Volume 7, Issue 1 (Winter 2021)                   Iran J Neurosurg 2021, 7(1): 37-48 | Back to browse issues page

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Vieira Netto L A, Araújo Peres L F, Matos Pereira N, Jardim Zaccariotti A, Arruda Zaccariotti V, Silva Marques R A, et al . Outcomes of Surgical Decompression for Spinal Metastases From Gynecological Cancers: A Retrospective Cohort Study. Iran J Neurosurg. 2021; 7 (1) :37-48
URL: http://irjns.org/article-1-250-en.html
1- Faculty of Medicine, Federal University of Goiás, Goiânia, Brazil.
2- Department of Neurological Surgery, Clinics Hospital of the Faculty of Medicine, Federal University of Goiás, Goiânia, Brazil.
3- Department of Neurological Surgery, Clinics Hospital of the Faculty of Medicine, Federal University of Goiás, Goiânia, Brazil. , drigocavalcante@yahoo.com.br
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1. Introduction
Cancer is one of the leading causes of death in the world. The global incidence has risen to 18.1 million new cases and 9.6 million deaths in 2018 [1]. According to the Centers for Disease Control (CDC), gynecological cancer is any cancer that commences in women’s reproductive organs; thereby, there are five types of gynecological cancer: cervical, ovarian, uterine, vaginal and vulvar, each one with different signs, symptoms and risk factors [2].
In the United States, in 2020, the estimated incidence of female system cancer was 113,520 new diagnoses and 33,620 deaths [3]. In Brazil, the estimated incidence of new diagnosis in 2020 was 16,710 of cervical or cervix cancer, 6,650 of ovarian cancer, and 6,540 of the uterine corpora, with 6,526 deaths of cervical cancer in 2018 [4]. Nowadays, gynecological cancer is consolidating as a public health problem in Brazil. The persistence of Human Papillomavirus (HPV) infections in the population are one of the main factors. It is related to early sexual activity, immunosuppression, multiparity, smoking, and prolonged oral contraceptives. Its incidence has progressively grown and could prevented many deaths with early detection actions and prevention campaigns [5].
Bone metastases from cervical, endometrial, and ovarian cancer are 1.1–5.2%, 0.3–1.8% and less than 1%, respectively [6, 7]. When the tumor infiltrates the spine which made up 52.8% of all bone metastases pain, pathological fractures, and disability are among the most common signs and symptoms. Hence, a decrease in survival rate is observed due to a high systemic tumor burden yielding a reduction of Quality of Life (QoL) caused by disability, severe mechanical pain, and neurological deficits [6, 8].
Aiming to get answers about the best treatment for Mtastatic Spinal Cord Compression (MSCC), Patchell et al. conducted a seminal study that compared the treatments for this condition. In that study, the surgical procedure for spinal cord decompression followed by radiotherapy showed a striking improvement in neurologic status, maintenance, and recovery of ambulation, and reduce pain, increasing the patient’s QoL. Since that study, surgical decompression plus radiotherapy have become the standard of care for patients presenting MSCC with good clinical performance [9, 10].
Nonetheless, the decision-making process to appropriately select patients for surgical treatment is challenging. The surgeon should trade-off the risks and potential benefits of this approach [11]. In this context, the NOMS framework has introduced the concept of the tumor board’s decision, incorporating new technologies, such as new chemotherapeutic agents and stereotactic radiosurgery. This latter treatment’s option obviates invasive surgical approaches for these lesions [12].
Herein, the authors aim to analyze the results of surgical decompression and stabilization in patients presenting metastatic spinal disease from gynecological cancer followed by radiotherapy treatment, focusing on assessing the pain level, the neurological status, analyzing the overall survival, and prognostic factors.

2. Methods and Materials/Patients
This study was authorized by the ethics committee (CAAE number: 10607319.0.0000.0031). A total of 18 patients, who underwent surgical decompression followed by stabilization, were retrospectively reviewed from 2012 to 2019.
Inclusion criteria were patients diagnosed with secondary symptomatic spinal cord compression or nerve root compression for spinal metastases from gynecological cancer, the presence of mechanical pain, spinal instability, and neurological deficits. The exclusion criteria were the lack of complete data in the medical records and if the patient presented complete neurological deficits more than 72 hours at admission. At first, the surgical procedure was generally performed, placing pedicle screws in the vertebral bodies (stabilization) followed by decompression. This procedure was carried out with bilateral laminectomy and the dura-mater decompression in 360º degrees (separation surgery) through a posterior transpedicular approach with minimal posterior vertebral body resection, dissecting the tumor entirely off the dural-sac (Illustrative Case 9; Figure 1).

Only in illustrative case nine, we performed a posterior followed by a lateral approach for vertebral body resection (360º degree approach). In most cases, we placed pedicle screws two levels above and below the affected vertebra. Only one patient (case 12) had cervical lesion, in which the decompression was performed by anterior approach with cage reconstruction.
The evaluation of preoperative and postoperative neurological status was performed using the American Spinal Injury Association Impairment Scale (ASIA): ASIA A (no sensory or motor function preserved in sacral segments S4-S5), ASIA B (sensory, but not motor, function preserved below the neurologic level, and extends through sacral segments S4-S5), ASIA C (motor function preserved below the neurologic level, and most key muscles below the neurologic level have a muscle grade of less than 3), ASIA D (motor function preserved below the neurologic level, and most key muscles below the neurologic level have a muscle grade that is greater than or equal to 3) and ASIA E (sensory and motor functions are normal) [13]. 
The spine stability was evaluated using the Spinal Instability Neoplastic Score (SINS). It takes into account spine location (location of the neoplasm in junctional regions of the spine were graded as a 3, in nonjunctional segments and not articulating with the rib cage or pelvis were graded as a 2, in segments articulate with the rib cage from T3-T10 received a score of 1, and in nonjunctional sacral spine received a score of 0), mechanical pain (pain with movement, upright posture, or loading of the spine and/or this pain is relieved with recumbence received a score of 3, pain without mechanical characteristics received a score of 1, and pain-free lesion received a score of 0), bone lesion quality (lytic lesions received a score of 2, mixed blastic lesions with lytic bone lesions received a score of 1, and blastic lesions received a score of 0), radiographic spinal alignment (subluxation or translation received a score of 4, kyphosis and/or scoliosis received a score of 2, and normal alignment received a score of 0), vertebral body collapse (no vertebral body involvement received 0 points, those with greater than 50% vertebral body involvement with no collapse received 1 point, those with less than 50% collapse received 2 points, and those with greater than 50% collapse received 3 points), and posterolateral involvement (bilateral involvement of pedicles, facets, and/or costovertebral joints received a score of 3, unilateral posterior involvement received a score of 1, and no tumor involvement of the posterior elements received a score of 0), being classified as stable (SINS 0-6), potentially unstable (SINS 7-12), and unstable (SINS 13-18) [14]. 
The pain level was evaluated using the Visual Analogue Scale (VAS), score as follows: VAS (0–4): mild pain; VAS (5–8): moderate pain; VAS (9–10): severe pain [15, 16]. Postoperative pain level and neurological status were evaluated on the fifteenth-day postoperative time – the first clinical outpatient visit after the surgical procedure. Spinal instability scores using the preoperative computed tomography and magnetic resonance imaging scans according to the SINS. The date of death was collected through the medical records or by contacting the family. All patients were followed up during our study. The variable was considered a continuous variable for the analyses of pain level, and the paired t-test of the mean was used.
The analyses of comparison and correlations among the variables used the chi-square test, the Pearson or Spearman correlation test, when necessary, principally for the SINS, ASIA, and VAS variables. Statistically significant results were defined P<0.05. The survival rate was analyzed using the Kaplan–Meier method. All statistical calculations were performed using SPSS Statistics, version 22.0 (IBM Corp., Armonk, NY, USA).

3. Results
The database includes 18 patients whose ages range from 30 to 78 years at the time of admission. The mean age was 54.4 years. Regarding skin color, we found five cases of white patients (n=5; 27.7%) and 13 cases of brown patients (n=13; 72.2%) (Table 1) [17]. The most common type of cancer was cervical cancer (n=12, 66.7%), followed by endometrium cancer (n=4; 22.2%) and ovarian cancer (n=2; 11.1%) (Table 1).

Regarding the analysis of visceral metastases, nine patients (n=9; 50%) had visceral metastases and nine patients (n=9; 50.0%) had no visceral metastases. Among those with visceral metastases, four patients (n=4; 44.4%) had only one visceral metastasis, while five patients (n=5, 55.6%) had two or more visceral metastases (Table 1).
The most common vertebral regions affected by metastases were: first lumbar region (n=30; 50.0%), followed by thoracic region (n=22; 36.7%), sacral region (n=5; 8.3%) and cervical region (n=3; 5.0%) (Table 2).

The most common preoperative VAS was from 9 to 10, with 15 patients (n=15; 83.3%), followed by VAS from 5 to 8, with three patients (n=3; 16.7%). No patients had preoperative VAS from 0 to 5. Regarding postoperative VAS, three patients (n=3; 16.7%) had VAS 0 (no pain), 13 patients (n=13; 72.2%) had VAS from 1 to 4, two patients (n=2; 11.1%) had VAS 5 or 6 and none had VAS from 7 to 10 (Table 2). The Mean±SD of the pain level, pre- and postoperative were 9.39±0.79 and 2.28±1.44, respectively. There was no statistical significance in the t-test (P=0.39) (Table 3). 

As commonly preoperative neurological deficits, we found paraplegia and paraparesis. Therefore, ASIA analysis revealed that most patients had preoperative ASIA D (n=9; 50%), followed by ASIA B (n=3; 16.7%), and finally ASIA A, C and E (n=2; 11.1%, each one). Regarding postoperative ASIA, the most common was ASIA E (n=12; 66.6%), followed by ASIA D with three patients (n=3; 16.6%) and ASIA A, B and C, with one patient each (n=1, 5.6%) (Table 3).
It is important to note that a total of 16 of the cases (n=16; 88.9%) had ASIA grades of A–D before the surgery. This number was significantly reduced to five (n=5; 27.8%) patients after the decompression (P<0.001; chi-square test). The analyses of correlations showed that there was statistical significance in pre- and postoperative ASIA (P<0.001).
The analyses of the SINS showed that the majority of the patients had SINS 13–18 points (n=13, 72.2%), and only five (27.8%) patients had a potentially unstable spine with SINS of 7–12 points (P=0.101; chi-square test). The correlations showed no statistical significance in SINS analyses with preoperative ASIA (P=0.101).
A total of 16 patients (n=16; 88.9%) died within one year of surgical treatment, and only two patients (n=2; 11.1%) survived after this period. Kaplan–Meier analysis revealed a 3-month survival rate of about 43.2% (7 patients), a 5-month survival rate of approximately 18.5% (3 patients), a 16-month survival rate of about 6.2%, and overall median survival was 6.1 months (95% Confidence Interval [CI] 1.10–11.13 months). The comprehensive survival analysis is demonstrated by Kaplan–Meier curve (Figure 2).

The mean survival of non-ambulatory patients (ASIA preoperative A, B and C) before the surgical procedure was 3.2 months (95% CI 2.19-4.37 months); whereas, 7.36 months (95% CI 0.03-14.69 months) for ambulatory patients (ASIA preoperative D and E) before the surgical procedure (P=0.006 – Log-rank Mantel–Cox); 3.3 months (95% CI 2.24-4.42 months) for non-ambulatory patients (ASIA postoperative A, B and C) after the surgical procedure in comparison to 7 months (95% CI 0.23–13.76 months) for ambulatory patients (ASIA postoperative D and E) (P=0.007 – Log-rank Mantel–Cox).
The test of equality of survival distributions for different levels of SINS revealed that the median overall survival for patients with indeterminate instability was 4.8 months (95% CI; 0–10.35 months); 6.73 months (95% CI; 0–13.62 months) for patients with instability (P=0.126 – Log-rank Mantel–Cox). The survival distributions for different levels of SINS are shown in Figure 3

4. Discussion
Surgery and radiotherapy provide a better QoL than radiotherapy alone [10]. This combination reduces the necessity for pain relief medication, and patients retain the ability to walk longer [10, 11, 18, 19]. Our results showed an improvement in the pain score, nonetheless without statistical significance (P=0.39). All of our patients had severe mechanical preoperative pain. They improved the level of postoperative mechanical pain, with mild or moderate pain in 15 patients and absence of pain in three patients. In this series, pain relief was similar to the literature published data, which reported a pain improvement ranging from 70 to 98.3%; even though it was not found a statistical difference in our series, the authors noted a strong clinical significance [9, 18, 19, 20, 21, 22].
In relation to neurologic status, the number of cases with preoperative ASIA A–D in our series was 16 (n=16; 88.9%), being significantly reduced to five (n=5; 27.8%) postoperatively (P<0.001). This finding evidenced that surgical intervention brought about gains in neurological function. Similarly, Cavalcante et al. showed an improvement of 53% in the neurological status (from ASIA B-D to ASIA E) in patients who underwent a tumor decompression and stabilization [9]. In another study, patients with an ASIA score of C or D benefit more regarding the Brief Pain Inventory (BPI) interference construct than those with an ASIA score of E (P=0.04) [23]. Indeed, Gao et al. found that 16 out of 22 operated patients improved neurological function and maintained ambulatory ability in all 11 patients who could ambulate before surgery [6]. 
The SINS score introduction has brought greater clarity among physicians of different specialties regarding recognize spinal instability in patients harboring spinal metastases. Thus, it avoids delays in referring patients with potential instability or spinal instability [24]. In our 18 patients, the SINS analysis presented mechanical failure, in which 72.2% (n=13) had unstable spine; 27.8% (n=5) had potentially unstable spine, contrary to other studies in which the majority of patients who underwent surgery had an impending instability (47% to 71%) [25, 26, 27]. The SINS score reinforces the necessity of mechanical stabilization for patients who can tolerate a surgical procedure such as open or minimally invasive approaches and predicts the improvement of mechanical pain during the postoperative period. However, there was no statistical significance concerning survival and SINS, as well as other similar studies [25, 26]. 
The authors found an Overall Survival (OS) rate after decompression surgery of 6.1 (95% CI 1.1–11.1) months, in agreement with a study [9] in which the mean OS was 6 (95% CI 3.4–7.4) months, and lower than Liu et al.’s study, in which the OS rate was 27 months. Still, only six cases were analyzed, not representing a large cohort [28]. In Gao et al.’s series, the first- and second-year survival rates in all patients were 60.7% and 41.0%, respectively, and the median OS time was 15.0 (10.4–19.6) months [6]. This lowest overall survival in our study could be explained by a high systemic tumor burden found in our patients compared to similar series.
Nine patients had visceral metastases (n=9; 50%), but there was no correlation as a prognostic factor for decreased survival rate. In disagreement with another study, in which patients who had visceral metastases had a median survival of 5.3 (95% CI; 3.4–7.2) months, which was much lower than the median survival of patients with cord-restricted disease (17.8 months) (95% CI 12.5–23.1) [9]. However, it is crucial to understand that overall survival and QoL are two different issues. It is interesting to note that stronger predictors for survival, such as tumor type, spinal metastasis, and visceral metastases’ numbers, were not relevant for assessing the QoL [9, 28].
Analyzing patient’s survival in Helweg-Larsen et al.’s study, it was observed that the ambulatory function (median 7.9 months) after surgical treatment improved the survival rate in comparison to non-ambulatory patients (median 1.2 months). Likewise, in this series, patients who had an ambulatory function before and after the surgical treatment had a conspicuous improvement on overall survival, being these findings statistically significant [7]. This data emphasizes the importance of early metastatic disease detection to prevent the deficits and improve the overall survival.
Although the authors have presented one of the most extensive case series of spinal metastases from gynecological cancer ever reported, this study has some limitations due to its small sample size, lack of controls, and retrospective design.

5. Conclusion
The decompressive surgery and stabilization ensure spinal stability, improve the patient´s neurological status, and reduce pain. Despite that, patients affected by metastatic spinal disease usually have a dismal prognosis, with a low survival rate. Indeed, more prospective studies with a more significant number of patients are necessary for more conclusions concerning prognostic factors and the relationship between survival and decompressive surgical treatment in these patients.

Ethical Considerations
Compliance with ethical guidelines

This study was authorized by the Ethics Committee of Araújo Jorge Hospital (CAAE No.: 10607319.0.0000.0031).

This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.

Authors' contributions
Conception and design: Luiz Alves Vieira Netto, Luís Felipe Araújo Peres, Alice Jardim Zaccariotti, Nayara Matos Pereira and Rodrigo Alves de Carvalho Cavalcante; Data collection: Luiz Alves Vieira Netto, Luís Felipe Araújo Peres, Alice Jardim Zaccariotti and Nayara Matos Pereira; Data analysis and interpretation: Edésio Martins; Drafting the article: Luiz Alves Vieira Netto, Luís Felipe Araújo Peres, Alice Jardim Zaccariotti, Nayara Matos Pereira and Rodrigo Alves de Carvalho Cavalcante; Critically revising the article: Rodrigo Alves de Carvalho Cavalcante, Vladimir Arruda Zaccariotti, Romulo Alberto Silva Marques and João Batista Arruda; Reviewing submitted version of manuscript: Luiz Alves Vieira Netto, Luís Felipe Araújo Peres, Nayara Matos Pereira, Alice Jardim Zaccariotti, Vladimir Arruda Zaccariotti, Romulo Alberto Silva Marques, João Batista Arruda and Rodrigo Alves de Carvalho Cavalcante; Approving the final version of the manuscript: Rodrigo Alves de Carvalho Cavalcante.

Conflict of interest
All authors declare no conflict of interest.

All authors want to thank Mr. Daniel Eugene Kent for his assistance in preparing the manuscript.

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Type of Study: Research | Subject: Spine

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