The goals of treatment of skull base neoplasms are to maximize oncologic outcomes and optimize functional outcomes. Several studies have investigated the former, but fewer examine the latter. This article reviews the available evidence for several functional outcomes, including endocrine, nasal, neurologic, visual, and quality of life outcomes for both endoscopic and open approaches. The quality of evidence for each outcome is compared for endoscopic and open approaches using the Oxford Centre for Evidence-based Medicine guidelines, and recommendations are made. Future longitudinal comparative outcome studies are needed to better delineate the functional status of patients undergoing skull base surgery.
| EBM Question | Level of Evidence | Grade of Recommendation |
|---|---|---|
| Is functional outcome from endonasal surgery better to open craniofacial surgery? | 4-2a | C-B |
Most studies in skull base surgery have focused on local tumor control and improving disease-specific survival. Despite advances in instrumentation and surgical technologies, no significant improvements in these specific outcome measures have been made. Longitudinal studies with long-term follow-up are being undertaken to compare the oncologic results between endoscopic and open techniques, and the early results seem to be promising, with comparable and even improved local control rates.
As long-term survival and tumor control outcomes data are awaited, much attention has shifted toward functional outcomes. The interest in functional outcomes is particularly relevant to patients with skull base neoplasms, because both the disease process and the treatment can be highly morbid to the nose and sinuses and adjacent vital structures, including the orbit, brain, and carotid arteries. Injury to these structures can result in temporary or permanent functional limitations. This article reviews the available evidence for functional outcomes after skull base surgery to determine how these differ for endoscopic and open approaches. The Oxford Centre for Evidence-based Medicine Levels of Evidence are used to provide recommendations ( Tables 1 and 2 ) for each functional outcome.
| Level | Therapy/Prevention/Etiology/Harm |
|---|---|
| 1a | Systematic review (with homogeneity) of randomized controlled trials |
| 1b | Individual randomized controlled trial (with narrow CI) |
| 1c | All or none a |
| 2a | Systematic review (with homogeneity) of cohort studies |
| 2b | Individual cohort study (including low-quality randomized controlled trials; eg, <80% follow-up) |
| 2c | “Outcomes” research; ecological studies |
| 3a | Systematic review (with homogeneity) of case-control studies |
| 3b | Individual case-control studies |
| 4 | Case-series (and poor-quality cohort and case-control studies) |
| 5 | Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles” |
a Met when all patients died before the treatment became available, but now some survive on it; or when some patients died before the treatment became available, but now none die on it.
| A | Consistent level 1 studies |
| B | Consistent level 2 or 3 studies or extrapolations from level 1 studies |
| C | Level 4 studies or extrapolations from level 2 or 3 studies |
| D | Level 5 studies or troublingly inconsistent or inconclusive studies of any level |
Defining functional outcomes
Starfield defines functional status as “the capacity to engage in activities of daily living and social role activities.” Physical morbidity incurred by skull base neoplasms directly impacts one’s functional status. Functional status is often the result of a combination of factors, some of which may include the disease, the treatment, coping strategies of the individual, and the individual’s support network.
Many quality-of-life instruments contain items to measure functional status. However, outcomes collected from instruments are often subjective and may vary based on the individual patient or the method of administration. A variety of functional outcomes are specific to skull base surgery. Collecting information about these outcomes requires good follow-up of postoperative patients and, in certain instances, objective measurement of various outcomes.
Functional outcomes
The following functional outcomes relating to skull base pathology are described and the evidence for endoscopic and open approaches are compared and discussed:
- 1.
Endocrine outcomes
- 2.
Nasal outcomes
- 3.
Neurologic outcomes
- 4.
Visual outcomes
- 5.
Quality of life outcomes.
Between 1998 and 2008, the authors performed a retrospective review at the University Health Network in Toronto of 138 patients who underwent skull base surgery. Of these patients, 73 underwent open approaches and 65 endoscopic approaches. The median follow-up for open cases was 48 months compared with 17 months for endoscopic cases, suggesting a more recent switch to endoscopic approaches. Postoperative physical morbidity leading to functional limitation was categorized into endocrine, nasal, neurologic, visual, and “other” outcomes. These outcomes were compared according to surgical approach ( Table 3 ). Patients who underwent endoscopic approaches had more postoperative nasal morbidity (80% vs. 68.5%; P = .003), whereas patients treated with open approaches had more visual morbidity (28.8% vs. 9.2%; P = .02) after adjusting for tumor location and preoperative symptoms. However, these results are retrospective; prospective comparative studies are needed to confirm these findings.
| Postoperative Symptom Type | Endoscopic Approach (%) | Open Approach (%) | Adjusted P Value |
|---|---|---|---|
| Endocrine | 4.6 | 1.4 | .52 |
| Nasal | 80 | 68.5 | .003 |
| Neurologic | 16.9 | 24.7 | .45 |
| Visual | 9.2 | 28.8 | .02 |
| Other a | 13.8 | 13.7 | .86 |
a Other symptoms include those that do not directly fit into one of the above, such as dry mouth, fatigue, and weight loss.
Functional outcomes
The following functional outcomes relating to skull base pathology are described and the evidence for endoscopic and open approaches are compared and discussed:
- 1.
Endocrine outcomes
- 2.
Nasal outcomes
- 3.
Neurologic outcomes
- 4.
Visual outcomes
- 5.
Quality of life outcomes.
Between 1998 and 2008, the authors performed a retrospective review at the University Health Network in Toronto of 138 patients who underwent skull base surgery. Of these patients, 73 underwent open approaches and 65 endoscopic approaches. The median follow-up for open cases was 48 months compared with 17 months for endoscopic cases, suggesting a more recent switch to endoscopic approaches. Postoperative physical morbidity leading to functional limitation was categorized into endocrine, nasal, neurologic, visual, and “other” outcomes. These outcomes were compared according to surgical approach ( Table 3 ). Patients who underwent endoscopic approaches had more postoperative nasal morbidity (80% vs. 68.5%; P = .003), whereas patients treated with open approaches had more visual morbidity (28.8% vs. 9.2%; P = .02) after adjusting for tumor location and preoperative symptoms. However, these results are retrospective; prospective comparative studies are needed to confirm these findings.
| Postoperative Symptom Type | Endoscopic Approach (%) | Open Approach (%) | Adjusted P Value |
|---|---|---|---|
| Endocrine | 4.6 | 1.4 | .52 |
| Nasal | 80 | 68.5 | .003 |
| Neurologic | 16.9 | 24.7 | .45 |
| Visual | 9.2 | 28.8 | .02 |
| Other a | 13.8 | 13.7 | .86 |
a Other symptoms include those that do not directly fit into one of the above, such as dry mouth, fatigue, and weight loss.
Endocrine outcomes
Hormonal Stabilization
Endocrine outcomes are particularly relevant as they relate to skull base tumors in the sella, suprasellar region, and surrounding areas. Endocrine outcomes can be divided into improvement in preoperative endocrinopathies or the development of new endocrinopathies as a result of surgical intervention. Rotenberg and colleagues. performed a systematic review of studies comparing open (transseptal microscopic or transnasal microscopic) and endoscopic approaches for pituitary pathology. In this review of 11 studies, 3 of them, 1 of which was a randomized trial and 2 of which were cohort studies, compared effectiveness of hormonal stabilization between endoscopic and microscopic approaches. None of these studies reported statistical differences between the groups.
Dorward reviewed endocrinologic outcomes of endoscopic and microscopic approaches for all pituitary adenomas using methodology applied in a previous systematic review. The details of the search strategy used are unclear; however, the results compared pooled hormonal stabilization rates from 20 studies using endoscopic approaches to an undisclosed number of pooled microscopic studies. The definitions for endocrinologic cures vary by primary study, but the pooled cure rates favor endoscopic approaches (75% vs. 73%) for all adenomas. The authors of this article suggest that the benefit is incremental for macroadenomas (70% vs. 45% cure rate) compared with microadenomas (84% vs. 77% cure rate). Most of the primary studies included in this review include retrospective cohort studies. Fig. 1 depicts endocrinologic cure rates in various functioning adenomas. All functioning adenomas except for adrenocorticotropic hormone–secreting microadenomas had better cure rates using the endoscopic approach. However, no statistical meta-analyses were performed.
Dorward also examined the rates of anterior pituitary dysfunction in his review of the endoscopic and microscopic literature. In the analysis of 1980 cases of endoscopic resection of pituitary tumors, the overall rates of anterior pituitary dysfunction were 5.4%. For microscopic studies, the rate of anterior pituitary dysfunction was 5%; however, the methods of meta-analysis and the included studies are unclear. The author notes that a survey administered to surgeons using the microscopic approach for resection of pituitary adenomas suggests a 19.4% rate of anterior pituitary dysfunction.
Level of Evidence: 2a
Recommendation
- 1.
For pituitary macroadenomas, endoscopic approaches may offer better endocrinologic cure rates compared with microscopic (open) approaches (grade B).
- 2.
For pituitary microadenomas, whether endoscopic approaches are superior to microscopic approaches or vice versa for endocrinologic cure is unclear (grade B).
- 3.
Whether endoscopic approaches are superior to microscopic approaches or vice versa for minimization of anterior pituitary dysfunction is unclear (grade B).
Diabetes insipidus
In a systematic review of comparative studies between endoscopic and microscopic approaches for pituitary adenomas, seven studies were reviewed that compared either transient or permanent diabetes insipidus (DI), one of which was a randomized trial, five of which were cohort studies, and one was a case-series. One study noted increased rates of DI in the microscopic group immediately postoperatively (<2 weeks), but no significant difference was seen at 6 months. Another study showed a higher rate of DI for the sublabial microscopic approach (33%) compared with the endoscopic (7%) and transnasal microscopic (5%) approaches. However, no statistical analyses were performed. The authors of the review conclude that endoscopic approaches are associated with fewer cases of transient postoperative DI, but these differences equalize over time.
Level of Evidence: 2a
Recommendation
No conclusive evidence exists that either endoscopic or microscopic approaches for skull base neoplasms offer better rates of DI (grade B).
Nasal Outcomes
Rotenberg and colleagues describe six studies that compare nasal outcomes of endoscopic and open (transnasal microscopic and sublabial microscopic) approaches for pituitary adenomas. In three of these studies, rates of septal perforations were insignificant between the groups. One group reported more septal perforations in the microscopic group, although no statistical analysis was performed. Another group reported significantly more epistaxis in the microscopic group, and another group reported more rhinologic complications in the microscopic group in a randomized trial. These data conflict with data obtained by the authors of this article in a retrospective analysis adjusting for tumor location and preoperative symptoms that suggest that open approaches are associated with significantly fewer nasal complications compared with endoscopic approaches.
In a prospective cohort study, the authors prospectively collected rhinologic outcome data for 1 year for a total of 63 patients who underwent endoscopic skull base surgery for various tumors. Nasal crusting was the most common (98%) symptom reported, followed by nasal discharge (46%), whereas loss of smell was reported by only 9.5% of patients. Crusting was short-lived, with half of the patients achieving a crust-free nose by 101 days (95% CI, 87.8–114.2 days). More complex operations (defined by surgical manipulation of more than one anatomic module) had significantly longer times to achieve absence of crusting. However, no independent risk factors were seen in a multivariable analysis predisposing patients to longer periods of postoperative crusting. These data are corroborated by another study that suggests nasal morbidity, as indicated by the SinoNasal Outcome Test 22 (SNOT-22) questionnaire, gradually improves with time. These prospective data suggest that crusting may in fact be underreported in other trials and reviews. No large-scale functional outcome studies have reported nasal outcomes for patients undergoing open skull base surgery.
Level of Evidence: 1b–2b
Recommendation
Conflicting evidence exists regarding whether open approaches or endoscopic approaches have superior nasal outcomes, and a paucity of studies have compared these approaches for nasal outcomes. Further good-quality studies are needed (grade D).
Neurologic Outcomes
In a single institution, neurologic outcomes were compared between patients undergoing endoscopic approaches and those undergoing open approaches for clival tumors. In this study, 17 patients underwent endoscopic approaches and 48 underwent open approaches, including anterior (transfacial or transoral) approaches or lateral approaches (pterional, fronto-orbito zygomatic approaches). On patient (6%) who underwent endoscopic approaches experienced neurologic worsening (new hemiparesis), compared with 33% who underwent open approaches. These neurologic symptoms included worsening hemiparesis, brainstem compression, and new cranial nerve deficits. Another series of chordomas resected endoscopically reported no neurologic deficits postoperatiely, and a report of chordomas resected through open approaches (retrosigmoid, pterional, subtemporal) noted a 28% rate of neurologic complications, including cranial nerve palsies, hemiparesis, and hemiplegia.
Reports of poor neurologic outcomes, however, are not universal for open skull base surgery. In a series of 81 olfactory groove meningiomas resected with open approaches, one group reported no new neurologic deficits except for anosmia. Similarly, endoscopic approaches for anterior cranial base meningiomas may be associated with a low complication rate, with only 1 patient of 35 experiencing neurologic compromise (new hemiparesis and cognitive impairment) after endoscopic resection.
Level of Evidence: 4
Recommendation
There is some suggestion in poorly designed cohort studies and case-series that endoscopic approaches may have better neurologic outcomes. However, selection biases for endoscopic approaches and heterogeneity in outcomes by location and pathology make these results difficult to interpret (grade C).
Visual Outcomes
In a review of visual outcomes in microscopic versus endoscopic pituitary surgery, Schaberg and colleagues describe two studies in which complete visual recovery from preoperative visual deficits was experienced by 50% and 70% of patients, respectively, after endoscopic surgery. They compare this to a large-scale microscopic series in which complete visual recovery is experienced by only 40% of patients.
Stamm and colleagues recently reviewed the published series for endoscopic and transcranial management of craniopharyngiomas. The rate of visual recovery in seven small series (between 1 and 10 patients) ranged from 56% to 100%, whereas the rate of visual recovery in the transcranial studies ranged from 64% to 89%. Although none of the endoscopic series reported visual worsening, two of the microscopic series reported visual worsening (3% and 8%).
The authors compared the incidence of postoperative visual complaints in 65 patients undergoing endoscopic approaches and 73 patients undergoing open approaches for skull base pathology, and noted that patients with open approaches had more postoperative visual complaints (28.8% vs. 9.2%, adjusted P = .02) after adjusting for confounders such as preoperative symptoms and tumor location.
Level of Evidence: 4
Recommendation
There is some suggestion in poorly designed cohort studies and case-series that endoscopic approaches may have better visual outcomes. However, selection biases for endoscopic approaches and heterogeneity in outcomes according to location and pathology make these results difficult to interpret (grade C).
Quality of Life
A recent movement has occurred toward better elucidating the quality of life in patients who undergo skull base surgery. Much of this impetus is rooted in the fact that oncologic outcomes have reached a relative plateau, and that surgery in this anatomic region can be fraught with significant impairments in functional status. The goals of therapy are now balanced between maximizing oncologic control and minimizing functional disability.
Despite this new interest, no large multi-institutional studies have examined quality of life in patients undergoing skull base surgery. However, some single institutional experiences with quality of life for endoscopic surgery and open skull base surgery have been reported. However, the current data are limited in that no direct comparative studies have been performed in the form of either randomized trials or matched case-control series.
In a cross-sectional study of 54 patients after endoscopic pituitary surgery with follow-up ranging from 4 to 20 months, Karabatsou and colleagues studied quality of life using the SF-36. When compared with normative data, patients who underwent surgery for pituitary adenomas only differed from healthy individuals in the general health domain ( P = .002) but were no different with respect to all other domains (physical functioning, role limitations physical, role limitations emotional, energy, emotional well-being, social functioning, bodily pain). Among patients undergoing surgery, those with Cushing disease had significantly lower scores in role-limitations emotional ( P = .02). The only published report of disease-specific quality of life for endoscopic surgery used the anterior skull base quality of life instrument to prospectively follow 51 patients who underwent skull base surgery. The data from this study suggest that overall quality of life and functional status tend to improve over the course of the year after surgery. These data corroborate those for patients who have undergone open approaches for skull base neoplasms.
Gil and colleagues studied quality of life for patients undergoing open skull base surgery using the anterior skull base surgery disease-specific quality of life in a cross-sectional study. Forty patients completed the anterior skull base questionnaire at various time points (minimum of 3 months) after surgery. Overall, a trend seemed to be present toward improved outcomes starting 6 months after surgery. The only risk factor for poorer overall quality of life scores in this study was whether the tumor was malignant versus benign ( P <.05).
Although no head-to-head studies have compared open and endoscopic approaches, when comparing the data from Gil and colleagues and Pant and colleagues using the same disease-specific quality of life questionnaire ( Figs. 2 and 3 ), the authors of this article note that the open surgical patients have mean scores between 2 and 3 (on a scale from 1 to 5), whereas the patients who underwent endoscopic approaches have mean scores greater than 4. This comparison is necessarily fraught with limitations given the heterogeneity of tumors, the different indications for surgery, and the various rates of malignancy. Also, the ASB questionnaire was not designed nor validated for patients undergoing endoscopic approaches.
