Adjuvant versus On-progression Gamma Knife Radiosurgery for Residual Nonfunctioning Pituitary Adenomas: A Meta-analysis of 416 Patients

Introduction: Gamma Knife Radiosurgery (GKRS) is an effective treatment for preventing the regrowth of residual or recurrent nonfunctioning pituitary adenomas (NFPAs) after transsphenoidal surgery. The optimal timing of GKRS, whether as an adjuvant procedure after surgery or delayed until tumor progression is detected on imaging, remains controversial. This meta-analysis aims to determine the best timing for GKRS in managing residual or recurrent NFPAs.

Methods: We conducted a comprehensive database search until September 10, 2024, to identify studies that compared adjuvant versus GKRS administered upon tumor progression. The primary outcomes were the incidence of new endocrinopathies, including hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency, as well as tumor control (defined as either stability or reduction in residual tumor volume). Data analysis involved pooled risk ratios (RR) for categorical data and standardized mean differences (SMDs) for continuous variables.

Results: Out of 750 articles, 3 retrospective cohort studies involving 416 patients met the inclusion criteria. There were no significant differences between the adjuvant and on-progression GKRS groups in the incidence of new endocrinopathies, including hypocortisolism (RR=0.91, 95%CI=0.21-3.99, p=0.90), hypothyroidism (RR=0.93, 95%CI =0.20-4.42, p=0.93) or GH deficiency (RR=1.58, 95%CI=0.44-5.64, p=0.48). There was no difference in tumor control rates between GKRS protocols (RR = 0.17, 95%CI=0.84-1.16, p=0.86)

Conclusion : This meta-analysis found no significant difference in the incidence of new endocrinopathies such as hypocortisolism, hypothyroidism, GH deficiency, or tumor control between adjuvant and on-progression GKRS for residual NFPA. These findings suggest that the timing of GKRS does not significantly affect key clinical outcomes. This flexibility allows clinicians to tailor GKRS timing to individual patient needs and preferences. Further randomized controlled trials with larger sample sizes and more homogeneous NFPA populations are needed to confirm these findings.