Validation and modification of the PANOMEN 3 classification for predicting long-term recurrence/progression and quality of life in patients with pituitary adenomas: a multicentre retrospective cohort study.

PURPOSE: Pituitary adenomas (PAs) are common intracranial tumours with heterogeneous behaviour. Accurate risk stratification is critical for predicting recurrence/progression and for guiding management. The pituitary adenoma nomenclature 3 (PANOMEN 3) classification, introduced in 2024, integrates clinical, radiological, and pathological factors; however, its prognostic utility and histopathological criteria remain uncertain.

METHODS

This multicentre retrospective cohort study included 804 patients with PAs surgically treated between January 2010 and December 2023. Patients were classified using the original PANOMEN 3 system and a modified system incorporating silent corticotroph adenomas (SCAs) as high-risk subtypes, revised proliferative activity criteria (Ki-67 ≥ 3%, mitotic index > 2/10 high-power fields, or p53 positivity), and Trouillas clinicopathological grading. Recurrence-free survival was analysed using Kaplan-Meier and Cox regression models. Predictive performance was assessed using receiver operating characteristic curves. Health-related quality of life (HRQoL) was measured using the EuroQol 5 Dimensions-3 Levels (EQ-5D-3 L) and EuroQol Visual Analogue Scale (EQ-VAS) preoperatively and six months postoperatively.

RESULTS

Over a median follow-up of 5.0 years, 169 patients (21.0%) experienced recurrence/progression. The original PANOMEN 3 classification showed moderate predictive accuracy. The modified classification markedly improved predictive performance to match Trouillas' grading. Higher PANOMEN 3 grade was associated with poorer HRQoL outcomes.

CONCLUSION

The PANOMEN 3 classification provides clinically relevant prognostic value for recurrence/progression and postoperative HRQoL in PAs. The inclusion of SCAs and refined proliferative criteria enhanced predictive accuracy and demonstrated its potential as a comprehensive risk stratification tool. Prospective studies, including non-surgical cohorts, are warranted to confirm its generalisability.