Vestibular schwannomas (VS) comprise 8% of all intracranial tumors and 90% of cerebellopontine angle and internal auditory canal neoplasms. Secondary to the widespread adoption of screening protocols for asymmetrical hearing loss and the increasing use of advanced imaging, the number of VS diagnosed each year continues to rise, while the average size has declined. Microsurgery remains the treatment of choice for large tumors, however the management of small- to medium-sized VS remains highly controversial with options including observation, radiotherapy, or microsurgery. Within this chapter, the authors provide an overview of the contemporary management of VS, reviewing important considerations and common controversies.
Key points
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The majority of patients with small to medium tumors experience high rates of tumor control and excellent facial nerve outcomes, regardless of treatment modality.
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At 10 years, less than a one-quarter of patients who started with serviceable hearing will maintain class A or B hearing regardless of the treatment modality employed.
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There is compelling evidence that, in the long term, patient-related factors are the primary drivers of quality of life, and treatment strategy has less impact.
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Long-term follow-up should be prioritized in vestibular schwannoma outcomes, where the majority of patients are expected to survive many decades beyond their diagnosis and treatment.
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Patients should receive individualized management based on personal priorities, health status, anticipated life expectancy, and symptoms.
Introduction
Understanding the history of vestibular schwannoma (VS) treatment is to know the development of modern lateral skull base surgery. VS is the model disease that defined a specialty, leading to the refinement of middle and posterior fossa skull base approaches, intraoperative cranial nerve monitoring, and collaboration between the neurotologist and neurosurgeon. The first surgeon to successfully remove a VS remains disputed secondary to uncertainties over tumor pathology, with either Charles Ballance in 1892 or Thomas Annandale in 1895 deserving credit. The first significant breakthrough in the treatment of VS came with Cushing’s introduction of the mastoid-to-mastoid bilateral suboccipital craniotomy with subtotal resection in place of finger enucleation, decreasing mortality from 80% to less than 20%. Subsequently, Walter Dandy, Cushing’s protégé and later rival, advocated a unilateral approach with complete tumor removal.
In 1951, Swedish neurosurgeon, Lars Leksell introduced the concept of stereotactic radiosurgery (SRS) with the first VS treated in Stockholm with a fixed cobalt 60 source unit in 1969, citing the significant morbidity of surgery and Cushing’s own reference to the need for noninvasive treatment methods. Simultaneously, microsurgical advances came in the 1960s with William House and the adoption of the operating microscope and otologic drill, resulting in a further reduction in patient mortality and improved prospects of cranial nerve preservation with surgical removal of VS. It was during this time that the middle fossa craniotomy and the translabyrinthine approaches were revisited after being abandoned for 6 decades because of technical limitations of the time. The last significant advancement within the field of VS microsurgery came with the utilization of cranial nerve monitoring, first pioneered by Delgado and colleagues in 1979.
Current management options for VS include observation with serial imaging, external beam radiation in the form of SRS (1–5 fractions) or stereotactic radiotherapy (>5 fractions), and microsurgical resection. Practically speaking, the viability of modern treatment modalities differ for small to medium tumors (<3 cm) compared with large VS; therefore, these 2 populations are usually discussed separately. In contrast with large tumors with problematic brainstem compression and symptoms of mass effect where surgery is strongly preferred, many smaller tumors can be managed effectively with observation, radiation, or microsurgical resection. Despite the significant volume of literature analyzing VS outcomes, the management of small to medium VS remains highly controversial. The fact that many VS centers are either dominated by SRS or microsurgery suggests that in most environments, provider bias remains the strongest factor dictating treatment. However, it also should be acknowledged that a number of patients seek out various centers with the intent of receiving a particular therapy. The remaining discussion is dedicated to understanding the advantages, limitations, and controversial aspects of the 3 available treatment modalities.
Microsurgery
Historically, and before the widespread availability of SRS, surgical resection was the preferred treatment for VS. The primary advantages of gross total surgical resection (GTR) include a high rate of long-term tumor control, improvement in symptoms of mass effect, definitive histopathologic confirmation of benign schwannoma, and potentially less intense imaging surveillance going forward. It is also sometimes presented that clinical outcomes of SRS after microsurgery, in cases of recurrence or less than GTR, are more favorable than microsurgery after SRS, in cases of continued tumor growth after radiation. This, in addition to the fact that recurrence after gross total resection is lower than reported SRS failure, is often used as an argument for microsurgery when all else is equal. Conversely, the primary disadvantages of surgery include a greater risk of permanent facial palsy, headache, treatment-related hearing loss, cerebrospinal fluid leak, meningitis, and very rarely stroke or death. Additionally microsurgery requires general anesthesia and a 3- to 5-day hospital stay on average with increased upfront cost, whereas SRS is performed with local anesthesia as an outpatient. Although somewhat controversial, frequently cited indications for primary microsurgery include younger patient age, larger tumor size with symptoms attributable to mass effect, ongoing dizziness, cystic tumors, and small anatomically favorable tumors with good hearing.
Over the last 100 years, there have been a number of described surgical approaches to the internal auditory canal (IAC) and cerebellopontine angle (CPA); however, the retrosigmoid, translabyrinthine, and middle cranial fossa remain the most commonly used techniques today, each with their own merits and limitations. The translabyrinthine approach was first described in 1904 by Panse, but was not popularized until the 1960s, paralleling the adoption of the operating microscope and drill to skull base surgery ( Fig. 1 ). The translabyrinthine craniotomy sacrifices hearing as a part of the operation and therefore is generally reserved for patients with nonserviceable hearing or cases where hearing preservation is not realistically feasible because of tumor size. The primary advantages of the translabyrinthine approach include minimal to no brain retraction, reliable distal identification of the facial nerve at the meatal foramen, and extradural drilling, which reduces subarachnoid bone dust dissemination and risk of intracranial injury from the rotating drill. Additionally, this approach best mitigates dizziness in patients presenting with vertigo and carries a lower risk of headaches than the retrosigmoid craniotomy, explained by minimal division of nuchal musculature and lack of intradural drilling. Although some groups only use the translabyrinthine approach for smaller tumors, others report that, with modifications, tumor size is not a limiting factor. It has been our experience that the standard translabyrinthine approach can be more limiting than the retrosigmoid approach with very large tumors that extend far ventral to the porus acusticus, or with an unfavorable facial nerve course over the superior pole of a large tumor. Additionally, a view of the caudal aspect of a large VS can be problematic in the setting of a high jugular bulb. However, these limitations can often be overcome with additional retrosigmoid bony decompression, skeletonization of the jugular bulb, more extensive anterior IAC trough development, and patience with internal debulking, capsule infolding, and tumor mobilization.
The suboccipital approach for VS removal was first performed by Woolsey in 1903 and became popularized by Krause, followed by Cushing and Dandy years later. The modern version of the retrosigmoid craniotomy is perhaps the most versatile of the 3 approaches, granting a panoramic view for removal of giant VS or the option for hearing preservation with small favorable medial tumors ( Fig. 2 ). During hearing preservation, access to the lateral third of the IAC is limited by the position of the posterior semicircular canal and vestibule; however, view to the medial tumor in the cistern is uninhibited. Some have reported the use of angled endoscopy for final inspection or disease removal at the fundus in cases of hearing preservation. It is helpful to carefully examine preoperative thinly sliced heavy T2 weighted sequences such as fast imaging employing steady-state acquisition (FIESTA) or constructive interference in steady state (CISS) to ascertain extent of tumor penetration within the IAC.
The choice between a retrosigmoid craniotomy or translabyrinthine approach for medium to large sized tumors for which hearing preservation is not a consideration, is often weighted toward surgeon preference. When versed in both approaches, the total operative time is not significantly different between the 2, with the main distinction being that meatal drilling and CPA access are performed before the tumor is engaged with the translabyrinthine approach, whereas IAC drilling is performed in a staged fashion after removing posterior fossa tumor during the retrosigmoid approach. Additionally, we have not noted a difference in facial nerve outcomes or risk of cerebrospinal fluid leak. The 2 theoretic drawbacks of the retrosigmoid craniotomy are the need for intradural drilling of the IAC and cerebellar retraction. Additionally, several studies have found that the risk of headaches is greater with retrosigmoid craniotomy than the translabyrinthine approach, particularly within the first postoperative year.
The third and least commonly used approach is the middle fossa craniotomy ( Fig. 3 ). This technique was first described by Parry in 1904 for vestibular nerve section, but was abandoned for approximately 60 years because of the severe morbidity associated with the inexact surgical techniques using unmagnified mallet and chisel bone removal. In 1961, House revisited the middle fossa technique initially for removal of extensive otosclerosis, but soon realized its merits for IAC exposure for VS. The middle fossa craniotomy uses extradural subtemporal access to the IAC and is primarily used for hearing preservation attempts with small, laterally based tumors. As a result of more limited access to the posterior fossa and because of poor prospects of hearing preservation with larger tumors, most surgeons limit tumor size to less than 0.5 cm in the CPA when considering a middle fossa approach. Although this point is often debated, proponents of the middle fossa craniotomy cite improved access to lateral tumor extent, compared with the retrosigmoid approach. The primary disadvantages of the middle cranial fossa approach are limited access to the posterior fossa and the need for temporal lobe retraction, which adds a very small risk of seizure, aphasia, and stroke. Additionally, because the IAC is accessed from above, the facial nerve position is often less optimal, requiring the surgeon to work around the nerve while removing tumor. Thus, when comparing tumors size and operative approach, the risk of facial paresis is greater with the middle fossa approach compared with others. This has led some groups to perform preoperative vestibular testing and more detailed imaging studies to ascertain nerve of origin because, theoretically, tumors arising from the superior vestibular nerve are more favorable than inferior vestibular nerve tumors with regard to both the degree of facial nerve manipulation that may be required as well as risk to hearing and the cochlear nerve. With vestibular testing, abnormal caloric testing may indicate a superior vestibular nerve tumor, whereas vestibular evoked myogenic potential results may be used to identify inferior vestibular nerve origin. However, once a tumor has reached a larger size, these methods of prediction become less reliable.
Stereotactic Radiotherapy
The concept of combining a stereotactic head frame with collimated x-ray beams was conceived by Lars Leksell of Sweden in 1951. To date, the majority of the published outcomes for VS are from centers using the Leksell Gamma Knife system (Elekta AB, Stockholm, Sweden), incorporating a rigid head frame and between 192 (model Perfexion) and 201 (model U, B, C models) fixed sources of cobalt-60 ( Fig. 4 ). During treatment planning, varying numbers of isocenters using different sized collimators, variably weighted, are used to create a radiation dose plan that highly conforms to the radiographic tumor volume on thin slice (1 mm) gadolinium enhanced MRI. The very steep radiation fall-off above the traditionally prescribed 50% isodose line results in a very conformal dose plan while minimizing dose to adjacent sensitive structures.
Early SRS series commonly used high-dose treatment plans (>16 Gy marginal dose) that achieved excellent tumor control (∼98%); however, rates of early hearing loss, as well as facial and trigeminal neuropathy, were high. With time, several groups trialed dose de-escalation, to 13 and 14 Gy, and more recently 11 and 12 Gy, for patients with good pretreatment hearing. At these levels, the risk of permanent facial palsy is less than 1% and more than 90% of patients still achieve durable tumor control. Clearly, at some point continuing to lower the dose to achieve better rates of hearing preservation will result in a noticeable decline in tumor control; however, at least in the sporadic VS population, this threshold has not yet been reached. Recently, minimizing cochlear dose during SRS to reduce the risk of hearing loss has become a popular topic. Until there is evidence that tumor control is achieved at much lower doses than 12 Gy, we believe that undertreating the lateral tumor margin to achieve a cochlear dose of less than 4 Gy is not advisable. It is clear that cochlear dose is only one of many factors that influence hearing decline after SRS. In our center, we commonly use a marginal dose of 12.5 Gy prescribed to the 50% isodose line for patients with sporadic tumors and serviceable hearing and 13 to 14 Gy for patients with nonserviceable hearing. In our experience, tumor control is more problematic for patients with neurofibromatosis type 2, where we feel a higher dose paradigm is justified.
Because the risk of immediate profound hearing loss after SRS is very low, this treatment was initially touted as a hearing preservation strategy. However, as our experience grows, it is clear that treatment at even lower marginal doses, such as 12 Gy, results in accelerated hearing loss. Several studies have documented surprisingly similar patterns of audiometric decline after SRS. Within the first 2 years after treatment, there may be a rather steep drop in serviceable hearing, with a more shallow but steady decline thereafter.
One final aspect of SRS treatment that deserves review is the concern over radiation-induced malignancy. The modified Cahan criteria were established to help determine with reasonable probability whether a malignancy truly developed as a result of prior radiation rather than by chance or from an unrelated cause. To date, there have been fewer than 10 radiation-associated malignancies reported in patients with VS. Using the denominator of all patients treated worldwide, the risk of developing a radiation-induced cancer after SRS is less than 1 in 1000. It seems that this risk is greater in the neurofibromatosis type 2 population, where patients already harbor a mutation in a tumor suppressor gene. One-half of radiation-associated malignancies occurring after SRS for VS have developed in neurofibromatosis type 2 patients; however, this group only represents 5% of the VS population. When interpreting these estimates, it is important to realize that the Cahan criteria are not perfect, because malignancy may occur coincidentally, even after microsurgery. And because tissue biopsy is rarely performed before SRS, it is also possible that a small number of reported cases involving presumed VS were in fact malignancies all along. Regardless, to keep perspective, it is clear that the rate of radiation induced malignancy is extremely low in patients with sporadic VS, significantly below the lowest rates of mortality in surgical series from large experienced centers. Therefore, patients should be informed about this rare risk, but it should not be used to direct treatment.
Observation
Ironically, one of the greatest advances in VS management has been an understanding that many patients do not require treatment. Observing a central tenant of the skull base specialty, in the setting of benign disease, we should avoid inflicting more morbidity with treatment than the disease is expected to produce over the anticipated lifespan of the patient. In the early era of modern skull base surgery, the mere diagnosis of VS warranted aggressive tumor resection, prioritizing disease eradication even over facial nerve outcome. Beginning in the mid 1970s, several centers began adopting an expectant approach using a primary “wait-and-scan” policy for small tumors. Particularly within the last 15 years, a growing number of publications characterizing the natural history of disease have emerged. Most studies have observed that more than 50% of intracanalicular tumors do not grow after diagnosis and a small percent actually regress. Of course, because VS are not thought to be congenital lesions, every VS must enter a phase of growth to achieve the size seen at diagnosis; however, it seems that tumors may enter periods of extended or indefinite quiescence with time. To date, no consistent association between growth and tumor size or patient age have been identified. However, because the typical growth rate of enlarging tumors is 1 to 2 mm/y, observation poses extremely little risk to the patient, provided reliable follow-up can be maintained.
Perhaps the most controversial aspect of observation is the risk to hearing. Several studies have documented the long-term pattern of hearing loss in untreated tumors. These studies confirm that better hearing at diagnosis portends the greatest chance for long-term serviceable hearing. The primary argument against observation is the belief that immediate or proactive treatment with SRS or microsurgery may protect useful long-term serviceable hearing, believing that waiting for growth reduces the success of hearing preservation treatment. For reasons outlined elsewhere in this article, the authors believe that overall, the greatest number of serviceable hearing years comes with observation compared with proactive treatment.
Undoubtedly, observation will become increasingly important in coming years with the growing number of small tumors diagnosed in patients with minimal attributable symptoms. Additionally, this strategy is appealing in the cost-consciousness climate of today. However, over a period of time the cumulative price of frequent MRI surveillance with observation may exceed the cost of early treatment. At the authors’ centers, most patients with tumors less than 2 cm are observed initially and treatment is generally reserved for those with documented tumor growth.
Introduction
Understanding the history of vestibular schwannoma (VS) treatment is to know the development of modern lateral skull base surgery. VS is the model disease that defined a specialty, leading to the refinement of middle and posterior fossa skull base approaches, intraoperative cranial nerve monitoring, and collaboration between the neurotologist and neurosurgeon. The first surgeon to successfully remove a VS remains disputed secondary to uncertainties over tumor pathology, with either Charles Ballance in 1892 or Thomas Annandale in 1895 deserving credit. The first significant breakthrough in the treatment of VS came with Cushing’s introduction of the mastoid-to-mastoid bilateral suboccipital craniotomy with subtotal resection in place of finger enucleation, decreasing mortality from 80% to less than 20%. Subsequently, Walter Dandy, Cushing’s protégé and later rival, advocated a unilateral approach with complete tumor removal.
In 1951, Swedish neurosurgeon, Lars Leksell introduced the concept of stereotactic radiosurgery (SRS) with the first VS treated in Stockholm with a fixed cobalt 60 source unit in 1969, citing the significant morbidity of surgery and Cushing’s own reference to the need for noninvasive treatment methods. Simultaneously, microsurgical advances came in the 1960s with William House and the adoption of the operating microscope and otologic drill, resulting in a further reduction in patient mortality and improved prospects of cranial nerve preservation with surgical removal of VS. It was during this time that the middle fossa craniotomy and the translabyrinthine approaches were revisited after being abandoned for 6 decades because of technical limitations of the time. The last significant advancement within the field of VS microsurgery came with the utilization of cranial nerve monitoring, first pioneered by Delgado and colleagues in 1979.
Current management options for VS include observation with serial imaging, external beam radiation in the form of SRS (1–5 fractions) or stereotactic radiotherapy (>5 fractions), and microsurgical resection. Practically speaking, the viability of modern treatment modalities differ for small to medium tumors (<3 cm) compared with large VS; therefore, these 2 populations are usually discussed separately. In contrast with large tumors with problematic brainstem compression and symptoms of mass effect where surgery is strongly preferred, many smaller tumors can be managed effectively with observation, radiation, or microsurgical resection. Despite the significant volume of literature analyzing VS outcomes, the management of small to medium VS remains highly controversial. The fact that many VS centers are either dominated by SRS or microsurgery suggests that in most environments, provider bias remains the strongest factor dictating treatment. However, it also should be acknowledged that a number of patients seek out various centers with the intent of receiving a particular therapy. The remaining discussion is dedicated to understanding the advantages, limitations, and controversial aspects of the 3 available treatment modalities.
Microsurgery
Historically, and before the widespread availability of SRS, surgical resection was the preferred treatment for VS. The primary advantages of gross total surgical resection (GTR) include a high rate of long-term tumor control, improvement in symptoms of mass effect, definitive histopathologic confirmation of benign schwannoma, and potentially less intense imaging surveillance going forward. It is also sometimes presented that clinical outcomes of SRS after microsurgery, in cases of recurrence or less than GTR, are more favorable than microsurgery after SRS, in cases of continued tumor growth after radiation. This, in addition to the fact that recurrence after gross total resection is lower than reported SRS failure, is often used as an argument for microsurgery when all else is equal. Conversely, the primary disadvantages of surgery include a greater risk of permanent facial palsy, headache, treatment-related hearing loss, cerebrospinal fluid leak, meningitis, and very rarely stroke or death. Additionally microsurgery requires general anesthesia and a 3- to 5-day hospital stay on average with increased upfront cost, whereas SRS is performed with local anesthesia as an outpatient. Although somewhat controversial, frequently cited indications for primary microsurgery include younger patient age, larger tumor size with symptoms attributable to mass effect, ongoing dizziness, cystic tumors, and small anatomically favorable tumors with good hearing.
Over the last 100 years, there have been a number of described surgical approaches to the internal auditory canal (IAC) and cerebellopontine angle (CPA); however, the retrosigmoid, translabyrinthine, and middle cranial fossa remain the most commonly used techniques today, each with their own merits and limitations. The translabyrinthine approach was first described in 1904 by Panse, but was not popularized until the 1960s, paralleling the adoption of the operating microscope and drill to skull base surgery ( Fig. 1 ). The translabyrinthine craniotomy sacrifices hearing as a part of the operation and therefore is generally reserved for patients with nonserviceable hearing or cases where hearing preservation is not realistically feasible because of tumor size. The primary advantages of the translabyrinthine approach include minimal to no brain retraction, reliable distal identification of the facial nerve at the meatal foramen, and extradural drilling, which reduces subarachnoid bone dust dissemination and risk of intracranial injury from the rotating drill. Additionally, this approach best mitigates dizziness in patients presenting with vertigo and carries a lower risk of headaches than the retrosigmoid craniotomy, explained by minimal division of nuchal musculature and lack of intradural drilling. Although some groups only use the translabyrinthine approach for smaller tumors, others report that, with modifications, tumor size is not a limiting factor. It has been our experience that the standard translabyrinthine approach can be more limiting than the retrosigmoid approach with very large tumors that extend far ventral to the porus acusticus, or with an unfavorable facial nerve course over the superior pole of a large tumor. Additionally, a view of the caudal aspect of a large VS can be problematic in the setting of a high jugular bulb. However, these limitations can often be overcome with additional retrosigmoid bony decompression, skeletonization of the jugular bulb, more extensive anterior IAC trough development, and patience with internal debulking, capsule infolding, and tumor mobilization.
