Predictors of Durable Remission After Successful Surgery for Cushing Disease: Results From the Multicenter RAPID Registry

Author:

Findlay Matthew C.12,Tenhoeve Sam12,Alt Jeremiah3,Rennert Robert C.1,Couldwell William T.1,Evans James4,Collopy Sarah4,Kim Won5,Delery William5,Pacione Donato6,Kim Albert7,Silverstein Julie M.78,Chicoine Michael R.9,Gardner Paul10,Rotman Lauren11,Yuen Kevin C. J.12,Barkhoudarian Garni13,Fernandez-Miranda Juan14,Benjamin Carolina15,Kshettry Varun R.16,Zada Gabriel17,Van Gompel Jamie18,Catalino Michael H. S.19,Little Andrew S.12,Karsy Michael2021ORCID

Affiliation:

1. Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah, USA;

2. School of Medicine, University of Utah, Salt Lake City, Utah, USA;

3. Department of Otolaryngology—Head and Neck Surgery, University of Utah, Salt Lake City, Utah, USA;

4. Department of Neurosurgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA;

5. Department of Neurosurgery, University of California Los Angeles, Los Angeles, California, USA;

6. Department of Neurosurgery, New York University, Lagone Medical Center, New York, New York, USA;

7. Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri, USA;

8. Division of Endocrinology, Metabolism, & Lipid Research, Washington University School of Medicine, St. Louis, Missouri, USA;

9. Department of Neurosurgery, University of Missouri, Columbia, Missouri, USA;

10. Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburg, Pennsylvania, USA;

11. Department of Neurosurgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA;

12. Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona, USA;

13. Department of Neurosurgery, Providence Medical Center, Los Angeles, California, USA;

14. Department of Neurosurgery, Stanford University, Palo Alto, California, USA;

15. Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA;

16. Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA;

17. Department of Neurosurgery, University of Southern California, Los Angeles, California, USA;

18. Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota, USA;

19. Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA;

20. Global Neurosciences Institute, Philadelphia, Pennsylvania, USA;

21. Department of Neurosurgery, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

Abstract

BACKGROUND AND OBJECTIVE: Cushing disease (CD) affects mortality and quality of life along with limited long-term remission, underscoring the need to better identify recurrence risk. The identification of surgical or imaging predictors for CD remission after transsphenoidal surgery has yielded some inconsistent results and has been limited by single-center, single-surgeon, or meta-analyses studies. We sought to evaluate the multicenter Registry of Adenomas of the Pituitary and Related Disorders (RAPID) database of academic US pituitary centers to assess whether robust nonhormonal recurrence predictors could be elucidated. METHODS: Patients with treated CD from 2011 to 2023 were included. The perioperative and long-term characteristics of CD patients with and without recurrence were assessed using univariable and multivariable analyses. RESULTS: Of 383 patients with CD from 26 surgeons achieving postoperative remission, 288 (75.2%) maintained remission at last follow-up while 95 (24.8%) showed recurrence (median time to recurrence 9.99 ± 1.34 years). Patients with recurrence required longer postoperative hospital stays (5 ± 3 vs 4 ± 2 days, P = .002), had larger average tumor volumes (1.76 ± 2.53 cm3 vs 0.49 ± 1.17 cm3, P = .0001), and more often previously failed prior treatment (31.1% vs 14.9%, P = .001) mostly being prior surgery. Multivariable hazard prediction models for tumor recurrence found younger age (odds ratio [OR] = 0.95, P = .002) and Knosp grade of 0 (OR = 0.09, reference Knosp grade 4, P = .03) to be protective against recurrence. Comparison of Knosp grade 0 to 2 vs 3 to 4 showed that lower grades had reduced risk of recurrence (OR = 0.27, P = .04). Other factors such as length of stay, surgeon experience, prior tumor treatment, and Knosp grades 1, 2, or 3 failed to reach levels of statistical significance in multivariable analysis. CONCLUSION: This multicenter study centers suggests that the strongest predictors of recurrence include tumor size/invasion and age. This insight can help with patient counseling and prognostication. Long-term follow-up is necessary for patients, and early treatment of small tumors may improve outcomes.

Funder

Barrow Neurological Foundation

Lodestar Foundation

Foundation for Barnes-Jewish Hospital

Publisher

Ovid Technologies (Wolters Kluwer Health)

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