Management after initial surgery of nonfunctioning pituitary adenoma: surveillance, radiotherapy or surgery?

Abstract

Introduction: The first line of treatment for nonfunctioning pituitary adenoma (NFPA) is surgery. Adjuvant radiotherapy or surveillance and new treatment (second surgical operation or salvage radiotherapy) in case of recurrence are options discussed at the multidisciplinary tumor board. The purpose of this study was to evaluate the therapeutic outcome for each option.

Methods: The records of 256 patients followed with NFPA between 2007 and 2018 were retrospectively reviewed. Mean age at initial surgery was 55 years [18-86]. Post-operative MRI found a residual tumor in 87% of patients. Mean follow-up was 12.1 years [0.8-42.7].

Results: After initial surgery, 40 patients had adjuvant radiotherapy. At 5, 10 and 15 years progression-free survival (PFS) was significantly different after surgery alone (77%, 58% and 40%) compared to surgery and adjuvant radiotherapy (84%, 78% and 78%) (HR = 0.24 [0-0.53] p < 0.0005). Overall, after first, second or third surgical operation, 69 patients had adjuvant radiotherapy and 41 salvage radiotherapy. Five-year PFS was similar for adjuvant (90%) and salvage radiotherapy (97%) (p = 0.62). After a second surgical operation, 62% and 71% of patients were irradiated after 2 and 5 years respectively. The risk of corticotropic and thyrotropic deficiency rates were 38% and 59% after second or third surgical operation and 40% and 73% after radiotherapy. Brain tumors occurred in 4 patients: 1 meningioma present at initial surgery, and after radiotherapy, 1 neurinoma which appeared at 5 years, 1 glioblastoma at 13 years and 1 meningioma at 20 years.

Conclusion: Among patients treated by surgery for NFPA, a "wait-and-see" attitude should be an option since adjuvant radiotherapy is not superior to salvage radiotherapy. However, in case of recurrence or progression, the authors recommended delivery of salvage radiotherapy to avoid a second surgical operation.

Keywords: Non-functioning pituitary adenoma; Radiotherapy; Surgery; Wait and see.

Fig. 1

Flow chart of treatment sequence for the entire cohort of patients. S surgery, aRT adjuvant radiotherapy, sRT salvage radiotherapy. Patients without further intervention are indicated in the circles

Fig. 2

A PFS after initial surgery for the whole cohort. Patients exposed to relapse are shown in lines 1 and 2, and patients followed are shown in third line. B PFS for patients with available data for post-operative residual tumor after first surgery (N = 228). Patients could have wait and see attitude and had post-operative residual tumor (N = 168) or without residual tumor (N = 29) or could be treated with adjuvant RT, all with residual tumor (N = 31). No patient treated by adjuvant radiotherapy had residual tumor. Patients without information concerning their residual tumor were excluded from this analysis (N = 28)

Fig. 3

A PFS according to histological subtypes: Gonodotrophic: 99 vs. other subtypes (null-cell = 74, corticotroph = 9, plurihormonal = 12, lactotroph = 1, thryreotroph = 1) (p = 0.285) B PFS after adjuvant RT or salvage RT is no different (p = 0.17) C Radiation-free survival after second surgical operation