This document reviewed appropriateness of treatment for metastatic neoplastic vertebral fractures. Conclusions are drawn from a methodology1, designed to provide answers to clinical scenarios regarding care of metastatic neoplastic fractures based on the existing evidence2-60 and clinical expertise from a balanced panel of thought leaders. Scenarios that are “appropriate with agreement” are clearly reasonable to consider. Scenarios that received a final rating of “uncertain” or “disagreement” may be reasonable to consider but should also incorporate additional patient-specific information. Scenarios with a final rating of “rarely appropriate” are most likely not a reasonable treatment option for the given scenario. Uncertain ratings likely arise when the strength of the current literature is weaker and experience with the treatment has been variable. These are often scenarios in which success has been realized but results are more inconsistent and controversial, or the potential for harm is higher. In these cases, more scientific study is needed to clarify the recommendation. This is not a declaration that these treatments are appropriate or inappropriate. Rather they can be considered but deserve more scrutiny on an individual basis.

Medical treatment encompassed a wide range of therapies. Segmenting each discrete therapy was beyond the scope of this study and therefore, more granular recommendations could not be made. Regardless, it is important to note that medical treatment was determined to be of value in some form for all patients with neoplastic vertebral fractures.

Treatment of neoplastic vertebral fractures are often palliative and directed towards improved quality of life.61, 62 Therefore, unlike osteoporotic fractures, treatment should initiate promptly as the bone destruction does not heal without intervention.36, 18 The objective, therefore, is to use a combination of treatment options to improve clinical outcomes, while minimizing complications and morbidity.63-65 Multispecialty discussion and a treatment plan is crucial in the management of patients with neoplastic vertebral fractures.66 It was apparent during discussions at the rater meeting that treatment modalities for neoplastic fractures were often considered in combination, consistent with multiple studies.67-71 However, this study can only provide recommendations for each treatment individually and does not provide specific appropriateness for combination therapy.

The results suggest emergence of algorithms for care, which are reflected in the decision trees (Figures 2 and 3). Surgical indications were largely driven by stenosis, instability, and prognosis, and to some extent pain and fracture morphology. This is consistent with the classic study by Patchell75, where surgical decompression and stabilization followed by radiotherapy provided the best outcome for treatment of solid organ spinal metastases with abnormal neurology due to spinal cord compression. Other studies also support the above indications for surgery.73-78 Cement augmentation could be used in combination with surgical reconstruction. Scenarios that supported cement augmentation alone or in combination with radiation and/or ablation were primarily driven by the absence of stenosis and neurological deficits and presence of stability. Pain and favorable fracture morphology were also important. While they are not without potential complications, several studies support the use of cement augmentation for the right indications in the treatment of neoplastic compression fractures.79-86

The single driver for radiation was radiosensitivity. Without knowing tumor type, efficacy of radiation treatment is difficult to assess since there is a gradation of sensitivity to radiation depending on characteristics of the tumor. Also, radiotherapy may be done with different protocols and modalities including but not limited to conventional, stereotactic, and proton beam.87,88 Recommendations for detailed radiotherapy options was not the objective of this study, but rather to determine what features of the tumor in general suggested appropriateness for consideration of radiotherapy. Several studies have shown efficacy of XRT for treatment of spinal metastases, although depending on the extent of disease, this is often combined with other treatment, including surgery which often precedes radiotherapy.72,76,89-92 For the purpose of rating in this study, radiation therapy was considered for appropriateness even if it was not the initial first line of treatment.

A possible algorithm includes first evaluating the patient for reconstructive surgery. The most important variables in determining the final appropriateness of surgery included stability, spinal stenosis, prognosis, and pain. Scenarios with unstable fractures, spinal stenosis with neurologic changes, VAS pain scores > 6, and a good prognosis were more likely to receive a final rating of “Appropriate with Agreement”. Stable fractures without spinal stenosis, a poor prognosis, or lower pain scores were less likely to receive a recommendation for surgery. Radiation therapy received a final recommendation of “Appropriate with Agreement” in 100% of scenarios listed as radiosensitive and never received a recommendation of “Rarely Appropriate.” Thus, radiation therapy should always be considered in the treatment of neoplastic vertebral fractures.

In the absence of clear surgical indications, cement augmentation is a consideration for the treatment of focal mechanical pain due to tumor destruction. The results suggest that cement augmentation is appropriate to consider in some scenarios. Patients without spinal stenosis and with stable fractures but VAS pain scores > 6 may be appropriate candidates for considering cement augmentation. There are situations where surgery is less appropriate due to comorbid conditions. In those circumstances, and where there is vertebral compression or destruction of the posterior vertebral wall, cement augmentation can be considered for pain relief with the use of high precision imaging guidance (such as CT) and with very controlled delivery of cement. While high quality studies do not exist, there are several studies that suggest cement augmentation can produce favorable outcomes for pain relief in select patients.93-97

Ablation is an evolving procedure requiring more research and clinical experience to determine appropriate use in the treatment of neoplastic fractures.98-102 Currently, ablation is often used to change the consistency of the tumor prior to cement augmentation.103-106 Consistent with the limited available high-level evidence, no scenarios received a final rating of appropriate with agreement for ablation as a treatment option. There were a substantial number of uncertain ratings, and this suggests that further experience and research is needed to help clarify the role of ablation.

These criteria do not represent a “standard of care,” nor are they intended as a rigid treatment protocol. AUC define appropriateness of a treatment modality. It is anticipated that there will be patients who will require less or more treatment than the average patient for a given scenario. It is also acknowledged that in atypical cases, treatment falling outside these criteria will sometimes be necessary. However, it does provide an evidence-based document to help guide decision-making. The descriptions are important. “Appropriate” does not mean a practitioner must follow a treatment but rather, the treatment would be reasonable to consider with likelihood of more benefit than harm. “Uncertain / maybe appropriate or Disagreement” implies either a lack of evidence or conflicting evidence that combined with experience does not establish clear certainty for treatment for a given scenario. Lastly, “rarely appropriate” is a fairly strong declaration of opposition but does not mean that a scenario would be ill-advised in all circumstances.