Staged Resection of Difficult-to-Treat Intracranial Meningiomas: A Systematic Review of the Indications, Surgical Approaches, and Postoperative Outcomes

Abstract

Introduction  Meningiomas—the most common extra-axial tumors—are benign, slow-growing dural-based lesions that can involve multiple cranial fossae and can progress insidiously for years until coming to clinical attention secondary to compression of adjacent neurovascular structures. For complex, multicompartmental lesions, multistaged surgeries have been increasingly shown to enhance maximal safe resection while minimizing adverse sequela. Here, we systematically review the extant literature to highlight the merits of staged resection.

Methods  PubMed, Scopus, and Web of Science databases were queried to identify articles reporting resections of intracranial meningiomas using a multistaged approach, and articles were screened for possible inclusion in a systematic process performed by two authors.

Results  Of 118 identified studies, 36 describing 169 patients (mean age 42.6 ± 21.3 years) met inclusion/exclusion criteria. Petroclival lesions comprised 57% of cases, with the most common indications for a multistaged approach being large size, close approximation of critical neurovascular structures, minimization of brain retraction, identification and ligation of deep vessels feeding the tumor, and resection of residual tumor found on postoperative imaging. Most second-stage surgeries occurred within 3 months of the index surgery. Few complications were reported and multistaged resections appeared to be well tolerated overall.

Conclusions  Current literature suggests multistaged approaches for meningioma resection are well-tolerated. However, there is insufficient comparative evidence to draw definitive conclusions about its advantages over an unstaged approach. There are similarly insufficient data to generate an evidence-based decision-making framework for when a staged approach should be employed. This highlights the need for collaborative efforts among skull base surgeons to establish an evidentiary to support the use of staged approaches and to outline those indications that merit such an approach.

Introduction

Meningiomas—the most common extra-axial tumors—are durally based, overwhelmingly benign lesions characterized by insidious growth. ^{1 2} Owing to their benign nature, lesions can grow asymptomatically for years, only reaching clinical attention when they are incidentally discovered or compress adjacent neurovascular structures. With this growth, lesions can come to involve multiple cranial fossae. At the point lesions become symptomatic, surgical resection is indicated. Lesions involving multiple intracranial compartments and those deeply seated masses closely apposing the cranial nerves and Circle of Willis may require a multistaged approach for adequate lesion exposure so as to allow for maximal safe resection. Staging may also involve compartmentalizing the goals of the operation by staging the approach followed by staging the resection. ³

The use of staged approaches dates to 1925, when Walter Dandy described the use of staged surgery for the treatment of large vestibular schwannomas to ensure gross total resection, optimize survival outcomes, and minimize recurrence. ⁴ Similar rationale motivates the use of staged approaches presently, which have been to many different types of brain tumors. Tumors left behind from the first surgery have reduced vascularity and become less adherent to brain parenchyma during the second surgery. ^{4 5} For large vestibular schwannomas (≥3 cm), staged craniotomies have been employed to maximize tumor debulking while maximizing the odds of preserving facial nerve function. ^{5 6} The clinical data for staged resection of large vestibular schwannomas suggest that there is not an increased risk of morbidity despite the need for patients to undergo multiple operations. ^{5 6} Similar data on the use of staged resections for meningiomas are sparser and that which are available are largely derived from single-center experiences.

Perhaps due to this, there are no established parameters for when it is appropriate to employ a staged approach for intracranial meningiomas. The objective of the study was therefore to collate the available literature focusing on the outcomes of staged resection and listed indications, alongside a case presentation of this staging ( Fig. 1 ) so as to provide a starting point from which to work toward a systematic framework for the use of a staged approach for the treatment of intracranial meningioma.

Fig. 1.

Resection of a large anterior cranial fossa meningioma managed via a staged approach with an initial endoscopic endonasal approach (EEA) to devascularize and debulk the tumor followed by a second pterional craniotomy for gross total resection. (A) Preoperative coronal and (B) preoperative sagittal T1 weighted scans with gadolinium demonstrating a large homogenously enhancing dural-based mass of the anterior skull base in a patient who presented with confusion, headaches, and loss of olfaction. (C) Preoperative axial perfusion scan capturing the degree of vascularization of this meningioma from the anterior skull base. (D) Preoperative FLAIR sequences demonstrating the degree of surrounding brain edema from the mass effect of the tumor. (F) Postoperative coronal and F. Postoperative sagittal T1 weighted scans with gadolinium after a stage I EEA to devascularize and debulk the tumor from its skull base origin without any brain retraction. (G) Postoperative axial perfusion scan capturing devascularization of the tumor after a stage I EEA. (H) Postoperative axial T1 weighted scans with gadolinium after a stage I EEA. (I) Postoperative coronal. (J) Postoperative sagittal. (K) Postoperative axial T1 weighted scans with gadolinium after a stage II right-sided pterional craniotomy to resect a devascularized and much smaller tumor compared to its original size demonstrating gross total resection L. Postoperative axial diffusion weighted scan with no evidence of restriction suggestive of stroke after surgery.

Methods

Search Strategy

A systematic review was performed to identify studies examining multistaged intracranial resection of meningiomas in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. ⁷ The authors sought to evaluate the surgical indications for staging meningioma resection, the specific approach for each stage, timing between stages, and reported complications. In order to do so, a literature search was conducted using PubMed, Scopus, and Web of Science databases according to the PRISMA recommendations. ⁷ The search strategy used Boolean terms as follows: (“staged”) AND (“surgery” OR “resection” OR “operation” OR “procedure” OR “removal”) AND (“meningioma”).

Inclusion/Exclusion Criteria

Studies were included if they: (1) described the use of two or more open or endoscopic stages for surgical resection of meningioma, (2) included only solitary, nonsyndromic meningiomas (i.e., cases of neurofibromatosis type 2, meningiomatosis, and multiple intracranial meningiomas were excluded); and (3) had full-text articles available in English. Articles were excluded if: (1) data for staged and unstaged operations were aggregated; (2) they described spinal meningiomas; (3) preoperative embolization was counted as one of the separate stages; and (4) they did not present primary data.

Search results were screened against title and abstract by two independent reviewers (J.G. and H.S.), with disagreements being resolved by a consensus of the other authors. Full texts of included articles were then screened to determine suitability for inclusion in the final review. The references of all included studies were examined to identify additional studies missed for inclusion.

Data Extraction

Using a standardized data collection form, the following variables were extracted from each article: study sample size, number of patients undergoing staged surgery, year published, mean age, gender, tumor location, tumor type, timing between staged surgeries, indication for use of a staged approach, surgical approaches employed, complications, and use of radiotherapy. Meningiomas were further categorized into three groups based on their location and the assumed risk of resection and feasibility and radical removal. Group I included meningiomas located at convexity, parasagittal, and lateral sphenoid. Group II included meningiomas located at falx, frontobasal, medial sphenoid, parasellar, and tentorium. Group III included meningiomas located at cavernous sinus, petroclival, petrosal, cerebellopontine angle, and foramen magnum. The extent of tumor resection was classified according to the Simpson grades, with grade I indicating total resection of tumor with excision of its dural and bony attachment, grade II indicating total resection of tumor and coagulation of its dural attachment, grade III indicating total tumor resection without resection or coagulation of its dural attachment and its extradural extension, and grade IV indicating subtotal tumor removal. Data extraction was performed by the two authors that performed the initial search and screen.

Results

Literature Search

The systematic search yielded 241 results, with 80 papers from PubMed, 67 papers from Web of Science, and 94 papers from Scopus. There were 118 total papers after the elimination of duplicates. No additional papers were identified that did not appear in the search. After the application of exclusion criteria during the title and abstract screening, 67 articles were excluded and 51 articles were retrieved for full-text review. A total of 36 studies ^{3 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42} containing data on 169 patients undergoing multistaged resection for meningiomas were included in the final review ( Fig. 2 ).

Fig. 2.

PRISMA flowsheet for articles selected in the systematic review.

Demographics

Demographics of included patients are summarized in ( Table 1 ). Mean age across all studies was 42.6 ± 21.3 years (range, 7–72 years). The most common locations for the utilization of a multistaged approach were the petroclival fissure (57%), greater sphenoid wing (7.0%), and falcotentorial junction (5.3%). Reported subtypes included clear cell meningiomas, intraosseous meningiomas, transitional meningiomas, and papillary meningiomas.

Table 1. Characteristics of studies included in the systematic review.

Author	Number of patients undergoing staged surgery	Year published	Patient age	Gender	Timing between surgeries	Comment
Tsurubuchi et al 8	1	2020	7	M	1 mo	Dumbbell-type pediatric clear cell meningioma
Luetjens et al 9	3	2011	49, 68, 70	3F	4 mo	–
Takase et al 10	2	2017	62,54	2F	–	–
Hart and Giannotta 11	6	2003	–	–	–	Large multicompartmental meningioma
Pintea et al 12	12	2016	–	–	Mean 14 ± 8 d	–
Tamaki and Yin 13	1	1999	45	5F	–	–
Hussaini et al 14	1	2015	50	F	–	Intraosseous meningioma
Tekkök et al 15	1	1997	33	M	–	Dumbbell shaped transitional meningioma
Vachhrajani et al 16	1	2008	14	F	6 mo	–
Hamilton et al 17	1	2020	69	M	–	Papillary meningioma
Behari et al 18	3	2010	–	–	–	–
Campero et al 19	1	2019	32	M	2 mo	Dumbbell skull base meningioma
Klironomos et al 20	1	2019	47	F	0.5 mo	–
Gosal et al 21	3	2018	–	–	–	Large-giant tumors >3.5 cm in size
Javed and Sekhar 22	24	1991	–	–	–	–
Nakase et al 23	6	1998	–	–	1 mo =	–
Ansari and Riyaz 24	4	2020	–	3M,1F	Range 5–8 d	Giant meningiomas
Kumar and Wani 25	2	2006	–	M		–
Zhao et al 26	3	2019	63, 67, 63	3F	1 wk (two of the three patients) and 3 mo (one of three patients)	–
Ahn et al 27	1	2005	7	1F	–	Clear cell meningioma
Nakashima et al 28	1	2018	19	1F	13-mo timing between the first and second stage, 5 mo timing between the second and third stages	–
Matsui 29	4	2012	–	–
Sanna et al 30	2	2007	32, 42	4M/9F	–	–
Roberti et al 31	38	2001	–	–	–	–
Tsutsui et al 32	1	2016	72	1M	–	Transitional type
Juratli et al 33	1	2015	5	1F	–	Clear cell meningioma
Arivazhagan et al 34	4	2008	–	–	–	–
Wu et al 35	1	2014	22	1M	–	–
Aras et al 36	2	2013	28, 15	2M	–	–
Nakamura and Samii 37	1	2003	41	M	–	–
Almefty et al 3	13	2014	–	–	1 d	Total petrosectomy indicated for large tumors in patients with absent hearing
Miranda et al 38	1	2020	12	F	1 d	EEA for the first stage
Attia et al 39	1	2013	55	M	2.5 mo	EEA for the second stage
Koutourousiou et al 40	18	2004	–	–	1 d	EEA for both stages
Sivakumar et al 41	3	2019	53,69,43	2M, 1F	Several days	EEA either as first (1/3) or second stage (2/3)
Yokoi et al 42	1	2019	54	M	6 mo	EEA for the second stage

Abbreviations: EEA, endoscopic endonasal approach; F, female; M, male; No., number.

Indication for Staged Surgery of Meningiomas

The primary reasons for attempting to remove large meningiomas through a staged approach include the following: extensive tumor size, remove residual tumor found on postoperative imaging, removing supratentorial tumor burden in large petroclival tumors, to monitor for symptoms before removing the bulk of large tumors, tumor adhesion to perforating vasculature, tumor encasement around neural elements, removal of components of tumor found in the neck, to minimize excessive blood loss, to stage the approach and resection independently due to the complexity and duration of the exposure, and to prevent excessive retraction of the brain parenchyma ( Table 2 ). When categorizing meningiomas based on their locations, adhesion to perforating vasculatures was the most common indication in Group I while achieving maximum resection was the most common indication for Group II. Extensive tumor size was the most common indication for Group III ( Supplementary Table S1 ). Approaches featuring endoscopic assistance revealed a unique indication. While most uses of endoscopy were ultimately due to extensive tumor size with extracranial extension amenable to endonasal approaches, Koutourousiou et al reported including an additional transcranial stage after abandoning endoscopic endonasal surgery due to a fibrous tumor consistency. ⁴⁰ There was one patient whose staged surgery was not planned prior to the index surgery. However, Zhao et al did not specify the reason for the unplanned staged surgery. ²⁶

Table 2. Indications and complications of staged surgery as reported in the included studies.

Author	Indications for staged surgery	Complications
Tsurubuchi et al 8	Extensive tumor size	Left corneal and facial hypesthesia
Luetjens et al 9	Tumor too extended, best to treat most affected side in first surgery and monitor vision prior to proceeding with final surgery	Transient visual acuity declines that lasted 3 mo
Takase et al 10	Tumor adhesion to perforator arteries	1 no complications; 1 transient motor weakness after minor basal ganglia infarct, transient hemiparesis
Hart and Giannotta 11	Tough tumor consistency, shared pial vascularity, major vessel encasement and cranial nerve invasion	Permanent 4th nerve palsy in 1/6 patients
Pintea et al 12	To resect supratentorial portion of the tumors	–
Tamaki and Yin 13	–	No complications
Hussaini et al 14	–	No complications
Tekkök et al 15	–	–
Vachhrajani et al 16	–	No complications
Hamilton et al 17	To remove residual tumor	No complications
Behari et al 18	Extensive tumor size and encroachment of vital structures	–
Campero et al 19	Further remove residual tumor causing symptoms	No complications
Klironomos et al 20	Size and extension of the tumor to both middle and posterior fossa	Transient diplopia after first stage
Gosal et al 21	Extensive tumor size	–
Javed and Sekhar 22	Large/giant tumor needs complex/staged approaches	–
Nakase et al 23	Tumor was too large, therefore problems associated with the tumor were resolved in the first surgery, so total resection could be accomplished in the second operation	No complications
Ansari and Riyaz 24	The staged approach allowed for a true total resection (including the affected bone). In the transcranial stage, the brain is more relaxed with less edema, reducing the need for retraction, which hopefully resulted in better outcomes	2 no complications; 1 impaired gag reflex; 1 death due to unrelated cardiac event
Kumar and Wani 25	The tumor was too complex, specific reason not stated	Seventh cranial nerve paresis and left cerebellar signs, improved by 3 y follow up
Zhao et al 26	To achieve maximum resection of the meningioma	1 patient had permanent weakness of the lower extremities, dysarthria
Ahn et al 27	–	–
Nakashima et al 28	The first surgical procedure occluded main feeders for the tumor that originated from the anterior and lateral posterior choroidal arteries via a transsylvian approach. The second surgery was performed for the purpose of removing excess tumor. A third stage was also used to resect the remaining tumor.	A seizure disorder arose in the patient 10 mo after the staged resection of the tumor. This was controlled with an anticonvulsant. Additionally, the patient also experienced a right homonymous hemianopsia after the third and final procedure, but this was seen to gradually improve over time.
Matsui 29	Giant petroclival tumors with significant supra-infratentorial extension, to minimize the risk of retraction induced brain contusion	Facial palsy, hydrocephalus, severe meningitis, facial pain, auditory dysfunction, dysphagia, defect of visual field
Sanna et al 30	Huge tumor component into the neck	Ipsilateral hearing loss as well as nerve palsy in the face
Roberti et al 31	–	–
Tsutsui et al 32	–	No complications
Juratli et al 33	To achieve a more extensive resection of the clear cell meningioma in the patient	No complications
Arivazhagan et al 34	Excessive intraoperative blood loss in the first surgery, which required the rest of the surgery to be performed at a different stage	–
Wu et al 35	Symptoms of limited right eye movement along with facial numbness was recognized 3 mo after the first stage, and a second stage of surgery was chosen to be performed	Facial numbness and difficulty with vision in the right eye was experienced by the patient after the first surgery
Aras et al 36	–	No complications from the staged approach.
Nakamura and Samii 37	Large tumor, encased basilar artery and the upper border of the tumor reached the level of the foramen of Monro	Transient cranial nerve 3 deficit, temporary somatotropic axis and gonadotropic insufficiency treated with testosterone replacement therapy
Almefty et al 3	When a total petrosectomy is planned	–
Miranda et al 38	Large intranasal and intracerebral components suitable for endoscopic-then-transcranial resection	Mild pneumocephalus resolved with vascularized vastus lateralis flap closure
Attia et al 39	–	Left-sided loss of vision, oculomotor palsy and numbness; transient hydrocephalus, wound infection, periorbital cellulitis (all complications post-craniotomy)
Koutourousiou et al 40	To prevent extensive blood loss, surgical and anethesia time, and surgeon fatigue with large tumors	6 patients experienced CSF leak, 5 PE/DVT, 1 sinus infection, 1 respiratory failure
Sivakumar et al 41	Extensive tumor size	1 patient experienced cranial nerve III, V1-V3, VIII palsy on 60-mo follow-up
Yokoi et al 42	To minimize risk of complications given tumor size and location	No complications

Abbreviations: CSF, cerebrospinal fluid; PE, pulmonary embolism; DVT, deep vein thrombosis.

Time Before Subsequent Surgeries

Most second-stage surgeries were performed <3 months after the initial surgery ( Table 2 ). Total amounts of time between surgeries ranged from 1 day to 13 months, with a mean of 1.71 ± 2.54 months.

Complications of the Staged Approach

There were no intraoperative deaths or perioperative deaths proximately associated with the surgery. However, there was one study reporting a perioperative death that was attributed to an unrelated cardiac issue. ²⁴ One patient was reported to have permanent lower extremity weakness, ²⁶ and one patient reported a seizure disorder 10 months postoperatively that was controlled with an anticonvulsant. ²⁸ One patient with an extensive spheno-orbital meningioma was reported to have permanent left-sided vision loss, left-sided oculomotor palsy, and left-sided numbness following a combined approach with endoscopic endonasal and orbitozygomatic stages. ³⁹ In total, 5 out of 30 cases reported transient cranial nerve deficits, while 9 out of 14 cases reported permanent cranial nerve deficits. Of the studies utilizing endoscopic endonasal approaches (EEA), 8 out of 24 patients were reported to have cerebrospinal fluid (CSF) leak or pneumocephalus. Eleven studies (11 out of 27, 41%) observed no complications occurred in their cohort of patients ( Table 2 ). Grouping according to meningioma locations demonstrated visual field deficit was the most common complication in all three groups. Patients in group III were also more likely to suffer from cranial nerve palsy and CSF leak ( Supplementary Table S1 ).

Approaches for Tumor Resection

A wide variety of approaches were performed per tumor location. Approaches included lateral suboccipital, anterior petrosal, pterional, infratemporal, posterior temporal, posterior fossa, retrolabyrinthine approach, frontotemporal, anterior clinoidectomy, orbitozygomatic, presigmoid, transzygomatic, retromastoid, supracerebellar, and transcochlear. Additionally, five studies utilized EEA as a surgical stage. ^{38 39 40 41 42} A complete description can be found in Table 3 . Based on meningioma locations, group III has a higher rate of achieving Simpson resection grade I and II, while group I has a higher rate of Simpson resection grades III and IV ( Supplementary Table S1 ).

Table 3. Tumor location and common approaches for multistaged tumor resection.

Author	Tumor location	Surgical approaches
Tsurubuchi et al 8	Extended from left lateral wall of cavernous sinus, left Meckel cave, to the cerebellopontine angle	1st: Lateral suboccipital approach; 2nd: Anterior petrosal approach
Leutjens et al 9	Sphenoid wing with orbital and temporobasal extension	1st: Pterional approach; 2nd: Pterional
Takase et al 10	Posterior clinoid process	Patient one, 1st: Anterior clinoidectomy; 2nd: Fronto-temporal craniotomy with wide splitting of the Sylvain fissure, Patient two, 1st: Right-sided fronto-temporal orbito-zygomatic osteotomy with an extra-dural optic canal opening and an anterior clinoidectomy; 2nd: two-piece
Hart and Giannotta 11	Cranial base	Three patients underwent temporopolar alternating in conjunction with combined petrosal strategies (2 surgeries) Two patients underwent an infratemporal approach combined with petrosal approach (2 surgeries) One patient underwent orbitozygomatic and a combined petrosal paradigm (3 surgeries)
Pintea et al 12	Petroclival and lateral posterior pyramid meningioma	–
Tamaki and Yin 13	Olfactory groove	–
Hussaini et al 14	Sphenoid bone	–
Tekkök et al 15	Jugular foramen extending intracranially over the jugular tubercle and extracranially into the parapharyngeal space	–
Vachhrajani et al 16	Junction of the transverse and sigmoid sinuses with both intracranial and supratentorial growth with lateral dural venous sinus extension	1st: Posterior temporal craniotomy; 2nd: Extended posterior fossa craniotomy with retrolabyrinthine approach
Hamilton et al 17	Right frontal lobe	1st: Right frontal craniotomy; 2nd: Right frontal craniotomy with neuronavigation and microsurgical subpial dissection
Behari et al 18	Petroclival	1st: Presigmoid; 2nd: Retrosigmoid
Campero et al 19	Left cerebellopontine, extended to cavum of Meckel	1st: Left retrosigmoid craniotomy; 2nd: Transzygomatic approach
Klironomos et al 20	Petroclival	1st: Right anterior petrosectomy; 2nd: Right retrosigmoid craniotomy
Gosal et al 21	Petroclival	Patient one, 1st: staged anterior petrosectomy; 2nd: retromastoid suboccipital craniectomy, Patient two, 1st: Staged presigmoid, 2nd: half-and-half approach(trans-Sylvian with subtemporal)
Javed and Sekhar 22	Clival/petroclival	–
Nakase et al 23	Cavernous sinus meningiomas, sphenoid-ridge meningioma, cerebello-pontine angle meningioma	Unspecified stages: frontotemporal-orbitozygomatic approach, posterior transpetrosal approach, anterior transpetrosal approach
Ansari and Riyaz 24	2 falcotentorial, 1 anterior and middle parasagittal, 1 sphenoid wing	1st: Craniotomy where hypervascular bone was excised along with the opening of the dura in the first stage; 2nd: complete removal of tumor
Kumar et al 25	Posterior skull base	1st: Extended middle fossa approach; 2 nd : Retromastoid suboccipital approach
Zhao et al 26	Menigiomas located at the anterior portion of the falcotentorial junction	–
Ahn et al 27	Right temporal fossa	–
Nakashima et al 28	Trigone of the left lateral ventricle	1st: Transsylvian approach; 2nd: transsylvian approach; 3rd: high-parietal approach
Matsui 29	Petroclival	1st: Posterior transpetrosal; 2nd: Lateral suboccipital
Sanna et al 30	Jugular foramen	1st: Transcochlear approach; 2nd: Transcochlear approach
Roberti et al 31	Posterior and middle cranial fossa	–
Tsutsui et al 32	Falcotentorial junction expanding into supratentorial and infratentorial regions	–
Juratli et al 33	Right temporal fossa, petroclivical region	1st: Suboccipital craniotomy; 2nd: Frontotemporal craniotomy
Arivazhagan et al 34	–	–
Wu et al 35	Petroclivical meningioma	1st: Supratentorial tumor excision; 2nd: Retrosigmoid approach
Aras et al 36	Sylvian fissure (located in the distal region of the sylvian fissure in both patients)	1st: Right temporal craniotomy; 2nd: Right pterional approach
Nakamura and Samii 37	Ventral to brainstem	1st: Right lateral suboccipital retrosigmoid craniectomy; 2nd: right fronto-lateral craniotomy
Almefty et al 3	Petroclival	1st: preparation of transpetrosal total petrosectomy approach 2nd: tumor resection
Miranda et al 38	Olfactory groove with nasal cavity invasion	1st: Endoscopic endonasal 2nd: Frontotemporal craniotomy
Attia et al 39	Spheno-orbital: infratemporal fossa, pterygopalatine fossa, sphenoid sinus, and ethmoid sinus	1st: Frontotemporal orbitozygomatic 2nd: Endoscopic endonasal
Koutourousiou et al 40	Olfactory groove	1st: Endoscopic endonasal 2nd: Endoscopic endonasal
Sivakumar et al 41	Cavernous sinus, Meckel's cave, petroclival	Retrosigmoid, pterional, minipterional and endoscopic endonasal debulking (occurred after craniotomy in 2 cases, before in 1 case)
Yokoi et al 42	Sphenoid ridge with cavernous sinus involvement	1st: Endoscopic endonasal transsphenoidal 2nd: Craniotomy

Discussion

In the present review, we summarize the published literature on the staged resection of meningiomas to serve as a starting point for the development of a systematic framework for when a staged operation is indicated for these lesions. The bulk of the evidence is derived from case reports and single institution series, limiting the strength of the conclusions reached. Based upon the available data though, the indications employed for a staged approach vary by anatomic location. For lesions of the cranial convexity, adhesion to perforating vasculatures was the most listed indication, though the majority of included cases failed to explicitly state the indication for a staged approach. For parafalcine lesions and lesions of the anterior cranial fossa, staged approaches were most commonly employed so as to maximize the extent of safe resection. By contrast, lesions of the posterior fossa most commonly underwent staged resection due to their large size. The overall small number of patients for whom the rationale for a staged approach was given highlights a limitation of the available literature and a need for a more systematic approach to these lesions. The limited study sizes further demonstrate that the present results are subject to a high risk of publication bias and additionally preclude a meaningful inferential statistical analysis.

Considerations for a Staged Approach

The most common indications for performing staged resections in the identified studies included removing residual disease found on postoperative imaging, removing tumors due to extension of the tumor to different anatomical locations, and removing tumors encroaching on critical vascular and eloquent structures. The factors that make meningiomas complex and difficult to safely remove in a single operation can be mitigated through staged surgeries which allow for more measured and safer complete resection. ^{12 24} We detail a flow diagram that was created based on our own experiences along with the trends and patterns we observed in this literature review in Fig. 3 , which we created to provide an organized algorithm that can aid skull base surgeons in the preoperative planning phase.

Fig. 3.

Flow diagram for preoperative planning utilizing staged resection for difficult to treat meningiomas.

Petroclival meningiomas, which are among the most challenging tumors to resect given their deep location within the skull base and their predilection to encase surrounding critical neurovascular structures, were by far the most prevalent of the meningiomas featured in our review cohort. This underscores the consistent need for complex and nuanced management in this anatomical location. ^{22 33 43 44} While great strides have been made in reducing the morbidity and mortality of petroclival meningioma resection, ⁴⁵ they remain among the most formidable of skull base tumors. In line with recent trends to abandon traditionally more extensive and potentially morbid approaches, ⁴⁶ Samii et al recommended avoiding transpetrosal approaches and considered less invasive frontotemporal orbitozygomatic and retrosigmoid suprameatal routes ⁴⁷ as part of a staged strategy to treat petroclival meningiomas. ⁴⁵ In securing separate anterior and posterior access, safety is not compromised, as staging allows for the resection of the tumor through two different surgical corridors. ⁴⁵ Others have advocated a different staged strategy; given the predilection for petroclival meningiomas to span the middle and posterior cranial fossa, ⁴⁸ a single, wide exposure such as the total petrosectomy featured by Almefty et al, ³ may be appropriately employed. In these scenarios, staging can be utilized to separate the complex approach stage from the resection stage given the impracticality of completing both within the time constraints of a single operating room day. This strategy allows for the surgical team to be better prepared and rested for the resection itself which is the most critical aspect of the procedure where the potential for morbidity is high and the commitment to careful microsurgery is required.

In a systematic review of 1,000 petroclival meningioma resections using single-staged approaches, Diluna and Bulsara et al reported a postoperative neurological deficit rate of 34%. ⁴⁹ Of the included multistaged surgeries for petroclival meningiomas in this study, the reported postoperative neurological deficit was similar at 36.4% when considering either transient or permanent postoperative neurological deficit. While conclusions on staged resection's efficacy for the preservation of cranial nerves is currently limited by sample size, this may indicate that petroclival meningiomas necessitating staged resection do so as a consequence of their size and encroachment upon neurovasculature. Future investigations comparing staged resection with nonstaged resection that match for variables such as tumor location, size, and approach are needed.

In regard to petroclival meningiomas, the retrosigmoid or presigmoid approach in combination with a variety of other approaches appear to be the most frequently used for resection. The retrosigmoid approach in principle provides appropriate access for meningiomas with extension into the posterior fossa. Meningiomas with significant extension laterally from the petroclival junction can displace the brainstem creating a “natural” corridor thus increasing the accessibility to the lower and upper petroclival surfaces. The early visualization of the cranial nerves offered by this approach in the posterior fossa coupled with the accessibility to the petroclival region makes it an efficient and facile approach for many neurosurgeons who prefer it over more complex skull base approaches (as illustrated by several cases). ^{12 18 19 20 37 45} Suprameatal drilling offers the added advantage of removing tumor burden that extends into the middle cranial fossa through Meckel's cave, but these advantages can be limited by larger tumors with significant tumor burden in the middle cranial fossa. Alternatively, the presigmoid approach allows for exposure of the upper clival region during the resection of large meningiomas. While this approach may offer expansive exposure of the petroclival region, ^{7 50} its use in the resection of lower petroclival meningiomas is limited due to obstruction of the corridor by the sigmoid sinus, which may necessitate division and possible subsequent reconstruction. ²² Finally, it is important to note that a diverse set of approaches were performed during staged resection of meningiomas with an acceptable complication profile despite an increased number of operations, total surgical time, and multiple inductions of anesthesia.

In addition to identifying two prominent approaches used in the staged resection of meningiomas, this study also identifies the utility of multistaged approaches in the resection of meningiomas with high vascularity. More specifically, it is important for the surgeon to initially debulk and devascularize highly vascular meningiomas so as to make them more amenable for resection. The lack of a vascular supply softens tumor consistency during the resection and allows for improved visualization with more efficient preservation of planes between the tumor and the surrounding brain. This can minimize morbidity and potential mortality, from injury to critical local vasculature while maximizing the extent of resection. ^{10 22 24} Staged removals were performed with the initial surgery acting as the devascularization procedure, which resulted in generally favorable outcomes. ^{24 51} Additionally, hypervascular tumors in the lateral ventricle most often require devascularization due to the involvement of feeders from the anterior and/or posterior choroidal arteries. It also appears that hemodynamic instability resulting from significant blood loss incurred during resection of vascular meningiomas played a role in the intraoperative decision to pause and resume surgery at a later time. ³⁴

The role of adjuvant radiotherapy in treating meningiomas remains controversial. When possible, gross total resection with minimal brain manipulation should be attempted. ⁵² However, with large or multicompartmental meningiomas, an attempt at gross total resection may increase the risk of neurological deficits and other morbidities. ¹¹ Some studies have demonstrated the feasibility of combining subtotal resection and postoperative irradiation using either conventional radiotherapy or stereotactic radiosurgery, such as Gamma knife or Cyber Knife. ^{53 54 55} He et al in a meta-analysis of 17 articles found that postgross total resection radiotherapy could help improve the 5-year local control rate (odds ratio [OR] = 2.59, 95% confidence interval [CI] 1.40–4.81, p = 0.002) and 5-year progression-free survival rate (OR = 1.99, 95% CI 1.35–2.95, p = 0.001) but did not significantly improve 5-year overall survival rate (OR = 1.07, 95% CI 0.60–1.91, p = 0.828). ⁵⁶ Zhao et al proposed that radiotherapy might be more useful in patients with high-grade meningioma without a Simpson-grade I resection than patients with small and stable residual tumor on serial postoperative scans. Due to the insufficient data, our study was only able to show that a total of 40 patients (23.7%) received adjuvant radiotherapy following the staged procedure, with group I having the highest rate. No meaningful statistical analyses and conclusion can be drawn for the effects of adjuvant radiotherapy on the survival rate.

Moreover, skull base meningiomas have a predilection to encase surrounding neurovasculature as well as displace cranial nerves. ⁸ Staged resection of vestibular schwannomas has been shown to achieve a significantly higher rate of facial nerve preservation compared to single-stage resection. ⁵⁷ For meningiomas, overall comparisons of cranial nerve deficits between staged and nonstaged resections are complicated by the variety of intracranial locations—each with their own unique burden on surrounding neurovascular structures. In an attempt to elucidate the effects of meningioma location on outcomes, we classified meningiomas into three groups according to their surgical risk ( Supplementary Table S1 ). ⁵⁸ We found that morbidity occurred at a higher rate in group III compared to groups I and II, which validated our classification. It is, however, worth noting that stratifying tumor locations based on the estimated risk may be controversial and our distinction between group II and III was not always a clear-cut, as some meningiomas may cross the boundaries of these locations. More studies are required to discover the influence of tumor location on reasons of staging, procedure-related complications, and sequence in which the procedures are performed.

Tumor shape also can complicate the surgical management of meningiomas and make tumors more difficult to resect. In one case, a large skull base dumbbell meningioma was found in a 7-year-old boy. ⁸ It extended from the left lateral wall of the cavernous sinus where it traversed through the left Meckel's cave on its way to the cerebellopontine angle. ⁸ The tumor was located under the left VII and VIII nerves, and after debulking of the tumor, the left trigeminal nerve was found to be displaced inferiorly by the residual tumor. ⁸ Residual tumor remained because of the high difficulty in controlling bleeding as the mass was firmly attached to the brainstem surface (made possible by its dumbbell shape and extensive size). ⁸ Drawing upon previously reviewed literature of dumbbell meningiomas, young age, and neurofibromatosis may be related to the development of these lesions. ⁵⁹ However, as there are still a small number of cases of dumbbell meningiomas reported in the literature, one cannot make conclusive comments on what factors affect their development and surgical approaches must be determined on a case-by-case basis. ⁵⁹

Ultimately, strategic implementation of staged approaches can help prevent complications that a single surgery/approach may not, as Samii et al illustrate in their justification for a staged frontotemporal orbitozygomatic and retrosigmoid suprameatal petroclival meningioma approach over a more traditional, single-staged petrosal approach. ⁴⁵ While petrosal approaches have their own advantages, such as lessened brain retraction and a shorter operative distance, ^{48 60} they incur greater rates of CSF fistula and cranial nerve deficits. ^{60 61 62 63 64} Instead, employing two even smaller approaches, now in a staged fashion, retains the benefits accrued when abandoning more traditional approaches while obviating the risks. ⁴⁷ Admittedly, multistaged surgeries seemingly imply an extensive surgery; however, this is not to be confused with greater invasiveness, as the essence of staged surgical approaches is that of achieving surgical efficiency in otherwise high morbidity resections. Therefore, multistaged surgery may represent a viable option for resecting meningiomas with large extension while offering minimal morbidity when compared to single-staged approaches.

Case Example

Fig. 1 illustrates an example of a tumor that in the hands of the senior author represents an ideal case for a staged approach. The lesion demonstrated is a large olfactory groove/planum sphenoidale meningioma that superiorly displaces the anterior cerebral arteries (ACAs) and spreads laterally over the orbital rooves. Preoperative perfusion imaging showed the lesion to be highly vascular, and given the nature of these lesions, it was suspected that the tumor derived its blood supply from the dura of the anterior fossa floor. Consequently, an endoscopic endonasal, transplanum approach to identify and coagulate the feeding vessels was felt to be reasonable (comparison of Figs. 1C and 1G shows the resultant devascularization of the lesion). Such an approach would be unable to resect the portions of the tumor extending laterally over the orbits, however, and additionally would place on the backside of the lesion, meaning they would not be visible (for protection) until the very end of resection. Consequently, a second stage with an open right-sided pterional craniotomy was employed, which enabled resection of the residual mass while preserving the ACA vascular tree ( Fig. 1L shows postoperative diffusion-weighted imaging without evidence of stroke).

Limitations

This study has several limitations. First, studies included in this systematic review were all retrospective in nature, and none were performed prospectively or did any of the studies directly compare outcomes of single-staged surgery versus multistaged surgery of patients with similar tumor characteristics. More studies directly comparing complications and outcomes, such as blood loss, cranial nerve palsies, and vascular injuries, between multistaged and nonstaged surgical approaches are required to demonstrate the benefit of staged devascularization surgery. Second, since most of these reports were case studies or retrospective studies that included only a small number of patients, the risk of publication bias is high. Neurosurgeons may not have reported or been awarded publication of studies depicting adverse outcomes. Third, there was substantial heterogeneity between studies in terms of their reported indications of a staged approach. Studies investigating indications of staged resection are therefore needed, as it may help clinicians to better consult patients and discern the best treatment method for a selected patient. Lastly, variables, including demographics, treatment approaches, complications, and outcomes, were not standardized among studies. For example, indications for multistaged surgery and surgical outcomes were described in portion in some studies or completely not addressed at all in other manuscripts. As such, no meaningful statistical analysis could be performed using the set of included studies in this systematic review. Future studies reporting outcomes after multistaged surgeries would benefit from utilizing a set of reporting guidelines for better standardization of outcomes to allow for more a robust analysis of the data related to staged resection of meningiomas ( Table 4 ).

Table 4. Suggested reporting guidelines for future multistaged meningioma resection surgeries.

Section	Item	Description
Baseline characteristics	1. Age	Indicate the age of the patient at the time of surgical intervention
	2. Sex	Indicate the patient's sex
Patient preoperative data	3. Patient's preoperative symptoms	Indicate any preoperative symptoms of the individual before surgery
	4. Location of meningioma	Indicate specifically the location of the tumor
	5. Meningioma volume	Indicate the volume of the tumor specified in cm 3
	6. Tumor extension	Indicate any areas of tumor extension and whether the tumor has extension to the supratentorial area or infratentorial area of the brain
	7. Encroachment on specific nearby neurovascular structures	Specifically indicate which blood vessels or cranial nerves the tumor encroaches. Also indicate if it is near the brainstem.
	8. Indication for multi-staged resection	Specifically indicate why the authors chose a multi-staged approach for surgery
Surgical data	9. Approach for resection	Specifically indicate which operative approach was chosen for the first and second surgery
	10. Rationale for approach	Indicate rationale for chosen combination of approaches
	11. Number of stages in operative plan	Specify the number of operative stages
	12. Plan of surgery	Indicate if a multi-staged surgery was preplanned before the first surgery was performed
	13. Duration of each surgery	Indicate total duration of each surgery in minutes
	14. Brain retraction	Indicate any areas of the brain retracted for a prolonged amount of time
	15. Duration of brain retraction	Indicate total duration of brain retraction in minutes
	16. Duration of time between first and second surgery	Indicate number of days between the first and second surgery
	17. Complications of surgery	Indicate any complications of surgery to include new cranial nerve deficits or blood loss
	18. Complications specific to multi-staged approach	Indicate if any obvious complications occurred due to a multi-stage specific approach
Postoperative data	19. Reduction of preoperative symptoms	Indicate if any preoperative symptoms resolved or improved after surgery
	20. Specify whether each new complication was temporary or permanent	Indicate if the new postoperative complications were temporary or permanent
	21. Timing of temporary symptoms	Indicate how long temporary deficits occurred after surgery
	22. Resection status by Simpson grading	Indicate extent of resection by Simpson grading
Long-term radiologic follow-up (if available)	23. Specify any recurrences	Indicate the occurrence of any recurrence
	24. Specify the length of follow-up for recurrence status	Specify total length of follow-up

Note: Describes items that were not reported for each study included in the present review.

Conclusion

In this review, we present what is—to our knowledge—the first and most comprehensive study on staged resection of meningiomas. Our findings suggest that the clinical data available on this topic makes it challenging to clearly define indications for planning staged surgery for meningiomas. Nevertheless, staged resection appears to be well tolerated with no significant adverse effects reported in any of the studies. There were also no complications reported for multiple inductions of anesthesia or increased lengths of surgical time. Because staged resection is a clinical entity that has been previously reported through numerous small series and case reports, there is a lack of studies defining clear indications for staging. We, therefore, encourage skull base surgeons to publish their reasoning for staging surgical resection of meningiomas so that the skull base community may gain an improved understanding of the circumstances in which these approaches may benefit clinical practice.