Interventional procedure overview of radiofrequency ablation as an adjunct to balloon kyphoplasty or percutaneous vertebroplasty for palliation of painful spinal metastases

Efficacy summary

Pain reduction

In a systematic review of 15 studies on RFA with cement augmentation for spinal metastases, pooled analyses indicate that RFA treatment reduced pain in the short term (VAS scores reduced at 3 to 5 weeks: SMD 2.24, 95% CI 1.55 to 2.93; 8 studies, n=286) at medium term (3 to 4 months: SMD 3.00, 95% CI 1.11 to 4.90; 4 studies, n=98) and long-term follow up (5 to 6 months: SMD 3.54, 95% CI 1.96 to 5.11; 4 studies, n=144; Murali 2021).

In a systematic review of 9 studies (4 prospective and 5 retrospective) on RFA as a palliative treatment in 583 patients with painful metastatic spinal lesions, all studies reported that patients experienced a reduction in pain (72% [437/583] of these patients had an additional vertebroplasty treatment). Pain was measured using instruments such as VAS and NPRS, in which higher scores represented worst pain. In the 4 prospective studies, 1 study (Bagla 2016) reported a statistically significant decrease in pain from baseline NPRS score of 5.9 to 2.6 at 1 month and 2.1 at 3 months (a decrease of 3.3 and 3.8 points, respectively; p<0.0001). Similar results (decrease in baseline VAS mean score from 7.5 to 2.7, p<0.0005 after 1 week) were reported in another study (Nakatsuka 2009). Local pain relief was reported in 87% (13/15) of patients at 2 to 4 weeks (Georgy 2009) and sustained in 90% (9/10) of patients during survival period (Nakatsuka 2009). In another study (Proschek 2009), pain at baseline (mean VAS score 7.6 in RFA group [n=8] and 7.9 in RFA plus vertebroplasty group [n=8]) decreased to 4.0 (p<0.008) in the RFA group and 3.5 (p<0.005) in the RFA plus vertebroplasty group, respectively, at 15 to 36 months follow up (Rosian 2018).

A systematic review of 8 studies (4 prospective and 4 retrospective) of RFA plus additional cement augmentation in 239 patients with painful spinal metastases reported statistically significant pain relief compared with baseline (mean baseline VAS scores ranged between 5.9 and 8; mean baseline NRS scores ranged between 5.9 and 8). Five studies reported more than 4 points of pain reduction (mean score ranged from 4 to 5.7) and 2 studies reported more than 2 points of pain reduction (mean score 3.3 and 3.8) between baseline and last follow up (range 1 week to 6 months). Two studies reported results separately for the group having RFA plus cement augmentation compared with the group having RFA alone. One study (Nakatsuka 2009) reported that at 1‑week follow up, VAS decreased from baseline 4.3 to 1.7 (p=0.0004) in the RFA alone group (n=4) and from 6.6 to 1.7 (p=0.003) in the RFA plus cement augmentation group (n=6). Similarly, in another study (Proschek 2009) between 15 to 36 months of follow up, VAS decreased from 7.9 to 4 (p=0.008) in the RFA alone group (n=8), and from 7.6 to 3.5 (p=0.005) in the RFA plus cement augmentation group (n=8; Cazzato 2018).

A systematic review of 8 retrospective studies on combined RFA and vertebral stabilisation techniques for palliative treatment of vertebral metastases reported a decrease in pain VAS scores from baseline. RFA followed by percutaneous kyphoplasty (in 3 studies) resulted in decreased pain scores from baseline and between 1 week to 6 months of follow up (VAS scores at baseline ranged from 7.2 to 7.9 and at last follow up ranged from 2.96 to 3.82). RFA followed by vertebroplasty (in 4 studies) resulted in decreased pain scores from baseline and between 3 days to 15 months of follow up (VAS scores at baseline ranged from 6.3 to 8.5 and at last follow up ranged from 2.4 to 3.5; Greif 2019).

A prospective case series of 100 patients with painful metastases who had RFA plus additional cement augmentation (in 97%) reported that the mean worst pain score (measured using the Brief Pain Index) decreased from 8.2 at baseline to 3.5 at 6 months follow up (n=22; p<0.001 for all visits). Patients experienced significant improvement in average pain for all visits (from 6.0 at baseline to 2.9 at 6 months, p<0.001) and pain interference (from 6.1 at baseline to 2.5 at 6 months, p<0.001; Levy 2020).

A retrospective comparative case series of 87 patients with spinal metastatic tumours (125 vertebral bodies) compared RFA combined with bone cement (35 patients with 47 vertebral segments) with bone cement alone (52 patients with 78 vertebral segments). This reported that pain scores (measured using VAS) and disability scores (measured using ODI scores) for the 2 groups improved significantly at 3 days and at 1 month compared with baseline. But no significant difference was seen between the groups. At 6-month follow up, pain scores and disability scores were statistically significantly lower in the RFA combined with bone cement group than those in bone cement alone group (Lv 2020).

A retrospective analysis of 64 patients comparing RFA plus vertebral augmentation (n=34) with kyphoplasty alone (n=30) reported an overall decrease in pain scores for all treatment groups from baseline and between 7 to 14 days (RFA with SpineStar system 6.9 to 3.3; RFA with OsteoCool system 6 to 3.28; kyphoplasty alone 6.3 to 3.69). However, a difference of square means analysis showed no statistical difference in pain scores at each time interval between the 2 RFA systems, and there was no statistical difference in pain scores when each RFA system was compared with kyphoplasty alone (Jain 2020).

A retrospective analysis of 26 patients (with 28 spinal metastases) who had RFA plus cement augmentation (n=17) or RFA plus radiotherapy (n=10) reported that there was a significant decrease in the pain scores in both the groups (RFA plus cement augmentation group VAS score decreased from baseline 4.2 to 2.7 at 3 weeks and 2.1 at 12 weeks, p<0.0001; RFA plus radiotherapy group VAS score decreased from baseline 4.5 to 2.7 at 3 weeks and 1.6 at 12 weeks, p<0.0001). However, there was no significant difference in pain scores between the 2 groups at these follow-up periods (p=0.96; Prezzano 2019).

In a retrospective analysis of 169 patients with spinal metastases comparing combined percutaneous vertebroplasty with radiofrequency ablation, 125I seed implantation, zoledronic acid or radiotherapy, there was no statistically significant difference in VAS, ODI scores or WHO pain relief during the follow-up periods (24 hours, 1 month or 6 months, all p<0.05). Patients who had PVP plus 125I seed implantation (n=49) reported significantly decreased VAS scores from a baseline of 8.16 to 2.39 at 6‑month follow up (p<0.005), and WHO pain relief was reported in only 67% patients (6 months after treatment). Patients who had PVP plus radiotherapy (n=31) reported decreased VAS scores (from baseline 7.91 to 4.63 at 6 months, p<0.005) and had better pain relief, with the highest WHO pain relief reported by 84% of patients. The PVP plus zoledronic acid group (n=38) reported decreased VAS scores (from baseline 8.02 to 3.99 at 6 months, p<0.05) but only 66% of patients had WHO pain relief at 6 months. The PVP plus RFA group (n=51) also reported decreased VAS scores from baseline 8 to 4.3 at 6 months (p<0.05; Lu 2019).

A retrospective cohort study of 166 patients with spinal osseous metastases (266 tumours) who had RFA combined with vertebral augmentation reported a statistically significant improvement in pain (measured using BPI scores) from baseline 8 to 3 at all follow-up periods (p<0.001 for all; Tomasian 2021).

Progression or recurrence of vertebral metastases

In the systematic review of 15 studies, 13% (51/387) of patients with different tumour histologies reported failure of local tumour control or tumour recurrence between 2.5 months and 5 years follow up (Murali 2021).

In the systematic review of 9 studies, 1 study (Proschek 2009) reported that none of the patients had a local relapse after treatment with RFA alone or RFA in combination with vertebroplasty (Rosian 2018).

In the systematic review of 8 studies (Cazzato 2018), 3 studies reported local tumour control and progression outcomes. One study (Anchala 2004) reported stable disease in 77% of patients at an average 82-day follow up, and local progression was noted in 23% of patients at an average 82-day follow up. Another study (Greenwood 2015) reported locally stable disease in 92% (12/13) of patients at 3 months and 100% at 6‑month follow up. In another study (Yang 2017), 67% of patients did not have tumour progression at 2‑year follow up.

The retrospective comparative case series of 87 patients with spinal metastatic tumours (125 vertebral bodies) compared RFA combined with bone cement (35 patients with 47 vertebral segments) with bone cement alone (52 patients with 78 vertebral segments). It reported that the tumour recurrence rate in RFA combined with bone cement group was significantly lower than those in the bone cement alone group (11% compared with 31%, p<0.05; Lv 2020).

The retrospective analysis of 26 patients (with 28 spinal metastases) who had RFA plus cement augmentation (n=17) or RFA plus radiotherapy (n=10) reported that at a median follow up of 8.2 months, local failure (recurrence or progression within the treated vertebral level) was noted in 47% (8/17) of metastases treated with RFA plus cement augmentation compared with 9% (1/11) of metastases treated with RFA plus radiotherapy (p=0.049). Time to local failure was 44 weeks in patients who had RFA plus cement augmentation but was not yet reached in those treated with RFA plus radiotherapy (p=0.016). There was no difference in distant failure (any disease progression outside of the treated vertebral level) between the 2 groups (p=0.70). Time to distant failure was not statistically significantly different between the 2 groups (RFA plus cement augmentation: 11.3 weeks versus RFA plus radiotherapy: 36.3 weeks, p=0.15; Prezzano 2019).

Health-related quality of life (HRQoL)

In the systematic review of 15 studies, 5 studies reported outcomes on HRQoL using different measures (FACT‑G7, FACT-BP and ODI). Four studies reported a significant reduction in disability and improvement in HRQoL in the short term (within 3 months follow up). Mid-term (at 3 to 12 months) and long-term outcomes (over 12 months follow up) were not consistent across studies and remained clear (Murali 2021).

In the systematic review of 9 studies, HRQoL was assessed in 2 studies using different measures (FACT‑G7, FACT-BP and ODI). In 1 prospective study of 50 patients treated with RFA plus cement augmentation (Bagla 2016), significant improvements in mean scores for disability and cancer-specific health-related quality of life from baseline to 3 months were reported (ODI improved from 52.9 to 37.0, p<0.01; FACT-G7 improved from mean 11 to 16.2, p=0.0001; FACT-BP improved from 22.6 to 38.9, p<0.0001). In a study of 16 patients (Proschek 2019), 8 who had RFA alone and 8 who had RFA plus vertebroplasty, improved quality of life was reported (mean ODI scores improved from 64% at baseline to 33%, p=0.06 at 3 to 6 months follow up in the RFA group; and from 66% at baseline to 35%, p=0.071 at 15 to 36 months follow up in the RFA plus vertebroplasty group; Rosian 2018, Cazzato 2018).

In the retrospective analysis of 169 patients, the PVP plus RFA group (n=51) reported the lowest ODI scores (decreased from baseline score 71 to 37 at 6 months, p<0.05) whereas the PVP plus zoledronic acid group (n=38) reported the highest ODI scores (from baseline score 68 to 49 at 6 months, p<0.05; Lu 2019).

The prospective case series of 100 patients with painful metastases who had RFA reported a significant improvement for all visits in quality of life measured using European Quality of Life questionnaires (from 0.48 at baseline to 0.69 at 6 months, p<0.006; Levy 2020).

Medication use

The retrospective analysis of 64 patients comparing RFA plus vertebral augmentation (n=34) with kyphoplasty alone (n=30) reported that the 2 RFA groups and the kyphoplasty alone group had similar opioid usage during the first month after the procedure (p=0.82; Jain 2020).

Survival

The retrospective analysis of 26 patients (with 28 spinal metastases) who had RFA plus cement augmentation (n=17) or RFA plus radiotherapy (n=10) reported that median survival in the RFA plus cement augmentation group was 31.9 weeks, compared with 55.3 weeks for the RFA plus radiotherapy group (p=0.0045; Prezzano 2019).

Vertebra height

The retrospective comparative case series of 87 patients with spinal metastatic tumours (125 vertebral bodies) compared RFA combined with bone cement (35 patients with 47 vertebral segments) with bone cement alone (52 patients with 78 vertebral segments). It reported that the postoperative vertebral body height of the 2 groups significantly increased compared with baseline. The difference was statistically significant (p<0.001) but no significant difference was seen between the 2 groups (p>0.05; Lv 2020).