Comparison of Quality of Life After Transnasal Endoscopic vs Open Skull Base Tumor Resection FREE

The development of new surgical techniques and the use of adjuvant radiation therapy have had a major impact on the long-term survival of patients with lesions involving the anterior cranial fossa.¹ Treatment of these tumors, however, may also be associated with considerable morbidity that impairs the patients' quality of life (QOL).^2- 3 Assessment of QOL is aimed toward improving treatment modalities, promoting the restoration of the patient's usual ability to function, and accelerating his or her return to normal daily activities and lifestyle. Estimation of the influence of surgical procedures on QOL can also serve as a means by which the most appropriate surgical approach can be selected for a given patient. A multidimensional evaluation of QOL involves retrieving information on the physical, emotional, social, and economical aspects of the patient's lifestyle as well as on specific symptoms associated with the disease. Accurate interpretation of the data requires disease-specific instruments that cover the morbidity associated with the site of cancer and its treatment.^4- 5

Previous reports have established the craniofacial and subcranial approaches as reliable surgical techniques for the removal of anterior skull base tumors.^6- 7 Endoscopic transnasal surgery became a suitable alternative to those traditional approaches during the last decade.^8- 9 The technical reproducibility and associated morbidity of the open and endoscopic approaches have been studied extensively,¹⁰ but, to our knowledge, their impact on the patient's QOL has never been compared.

The aim of this study was to compare the influence of open and endoscopic skull base surgery on patients' QOL in a single medical center. Both procedures were performed by the same surgical team. The psychological, social, and physical well-being of patients was assessed with a disease-specific multidimensional questionnaire.

The study was based on the hospital charts and QOL questionnaires of 78 patients who underwent surgery for extirpation of skull base tumors at our institution between 2003 and 2010. Of the 78 patients, 37 were operated on through the subcranial approach (from 2003-2007) and 41 through the expanded endoscopic approach (EEA) (from 2008-2010). All operations were performed by the same interdisciplinary team at the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel (N.M. and Z.G. performed the endonasal procedures; A.A., N.M., D.M.F., and Z.G. performed the open procedures). We included patients who had undergone the surgery more than 6 months before the study began.^11- 13 In the EEA group, 12 of 41 patients (29%) had undergone the surgery less than 12 months before answering the questionnaire, and in the subcranial group, 11 of 37 patients (30%) had undergone surgery less than 12 months before answering the questionnaire. These differences were not statistically significant (P = .99).

Other inclusion criteria were age 16 years and older, ability to read and write, no severe preoperative psychopathologic or cognitive impairment, and provision of informed consent to participate in this survey. Patients with postoperative impairment were included in the study. All the candidates who agreed to fill out a questionnaire also gave a full medical history and underwent a physical examination on the same day. Comorbidity was defined according to the Charlson Index as follows: 1 point, myocardial infarct, congestive heart failure, peripheral vascular disease, cerebrovascular disease, chronic lung disease, connective tissue disease, ulcer, and chronic liver disease; 2 points, moderate kidney disease, diabetes, and diabetes with complication.¹⁴ Other conditions that are found in the Charlson Index (such as other malignancy or AIDS) were not encountered in our cohort.

We used the seventh edition of the 2010 American Joint Committee on Cancer (for T classification of paranasal sinus tumors). In the EEA cohort, there were 5 T4 chordomas or sarcomas, 1 T4 sinonasal undifferentiated carcinoma, and 1 stage I plasmocytoma. In the subcranial group, there were 3 cases of T4 squamous cell carcinoma, 2 Kadish stage C esthesioneuroblastomas, 2 T4 sarcomas, and 1 case each of T4 melanoma, T4 sinonasal undifferentiated carcinoma, and stage I plasmocytoma. Overall, there were 7 patients with malignant tumors in the EEA group: 6 had T4 classifications, and 1 had stage I plasmocytoma. In the subcranial group, there were 10 patients with cancer: 7 had T4 classifications, 2 had Kadish stage C esthesioneuroblastomas, and 1 had stage I plasmocytoma.

We used the Anterior Skull Base Surgery Questionnaire, the development, reliability, and validity of which have been described elsewhere.¹⁵ Briefly, 6 relevant domains were used: role of performance, physical function, vitality, pain, specific symptoms, and impact on emotions. The questionnaire was constructed after a review of the literature that yielded a pool of questions related to general QOL issues and from questionnaires related to head and neck cancer. Additional questions were included to cover symptoms that are specifically associated with anterior skull base tumors and their postoperative morbidity. These questions were compiled from interviews with the professional staff (head and neck surgeons, nurses, and social workers), patients, and caregivers. All the questions were geared toward detecting differences in QOL between the preoperative (1 month before surgery) and postoperative periods. The answers were self-reported by the patients on an ordinal scale, with 5 levels indicating any change in QOL as a direct result of the surgery. All questions had the same level of importance. To help control for response bias, some of the answers ranged from “large improvement” (score of 5) to “large deterioration” (score of 1), while others were presented the other way around. An independent physician conducted all the interviews for this study to avoid bias from surgeon-patient interaction. The study was approved by the institutional review board.

Internal consistency of each of the 6 domains was evaluated using the Cronbach α coefficient. The Cronbach α values for each domain were greater than 0.8 in both groups. The assessment of construct validity demonstrated that the direction of differences for each domain was as hypothesized (paired t test, P < .05).

The minimal clinically important difference (MCID) was calculated with the distribution-based method as described by Norman et al¹⁶ and by using half the baseline standard deviation of the overall QOL score. With the distribution-based method, the MCID was calculated to be 0.30 points (15% change) and 0.32 points (16% change) for the open and the EEA groups, respectively.

Clinical, demographic, and tumor variables were analyzed with qualitative and quantitative tests. The Fisher exact test (StatCalc 2.0; University of Louisiana, Lafayette) was used for contingency analysis. The t test was used to compare the different scores in each group (Microcal Origin; Microcal Software Inc). Multivariate analysis of variance was performed to identify independent predictors of QOL (JMP; SAS Institute Inc). P ≤ .05 was considered significant.

The study included 78 patients who were operated on via the subcranial approach and the EEA. The demographic characteristics of all the patients are shown in Table 1. There were no significant clinical or demographic differences between the 2 study groups.

We first sought to characterize the QOL score in the endoscopic group. The female patients in the EEA group reported significantly lower QOL scores than the males in all domains except the specific symptoms domain (Table 2). These differences were above the MCID. We next evaluated the association between other clinical and demographic variables on various QOL domains in the EEA group. No significant association was detected between QOL scores and age, comorbidity, adjuvant radiation therapy, prior surgery, or histologic type (benign vs malignant). Also, neither the type of surgery (pituitary tumors vs nonpituitary tumors) nor the anatomical region that was involved (cribriform, planum, sella, or clivus) was associated with reduced QOL scores.

In the open surgery group, patients with benign tumors reported higher scores than those with malignant tumors in the following domains: vitality (2.8 [0.7] vs 2.3 [0.5]) (mean [SD]), physical function (2.7 [0.4] vs 2.4 [0.4]), specific symptoms (2.9 [0.6] vs 2.08 [0.6]), and impact on emotions (2.8 [0.8] vs 2.3 [0.4]) (all P < .05). Similarly, adjuvant radiation therapy was associated with significantly lower scores than no radiation therapy in the specific symptoms (2.8 [0.6] vs 2.0 [0.6], respectively) and impact on emotions (2.8 [0.7] vs 2.3 [0.4], respectively) domains (P < .05). Patients older than 60 years also reported lower scores in the physical function domain than younger patients (2.3 [0.4] vs 2.7 [0.3], respectively; P < .05). These differences were above the MCID. The other variables were not statistically different (P >> .10).

Next, we compared the QOL scores according to the surgical approach (Figure). Patients who were operated on through the EEA reported better scores than those who were operated on via the subcranial approach in all domains except the specific symptoms domain. Univariate analysis revealed significant differences between the 2 groups in the physical function and impact on emotions domains (Table 3).

Although our analysis did not find differences in scores of patients undergoing EEA for pituitary vs nonpituitary operations, it is possible that the better scores reported by patients in the endoscopic group reflect the relatively higher number of pituitary operations in this group. For this reason, we repeated our analysis and included only patients undergoing nonpituitary surgery (Figure, B). Similar to what we found for the whole population, patients in the EEA group who underwent nonpituitary surgery still reported significantly better scores in the impact on emotions and physical function domains than patients in the subcranial group (P = .03 and P = .001, respectively).

Although the clinical and demographic characteristics of the patients in the 2 groups were not significantly different, the higher number of patients with malignant tumors in the subcranial group than in the endoscopic group (Table 1) may have influenced the QOL scores. To account for this potential bias, we performed a multivariate analysis of the data. The following parameters were included in the model: surgical approach (open vs endoscopic), sex, histologic type (malignant vs benign), age (<60 years vs ≥60 years), radiation therapy, and time after surgery (<12 months vs ≥12 months). The parameters that were statistically significant on multivariate analysis were as follows: in the physical function domain, surgical approach (P = .01), age (P = .02), and sex (P = .01); in the role of performance domain, histologic type (P = .03); and in the impact on emotions domain, surgical approach (P = .04). In the rest of the domains, there were no significant predictors of QOL. In agreement with our previous findings, our multivariate analysis showed that patients who underwent endonasal surgery reported significantly better QOL scores in the physical function and impact on emotions domains than those who underwent open surgery. Table 3 shows the results of the multivariate analysis.

The question of the clinical relevance of these differences can be answered by analyzing MCID scores. The MCID is defined as “the smallest difference in score in the domain of interest which patients perceive as beneficial and which would mandate a change in the patient's management.”¹⁷ The MCID was calculated using the distribution-based method.^16,18- 19 The differences that were statistically significant during comparison of the open and endoscopic approaches were all above the MCID (Table 3). Finally, we compared the clinical impact of surgery on the variables of the specific symptoms domain. Table 4 shows that the different variables in this domain were similar in both groups.

Surgery for the resection of skull base neoplasms can carry substantial morbidity.²⁰ Some of the factors that may influence the QOL of the patients include nasal secretions, visual disturbances, anosmia, pain, and facial disfigurement.²¹ Surgery may also have an impact on the psychological and behavioral aspects of a patient's daily lifestyle. The benefit of QOL assessment as a research tool is well established in the literature. In the setting of skull base surgery, it can measure the value of minimally invasive surgery over conventional modalities that have similar oncologic results.^22- 23

A 2009 publication by Eloy et al²⁴ compared the surgical results in cases involving patients undergoing endoscopic (n = 18) or open (n = 48) surgery for resection of anterior skull base tumors. The authors found no significant difference in complication and survival rates, but they reported a significant reduction in hospital stay and local recurrence in the endoscopic group. Because data on the impact of the different approaches on patient's QOL are very sparse, we compared the impact of open surgery with that of endoscopic surgery on the posttreatment QOL of patients undergoing skull base tumor resection in a single medical center. We used the Anterior Skull Base Surgery Questionnaire, a disease-specific instrument that was designed for anterior skull base surgery and validated by standard psychometric criteria.¹⁵ The same instrument was previously evaluated and validated for endonasal surgery.¹³ The overall results and our multivariate analysis showed that endoscopic resection of skull base tumors results in better QOL than open surgery, especially in the physical function and impact on emotions domains. The differences in QOL scores between the 2 groups were larger than the MCID threshold, suggesting that they were clinically important. The data support a potential advantage for minimally invasive surgery on the psychosocial, functional, and emotional status of patients undergoing skull base tumor resection. Interestingly, the scores for sinonasal morbidity (specific symptoms domain) were similar in both groups, suggesting that the influence of the surgical approach on QOL may be related to other factors, such as skin incisions, craniotomy, visual function, osteonecrosis, or encephalomalacia as well as on psychological issues, which are more prominent in patients undergoing open surgery.^25- 26

We found differences in QOL scores between male and female patients. It is conceivable that dissimilarity in patients' expectations or distinct coping mechanisms may have contributed to the differences in QOL between the sexes.²⁷ Also, malignant histologic type and adjuvant radiation therapy had a poor impact on QOL of patients undergoing open surgery, whereas such a difference was missing in the endoscopic group. Several factors could have contributed to the adverse effect of radiation therapy on the open surgery group. First, it was demonstrated that up to one-third of the patients who undergo radiation therapy after subcranial surgery present with osteoradionecrosis of the frontal bone segment.^25,28 Such a complication is a source of severe morbidity requiring reoperation and free flap reconstruction. Also, better emotional state and physical status after surgery may have contributed to the improved QOL scores in the endoscopic group. These results are consistent with previous findings showing impaired QOL after radiation therapy in patients who have undergone head and neck and skull base surgery.^12,29- 30

Most of the earlier studies on QOL after anterior skull base tumor resection involved patients who were operated on through open approaches,^29,31 and there are few similar data on patients who were operated on endoscopically.¹³ It was hypothesized that endoscopic surgery could negatively affect postoperative QOL because of the major sinonasal morbidity of that type of surgery.¹⁰ Although we detected similar scores in the specific symptoms domain in both groups, it emerged that endonasal surgery had little impact on the emotional and functional domains, while open surgery resulted in significant deterioration of QOL scores in the same domains. Minimally invasive techniques may therefore result in a better QOL, regardless of nasal morbidity.

The impact of surgery for resection of pituitary adenomas on the QOL of patients was also studied extensively during the last decade. In agreement with our current findings, the extent of cognitive impairment was shown to be more severe after transfrontal craniotomy than after less-invasive approaches.^32- 33 Several other studies concluded that patients who undergo transfrontal craniotomy have a poor outcome in terms of psychological well-being compared with those who undergo transsphenoidal resection.³⁴ Although these studies may obviously carry some bias, a better psychological well-being score is one of the reasons that the transsphenoidal approach gained popularity over more traditional approaches during the last few decades.

We are aware that this study has a potential methodological bias. The multivariate analysis results should be interpreted with caution. The absence of association between certain clinical variables and QOL scores in the whole cohort does not indicate that the same results are valid in each approach independently.Also, the study involves 2 groups of patients who were operated on by the same surgical team; therefore, it can be argued that the lower scores reported in the subcranial group reflect a more advanced disease stage than in the EEA group. Although we agree that this argument cannot be refuted, there are several reasons that such potential bias is fairly small. First, we found no significant differences in clinical or demographic variables between the 2 groups (Table 1). Second, when we compared the nonpituitary cases in the EEA group with those in the subcranial group, patients in the EEA group still reported significantly better scores. Finally, our multivariate analysis showed that the surgical approach was independently significant, while other variables, including malignancy, were controlled for. The finding of clinically significant differences in QOL scores for the 2 surgical approaches (EEA vs open) was obtained considering “all-comers,” where the groups are fairly heterogeneous. Given this approach, the findings may not be generalized to any particular subgroup of patients. Furthermore, the retrospective nature of the study could influence the interpretation of the data.

In conclusion, we compared long-term QOL among patients who underwent skull base surgery by the expanded endonasal approach with that among those who underwent open skull base surgery and found better scores in the role of emotions and physical function domains in the endoscopic group. Endoscopic skull base surgery was independently predictive of better QOL scores in these domains.