key findings described in the following sections.

Pennington et al. [31] suggested a potential cutoff value within the SINS 7–12 range, which could guide treatment decisions. They proposed that lesions with SINS scores of 9 or less might not require stabilization, and potentially unstable cases could be reclassified as stable or unstable, eliminating the “potentially unstable” category [31]. Hussain et al. [32] found that patients with SINSs of 10–12 experienced significantly greater reductions in pain and disability patient-reported outcomes scores after surgery than patients with SINSs of 7–9. Versteeg et al. [44] compared the SINSs in a multi-institutional series of 1,509 patients who underwent surgery or radiotherapy. The researchers found significantly higher scores in the surgical group (mean 10.7 vs. 7.2). However, the study included patients with neurological impairment, a condition that requires surgery. Vargas et al. [26] found higher SINSs in surgical patients compared to non-surgical patients and suggested a potential cutoff value >10 for surgical consideration. Kim et al. [28] found no significant correlation between SINS subgrouping (7–12) and the need for conversion to surgery after initial conservative therapy.

Four studies included in this review showed that VCFs developed in 19%–30% of patients after SBRT or stereotactic ablative body radiotherapy (SABR) [23,38,42,43]. Additionally, two studies yielded contradictory results regarding the association of SINSs of 7–12 and radiotherapy failure; one found such an association [41], and the other did not [22]. A meta-analysis by Kim et al. [45] suggested increasing the SINS cutoff value to better predict VCFs. Lam et al. [39] found that patients with SINSs ≥11 had 2–5 times higher odds of spinal adverse events after SBRT compared to those with scores ≤10.

Revising the SINS components could enhance treatment guidance. Kim et al. [28] found that patients with <50% vertebral body collapse or tumors in the semirigid region (T3–T10) had increased need for conversion to surgery after initial conservative treatment, suggesting that surgery might be preferable for SINS 7–12 patients with these factors. Similarly, other studies suggest that lytic lesions may indicate greater instability, potentially guiding treatment decisions toward surgery for SINS 7–12 patients [46,47]. Pennington et al. [31] found that lesion quality, lesion-associated pain, vertebral height loss, and posterior body involvement were significantly associated with stabilization.

Selection bias

One study received a strong rating because it included all neurologically intact patients in the SINS 7–12 groups [31]. Three studies categorized as A-class literature, received moderate ratings due to differences in baseline characteristics between patients selected for surgery and those selected for radiotherapy [14,19,20]. Seventeen studies received moderate ratings because they analyzed the effects of either surgery or radiotherapy [22,24,26–30,32–37,39,41–43]. Five studies received weak ratings due to limitations such as focusing only on specific cancer types or cohorts that did not fit the SINS 7–12 group, which restricted their generalizability to the broader SINS 7–12 population [21,23,25,38,40].

Study design

The study designs included 20 retrospective cohort studies, five prospective cohort studies, and one retrospective case-control study (Table 3). Although all received “moderate” ratings, the prospective studies had a stronger design due to their prospective nature.

Table 3

Quality assessment of the included studies by use of the EPHPP tool

Confounders

The potential confounders assessed in the included studies are presented in Tables 1 and 2. Twenty studies received strong ratings for presenting relevant baseline characteristics and controlling for imbalances in the analyses and designs (where relevant) [14,19–24,26–30,33,34,36,38–42]. Wänman et al. [25] controlled for some confounders, but missed some relevant characteristics, such as the rTokuhashi score, resulting in a moderate rating. Six studies received weak ratings because they presented several potentially confounders but did not clearly indicate whether these confounders were included in the analysis [31,32,35,37,43].

Blinding

Blinding was rated as moderate across all studies since none of the authors provided complete blinding descriptions. In retrospective studies, participants were likely unaware of the research questions. Blinding is crucial for subjective outcomes like pain or HRQOL, but less critical for objective parameters like survival or VCF. Some studies mentioned blinding but did not provide sufficient information for a strong or weak rating, making it difficult to assess the extent of blinding [14,25,32,41].

Data collection

The data collection rating was based on whether the methods used were valid and reliable. The validity of SINS evaluations has been assessed in several studies. Two studies [30,37] evaluating changes in SINS groups were rated strong, with Gallizia et al. [37] using a validated Visual Analog Scale for evaluating pain responses [48]. Twenty-two studies that measured outcomes such as LOS, ambulation, mean survival, and VCF were rated as strong [19–23,25–29,31–33,35,36,38–43]. Hussain et al. [32] received a strong rating for using the Brief Pain Inventory and MDASI-SP to assess patient-reported outcomes. Three studies received moderate ratings due to partially validated tools or limited reliability confirmation [14,24,34].

Withdrawals and dropouts

The assessment of withdrawals and dropouts did not apply to the only retrospective case-control study [41]. Twenty studies were rated strong with follow-up rates ≥80% [22–29,31,33,35–40,42,43]. Three studies received moderate ratings due to withdrawal rates lower than 79% [14,21,32]. Two studies received weak ratings: Dakson et al. [30] for a 48% follow-up rate and Masuda et al. [34] for an insufficient description of withdrawals and dropouts.

Global Score

Fifteen studies received strong global ratings, 11 received moderate global ratings, and none received weak ratings (Table 3). None of the studies were excluded following the quality assessment.

Interpretation of the results in the context of other evidence

When interpreting evidence regarding treatment selection for the 7–12 SINS group, A-class literature, which compared surgery and radiotherapy effects, was valued higher than B-class. The three A-class studies were conducted by Dial et al. [19], Versteeg et al. [14], and Vargas et al. [26], respectively. Dial et al. [19] found that combined surgical management and radiotherapy improved outcomes, including LOS, ambulation, and revision treatment rates, compared to radiotherapy alone. Versteeg et al. [14] found that surgically treated patients had clinically and statistically significant improvements in pain and HRQOL up to 1 year after surgery, whereas patients treated with radiotherapy alone did not maintain these effects. Vargas et al. [20] found that the average KPS improved more in the surgery group than in the radiation group, suggesting surgery might be a better treatment option for the SINS 7–12 group. However, there is a potential selection bias, as patients chosen for surgery might be different from those chosen for radiotherapy. Patients receiving radiotherapy alone might be less medically fit, which could explain the smaller improvements seen in that group. Dial et al. [19] tried to address potential biases by conducting a subgroup analysis of patients with rTokuhashi scores >8 (expected survival >6 months). Even in this subgroup, surgical stabilization with adjuvant radiotherapy showed better outcomes, including prolonged survival and improved ambulation, compared to radiotherapy alone.

Versteeg et al. [14] identified distinct clinical profiles in SINS 7–12 patients treated with surgery or radiotherapy. Surgically treated patients had more radioresistant tumors, worse ECOG-PS, a higher prevalence of minor neurological deficits, higher median SINSs (9.5 vs. 8), and a greater proportion of lytic tumors and mechanical pain. Dial et al. [19] found that patients receiving surgical stabilization before radiotherapy were younger, had better predicted survival, and had more radiation-resistant tumors. This suggests that differences in patient characteristics might have influenced treatment outcomes, making it uncertain whether radiotherapy patients would have benefited from surgery. The evidence discussed in this article suggests that surgery is an option for SINS 7–12 patients and can improve their HRQOL. Combined surgery and radiation also show promise. While radiation alone provides some improvement, it carries a higher risk of VCFs. Direct comparisons suggest that surgery±radiation is superior to radiation alone.

Importantly, SINSs alone are not sufficient for treatment decision-making in patients with spinal metastases; they are only suitable for evaluating spinal stability. Other factors not covered by the SINS might also play important roles [6]. Impaired neurological function should, in most cases, lead to surgery. A poor performance score and low expected survival time (less than 3 months) often lead to radiotherapy. Moribund patients may only receive palliative end-of-life care. Other key factors include the tumor’s radiosensitivity and chemosensitivity. Ultimately, treatment decisions should be patient-centered, taking into account individual needs and circumstances. A survey conducted by Catanzano et al. [18] revealed uncertainty regarding surgical decision-making for patients with SINS 7–12, even among experienced physicians dealing with high volumes of cases. Dial et al. [19] suggest that the need for spinal stabilization in addition to radiotherapy for these patients should be discussed in a multidisciplinary setting.

LMNOP framework is a decision-making tool that incorporates SINSs [49]. It comprises key factors that should be considered while determining the optimal treatment for spinal metastasis: the location of the disease in the spine (L), mechanical instability as graded by SINS (M), neurological status (N), oncology (particularly regarding radiosensitivity, O), and the patient’s fitness, wishes, prognosis, and response to prior therapy (P). NOMS is another decision-making framework [50]. However, it does not incorporate SINSs as a way of describing mechanical instability, but only in the context of movement-related pain. LMNOP provides a systematic but individualized approach to treatment decision-making for patients with spinal metastases.

Kwan et al. [51] recently reviewed current approaches for managing metastatic spine patients, with findings largely consistent with this article’s conclusions, but also several notable differences. Most notably, Kwan et al. [51] included 17 studies encompassing patients with both intermediate (SINS 7–12) and high (SINS 13–18) spinal instability, thereby broadening the patient population and potentially introducing treatment strategies not specifically tailored to the intermediate group. In contrast, the present review exclusively focused on studies involving patients with intermediate spinal instability (SINS 7–12), offering a more targeted analysis of this clinically ambiguous category. Furthermore, Kwan et al. [51] focused on comparing various surgical techniques for SINS 7–12 patients, while the present review evaluated surgery as a whole versus radiotherapy. This allowed for a broader examination of the choice between operative and nonoperative management. Our analysis was structured by dividing studies into two categories: (A) direct comparisons of surgery and radiotherapy, and (B) studies focusing on outcomes of either surgery or radiotherapy independently. Moreover, the EPHPP tool was used to assess the methodological quality of included studies, adding transparency and rigor to the review. Despite these methodological differences, both reviews highlighted the scarcity of high-quality evidence available and the need for further research to inform optimal treatment strategies for this patient population.

Limitations of the included evidence

The external validity of the studies was limited by selection bias, as previously discussed. The absence of randomized controlled trials (RCTs) increased the risk of bias. However, RCTs might be challenging in this context due to ethical concerns and the need for individualized decision-making. The SINS 7–12 study populations in the included studies were generally small, with only three studies involving more than 200 patients [14,19,42]. One study evaluated only 24 SINS 7–12 patients, which limited the statistical power [34]. One study focused exclusively on patients with prostate cancer who were surgically treated for MSCC [25], limiting its utility for informing treatment selection for patients with SINSs of 7–12. MSCC, which involves neurological impairment, almost always leads to surgery, and prostate cancer is only one of the cancers that can lead to spinal metastases. The studies assessed varied outcomes, limiting cross-study comparisons. The primary goal of treatment for spinal metastases is to preserve patients’ HRQOL [6]. This goal is achieved by reducing pain, preserving ambulation ability, and maintaining sphincter functions. Therefore, it can be argued that the most valuable outcome measures are HRQOL, ability to ambulate, pain, disability/activity, neurologic status, LOS, and performance status, while changes in SINS status, VCF development, and revision treatment are less valuable.

Limitations of the review

This review was limited by the scarcity of relevant articles, precluding statistical meta-analyses and forest plots. Potential publication bias may have contributed to missing data. Additionally, the review could only compare surgery and radiotherapy broadly, without differentiating between specific methods. Lastly, varying outcome measures made it impractical to combine study results statistically.

Implications of the results for practice, policy, and future research

This systematic review highlights the superiority of surgical intervention, either alone or in combination with radiation, for patients in the SINS 7–12 categories with metastatic spinal tumors. However, treatment decisions should consider multiple factors beyond SINS, including performance score, expected survival, primary tumor type, radiosensitivity, and neurologic function. The SINS 7–12 group may be heterogeneous, with some patients benefiting more from surgery and others from radiotherapy. A cutoff value of ≥10 might better predict the need for surgery. Additionally, some of the individual SINS components might have predictive value, suggesting a more nuanced approach to treatment decision-making. Future studies should compare treatment effects for the 7–12 SINS group, ideally through multi-institutional prospective cohort studies. These studies should measure important outcomes, such as HRQOL, pain, ambulation, and LOS, thus employing a multidisciplinary team approach to generate data.