Clinical trial NCT02357498: Transsphenoidal Extent of Resection Study
Official title: Prospective Multicenter Cohort Study Comparing Extent of Tumor Resection Between Microscopic Transsphenoidal Surgery and Fully Endoscopic Transsphenoidal Surgery for Nonfunctioning Pituitary Adenomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pituitary Adenoma
Keywords: pituitary
adenoma
transsphenoidal surgery
Lead sponsor: St. Joseph's Hospital and Medical Center, Phoenix
Sponsor class: OTHER
Collaborators: name: Saint John's Cancer Institute
name: Swedish Medical Center
name: Northwestern University
name: Ohio State University
name: Washington University School of Medicine
name: University of Pittsburgh Medical Center
First posted: 2015-02-06
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to compare the extent of resection (EOR) in patients with nonfunctioning pituitary adenomas undergoing transsphenoidal surgery using a microsurgical technique to those patients who have undergone surgery with a fully endoscopic technique. Another goal is to compare surgical complications, endocrine outcomes, visual outcomes, length of surgery, length of hospital stay, and readmission rates between the two transsphenoidal surgery techniques. This is an observational data collection study with no experimental procedures or experimental medicines. Endonasal transsphenoidal removal of a pituitary tumor is a unique procedure and there is little information comparing the two surgical techniques.

Detailed description: The treatment of choice for most patients with symptomatic nonfunctioning pituitary adenomas is transsphenoidal surgery to improve vision by decompression of the optic chiasm, to prevent the development of endocrine dysfunction, and to treat neurological symptoms such as headache or cranial neuropathies caused by the tumor. The most widely accepted surgical technique is microscopic transsphenoidal surgery, in which an operating microscope is used by the surgeon to provide surgical visualization and a nasal speculum is used to maintain the operative corridor. \[1-4\] Recently, fully endoscopic transsphenoidal surgery, in which surgical visualization is achieved using an endoscope, has been adopted by many pituitary surgeons because the technique offers superior panoramic and angled visualization of the surgical target and may permit greater tumor resection. \[5-10\] There is a vigorous debate in the neurosurgical community about the relative merits of the microscopic and endoscopic techniques. Proponents of the endoscopic technique argue that the superior visualization permits more aggressive tumor resection and better preservation of the normal pituitary gland. Proponents of the microscopic technique argue that it permits shorter operative times, results in similar surgical outcomes, and has a lower complication rate.

Despite the adoption of fully endoscopic surgery by many surgeons, no prospective studies have compared the extent of tumor resection (EOR) between microscopic and endoscopic approaches. Numerous retrospective studies have established the efficacy of each approach, but only a few studies present comparative data.\[11-13\] Recently, McLaughlin et al. noted that the addition of endoscopy to microscopic pituitary surgery enhances tumor removal, particularly in patients with tumors greater than 20 mm in diameter. \[14\] This study raises the intriguing possibility that certain subgroups of patients (e.g. patients with larger tumors) may benefit from endoscopic surgery. In patients with smaller tumors with no cavernous sinus invasion, others have shown that the techniques achieve similar EOR. \[15\] That endoscopy may permit more complete tumor resections is a testable hypothesis.

Eligibility criteria: Inclusion Criteria:

* Patients with suspected nonfunctioning pituitary macroadenomas (≥ 1 cm) with planned transsphenoidal surgery
* Adults (age 18-80 years)
* Medically stable for surgery
* Reasonable expectation that patient will complete study and be available for follow-up assessments

Exclusion Criteria:

* Prisoners
* Pregnant women
* Patients with suspected functioning pituitary adenoma
* Unable to obtain MRI of the pituitary (e.g., pacemaker, anaphylaxis to gadolinium, low GFR)
* Pituitary apoplexy

Primary outcomes:
measure: percentage of patients who have complete tumor removal (gross total resection) based on MRI .
timeFrame: 3 months post surgery
Secondary outcomes:
measure: volume of residual tumor
timeFrame: 3 months after date of surgery
measure: percentage of tumor removed
timeFrame: 3 months post surgery
measure: postoperative cerebral-spinal fluid (CSF) leak
timeFrame: 6 months (continuous) from surgery
measure: postoperative meningitis
timeFrame: 6 months (continuous) from surgery
measure: hypopituitarism
timeFrame: 6 months post surgery
measure: diabetes insipidus (DI)
timeFrame: 6 months post surgery
measure: visual outcomes
timeFrame: 3 months post surgery
measure: hypothyroidism
timeFrame: 6 months post surgery
measure: hypogonadism
timeFrame: 6 months post surgery
measure: growth hormone deficiency
timeFrame: 6 months post surgery
measure: adrenal insufficiency
timeFrame: 6 months post surgery
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute/St. Joseph's Hospital and Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
Study officials:
affiliation: Saint Joseph's Hospital and Medical Center/Barrow Neurological Institute
name: Andrew Little, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wilson CB, Rand RW, Grollmus JM, Heuser G, Levin S, Goldfield E, Schneider V, Linfoot J, Hosobuchi Y. Surgical experience with a microscopic transsphenoidal approach to pituitary tumors and non-neoplastic parasellar conditions. Calif Med. 1972 Nov;117(5):1-9.
citation: Hardy J. Transsphenoidal hypophysectomy. J Neurosurg. 1971 Apr;34(4):582-94. doi: 10.3171/jns.1971.34.4.0582. No abstract available.
citation: Fatemi N, Dusick JR, de Paiva Neto MA, Kelly DF. The endonasal microscopic approach for pituitary adenomas and other parasellar tumors: a 10-year experience. Neurosurgery. 2008 Oct;63(4 Suppl 2):244-56; discussion 256. doi: 10.1227/01.NEU.0000327025.03975.BA.
citation: Patel SK, Husain Q, Eloy JA, Couldwell WT, Liu JK. Norman Dott, Gerard Guiot, and Jules Hardy: key players in the resurrection and preservation of transsphenoidal surgery. Neurosurg Focus. 2012 Aug;33(2):E6. doi: 10.3171/2012.6.FOCUS12125.
citation: Dehdashti AR, Ganna A, Karabatsou K, Gentili F. Pure endoscopic endonasal approach for pituitary adenomas: early surgical results in 200 patients and comparison with previous microsurgical series. Neurosurgery. 2008 May;62(5):1006-15; discussion 1015-7. doi: 10.1227/01.neu.0000325862.83961.12.
citation: Gondim JA, Schops M, de Almeida JP, de Albuquerque LA, Gomes E, Ferraz T, Barroso FA. Endoscopic endonasal transsphenoidal surgery: surgical results of 228 pituitary adenomas treated in a pituitary center. Pituitary. 2010;13(1):68-77. doi: 10.1007/s11102-009-0195-x. Epub 2009 Aug 21.
citation: Cavallo LM, Prevedello DM, Solari D, Gardner PA, Esposito F, Snyderman CH, Carrau RL, Kassam AB, Cappabianca P. Extended endoscopic endonasal transsphenoidal approach for residual or recurrent craniopharyngiomas. J Neurosurg. 2009 Sep;111(3):578-89. doi: 10.3171/2009.2.JNS081026.
citation: Cavallo LM, Prevedello D, Esposito F, Laws ER Jr, Dusick JR, Messina A, Jane JA Jr, Kelly DF, Cappabianca P. The role of the endoscope in the transsphenoidal management of cystic lesions of the sellar region. Neurosurg Rev. 2008 Jan;31(1):55-64; discussion 64. doi: 10.1007/s10143-007-0098-0. Epub 2007 Oct 6.
citation: Jho HD, Alfieri A. Endoscopic endonasal pituitary surgery: evolution of surgical technique and equipment in 150 operations. Minim Invasive Neurosurg. 2001 Mar;44(1):1-12. doi: 10.1055/s-2001-13590.
citation: Jho HD, Carrau RL. Endoscopic endonasal transsphenoidal surgery: experience with 50 patients. J Neurosurg. 1997 Jul;87(1):44-51. doi: 10.3171/jns.1997.87.1.0044.
citation: Ammirati M, Wei L, Ciric I. Short-term outcome of endoscopic versus microscopic pituitary adenoma surgery: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2013 Aug;84(8):843-9. doi: 10.1136/jnnp-2012-303194. Epub 2012 Dec 15.
citation: Starke RM, Raper DM, Payne SC, Vance ML, Oldfield EH, Jane JA Jr. Endoscopic vs microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab. 2013 Aug;98(8):3190-8. doi: 10.1210/jc.2013-1036. Epub 2013 Jun 4.
citation: McLaughlin N, Eisenberg AA, Cohan P, Chaloner CB, Kelly DF. Value of endoscopy for maximizing tumor removal in endonasal transsphenoidal pituitary adenoma surgery. J Neurosurg. 2013 Mar;118(3):613-20. doi: 10.3171/2012.11.JNS112020. Epub 2012 Dec 14.
citation: Dallapiazza R, Bond AE, Grober Y, Louis RG, Payne SC, Oldfield EH, Jane JA Jr. Retrospective analysis of a concurrent series of microscopic versus endoscopic transsphenoidal surgeries for Knosp Grades 0-2 nonfunctioning pituitary macroadenomas at a single institution. J Neurosurg. 2014 Sep;121(3):511-7. doi: 10.3171/2014.6.JNS131321. Epub 2014 Jul 4.
citation: Little AS, Kelly D, Milligan J, Griffiths C, Rosseau G, Prevedello DM, Carrau R, Jahnke H, Chaloner C, O'Leary J, Chapple K, Nakaji P, White WL. Prospective validation of a patient-reported nasal quality-of-life tool for endonasal skull base surgery: The Anterior Skull Base Nasal Inventory-12. J Neurosurg. 2013 Oct;119(4):1068-74. doi: 10.3171/2013.3.JNS122032. Epub 2013 May 10.
citation: Gao Y, Zhong C, Wang Y, Xu S, Guo Y, Dai C, Zheng Y, Wang Y, Luo Q, Jiang J. Endoscopic versus microscopic transsphenoidal pituitary adenoma surgery: a meta-analysis. World J Surg Oncol. 2014 Apr 11;12:94. doi: 10.1186/1477-7819-12-94.
citation: Goudakos JK, Markou KD, Georgalas C. Endoscopic versus microscopic trans-sphenoidal pituitary surgery: a systematic review and meta-analysis. Clin Otolaryngol. 2011 Jun;36(3):212-20. doi: 10.1111/j.1749-4486.2011.02331.x.
citation: Rudmik L, Starreveld YP, Vandergrift WA, Banglawala SM, Soler ZM. Cost-effectiveness of the endoscopic versus microscopic approach for pituitary adenoma resection. Laryngoscope. 2015 Jan;125(1):16-24. doi: 10.1002/lary.24780. Epub 2014 Jun 17.
citation: Tabaee A, Anand VK, Barron Y, Hiltzik DH, Brown SM, Kacker A, Mazumdar M, Schwartz TH. Endoscopic pituitary surgery: a systematic review and meta-analysis. J Neurosurg. 2009 Sep;111(3):545-54. doi: 10.3171/2007.12.17635.
citation: Zhu M, Yang J, Wang Y, Cao W, Zhu Y, Qiu L, Tao Y, Xu Y, Xu H. [Endoscopic transsphenoidal surgery versus microsurgery for the resection of pituitary adenomas: a systematic review]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014 Mar;49(3):236-9. Chinese.
citation: Komotar RJ, Starke RM, Raper DM, Anand VK, Schwartz TH. Endoscopic endonasal compared with microscopic transsphenoidal and open transcranial resection of craniopharyngiomas. World Neurosurg. 2012 Feb;77(2):329-41. doi: 10.1016/j.wneu.2011.07.011. Epub 2011 Nov 1.
citation: Little AS, Gardner PA, Fernandez-Miranda JC, Chicoine MR, Barkhoudarian G, Prevedello DM, Yuen KCJ, Kelly DF; TRANSSPHER Study Group. Pituitary gland recovery following fully endoscopic transsphenoidal surgery for nonfunctioning pituitary adenoma: results of a prospective multicenter study. J Neurosurg. 2019 Nov 15;133(6):1732-1738. doi: 10.3171/2019.8.JNS191012. Print 2020 Dec 1.
citation: Little AS, Chicoine MR, Kelly DF, Sarris CE, Mooney MA, White WL, Gardner PA, Fernandez-Miranda JC, Barkhoudarian G, Chandler JP, Prevedello DM, Liebelt BD, Sfondouris J, Mayberg MR; TRANSSPHER Study Group. Evaluation of Surgical Resection Goal and Its Relationship to Extent of Resection and Patient Outcomes in a Multicenter Prospective Study of Patients With Surgically Treated, Nonfunctioning Pituitary Adenomas: A Case Series. Oper Neurosurg (Hagerstown). 2020 Jan 1;18(1):26-33. doi: 10.1093/ons/opz085.
citation: Little AS, Kelly DF, White WL, Gardner PA, Fernandez-Miranda JC, Chicoine MR, Barkhoudarian G, Chandler JP, Prevedello DM, Liebelt BD, Sfondouris J, Mayberg MR; TRANSSPHER Study Group. Results of a prospective multicenter controlled study comparing surgical outcomes of microscopic versus fully endoscopic transsphenoidal surgery for nonfunctioning pituitary adenomas: the Transsphenoidal Extent of Resection (TRANSSPHER) Study. J Neurosurg. 2019 Mar 22;132(4):1043-1053. doi: 10.3171/2018.11.JNS181238. Print 2020 Apr 1.
citation: Mooney MA, Sarris CE, Zhou JJ, Barkhoudarian G, Chicoine MR, Fernandez-Miranda JC, Gardner PA, Hardesty DA, Jahnke H, Kelly DF, Liebelt BD, Mayberg MR, Prevedello DM, Sfondouris J, Sheehy JP, Chandler JP, Yuen KCJ, White WL, Little AS; TRANSSPHER Study Group. Proposal and Validation of a Simple Grading Scale (TRANSSPHER Grade) for Predicting Gross Total Resection of Nonfunctioning Pituitary Macroadenomas After Transsphenoidal Surgery. Oper Neurosurg (Hagerstown). 2019 Nov 1;17(5):460-469. doi: 10.1093/ons/opy401.
citation: Mooney MA, Herro AM, Fintelmann RE, Mayberg MR, Barkhoudarian G, Gardner PA, Prevedello DM, Chicoine MR, Kelly DF, Chandler JP, Jahnke H, White WL, Little AS. Visual Field Outcome Reporting in Neurosurgery: Lessons Learned from a Prospective, Multicenter Study of Transsphenoidal Pituitary Surgery. World Neurosurg. 2018 Dec;120:e326-e332. doi: 10.1016/j.wneu.2018.08.069. Epub 2018 Aug 23.