PRAP study-partial versus radical adrenalectomy in hereditary pheochromocytomas

Abstract

Objective: Hereditary pheochromocytoma (hPCC) commonly develops bilaterally, causing adrenal insufficiency when standard treatment, radical adrenalectomy (RA), is performed. Partial adrenalectomy (PA) aims to preserve adrenal function, but with higher recurrence rates. This study compares outcomes of PA versus RA in hPCC.

Methods: Patients with hPCC due to pathogenic variants in RET, VHL, NF1, MAX, and TMEM127 from 12 European centers (1974-2023) were studied retrospectively. Stratified analysis based on surgery type and initial presentation was conducted. The main outcomes included recurrence, adrenal insufficiency, metastasis, and mortality.

Results: The study included 256 patients (223 RA, 33 PA). Ipsilateral recurrence rates were 9/223 (4%) after RA versus 5/33 (15%) after PA (P = 0.02). Metastasis and mortality did not differ between groups. Overall, 103 patients (40%) underwent bilateral adrenalectomy either synchronously or metachronously (75 RA, 28 PA). Of these, 46% developed adrenal insufficiency after PA.In total, 191 patients presented with initial unilateral disease, of whom 50 (26%) developed metachronous contralateral disease, most commonly in RET, VHL, and MAX. In patients with metachronous bilateral disease, adrenal insufficiency developed in 3/4 (75%) when PA was performed as the first operation followed by RA, compared to 1/7 (14%) when PA was performed as the second operation after prior RA (P = 0.09).

Conclusion: In patients with hPCC undergoing PA, local recurrence rates are higher than after RA, but metastasis and disease-specific mortality are similar. Therefore, PA seems a safe method to preserve adrenal function in patients with hPCC, in cases of both synchronous and metachronous bilateral disease, when performed as a second operation.

Keywords: adrenalectomy; cortical-sparing; genetics; pheochromocytoma; total.