Clinical results of multidisciplinary therapy including palliative posterior spinal stabilization surgery and postoperative adjuvant therapy for metastatic spinal tumor

Most cases of metastatic spinal tumor are systemic conditions with few treatment options [1‐3]. Cases of symptomatic spinal metastasis have increased because the survival time of patients with metastatic cancer has been extended by advances in cancer therapy [4]. Metastatic spinal tumor destroys the spine, which induces collapse of spinal support, infiltration into the spinal cord and cauda equina, and compression, which cause pain, paralysis, and disruption of activities of daily living (ADL). Surgeries performed for metastatic spinal tumor are mostly palliative, and use of these procedures in patients with short life expectancy is controversial [5].

Surgical treatment for metastatic spinal tumor with reduced invasiveness is now available, including minimally invasive spine stabilization (MISt) with percutaneous pedicle screws (PPSs) [6‐8] and balloon kyphoplasty [9]. Cancer chemotherapy has also advanced [10], and bone-modifying agents [11] for bone metastasis have been introduced. However, only a few studies have investigated whether these new treatments for metastatic spinal tumor contribute to life expectancy and ADL improvement. In this study, we examined use of not only conventional posterior decompression and fixation surgery but also MISt as palliative surgery and the frequency of postoperative adjuvant therapy for metastatic spinal tumor, with a focus on how much MISt contributed to decreasing surgical stress, early paralysis improvement, extended survival, ADL improvement, and rate of discharge to home.

The patients included 37 males (67.2%) and 18 females (32.7%), and the mean age at the time of surgery was 66.8 years old (Table 1). The primary lesion was lung cancer in 11 patients (20.0%), liver cancer in 9 (16.3%), prostate cancer in 6 (10.9%), myeloma in 5 (9.0%), kidney in 4 (7.2%), thyroid in 4 (7.2%), lymphoma in 3 (5.4%), gallbladder in 3 (5.4%), breast in 2 (3.6%), sarcoma in 2 (3.6%), others in 5 (9.0%), and unknown in 1 (1.8%). The level of the main lesion was the cervical spine in 9 patients (16.3%), thoracic spine in 34 (58.1%), and lumbar spine in 14 (25.4%). The grade of preoperative paralysis on the modified Frankel scale (Table 2) [13] was A in 2 patients (3.6%), B in 1 (1.8%), C in 19 (34.5%), D1 in 15 (27.2%), D2 in 1 (1.8%), D3 in 10 (18.1%), and E in 7 (12.7%). The mean preoperative visual analogue scale (VAS) for pain was 4.6. The Tokuhashi score [1‐3] was 0–8, indicating life expectancy < 6 months, in 40 patients (72.7%); 9–11, life expectancy ≥ 6 months, in 9 (16.3%); and 12–15, life expectancy ≥ 1 year, in 6 (10.9%); with an overall mean of 7.1. The spinal instability neoplastic score (SINS) [12] was 0–6, indicating instability, in 6 patients (10.9%); 7–12, threat of instability, in 48 (87.2%); and 13–18, stability, in one (1.8%); with a mean of 9.4. The epidural spinal cord compression scale (ESCCS) [14] for nerve compression was grade 0, indicating a tumor restricted to the bone, in one patient (1.8%); grade 1a, infiltration in the spinal canal, in 4 (7.2%); grade 1b in 4 (7.2%); grade 1c in 3 (5.4%); grade 2, nerve compression, in 23 (41.8%); and grade 3, marked exclusion of the nerve, in 20 (36.3%). The mean preoperative Barthel index [15] for ADL was 48.7.

The median postoperative survival time determined using the Kaplan-Meier method was 12.0 months (95% confidence interval 2.4–21.5) (Fig. 3). As for two sarcoma patients, they died 10 and 15 months after surgery. Regarding five myeloma patients, they were all alive at 4 to 30 months (mean 11.6 months) after surgery. Paralysis was improved by ≥ 1 grade or grade E was maintained in 35 patients (63.6%) (Table 3). The grade was C or lower before surgery in 22 patients (40.0%), but the number of patients with these grades decreased to 12 (21.8%) after surgery. The postoperative grade was E in 21 patients (38.1%). Paralysis aggravated in 2 patients (3.6%).

The surgical procedure was conventional posterior decompression and fixation in 31 patients (56.3%) and MISt in 24 (43.6%) (Table 4). The mean operative time was 201 min, the mean intraoperative blood loss was 474 ml, and the mean number of levels fused was 5.5. Perioperative complications included massive bleeding of ≥ 1500 ml during surgery in 5 patients (9.0%), death within 30 days after surgery in 3 patients (5.4%), epidural hematoma after surgery in 2 (3.6%), and wound dehiscence in 2 (3.6%). With regard to two postoperative epidural hematoma patients, they were treated with surgical evacuation immediately after diagnosis. As for two patients with wound dehiscence, they were treated with resuture and healed of wound properly.

As postoperative adjuvant therapy, chemotherapy was performed in 31 patients (56.3%), radiotherapy was used in 38 (69.0%), and a bone-modifying agent was administered in 39 (70.2%) (Table 5). The mean preoperative VAS for pain improved from 4.6 before surgery to 0.9 after surgery (P < 0.001), and the mean preoperative Barthel index for ADL improved from 48.5 before surgery to 74.5 after surgery (P < 0.001). In patients with mean preoperative Tokuhashi scores of ≤ 8, 9–11, and ≥ 12, the mean Barthel index improved from 47.5 to 65.9 (P < 0.001), 52.5 to 98.5 (P = 0.01), and 48.0 to 92.0 (P < 0.001), respectively (Fig. 4). Thirty-seven patients (67.2%) were discharged to home, including 48.8% (20/41), 66.6% (6/9), and 100% of patients with preoperative Tokuhashi scores of ≤ 8, 9–11, and ≥ 12, respectively.

Health conditions and quality of life (QOL) may be improved in survivors of advanced cancer with sufficient survivorship care [16]. Prevention of spinal metastasis-induced skeletal-related events (SREs) is an important aspect of survivorship care because pathological fracture is associated with increased mortality [17]. Surgery alone is insufficient to strengthen survivorship care for patients with metastatic spinal tumor, and administration of adjuvant therapy including radiotherapy, chemotherapy appropriate for the cancer type, and a bone-modifying agent (bisphosphonate or denosumab) followed by hormone replacement are necessary. However, there has been a tendency to focus only on the surgical method and short-term improvement of paralysis in evaluation of therapeutic effects.

Given that improvement of outcomes by surgical treatment alone is limited, we used chemotherapy, radiotherapy, and bone-modifying agents after surgery in 56, 69, and 70% of cases in this study, respectively. Of the cases excluding radiation-resistant cancer such as kidney and thyroid cancer, radiotherapy was performed in 38 out of 47 patients (80%). This resulted in improved ADL and greater discharge to home, compared with findings in our previous study [1]. The rate of conventional posterior decompression and fixation surgery decreased to 56%, whereas MISt increased. Performance of MISt at an early stage may have improved ADL, allowed discharge to home, and facilitated use of postoperative adjuvant therapy.

Accurate preoperative prediction of the outcome of surgery for metastatic spinal tumor is difficult [1‐3, 5], and this makes the significance of palliative surgery for patients with short life expectancy controversial. The mean Tokuhashi score was 7.1 in all patients and the score was 0–8 in 40 patients (72.7%), indicating life expectancy < 6 months. Performance of palliative surgery in patients with such a short life expectancy requires consideration of the risk of complications, expected benefits, and medical costs [18]. However, there is also the opinion that palliative surgery should be performed [19] because improvement of ADL by surgery may increase the opportunity for adjuvant therapy after surgery and indirectly extend survival. We also consider that survival can be extended beyond the preoperative life expectancy and ADL can be improved by multidisciplinary therapy including palliative posterior spinal stabilization surgery with reduced invasiveness and postoperative adjuvant therapy. Previous studies of minimally invasive posterior fixation as palliative surgery have focused on technical aspects, surgical invasiveness, and short-term improvement of paralysis, whereas few have examined outcomes of postoperative survival, ADL, and QOL. Improvement of QOL at 30 days after surgery [6] and median postoperative survival of 11.3 months [7] have been reported. In the current study, the median postoperative survival determined by the Kaplan-Meier method was 12.0 months, and the survival time was longer than the preoperative life expectancy in many patients. The mean Barthel index reflecting ADL improved to 74.5 after surgery, but this was not a marked improvement compared with that in our previous study [1]. In patients with mean preoperative Tokuhashi scores of ≤ 8, the mean Barthel index improved from 47.5 to 65.9. However, our criterion for discharge to home was Barthel index ≥ 70 or availability of sufficient care by family members for cases with Barthel index < 70.Hence, the rate of discharge to home was 67%, which showed a marked improvement but still not satisfactory.

Chemotherapy, radiotherapy, and treatment with bone-modifying agents can be performed at an outpatient clinic, and this may have contributed to improvement of postoperative patients’QOL. The limitations of this study were that the study design was retrospective without a control group, and there was insufficient evaluation of QOL, but the rate of patients treated with MISt increased, and MISt is advantageous in that the surgical wound is small and the wound heals rapidly. This may have facilitated early postoperative adjuvant therapy and led to the improved rate of discharge to home, which in turn resulted in improved QOL.

ADL improved and allowed discharge to home, and postoperative adjuvant therapy could be administered at a high rate in patients who received palliative posterior spinal stabilization surgery. Survival time extended beyond the preoperative life expectancy in many patients. Patients with a metastatic spinal tumor have short life expectancy and paralysis caused by spinal instability and spinal cord compression. However, multidisciplinary therapy including palliative posterior spinal stabilization surgery with reduced invasiveness and postoperative adjuvant therapy are effective in these patients.