The role of minimally invasive surgery within a multidisciplinary approach for patients with metastatic spine disease over a decade: A systematic review

Abstract

Background

Metastatic spine disease (MSD) occurs commonly in cancer patients causing pain, spinal instability, devastating neurological compromise, and decreased quality of life. Oncological patients are often medically complex and frail, precluding them form invasive procedures. To address this issue, minimally invasive spinal surgery (MISS) techniques are desirable. The aim of this study is to review published peer-reviewed literature and ongoing clinical trials to provide current state of the art.

Methods

A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, assessing MISS in MSD patients for the period 2013–2023. Innovations under development were assessed by querying and reviewing data from currently enrolling U.S. registered clinical trials.

Results

From 3,696 articles, 50 studies on 3,196 patients focused on spinal oncology MISS. The most commonly reported techniques were vertebral augmentation (VA), percutaneous spinal instrumentation, and radiofrequency ablation (RFA). Surgical instrumentation/stabilization techniques were reported in 10/50 articles for a total of 410 patients. The majority of studies focused on pain as a primary outcome measure, with 28/50 studies reporting a significant improvement in pain following intervention. In the United States, 13 therapeutic trials are currently recruiting MSD patients. Their main focus includes radiosurgery, VA and/or RFA, and laser interstitial thermal therapy.

Conclusions

Due to their medical complexity and increased fragility, MSD patients may benefit from minimally invasive approaches. These strategies are effective at mitigating pain and preventing neurological deterioration, while providing other advantages including ease to start/resume systemic/radiotherapy treatment(s).

Key Points.

• Minimally invasive spinal surgery (MISS) approaches to metastatic spine disease may be safely and effectively performed in cancer patients.

• Additional advantages of MISS include ease to start/resume systemic/radiotherapy treatment(s) needed to treat the primary cancer.

Importance of the Study.

Spinal metastases are common among the oncology population and represent a significant cause of disability. Minimally invasive spine surgery (MISS) approaches may be employed for the management of pain, instability, diagnostic, or neurological deterioration. Compared to traditional open approaches, MISS may be well tolerated in the medically complex cancer population to improve quality of life and facilitate starting/resuming adjunctive treatment. The current review outlines and analyzes trends in management strategies of MISS approaches for metastatic spine disease. Additionally, it provides a glimpse of upcoming treatments currently assesses in clinical trials.

With advances in cancer treatment, the number of cancer patients in the United States has increased with a current incidence of 439/100,000 population,¹ yearly mortality of 146/100,000¹ and yearly national expenditure of $190 billion.² The American Cancer Society estimated a 1.5% decline in the cancer death rate from 2019 to 2020 and approximated a 33% overall reduction in cancer deaths since 1991.³ The increase in overall (OS) survival further increases the likelihood of metastatic spine disease (MSD) in cancer patients.⁴ Bone is the third most common site of tumor metastases making the spine the most common site of metastatic bone lesions.⁵ Although primary and secondary malignancies can occur in the spine,⁶ metastatic spine disease constitute 90% of all malignancies.⁷

MSD is associated with a variety of symptoms. Patient presentation may include pain, pathological fractures, spinal canal compression causing spinal cord or nerve root deficit.⁸ Since all of the above contribute to decreased quality of life (QoL) and associated morbidity, a multidisciplinary approach is needed to consider all options, including medical, surgical, radiation, and supportive care.^9,10 Therapeutic interventional goals for MSD patients might include symptom relief, vertebral column stabilization, spinal cord/nerve root decompression, tissue diagnosis and/or cytoreduction.⁹ Such goals should fit into the broader picture of goals of care and treatment of the primary cancer. The role of each team members is therefore important to prepare a treatment plan that encompasses all aspects.

Pain secondary to MSD can be successfully treated by stereotactic radiosurgery (SRS) with pain control rate up to 90%.⁹ This outpatient procedure, in most centers delivered by a neurosurgeon and a radiation oncologist, also results in excellent tumor control ranging from 75% to 100%, depending on the histology.⁹ Surgical resection by radical procedures such as spondylectomy or vertebrectomy may be highly morbid, and confer 1-year control rates of only 30% in some series.¹¹ In cases where spinal instability and/or compression are the main issue, in addition to pain and cytoreduction, procedures to stabilize the spine are need.

Spine stabilization was initially shown to have a benefit on ambulation and QoL.¹² The field of spinal instrumentation has since evolved and MISS has become the mainstay in degenerative and trauma spine pathologies. With intraoperative imaging guidance, MISS offers several advantages compared to open procedures, including decreased complication rates,¹³ operative times, intraoperative blood loss, hospital length of stay (LOS), healing time¹³ which in turn decreases the time interval to initiating adjuvant therapies. Previous studies have included open instrumentation within the broad definition of MISS; however, this review focuses on both instrumented and noninstrumented nonopen therapies only.¹⁴ Additionally, prior reviews have included small numbers of studies, limiting findings and conclusions.^15,16 While the development of MISS techniques has taken place over the past half century, in the last 2 decades there have been substantial advances with intraoperative image guidance and robotics^17,18 resulting in improved precision of the implanted stabilization.¹³

Although MISS techniques and their outcomes have been well described in the degenerative, deformity and trauma spine surgery literature, their use in MSD has not been as well elucidated. The aim of this study is twofold. First, we aim provide a systematic review of currently used MISS techniques in MSD to define their potential role and pitfalls in the multidisciplinary treatment of MSD patients. Second, we aim at providing the current landscape of clinical trials utilizing MISS for MSD patients to identify future opportunities.

Methods

This study was based on the most recent Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.¹⁹ A comprehensive search strategy was designed to identify relevant studies regarding MISS use in spinal malignancies. The search terms used were [“minimally invasive” OR “minimally invasive spine surgery” OR “spine surgery” OR “endoscopy” OR “thoracoscopy” OR “Minimally Invasive Surgical Procedures”] AND [“spine” OR “spinal”] AND [“Spinal Neoplasms” OR “spinal tumor” OR “spinal metastasis”] along with others. The search was conducted using appropriate Medical Subject Headings (MeSH) and Boolean search terms. The electronic databases included in the search were PubMed, Ovid Medline, and Embase. These databases were searched for relevant studies published in English from January 1, 2013 to March 31, 2023. Institutional Review Board approval was not required for the current study.

The primary inclusion criteria included: (1) studies that evaluated the use of MISS in spinal oncology, (2) clinical in nature, (3) full text available, and (4) English language. Primary exclusion criteria included: (1) studies outside the time frame January 1, 2013 to March 31, 2023, (2) animal or cadaveric studies, (3) studies assessing open surgical management in spinal oncology, (4) case reports and case series with <10 patients, and (5) systematic reviews. Two independent reviewers (S.P. and A.S.) screened the titles and abstracts of the articles identified through the database search. Full-text articles were obtained for those that met the inclusion criteria. The screening was done using the Covidence software.²⁰ Aggregate complication rates were calculated by summating the total number of patients who experienced complications divided by the total number of patients who received surgical intervention in each study.

To assess clinical trials currently open and enrolling MSD patients, the authors queried https://clinicaltrials.gov/ on April 4, 2023 under the searches “Spine Metastases” and “Spine Tumor.” Only clinical trials designated as “Recruiting” were included. Duplicate studies and trials that were closed or not yet enrolling were removed.

Results

The initial literature search yielded 3,696 peer-reviewed publications from the three databases queried. Of these, 50 studies were included in the final review, for a total of 3,196 patients (Figure 1). Figure 2 summarizes the treatment modalities for studies included in this systematic review.

Figure 1.

PRISMA diagram for selection of MIS spine tumor articles included in systematic review.

Figure 2.

Treatment modalities for studies included in this systematic review. RFA = radiofrequency ablation.

Pain Control

Table 1 summarizes the 33 peer-reviewed publications included in this review focusing on spine stabilization using percutaneous vertebral augmentation (VA) techniques: percutaneous kyphoplasty (KP, N = 14), vertebroplasty (VP, N = 23), and pediculoplasty (PP, N = 1; 4 studies included multiple techniques).^{21–50,63,64}Table 2 summarizes MISS used for spinal stabilization data pertinent to 410 MSD patients with age average of 62 years and slight predominant female gender (53%).^{13,17,51–58}Table 3 summarizes the 6 peer-reviewed publications included in this review where radiofrequency ablation (RFA) was used for cytoreduction.^25,59–63 All studies provided Class III evidence without randomization; 42/50 were retrospective. The primary outcome of the 6 prospective cement augmentation studies was pain,^{24,26,32,34,46,48} and the primary outcome of the 3 prospective MISS stabilization studies was pain and neurological improvement.^53,55,58

Table 1.

Percutaneous Vertebral Augmentation Techniques for SMD (2013–2022)

Author (year)	Study Title	Journal	Study Type	N	Intervention	P < .05 VAS Improvement
Sun et al. (2013)21	Vertebroplasty for Treatment of Osteolytic Metastases at C2 Using an Anterolateral Approach	Pain Physician	Retrospective Study	13	PVP	Yes
Barragan-Campos et al. (2014)22	Percutaneous Vertebroplasty in Vertebral Metastases from Breast Cancer: Interest in Terms of Pain Relief and Quality of Life	Interv Neuroradiol	Retrospective Study	31	PVP	Yes
Sun et al. (2014)23	Percutaneous Vertebroplasty for Painful Spinal Metastasis With Epidural Encroachment	J Surg Oncol	Retrospective Study	43	PVP	N/A
Li et al. (2014)24	A preliminary comparative clinical study of vertebroplasty with multineedle or single-needle interstitial implantation of 125I seeds in the treatment of osteolytic metastatic vertebral tumors	J Neurosurg Spine	Prospective Study	29	PVP	Yes
Zheng et al. (2014)25	A preliminary study of the safety and efficacy of radiofrequency ablation with percutaneous kyphoplasty for thoracolumbar vertebral metastatic tumor treatment	Med Sci Monit	Retrospective Study	26	PKP, FRA	Yes
Andresen et al. (2014)26	Balloon Sacroplasty as a Palliative Pain Treatment in Patients with Metastasis-Induced Bone Destruction and Pathological Fractures	Rofo	Case Series	10	PVP	Yes
Gu et al. (2014)27	Safety and Efficacy of Percutaneous Vertebroplasty and Interventional Tumor Removal for Metastatic Spinal Tumors and Malignant Vertebral Compression Fractures	Am J Roentgenol	Prospective Study	31	PVP	Yes
Nas et al. (2015)28	Effectiveness of percutaneous vertebroplasty in cases of vertebral metastases	Diagn Interv Imaging	Retrospective Study	52	PVP	Data not provided
Xie et al. (2015)29	Efficacy of percutaneous vertebroplasty in patients with painful vertebral metastases: A retrospective study in 47 cases	Clin Neurol Neurosurg	Retrospective Study	47	PVP	Yes
Roedel et al. (2015)30	Has the percutaneous vertebroplasty a role to prevent progression or local recurrence in spinal metastases of breast cancer?	J Neuroradiol	Retrospective Study	55	PVP	Data not provided
Sun et al. (2015)31	Safety of percutaneous vertebroplasty for the treatment of metastatic spinal tumors in patients with posterior wall defects	Eur Spine J	Retrospective Study	120	PVP	Yes
Markmiller et al. (2015)32	Percutaneous balloon kyphoplasty of malignant lesions of the spine: a prospective consecutive study in 115 patients	Eur Spine J	Prospective Study	115	PKP	Yes
Bae et al. (2016)33	Percutaneous vertebroplasty for patients with metastatic compression fractures of the thoracolumbar spine: clinical and radiological factors affecting functional outcomes	Spine J	Retrospective Study	342	PKP, PVP	Inconclusive
Tian et al. (2016)34	Percutaneous Vertebroplasty for Palliative Treatment of Painful Osteoblastic Spinal Metastases: A Single-Center Experience	J Vasc Interv Radiol	Prospective Study	39	PVP	Yes
Noriega et al. (2016)35	Long-Term Benefits of Percutaneous Anatomical Restoration of Vertebral Compression Fractures Linked to Malignancy	Turk Neurosurg	Retrospective Study	32	PKP, PVP	Yes
Molloy et al. (2016)36	Is Balloon Kyphoplasty Safe and Effective for Cancer-Related Vertebral Compression Fractures With Posterior Vertebral Body Wall Defects?	J Surg Oncol	Retrospective Study	158	PKP	Data not provided
Wang et al. (2016)37	Clinical evaluation of percutaneous kyphoplasty in the treatment of osteolytic and osteoblastic metastatic vertebral lesions	Int J Surg	Retrospective Study	81	PKP	Yes
Liu et al. (2017)38	Incremental temperature cement delivery technique may prevent cement leakage in metastatic vertebral lesions	J Orthop Surg	Retrospective Study	129	PKP	No
Zhang et al. (2017)39	Safety and efficacy of multilevel vertebroplasty for painful osteolytic spinal metastases: a single-center experience	Eur Radiol	Retrospective Study	153	PVP	Yes
Bao et al. (2017)40	Percutaneous Vertebroplasty Relieves Pain in Cervical Spine Metastases	Pain Res Manag	Retrospective Study	9	PVP	Yes
Zhang et al. (2017)41	Percutaneous Kyphoplasty in the Treatment of Osteoblastic-Related Spinal Metastases	Clin Spine Surg	Retrospective Study	13	PKP	Yes
Stangenberg et al. (2017)42	Cervical vertebroplasty for osteolytic metastases as a minimally invasive therapeutic option in oncological surgery: outcome in 14 cases	Neurosurg Focus	Case Series	14	PVP	Data not provided
Kirkegaard et al. (2018)43	Percutaneous vertebroplasty is safe and effective for cancer-related vertebral compression fractures	Dan Med J	Retrospective Study	30	PVP	Data not provided
Sebaaly et al. (2018)43	Anterolateral Cervical Kyphoplasty for Metastatic Cervical Spine Lesions	Asian Spine J	Case Series	11	PKP	Yes
He et al. (2020)44	Kyphoplasty in the treatment of occult and non-occult metastatic vertebral tumors	Medicine	Retrospective Study	147	PKP	Yes
Tekin et al. (2020)45	How do vertebroplasty and kyphoplasty affect the quality of life of patients with multiple myeloma spinal metastasis?	Eur J Orthop Surg Traumatol	Retrospective Study	42	PKP, PVP	Yes
Xia et al. (2021)46	Combined percutaneous kyphoplasty/pediculoplasty by posterolateral transpedicular approach for painful cervical spine metastases—A single-center prospective study	J Pain Res	Prospective Study	11	PKP	Yes
Shi et al. (2021)47	Epidemiology and detection of cement leakage in patients with spine metastases treated with percutaneous vertebroplasty: A 10-year observational study	J Bone Oncol	Retrospective Study	309	PVP	Data not provided
Yan et al. (2022)48	Efficacy and Safety of the Safe Triangular Working Zone Approach in Percutaneous Vertebroplasty for Spinal Metastasis	Korean J Radiol	Prospective Study	87	PVP	Yes
Cui et al. (2022)49	Risk factors for predicting cement leakage in percutaneous vertebroplasty for spinal metastases	J Orthop Sci	Retrospective Study	230	PVP	Data not provided
Wang et al. (2022)47	Cement leakage in percutaneous vertebroplasty for spinal metastases: Open Access a retrospective study of risk factors and clinical outcomes	World J Surg Oncol	Retrospective Study	64	PVP	Yes
Ragheb et al. (2022)50	The Addition of Radiofrequency Tumor Ablation to Kyphoplasty May Reduce the Rate of Local Recurrence in Spinal Metastases Secondary to Breast Cancer	World Neurosurgery	Retrospective Study	50	PKP, RFA	Yes
Wang et al. (2022)50	Cement leakage in percutaneous vertebroplasty for spinal metastases: Open Access a retrospective study of risk factors and clinical outcomes	World J Surg Oncol	Retrospective Study	64	PVP	Yes

PKP = percutaneous kyphoplasty; PPP = percutaneous pediculoplasty; PVP = percutaneous vertebroplasty; RFA = radiofrequency ablation.

Table 2.

Studies on Minimally Invasive Stabilization Techniques for Spinal Tumors (2013–2023)

Author	Study Title	Journal	Study Type	N	Ambulation	Overall Survival	Neurological Status	MIS advantage
Lin et al. (2013)51	Minimally invasive solid long segmental fixation combined with direct decompression in patients with spinal metastatic disease	Int J Surg	Retrospective Study	25	—	50% survival at 12 months	Improvement in pain and Frankel score following surgery	Shorter recovery important in patients with decreased life expectancy
Tan et al. (2017)52	Minimally Invasive Direct Lateral Corpectomy of the Thoracolumbar Spine for Metastatic Spinal Cord Compression	J Neurol Surg A Cent Eur Neurosurg	Retrospective Study	19	—	50% survival at 6 months	Frankel score improvements in cohort	Short operative times, low EBL
Hamad et al. (2017)53	Minimally invasive spinal surgery for the management of symptomatic spinal metastasis	British J Neurosurg	Prospective Study	51	—	—	Improvement in pain and Frankel score following surgery	Low EBL, MIS is safe and effective in improving functional outcomes
Uei et al. (2018)54	Clinical Results of Minimally Invasive Spine Stabilization for the Management of Metastatic Spinal Tumors Based on the Epidural Spinal Cord Compression Scale	Biomed Res Int	Retrospective Study	56	—	12 vs 15 months	Improvement in ESCC grade 2 or below compared to higher grade	Higher rates of postop chemotherapy in ESCC grade or below cohort, short operative times and EBL
Barzilai et al. (2018)55	Minimal Access Surgery for Spinal Metastases: Prospective Evaluation of a Treatment Algorithm Using Patient-Reported Outcomes	World Neurosurgery	Prospective Study	51	Subjective improvement in ambulation	—	Improvement in pain	Faster recovery and return to baseline activity
Barzilai et al. (2019)56	Utility of Cement Augmentation via Percutaneous Fenestrated Pedicle Screws for Stabilization of Cancer-Related Spinal Instability	Oper Neurosurg	Retrospective Study	53	Subjective improvement in ambulation	—	Improvement in pain	Short operative time, EBL, hospital stay. Fenestrated screws are safe and effective in MIS for spinal tumors
Zhou et al. (2020)17	Minimally Invasive Pedicle Screw Fixation Combined with Percutaneous Kyphoplasty Under O-Arm Navigation for the Treatment of Metastatic Spinal Tumors with Posterior Wall Destruction	Orthop Surg	Retrospective Study	23	—	—	Improvement in pain up to 2 years	Short operative time, EBL, hospital stay
Nakanishi et al. (2022)57	Effect of Minimally Invasive Spine Stabilization in Metastatic Spinal Tumors	Medicina	Retrospective Study	51	—	22.0 ± 8.6 months	Frankel score improvements in cohort	Early start to chemotherapy, amenable to sick patients who cannot tolerate open surgery
Lin et al. (2022)58	Minimally invasive separation surgery for the treatment of spinal metastases with small incision and freehand pedicle screw fixation- the surgical learning curve	BMC Musculoskelet Disord	Prospective Study	62	—	—	Improvement in neurological functioning in 30% patients, Frankel grade improvements similar between early vs late groups	Not steep learning curve for adoption of MIS spinal oncology techniques
Shiber et al. (2023)13	The Evolution of Minimally Invasive Spine Tumor Resection and Stabilization: From K-Wires to Navigated One-Step Screws	J Clin Med	Retrospective Study	19	—	63% survival at 6 months	Improvement in neurological functioning in 53% of patients	Reduced complications, faster initiation of adjuvant therapy

EBL = estimated blood loss; ESCC = epidural spinal cord compression; MIS = minimally invasive surgery.

Table 3.

Radiofrequency Ablation for SMD (2013–2023)

Author	Study Title	Journal	Study Type	N	Intervention	P < .05 VAS Improvement
Zheng et al. (2014)25	A preliminary study of the safety and efficacy of radiofrequency ablation with percutaneous kyphoplasty for thoracolumbar vertebral metastatic tumor treatment	Med Sci Monit	Retrospective Study	26	RFA, PKP	Yes
Tomasian et al. (2018)59	Simultaneous Bipedicular Radiofrequency Ablation Combined with Vertebral Augmentation for Local Tumor Control of Spinal Metastases	Am J Neuroradiol	Retrospective Study	27	RFA	—
Wallace et al. (2016)60	Radiographic Local Control of Spinal Metastases with Percutaneous Radiofrequency Ablation and Vertebral Augmentation	Am J Neuroradiol	Retrospective Study	55	RFA	—
Tomasian et al. (2016)61	Spine Cryoablation: Pain Palliation and Local Tumor Control for Vertebral Metastases	Am J Neuroradiol	Retrospective Study	14	Percutaneous cryoablation	Yes
Khan et al. (2018)62	Efficacy and Safety of Percutaneous Microwave Ablation and Cementoplasty in the Treatment of Painful Spinal Metastases and Myeloma	Am J Neuroradiol	Retrospective Study	69	RFA	Yes
Ragheb et al. (2022)63	The Addition of Radiofrequency Tumor Ablation to Kyphoplasty May Reduce the Rate of Local Recurrence in Spinal Metastases Secondary to Breast Cancer	World Neurosurgery	Retrospective Study	50	RFA, PKP	Yes

PKP = percutaneous kyphoplasty; RFA = radiofrequency ablation; VAS = visual analog score.

The most commonly reported primary outcome was pain control rated using a visual analog pain score (VAS). A significant improvement (P < .05) in postprocedural pain compared to preprocedural pain was reported in 27 of 29 studies with pain as primary outcome. One study reported no significant difference and one had inconclusive results.

Neurologic Outcome and Overall Survival

Among the 10 studies reporting on MISS for spinal instrumentation, 2 studies reported improvements in ambulation following MISS stabilization surgery using patient-reported outcomes (PRO).^55,56 All 10 studies found a significant improvement in neurological status, with 5/10 studies reporting improvement in Frankel scores, a 5-point scale to determine degree of spinal cord injury,⁶⁵ by at least 1 point following stabilization.^{51–53,57,58} Of the 7 studies who reported on pain scores, all 7 studies reported significant pain improvement^{12–17,51,53–55} (Table 2). Overall survival (OS) reported by 5/10 studies ranged from 12 to 22 months.^{13,51,52,54,57} Compared to conventional spine stabilization, MISS studies reported shorter operative times,^17,56 decreased blood loss,^17,56 shorter length of stay (LOS) in hospital,^17,56 and faster initiation of adjuvant therapies.^13,57 Percutaneous procedures were safe, with low rates of worsening neurological status, and neurological improving rates ranging from 30% to 53% in included studies.^{13,51,53,57,58} For RFA procedures, 89%–96.7% of local tumor control was seen with shorter-term follow up (≤3 months) and up to 98% with a mean follow up of 39 months.^25,59–63 This highly effective procedure has been attributed to the efficacy of microwave ablation of tumor cells via coagulation necrosis, and in particular a highly effective response in bone, as osseous permeability allows for deep penetrance into tumor regions.⁶²

Adverse Events, Recurrence and Social Determinants of Health

In the 10 studies on MISS for surgical stabilization, there was an aggregate 9.3% complication rate, ranging from 0% to 13.7%. The most commonly seen adverse events were surgical complications (73.1%) reported in 9 of 10 studies.^17,51–58Table 2 including pseudoarthrosis,^51,53,56,57 hardware failure,⁵⁵ CSF leak,^54,58 deep wound infection⁵⁴, and epidural hematoma.^54,58 Medical complications accounted for 26.9% and included deep vein thrombosis,⁵⁴ chest infection (2 patients), and urinary tract infection (UTI) (1 patient).⁵³

Three (30%) studies included patients with disease recurrence, for a total of 8 patients (2 studies included a single patient with disease recurrence).

All of included studies reported data on age and gender; however, no studies reported on race, ethnicity, socioeconomic status, or other social determinants of health.

Current Landscape of Clinical Trials for MSD

Our clinical trial search initially yielded 100 total clinical trials, and 18 met entry criteria that were related to metastatic spinal disease, and currently enrolling patients (Table 4). Studies were excluded if they were closed or not actively enrolling patients, or had a primary study group outside of patients with metastatic spinal disease undergoing therapy. Thirteen of 15 trials were therapeutic and 2/15 were outcome studies. All 15 trials were single center and 4/15 (26.7%) were randomized. Trials were based in the United States. Across U.S. geographical quadrants, a significant higher number of therapeutic trials was found in the South quadrant compared to the other quadrants (P < .001). The most common therapeutic focus included radiosurgery, followed by vertebral body augmentation and/or RFA, and laser interstitial thermal therapy (LITT).

Table 4.

MISS Clinical Trials (Source: Clinicaltrials.gov, accessed April 6, 2023). All Trials Are Single Center

Focus	Principal Investigator	Enrollment Date	Outcomes
Immunotherapy/Radiosurgery	Cramer	03/2022	Pain, quality of life
LITT/Radiosurgery	Lee	09/2021	Local control rate, OS
Radiosurgery	Amini	11/2018	Efficacy
Radiosurgery	Fryman	12/2020	MRI sequence, pain
Radiosurgery	Kotecha	03/2021	Pain
Radiosurgery/RFA/VA	Kotecha	05/2020	Pain
Radiosurgery	Chao	02/2020	Local control rate, pain
Radiosurgery/RFA	Li	08/2016	Local control rate, OS
Radiosurgery	Ghia	01/2017	Local control rate
Radiosurgery	McClelland III	1/2023	Local control rate, pain, OS
Radiosurgery	Leeman	10/2019	OS
RFA/Vertebral augmentation	Sheth	11/2020	Technical success
Vertebral augmentation	Ghia	03/2015	Local control rate, pain, OS
Outcomes	Chou	11/2017	Survival, neurological status
Outcomes	Goodwin	12/2019	Quality of life

OS = Overall survival; RFA = radiofrequency ablation; VA = vertebral augmentation.

Discussion

This study reviews the use of MISS for MSD patients in treating spine instability. These techniques provide good pain control and additional potential clinical benefits compared to conventional surgical approached, including decreasing LOS and ease to start/resume systemic/radiotherapy treatment(s). Emerging new therapeutic minimally invasive options include SRS, vertebral body augmentation (VA) and/or RFA and LITT alone or in combination.

Pain control is an important aspect of MSD. Radiosurgery has been shown to provide excellent pain control.⁹ However, in some patients the loss of vertebral body height secondary to a pathological fracture can raise the question of instability prevention. Thus, VA can be clinically indicated. Our study showed that percutaneous VA provides good pain control with 23/36 (64%) studies where pain control was the primary outcome, reporting improved postprocedural pain improvement. This is lower than the pain control reported with SRS procures ranging from 75% to 100%. Additionally, VA does not result in cytoreduction while SRS does. On the other hand, VA provides the potential advantage of performing tissue diagnosis at the time of the procedure. This might be desirable in cases where the diagnosis is unclear and/or tissue is needed to facilitate targeted therapies.

While VA is generally considered a safe and effective procedure in treating pathological fractures and restoring vertebral body height in the case of spinal metastases, potential complications such as cement leakage, which is particularly high in the metastatic spinal disease population, might limit its use. In a recent 10-year observational study, a cement a leakage rate of 61% was reported in a 300 patient cohort.⁴⁷ While the majority of these leaks are clinically inconsequential, Wang et al. reported that in a series with a 57% leak rate, 28% of leaks entered the spinal canal, and 17% of leaks were intravascular.⁵⁰ Cement leakage resulted in neurological deficit from canal invasion, or pulmonary embolism from intravascular leakage. Prior studies have shown that incremental temperature delivery methods and lower cement volumes can mitigate leak rates.^38,49 In comparison, spinal SRS might result in vertebral compress fractures, which may be seen in up to 21% of segments; however, this rarely is of clinical significance.⁶⁶

RFA offers a multifaceted approach to local disease control of metastatic spinal tumors. In the 6 studies in the systematic review, RFA was found to be effective in pain control, with all 4 studies measuring VAS scores showing significant improvement following therapy.^25,61–63 In these studies, patients saw significant improvement from preoperative pain levels at both 3-month⁶¹ and 6-month time points.^25,63 Beyond pain control, RFA may offer diagnostic and cytoreductive capabilities. Local tumor control was shown to have rates up to 100% with RFA with shorter-term follow up, and studies showing rates of 97% with 10-month follow up, and up to 98% with a mean follow up of 39 months.^25,59–63 These results are comparable to symptom and tumor control seen with SRS, with reported up to 96% pain control rate, and a local control rate ranging from 84% to 95% with follow up between 12 and 21 months.⁵³ However, unlike SRS, RFA offers the ability to biopsy at the same time as the procedure, offering a diagnostic component that may be valuable in patients where tissue diagnosis is necessary. RFA is well tolerated with infrequently reported complications. Our review showed 4/6 articles reporting no complications,^25,59,60,63 one study reporting transient postoperative radiculopathy in 2 patients,⁶¹ and 1 study with a permanent S1 nerve root injury, and another with a thermal skin injury.⁶² By improving both pain and neurological outcome among this patient population, patient QoL is improved. While these procedures are largely not curative, their emphasis on prevention of local progression and improvement of symptoms for the patient must not be understated.

When spine instability is diagnosed in MSD patients,^10,42 spine stabilization is needed. MISS techniques have gained popularity for stabilization in spinal degenerative disorders as they result in decreased tissue disruption, blood loss, postoperative pain and morbidity, and provide faster recovery times compared to traditional open surgery techniques.^13,17,52,67 Additionally, MIS approaches have shown other benefits compared to open surgery, as seen by the low UTI rate (Table 2), which may be explained by a decreased rate of catheter placement, which has been associated with UTI in spine patients.⁶⁸ Our study shows that MISS has similar benefits in MSD patients. This is particularly important for the spinal oncology population as MSD patients often are medically complex with significant comorbidities, including coagulopathic and immunodeficiencies. In the current review, MISS techniques have been shown to confer a shorter postoperative recovery,⁵⁰ shorter operative times,^17,52,53,56 faster recovery, and initiation of adjuvant therapies.^{13,51,55,57,67} The shortened postoperative period is a key advantage to MISS, as adjuvant therapies, rather than surgical intervention, yield a survival benefit, and therefore a faster recovery from surgery is in the goal. Additionally, MISS has been shown to not have a steep learning curve, leading to easy adoption for spine surgeons who may not have a clinical focus in spinal oncology,⁵⁸ improving access of care to patients in this population.

Similar to open approaches, our review showed that MISS techniques are effective in restoring neurological function as well as correcting segmental and global alignment. Ambulation has previously been used as a primary outcome measure in patients with spinal epidural disease, as shown in the landmark study on surgical decompression of metastatic cancer causing spinal cord compression¹² Ambulation has been shown to be a reliable measure of functional outcome in patients with metastatic spinal cord compression, with Frankel grade as a validated measure of ambulation.^25,69 In the current review, all 6 of the 10 stabilization studies with ambulation as an outcome measure showed improvement in ambulation following surgical stabilization.^{13,51–53,57,58} This corroborates the concept that MISS approaches are effective in both preserving and restoring neurological function from metastatic spinal cord compression.

The field of MISS for MSD patients continues to move forward as shown by the currently 15 clinical trials validating the use of SRS, VA, and RFA, as well as introducing novel techniques to the spine, such as LITT,⁷⁰ previously shown to be safe and effective in the treatment of cranial metastases.⁷¹ Additional emerging technologies aim at making surgery safer and more effective for patients, including the use of robotic surgical systems.^18,72 An additional advance in MISS is the use of new instrumentation material using carbon fiber-reinforced polyetheretherketone implants. This results in less MRI artifact facilitating earlier detection of recurrence and improving accuracy of radiation dosing.⁷³

Previous reviews of MISS techniques for MSD have been limited in scope and applicability. As a result of a lack of robust literature on the use of MISS techniques for metastatic disease, multiple systematic reviews have included 10 or less studies, limiting generalizability to this patient population.^15,16 Additionally, as seen in the degenerative spine literature, the fluidity in defining minimally invasive spine may make comparing results of studies difficult due to a lack of consistency of inclusion criteria. Dhamija et al. includes open spinal instrumentation as minimally invasive approaches,¹⁴ while other studies define minimally invasive as percutaneous.¹⁵ In the current review, the definition of MIS is broadened to all percutaneous procedures (in addition to noninvasive procedures such as radiosurgery), including percutaneous instrumentation, VA, and more. The authors feel this definition better encapsulates the essence of this approach, by limiting surgical exposure, and subsequently associated morbidity.

Major gaps persist in the literature limiting our understanding of the MISS and procedures reviewed in our study. While the studies reviewed highlight technical advancement in surgical management, they lack longitudinal data demonstrating the interplay of stabilization with the disease course. Of the 10 studies, only 3 highlighted patients with recurrent disease, with 2 of the 3 studies citing a single patient. As surgical stabilization may offer a long-term management strategy compared to palliative treatments such as radiation therapy for pain management, further studies focused on deeper understanding of the multifaceted aspects of MSD, including QoL are needed. Additionally, the understanding of patient-specific factors in this population is poorly identified. In the studies on surgical stabilization, while all patient cohorts reported age and gender, no studies reported on race, ethnicity, or other social determinants of health (SDoH). Disparities are widely prevalent across many types of cancers.⁶⁸ Mowing forward a more granular documentation of SDoH will allow a better management of MSD.

Conclusions

In conclusion, MISS offers advantages over conventional surgery for patients with MSD, including shorter LOS, improved neurologic outcomes, and low complications. The field of spinal oncology is moving forward exploring new surgical adjuvants to improve precision and new techniques alone or in combination to further the care of MSD patients. A Team approach to MSD patients will continue to provide the best patient’s specific care for this expanding patient population.

Conflict of interest statement

None.

Data Availability

No new data were generated or analyzed in support of this research.