Key question

What is a safe timeframe, given the available treatment options?

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Considerations

Spinal metastasis can be complicated by symptomatic metastatic epidural spinal cord compression (MESCC) in 5-10% of patients (Boussios 2018 and Cole 2008). Recognizing red flags (e.g. new onset back pain, progressive back pain, nocturnal back pain, pain on palpation, and poor general health) could initiate timely referral prior to developing MESCC (van Tol 2023). Unawareness of referring physicians is reflected on the typical Friday peak in referral after grand rounds as well as poor prognosis of MESCC admitted in the weekend (Debono 2019; Dasenbrock 2011). In case of intractable pain, mechanical instability, or neurological deficits, cancer patients with a life expectancy of >3 months should be referred immediately to specialized centers. A Dutch retrospective study in a single tertiary center identified four types of delay (i.e. patient, diagnostic, referral and treatment delay) resulting in a total delay of 99 days from onset of symptoms until definitive treatment (van Tol 2023). Although longer than similar studies (Husband 1998 and Levack 2002), the study included also non-MESCC patients. Analysis showed that delayed presentation to a spine surgeon is the strongest predictor for poor postoperative outcome in MESCC patients (van Tol 2019). Weighing factors in survival prediction and functional outcomes preferably by a (regional) multidisciplinary consultation including a spine surgeon is essential for personalized treatment and quality of life (Nater 2020). Ideally, shared expertise by a spine surgeon, radiologist, neurologist, oncologist/hematologist, radiation oncologist, rehabilitation specialist and palliative care expert lead to an individualized treatment scheme depending on present symptoms, aggressiveness and radiosensitivity of the tumor, late-onset benefit expected by radiation and/or systemic therapy and radiological criteria (Debono 2024 and Nakata 2020).

In general, it is important to keep in mind that swift elective surgery leads to better outcomes for patients compared to emergency surgery. When confronted with patients presenting with MESCC, physicians need to avoid unnecessary delays with a specialized multidisciplinary team at all costs! Therefore, it is of upmost importance to install a referral system 24/7 regardless of specific grand rounds, attending physicians, or ward or center where patient presented himself (Kuah 2022). Also, by incorporating a swift diagnostic setting with laboratory testing and adequate imaging, postoperative complications can be minimized in the operating plan (Kuah 2022). A systematic review and meta-analysis on improved outcomes by Frankel or AISA scores regarding emergent (surgery within 24 hours after onset of neurological symptoms) vs. non-emergent (> 24h) and urgent (≤ 48h) vs. non-urgent (> 48h) surgeries was performed including studies with adult patients with known or unknown primary tumors, life expectancy of >3 months and neurological impairment at admission (Bresolin 2024). Seven retrospective articles were retained (Fan 2016, Lo 2017, Meyer 2022, Quraishi 2013, Tateiwa 2019, Younsi 2020 and 2021). When surgery was performed within 48 hours after onset of symptoms, 83% (95% CI 59.0 – 98.2%) patients showed improved neurological symptoms with a complication rate of 21% (95% CI 1.8 – 51.4%). When operated beyond this time frame, only in 37% (95% CI 12.2 – 65.4%) of the patients’ neurological symptoms improved with a higher complication rate of 29a% (95% CI 19.5 – 38.8%). In this review, 80% of patients regained some improvement in strength, while 45% regained the ability to walk upon discharge after urgent surgery. There was no significant difference in outcomes between patients performed within 24 hours (emergent surgery) or 48 hours (urgent surgery) of onset of neurological symptoms. Therefore, it is better to take time to ensure proper multidisciplinary communication and preparation for each specific case, allowing for treatment to be allocated in a tailored and individualized manner.  However, do not confuse this allocation phase with unnecessary delay in presenting the patient to a specialized multidisciplinary team!

In another study, positive effects on Karnofsky performance status (KPS) scores, mobility scores and survival were observed in both urgent and non-urgent surgery patient groups, but a time-independent negative effect was seen in the patient population requiring urgent surgery compared to the non-urgent surgery group (van Tol 2020). Multivariate analyses showed surgery performed within 72 hours after neurosurgical presentation was associated with lower EQ-5D and KPS scores and higher mortality rates, independent of confounders such as preoperative EQ-5D and KPS scores, neurological status, tumor prognosis and patient age.

The committee found no evidence on the timing of radiotherapy for people with MESCC. One prospective study analyzed 87 MESCC patients, evaluating the relationship between the time of developing motor deficit (categorized into slow vs. rapid onset) and functional outcomes after radiotherapy. It found that slower onset (over 14 days) leads to better functional outcomes post-radiation, while rapid deterioration within 48 hours predicts poorer results (Rades 2000). Radiotherapy was delivered within 6–12 h from the patient’s first presentation to the department. The recent published NICE guideline recommend rapid access to radiotherapy – if surgery is not indicated – to prevent neurological impairment as soon as possible and within 24 hours after contacting the radiation oncologist. This emphasizes the need for education of general practitioners and physicians involved in the care of patients with spinal metastases, and setup of efficient referral systems. Additional consults with oncologists and palliative cares experts are advised for pre-operative risk/benefit evaluation (Chen 2023 and Lape 2020). A Cochrane review including 544 patients with MESCC and a life expectancy of >3 months concurred the recommendation for surgery with a 48-hour window (George 2015). Although based on low to very low qualitive evidence, the NICE guideline review commission supports service configuration and delivery recommendations (see also Recommendations | Spinal metastases and metastatic spinal cord compression | Guidance | NICE) detailing clear processes and referral pathways, instalment of a MESCC coordinator with 24/7 coverage and multidisciplinary approach, as well as urgent imaging within 24 hours in case of MESCC and with 7 days in all other cases (NICE guideline  PMID: 37820023). Costs of urgent surgery are evidently higher than non-urgent surgical treatment due to in-hospital costs (e.g. diagnostic procedures, number of admission days and clinical/outpatient rehabilitation), highlighting the importance of swift referral and delivery processes (van Tol 2022).

Quality of evidence

No systematic literature review was conducted for this module. Therefore, the quality of the cited evidence has not been assessed using the GRADE approach.

Values and preferences of patients (and, if applicable, their relatives/caregivers)

The desired effects on patient-relevant outcomes are (very) significant. The undesired effects on patient-relevant outcomes are moderate. Patients find themselves in a highly vulnerable situation, in which they must undergo diagnostics and make treatment decisions on very short notice, weighing the expected benefits (survival and reduction of functional loss) against the risks (complications). A palliative care consultation can support the consideration of prognosis, patient wishes, and needs regarding decision-making.

Cost considerations

By timely referring patients to expert centers, expenses can be reduced due to shorter hospital stays and fewer urgent procedures. In addition, patient-related outcomes are expected to improve.

Health equity

The intervention may lead to a (potential) reduction in health equity. Patients with MESCC and sudden or progressive neurological symptoms should be referred to a tertiary center for diagnostics and treatment as soon as possible. This means that travel time and travel costs will become relevant factors. To reduce the risk of the "Friday effect" (delayed recognition of risks or the presence of MESCC by the consulted physician, depending on their training and awareness of MESCC risk and warning signs), consultating calls and referrals should be made with a very low threshold.

Acceptability

Ethical Acceptability

The intervention appears to be acceptable to those involved. The working group foresees no ethical objections. Patients who undergo surgical intervention live longer with less neurological impairment. Depending on a timely referral system and good shared decision-making, there can be a significant positive impact on quality of life.

Sustainability

The following sustainability aspects play a role in the intervention: transportation to tertiary centers.

Feasibility

The feasibility of the described intervention depends on the implementation of the decision tree with clear agreements between the referring center and the regional treatment center. The intervention appears to be feasible. In general, the intervention is already considered standard care in practice.

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