Minimal Invasive Scoliosis or Open Surgery

1. Purpose and Aims: The primary aim of this study is to evaluate the effectiveness of minimally invasive surgery (MIS) compared to traditional open surgery for the treatment of idiopathic scoliosis. While open surgery remains the gold standard for spinal correction, it is associated with significant tissue trauma, extended hospitalization, and postoperative pain. The emergence of MIS techniques offers potential benefits, including reduced tissue damage, shorter hospital stays, and faster recovery. However, the long-term outcomes and efficacy of MIS in scoliosis correction remain unclear due to the lack of high-quality evidence, particularly from randomized controlled trials (RCTs). This study is designed as a multi-center, two-arm, non-inferiority RCT to determine whether MIS can achieve comparable outcomes to open surgery in terms of: 1. Primary surgical outcomes: Reoperation rates, serious complications, surgical site infections, postoperative pain levels, and fusion success. 2. Secondary measures: Hospitalization duration, screw placement accuracy, neurophysiological events, blood loss, operative time, and patient-reported outcomes (PROMs). A key challenge in MIS is the accurate placement of implants in the deformed spine while minimizing disruption to surrounding tissues. The study will assess whether the use of intraoperative 3D imaging and robotic-assisted surgery (RAS) enhances precision while maintaining surgical success. By addressing these critical questions, this trial aims to provide high-quality evidence on the role of MIS in scoliosis treatment. If MIS proves to be as effective as open surgery while offering faster recovery and fewer complications, it could lead to a paradigm shift in scoliosis management, improving patient care and reducing healthcare burden. 2. Background: Idiopathic scoliosis is the most common spinal deformity, affecting 1.9-3.0% of the population and often requiring extensive surgical treatment during youth. Beyond the challenges of treatment and the high healthcare costs, scoliosis can significantly impact quality of life, both in adolescence and adulthood. Surgical intervention is typically indicated for Cobb angles exceeding 45 degrees in skeletally immature- and 50 degrees in skeletally mature patients. The standard approach involves posterior spinal fusion via open surgery, allowing near-anatomical correction but resulting in extensive tissue damage, prolonged hospitalization, and significant postoperative pain. Recent protocols such as Enhanced Recovery After Surgery (ERAS) have optimized pain management, enabling some patients to be discharged within 1-2 days. Minimally invasive surgery (MIS) has evolved in spine surgery, offering potential advantages such as reduced tissue trauma, lower blood loss, and faster recovery. However, its role in scoliosis surgery remains uncertain, particularly regarding its ability to achieve the same level of deformity correction and spinal fusion success as open surgery. One key challenge in MIS is accurate implant placement in a deformed spine while minimizing tissue disruption and preserving anatomical landmarks. This has led to the integration of intraoperative 3D imaging and robotic-assisted surgery (RAS) to enhance screw placement accuracy. To date, most evidence on MIS in scoliosis surgery comes from retrospective and observational studies, with a lack of randomized controlled trials (RCTs). While MIS has rapidly developed in the field of degenerative spine surgery, it is important to investigate whether MIS in patients with idiopathic scoliosis is non-inferior than traditional open surgery and at the same time not compromise other factors of a "successful" operation such as the degree of correction and fusion. 3. Study design: a. Research questions The primary objective of this project is to assess whether minimally invasive surgery (MIS) is non-inferior to traditional open surgery in terms of reoperation rates, serious complications, surgical site infections, pain, and fusion success in the long term. Additionally, the investigators aim to compare the two techniques regarding hospitalization time, screw placement accuracy, neurophysiological events, blood loss, operative time, and patient-reported outcome measures (PROMs). A randomized controlled trial (RCT) will be conducted to minimize selection bias and systematically evaluate the advantages and limitations of MIS compared to open surgery in scoliosis correction. The study follows a pragmatic approach, utilizing existing surgical techniques and infrastructures, including established MIS techniques, navigation systems, hospital and quality registries, and imaging systems. Randomization will be performed within the Swespine registry platform or RedCap. Definition of MIS: The technique preserves the posterior spinal musculature by avoiding detachment from the spinous processes and laminae, except where necessary for screw insertion. Surgeons may use either a single long incision or multiple short incisions, ensuring muscle-sparing principles while achieving spinal stabilization. b. Variables and measures The primary endpoint is the assessment of a group of variables by the statistical method of "win odds". The variables are in hierarchic order: i. No reoperations at 2 years after surgery. A reoperation is defined as a secondary surgical procedure related to the index procedure and involving the spine after the index procedure. ii. No serious complication related to the procedure. Serious complication is defined as a life-threatening complication or a complication related to substantial invalidity. iii. No early surgical site infection (SSI) that is defined with onset up to 12 weeks postoperatively. iv. No other infection related to the inpatient stay like pneumonia or urinary tract infection (UTI). v. Assessment of pain at 2 years follow-up: The numeric rating scale (NRS) for back and leg pain, respectively will be used measured on a scale from 0 (no pain) to 10 (worst possible pain). Data will be collected from Swespine or similar platforms. vi. The SRS-22r is a scoliosis specific questionnaire aiming to estimate quality of life in patients with scoliosis. It covers function, pain, self-image, mental health, and satisfaction. vii. Radiologically healed fusion at 2 years f-u. A radiologically healed fusion is defined as bone bridging along the originally operated levels. A vertebral segment will be considered fused if one or both of the following conditions is satisfied: a. Bone bridge over at least one facet joint b. Bone bridge between the vertebral bodies The following secondary objectives will be studied in comparisons between MIS and open operating procedures. i. Inpatient stay in days. ii. Total procedure time normalized to number of spinal levels. iii. Perioperative blood loss (in mL). iv. Postoperative pain relief assessed by NRS at discharge. Additionally, given and prescribed doses of analgesics will be registered from the hospital files. v. Health economics: Total cost per patient during the first 2 years of the study including cost of possible re-admissions and reoperations related to index surgery. vi. Accuracy at first attempt: Screws that are not placed and screws that are placed but repositioned after intraoperative verification are noted in the protocol. vii. Technical accuracy of screw placement at 2 years follow-up. An accurately placed screw is defined as of grade Ia and Ib according to Heintel classification. viii. Intraoperative neurophysiological monitoring. Motor evoked potential, sensory evoked potential and electromyography data will be collected to investigate any changes in neurophysiological parameters. Any deviations will be noted. ix. Patient reported outcome measures (PROMS) c. Patient selection Patients between 10-25 years old scheduled for spinal deformity surgery will be informed about the study at the time of an outpatient visit. Patient eligibility will be established before treatment randomization. Patients will be randomised preoperatively and strictly sequentially, as patients are eligible for randomisation. If a patient discontinues from the study, the patient number will not be reused, and the patient will not be allowed to re-enter the study. Inclusion criteria: (i) Written informed consent, (ii) idiopathic scoliosis, (iii) age between 10-25 years, (iv) posterior correction for scoliosis, (v) normal walking ability, (vi) major curve Cobb angle 75 or less. Exclusion criteria: (i) inability to give informed consent, (ii) other diagnosis of scoliosis than "idiopathic", (iii) rigid curves that require posterior or three-column osteotomy/ies, (iv) previous surgery at the operated levels, (v)BMI \> 35, (vi) psychological factors that make the patient unsuitable for inclusion in the study (e.g., substance abuse, developmental disability). d. Estimated sample size and power In order to use the win-odds method for a non-inferiority study the investigators performed more than 1000 simulations using the statistical software R. The primary variables listed in 6.1 were used to calculate the sample size and assumed that the outcomes are independent and that the outcomes were equally distributed among study arms (i.e. the investigators simulated a win-odds of 1.0). The power of the study was set to 80% with a lower limit of confidence interval for win-odds (also called non-inferiority limit) to above 0.60 and calculated a sample size of 150 individuals divided into two treatment arms. The possible number of dropouts until the 2-year follow-up was set to 20%, and the total sample size therefore adjusted to 180 individuals. The non-inferiority limit is the probability of a patient in the active arm (minimally invasive procedure) to win over a control patient given an evenly distributed number of ties. In the case that the MIS group shows slight benefits compared to the open surgery group then the non-inferiority limit will shift towards 1.0 as the win odds will be greater than 1.0 which was assumed in the sample size simulation. e. Statistical methods Primary variables: The investigators selected the above described seven variables in hierarchic order to conduct a win-odds analysis. The variables were selected based on the clinical impact that they have on the patient. The method of win-odds was first introduced as win-ratio in order to analyze composite endpoints based on clinical priorities. The method compares each treatment subject to all controls and the outcome is registered as "win", "lose" or "tie". In order to handle large numbers of ties the win-odds was introduced that assigns 50% of the ties to both the numerator and the denominator. Particularly in non-inferiority trials the use of win-odds instead of win-ratio may be more suitable since ties in non-inferiority studies may represent a comparable treatment effect and their number is substantial. Secondary variables For the secondary variables descriptive statistics will be used to characterize the data; means and 95% confidence intervals will be used for parametric data, medians and interquartile ranges for non-parametric data, and number (proportions) for categorical data. Data from the different groups will be compared based on the 'intention to treat' principle. Statistical expertise blinded for treatment allocation will perform the statistical analyses. f. Feasibility The Akademiska hospital in Uppsala performs approximately 80 spine deformity surgeries yearly and it is estimated that 1/4 of these meet the inclusion criteria for the study. Similar estimations are done for the rest of the centers with a total enrolment of approximately 50 patients per year. Our time plan includes study start (mid 2025), last patient included (2028) and last 2 year follow up (2029). Registry outcome data are collected preoperatively, at 1 year and 2 years. Registry data may also be collected at 5 and 10 years. A total of eight pilot cases has been already performed in Akademiska hospital during 2024 and early 2025 with satisfactory correction rate and a normal expected postoperative follow-up. g. Risk mitigation Since surgical intervention is the established standard of care, the investigators consider it ethically justifiable for research participants to be exposed to the inherent risks of the procedure. Minimally invasive surgical (MIS) techniques are already widely used in degenerative spine surgery and spinal trauma, where they are well-established and have demonstrated favorable outcomes. With this study, the investigators aim to evaluate and apply MIS for the treatment of idiopathic scoliosis. Two potential risks theoretically associated with MIS in scoliosis surgery are: i. Achieving optimal anatomical correction of scoliosis may be more challenging compared to traditional open surgery. ii. Bone fusion in the MIS group may be inferior to that in the open surgery group. iii. If a technical problem with the 3D/navigation system or RAS system is encountered during surgery, the patient will be kept in the group to which he or she was randomized. This means that a possible MIS approach needs to be converted to open technique to enable screw placement by free hand technique. The patient will remain in the group to which he or she was randomized to and will not be replaced. Despite these potential risks, the investigators believe it is essential to scientifically investigate the use of MIS in scoliosis patients. MIS has the potential to offer significant advantages, including fewer reoperations, faster rehabilitation, lower infection rates, reduced blood loss, and shorter hospital stays. The knowledge gained from this study could contribute to improved treatment strategies and enhanced quality of life for patients with idiopathic scoliosis.