Follow‑up and Outcomes
Postoperative complication was observed in one patient who had surgical site infection and recovered after debridement and antibiotic therapy. No surgical-related perioperative death occurred in this series, but one patient died 1 month after surgery due to rapid progression of the primary lung cancer. For other 29 patients, all had substantial pain relief after spinal surgery. The mean VAS score dropped from 7.2 (range 4 to 10) preoperatively to 2.9 (range 1 to 5) postoperatively. 10 (34%) patients had an improvement of neurological function in their 2-month follow-up. Frankel Grade showed 1-grade improvement in 9 (31%) cases and 2-grade improvement in 1 (3%) case. The general performance status of patients was also improved at least 1-grade of ECOG-PS in 9 (31%) patients, and the rate of patients with ECOG-PS of 0–2 raised from 52% (15 cases) to 69% (20 cases).
The mean follow-up duration was 11.8 (range 1 to 68) months for all patients. 25 (83%) patients died with a mean period of 10.5 months (range 1 to 68) between observing spinal metastasis and death, while 5 (17%) patients are still alive with a mean survival time of 18 months (range 6 to 46). According to Kaplan–Meier curve, the 1-year survival rate in all patients was 29.1%, with the median OS time of 9 (95% CI 4.2–13.8) months. Kaplan–Meier curve of OS for all 30 patients is shown in Figure 1A.
Among the five dimensions of the EQ‐5D‐3L, health problems in pain/discomfort improved most frequently, followed by anxiety/depression, mobility, self‐care, and usual activities. The mean EQ-5D-3L utility score was 0.3394 (median, 0.339; range −0.149 to 0.795) before surgery, while the mean utility score at 2-month follow-up rose up to 0.5884 (median, 0.604; range 0.22 to 0.887), and the difference was statistically significant (P < 0.001). Notably, the preoperative EQ-5D-3L utility score was less than zero in 6 patients (20%), emphasizing the terrible condition for patients with SCC caused by SCLC.
Univariate and Multivariate Analysis of Prognostic Factors
The univariate analysis of the prognostic factors affecting OS is shown in Table 1. Patients with postoperative ECOG-PS of 0–2 had a longer OS time than those with the score of 3–5 (P=0.022). OS time significantly increased in patients who received immunotherapy (P=0032). There were no significant differences in other patient-, tumor-, and treatment-related factors.
The above-mentioned two potential prognostic factors were then submitted to the multivariate Cox regression model, and the results showed that both were independent prognostic factors for OS (Table 2). Postoperative ECOG-PS of 3–5 was significantly associated with a higher risk of death (HR=3.14, P= 0.016). The risk of death was significantly decreased in patients who received immunotherapy (HR=0.32, P= 0.016). Kaplan–Meier curves of OS for postoperative ECOG-PS and immunotherapy are shown in Figure 1B and C.
Lung cancer is the most common malignant tumor worldwide. SCLC accounts for 15% of all lung cancers, with more than 180,000 cases per year.3 It is reported that more than a quarter of patients with SCLC developed spinal metastasis, but SCC was identified in only 4% of patients.13 Patients with metastatic SCC caused by SCLC who were candidate for surgical intervention were even rarer and poorly understood. To our knowledge, our study represents the largest series of SCC secondary to SCLC. In this study, 30 consecutive patients with SCLC undergoing surgical treatment for metastatic SCC in the past ten years were reviewed. Our study revealed that urgent decompressive surgery played an important role in improving patients’ QoL. Postoperative ECOG-PS and immunotherapy were independent prognostic factors.
Bone metastasis was considered to affect survival negatively. In the series of Kang et al,6 178 patients with SCLC at extensive-stage were reviewed, 61 of them had bone metastases at the time of diagnosis. 70.5% of patients received chemotherapy with or without palliative radiotherapy, 9.8% received palliative radiotherapy only, and 19.7% did not receive cancer treatment but supportive care. The results showed that OS of patients with bone metastases was shorter than that of patients without bone metastases (4.13 vs 6.17 months, p = 0.015). Early in 1989, Goldman et al,13 reviewed 24 patients with SCC caused by SCLC. Three patients underwent surgical decompression of the spinal cord and radiotherapy. Fourteen patients received radiotherapy, six in conjunction with dexamethasone. Seven patients were given symptomatic treatment only. The median survival from presentation of SCLC was 33 weeks, but only 6 weeks from SCC. In addition, several cases in the literature of spine or spinal cord metastasis from SCLC were also reviewed,19–27 and the main results are shown in Table 3. The survival time of those cases after spinal metastasis ranged from 6 days to 20 months. In our series, the median OS time was 9 months after spinal surgery. Two main reasons may account for the relatively better prognosis in ours. Firstly, the improvement in systematic chemotherapy and development of new therapeutic strategies in past decades contributed to a better overall prognosis in SCLC.28 Moreover, a stricter inclusion criterion was followed by us. Only patients who had both a slight systemic burden of tumor and a good performance status to tolerate surgical intervention and systematic therapy were included in our study.
Actually, surgery is not always recommended for spinal metastasis of SCLC. Radiotherapy or radiosurgery could be regarded as an appropriate choice for patients with bone-only disease. However, when it develops to SCC, surgery should be encouraged. In our series, all operative patients were presence of neurological risk, including both current neurological signs or symptoms and potential neurological compromise based on Bilsky epidural SCC scale. Mechanical instability assessed by SINS classification system is another indication for surgery in our series, for pathologic fractures do not respond to radiotherapy and chemotherapy. In addition, although pain control was one of the important goals of surgery, pain itself was not a sufficient prerequisite to performing operation.
With the advances in surgical technology and instrumentation, improved outcomes and a broader spectrum of interventions are available to patients with spinal metastatic tumors. Because few patients with extensive-stage disease of SCLC achieve overall treatment response, therapies for symptom control and improved QoL are of particular importance.4 In our series, unbearable pain, the most common chief complaint, was relieved substantially in all patients after operation. Improvements in neurological function and performance status were also observed in 10 and 9 patients, respectively. Notably, ambulation ability (Frankel Grade of D-E) was recovered in four patients who preoperatively lost ambulation ability, and five patients regained their self-care ability (ECOG-PS of 0–2) 2 months after surgery. Moreover, patient-reported QoL assessment has been recognized as one of the most important tools for evaluating treatments. In this study, EQ-5D-3L, which have been widely used in clinical trials over 25 years, was selected as a tool to evaluate the QoL from the perspective of patients, and the EQ-5D-3L utility scores showed a significant improvement postoperatively. Therefore, despite the short survival time in SCLC, spinal surgery played a critical role in improving patients’ QoL.
For metastatic spine tumor surgery, it is crucial to prevent postoperative complications to ensure that the iatrogenic effects will not exceed its potential benefits.29,30 In our series, both patients’ and surgeons’ aspects were controlled to reduce risk of postoperative complications. On the one hand, strict patient selection was conducted to exclude high-risk patients from surgery. On the other hand, surgeries were performed by specialized surgeons with at least 10-year experience in spine tumor surgery. As a result, only one patient suffered from surgical site infection. Patient-related risk factors for postoperative complications including advanced age, poor nutritional status, comorbidities, prior radiotherapy were not observed on this patient. Thus, whether the iatrogenic factors on him, such as preoperative embolization, intraoperative chemotherapy and etc., would influence the likelihood of postoperative complications would be our next research direction.
ECOG-PS is a standard criterion to comprehensively measure and evaluate the living ability of patients. ECOG-PS was reported to be an independent prognostic factor for patients with bone metastasis of SCLC,6 and patients with spinal metastasis of NSCLC.11 Similarly, our results showed that postoperative ECOG-PS of 0–2 significantly predicted favorable prognosis. Understandably, a good health status was important to enable patients to withstand the following systemic chemotherapy and immunotherapy. Meanwhile, bedridden-related problems (such as increased susceptibility to infection, decubitus ulcer, and deep vein thrombosis) could also be avoided in patients with the ability of ambulation and self-care. Therefore, although the goal of surgery for spinal metastasis is palliative, surgery may improve the survival time indirectly for a proportion of patients, especially who regained their self-care ability, by providing them with better performance statuses.
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