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Postsurgical outcomes of nonfunctioning pituitary adenomas: a patient-level meta-analysis

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Abstract

Background

Surgical resection is the main treatment for symptomatic nonfunctioning pituitary adenomas (NFPA). We aimed to analyze the impact of surgical approach, completeness of resection, and postoperative radiotherapy on long-term progression-free survival (PFS) of NFPA, using individual patient data (IPD) meta-analysis.

Methods

An electronic literature searched was conducted on PubMed, EMBASE, and Web of Science from database inception to 6 November 2022. Studies describing the natural history of surgically resected NFPA, with provision of Kaplan–Meier curves, were included. These were digitized to obtain IPD, which was pooled in one-stage and two-stage meta-analysis to determine hazard ratios (HRs) and 95%CIs of gross total resection (GTR) versus subtotal resection (STR), and postoperative radiotherapy versus none. An indirect analysis of single-arm data between endoscopic endonasal (EES) and microscopic transsphenoidal (MTS) surgical technique was also performed.

Results

Altogether, eleven studies (3941 patients) were retrieved. PFS was significantly lower in STR than GTR (shared-frailty HR 0.32, 95%CI 0.27–0.39, p < 0.001). Postoperative radiotherapy significantly improved PFS compared to no radiotherapy (shared-frailty HR 0.20, 95%CI 0.15–0.26, p < 0.001), including in the subgroup of patients with STR (shared-frailty HR 0.12, 95%CI 0.08–0.18, p < 0.001). Similar PFS was observed between EES and MTS (indirect HR 1.09, 95%CI 0.92–1.30, p = 0.301).

Conclusions

This systematic review and patient-level meta-analysis provides a robust prognostication of surgically treated NFPA. We reinforce current guidelines stating that GTR should be the standard of surgical resection. Postoperative radiotherapy is of considerable benefit, especially for patients with STR. Surgical approach does not significantly affect long-term prognosis.

Registration

PROSPERO CRD42022374034.

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Data availability

This manuscript makes use of publicly-available data from published studies, therefore no additional data are available for sharing.

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Acknowledgements

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Funding

No external funding was received for the conduct of this study.

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Author notes

  1. Khi Yung Fong and Mervyn Jun Rui Lim are co-first-author.

Authors and Affiliations

  1. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Khi Yung Fong, Shuning Fu & Chen Ee Low

  2. Division of Neurosurgery, University Surgical Centre, National University Hospital, Singapore, Singapore

    Mervyn Jun Rui Lim, Swati Jain, Kejia Teo, Vincent Diong Weng Nga & Tseng Tsai Yeo

  3. Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Yiong Huak Chan

  4. Division of Endocrinology, Department of Medicine, National University Hospital, Singapore, Singapore

    Doddabele Srinivasa Deepak

  5. Division of Otolaryngology - Head & Neck Surgery, National University Hospital, Singapore, Singapore

    Xinni Xu & Mark Thong

  6. Center for Cranial Base Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Paul A. Gardner

  7. Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Carl H. Snyderman

  8. Division of Neurosurgery, University Surgical Centre, National University Hospital, Level 8, National University Health Systems Tower Block, 1E Kent Ridge Rd, Singapore, 119228, Singapore

    Mervyn Jun Rui Lim

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Contributions

KYF, MJRL, DSD, XX, MT, SJ, KT, PAG, CHS, VDWN and TTY were responsible for the concept and design of the study. KYF, SF, CEL, and MJRL extracted data from studies. KYF, YHC and MJRL conducted the statistical analyses. KYF, YHC, MJRL and VDWN interpreted the data. KYF, SF, CEL, and MJRL drafted the manuscript. DSD, XX, MT, SJ, KT, PAG, CHS, VDWN, and TTY critically revised the manuscript for important intellectual content. KYF, MJRL, VDWN and TTY supervised the study.

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Correspondence to Mervyn Jun Rui Lim.

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Fong, K.Y., Lim, M.J.R., Fu, S. et al. Postsurgical outcomes of nonfunctioning pituitary adenomas: a patient-level meta-analysis. Pituitary 26, 461–473 (2023). https://doi.org/10.1007/s11102-023-01335-2

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