A systematic literature review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted ( Figure 1 ) in this study (11). An electronic search on Scopus, Cochrane Library and MEDLINE via PubMed database was performed using the following keywords: “minimal invasive surgery”, “minimally invasive surgery”, “MISS”, “MIS”, “conventional open surgery”, “traditional open surgery”, “open surgery”, “spinal metastasis”, “spine metastasis”, “vertebral metastasis”, “spinal metastatic disease” and their MeSH terms in any possible combinations using the logical operators “AND” and “OR”. The reference lists of relevant studies were forward screened to identify other studies of interest. The search was reiterated until October 3, 2021. The review protocol started on September 10, 2021 was registered on the International Prospective Register of Systematic Reviews (PROSPERO), ID: CRD42021283003.

In the present review, the full-text English written articles reporting comparisons of PPSF versus OPIF in patients with SM were considered eligible. No date of publication limits were set. Study with follow up shorter than 60 days were excluded from analysis. Expert opinions, studies on animals, unpublished reports, in vitro investigations, case reports, case series, letters to the editor, abstracts from scientific meetings and book chapters were excluded from review. The inclusion and exclusion criteria were summarized in Table 1 .

The review questions were formulated following the PICO scheme (12) (population (P), intervention (I), comparison (C), and outcome (O)) as follows:

Do the patients affected by spinal metastases (P) treated with PPSF surgery (I) have better clinical and functional outcomes (minor blood loss, surgical pain and complication) (O) compared to those treated with OPIF (C)?

Two independent authors (A.P. and R.V.) performed the title and abstract screening and collected data from the included studies. Any discordances were solved by consensus with a third author (A.S). The following data were extracted: demographic features, primitive cancer, level involved, Tokuhashi score, Frenkel or American Spinal Injury Association (ASIA) score, intraoperative blood loss, operative time, length of stay, clinical and functional outcomes, possible complications, and follow-up.

Numbers software (Apple Inc., Cupertino, CA) was used to tabulate the obtained data. Categorical variables are presented as frequency and percentages. Continuous variables are presented as means and standard deviation. Only one decimal digit was reported and was rounded up.

The mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were used for each relevant outcome measure. The measured outcomes were presented as a Forest plot. The χ2 test was used to evaluate the heterogeneity between included studies. The I² statistic was performed to estimate the proportion of total variation among analyzed studies; a value higher than 50% was interpreted as substantial heterogeneity. When a large value of I² was obtained a random-effect model was tested, else a fixed-effect model was used. The publication bias was analyzed, according to the MOOSE criteria ( Table 2 ) by creating a funnel plot for each outcome analyzed, analyzing its asymmetry. Review Manager Version 5.4.1 (Cochrane Collaboration, Software Update, Oxford, United Kingdom) was used for statistical analysis and generation of Forest plots.

The electronic research of the literature consisted of 1123 studies. Duplicates and non-English articles were removed. Screening by titles and abstracts was performed with subsequent full text reading of the remaining articles. A total of 7 studies met our inclusion criteria and fulfil the purpose of the review (13–19). One of the eligible study was excluded for a short follow up (30 days) (20). The patients included in the meta-analysis were 448, 253 were in the OPIF group whereas 195 were treated with PPSF. Table 3 summarizes the main characteristics of the included studies such as year of publication, study design and Level of Evidence (LoE), population and recorded variables, type of procedure and instrumented levels. Table 4 reports primary lesions and the SM locations as well as some demographic data. The mean age of the included patients was 60.7 and the M/F ratio was 1.09 with no differences between the two groups. The most frequent primary lesion was breast, followed by lung and liver.

The number of instrumented levels was not always specified. In five of the included studies, patients had posterior pedicle screw instrumentation of two levels above and two levels below the metastatic lesion at least. Data about that were inhomogeneous as two articles even reported the number of instrumented levels.

Among the included articles, the mean reported follow-up period was 16.2 months. The longest one was that by Kumar N et al. which last up to five years (19).

All the included studies reported postoperative complications, with 195 patients in the PPSF group and 249 in the OPIF group (13–19). The meta-analysis of these data showed an odds ratio of 0.48 (95% CI, 0.27 to 0.83; p= 0.009), showing a decreasing odd of complications in the PPSF group compared to OPIF ( Figure 2A ).

All the included studies reported intraoperative blood loss, with 195 patients in the PPSF group and 253 in the OPIF group (13–19). The meta-analysis of the data revealed a mean difference of -585.70 (95% IC, -848.28 to -323.13; p< 0.0001), thus suggesting a decreasing odd of complications in the PPSF group compared to OPIF ( Figure 2B ). Transfusions were reported in two studies only (16, 18)

The length of hospitalization was reported in 5 of the included papers, with 147 patients in the PPSF group and 202 in the OPIF group (13, 14, 16, 18, 19). The meta-analysis of the data revealed a mean difference of -3.77 (95% IC, -5.92 to -1.61; p= 0.0006), thus suggesting a decreasing mean hospital stay in the PPSF group compared to OPIF group ( Figure 2C ).

Six of the included studies reported the occurrence of postoperative infections, with 170 patients in the PPSF group and 228 in the OPIF group (13–16, 18, 19). The meta-analysis of these data showed an odds ratio of 0.31 (95% CI, 0.12 to 0.81; p= 0.02), showing a reduced infection rate in the PPSF group compared to the OPIF group ( Figure 2D ).

A total of three studies described the occurrence of reinterventions, with 64 patients in the PPSF group and 75 in the OPIF group (13, 15, 16). The meta-analysis of these data showed an odds ratio of 0.76 (95% CI, 0.25 to 2.27; p= 0.62), suggesting that both techniques demand a similar reintervention rate ( Figure 3A ).

A total of six studies described mortality, with 142 patients in the PPSF group and 197 in the OPIF group (13, 14, 16, 17, 19). The meta-analysis of these data showed an odds ratio of 0.79 (95% CI, 0.40 to 1.58; p= 0.51), demonstrating that both techniques have a similar mortality rate ( Figure 3B ).

Among the included studies, four articles described pre and post-operative VAS, with 103 patients in the PPSF group and 102 in the OPIF group (13, 17–19). The meta-analysis of the preoperative VAS data revealed a mean difference of -0.03 (95% CI, -0.30 to 0.25; p= 0.84), whereas the mean postoperative VAS difference was -0.55 (95% CI, -1.41 to 0.32; p= 0.22). The meta-analysis suggested that both techniques have a similar postoperative VAS ( Figure 3C ).

An heterogeneous set of scores was applied to assess preoperative health status and clinical outcomes but none of them was used in each of the included studies. Therefore, a statistical analysis was not possible. Preoperative evaluation of metastatic spine tumor prognosis was measured by using the Tokuhashi scoring system in half of the selected papers (15, 17–19). The Frankel Scale for spinal cord injuries was employed in four of the included studies to classify the pre- and postoperative extent of the neurological and functional deficit (14, 17–19). Many other scores were employed in search strategies, such as Oswestry Disability Index (ODI), American Spinal Injury Association (ASIA) Impairment Scale and Spinal instability neoplastic score (SINS), Tomita score, the Karnofsky performance scale index, etc. Also survival was not always specified. In fact, a total of four studies described the mean survival time but as data were presented in heterogeneous forms, it was not possible to perform a statistical analysis.

Both techniques, PPSF and OPIF, allow for a decompression of neurological structures. In fact conventional open or mini-open decompression was performed in all the included cases except for the PPSF group by Chi E J et al. (13). The OPIF procedure, with a midline incision and a large dissection of paraspinal muscle, allows wider neurological decompression, and major possibility of tumour lesion debulking (14, 15). On the other hand to obtain a satisfying decompression with PPSF approach, various techniques were described. In the case of a unilateral tumour spinal cord compression, the same paramedian access for screw placement could be used, through the use of dedicated retractors, for decompressive manoeuvres (18).

While in case of a 180 degree compression a midline mini-open could be performed with the possibility to obtain a sufficient posterior decompression (14–18). An hybrid approach could be the choice in cases that requires long fixation and wide neurological decompression (9).

SM patients treated with PPSF compared to those treated with OPIF have a lower rate of complications and infections, less intraoperative blood loss and a shorter hospital stay. A doubt still remains about mechanical complications, short and medium-term survival and post-operative pain.

A risk of bias assessment was performed by the MOOSE criteria of included study as reported in Table 2 . No obvious bias risk was found for the included study. A funnel plot for all analyzed outcomes was obtained. Nevertheless, no significant asymmetry was found.

Patients treated with PPSF, due to fast clinical recovery and surgical wound healing, could resume or start faster chemo- and radiotherapy than those treated with OPIF. This could play a crucial role in determining patient survival and local disease control (17).

The results of this meta-analysis suggest a minimal superiority of the PPSF treatment compared to OPIF in SMs patients who require spinal stabilization with or without neurological decompression. Therefore, PPSF should be considered the first-line choice in these patients if there are no contraindications.

Relative contraindications could be: (I) more than 6 levels of spinal fusion, (II) need for extensive neurological decompression, (III) correction of important post traumatic deformities.

This meta-analysis is not without limitations. First of all, all included studies are observational studies except one which is a randomized clinical trial. Secondly, the number of included studies is not large enough to perform a meta-regression analysis. Finally, the data of some studies on certain outcomes are too inhomogeneous to be able to perform an accurate analysis of the data.