Stereotactic Radiosurgery Outcomes for Atypical Pituitary Adenoma

Introduction: Atypical pituitary adenoma is a rare, locally aggressive sellar neoplasm, with an estimated incidence ranging from 3 to 15% of all pituitary adenomas. Although the pathologic features of mutated p53 and K_i-67 index?3% are consistently observed, atypical pituitary tumors demonstrate erratic, heterogeneous behavioral phenotypes, with some prone to recurrence while others are clinically indistinguishable from benign lesions. Given this unpredictable course, treatment paradigms are inconsistent, and outcomes following adjuvant stereotactic radiosurgery (SRS) for subtotally resected disease are lacking. Correspondingly, our study goal was to describe the presentation, treatment, and outcomes of our institutional experience with SRS for atypical pituitary adenoma.

Methods: Retrospective review of prospectively maintained institutional SRS database

Results: Database query identified 12 patients treated with SRS for atypical pituitary adenoma, 1991–2018. Two were excluded on the basis of pituitary metastases identified prior to SRS treatment (a.k.a. pituitary carcinoma); 1 was excluded for incomplete follow-up data. Of the 9 included study subjects, 7 were male (78%), median age at treatment was 55 years (range 20–63), and the interval between transsphenoidal resection (TSR) and SRS was < 16 months in 8 (89%), with one patient electing observation until definitive growth was noted at 44 months after resection. Nine had previously undergone TSR, and 3 had also been treated with radiotherapy prior to SRS (33%). Preoperative anterior pituitary hormonal function was normal in 6 (67%), partially deficient in 2 (22%), pan-hypopituitary in 1 (11%); preoperative visual fields and acuity were intact in 7 (78%). Median treatment volume was 9,400 mm³, treated to a median margin and maximum doses of 15 Gy and 30 Gy, and a median gland dose of 18 Gy.

Median follow-up was 72 months (range: 39–270). New post-SRS deficits developed in five patients (56%)—three partial and two pan-hypopituitary. One patient developed new visual symptoms (11%), but these were thought attributable to mass effect following treatment failure. One patient each developed radiation necrosis and ICA vasculopathy (11%). At last follow-up, five patients had stable disease since SRS (56%), one failed SRS and declined further treatment, and three failed SRS and went on to additional SRS, RT, or craniotomy. Of the four SRS failures, two progressed to pituitary carcinoma and died, one died of a stroke, and one stabilized, resulting in disease-specific and overall mortality rates of 22 and 33%, respectively. Of note, the patient who deferred initial adjuvant treatment was among the carcinoma deaths.

Conclusion: Atypical pituitary adenoma is a rare and challenging disease, with a poorly understood natural history. Based on our results, SRS provides an effective treatment in the majority of cases, with an acceptable side effect profile. Given the 22% rate of malignant transformation, as well as the anecdotal association in 1 patient with a long period of initial observation, we recommend consideration for upfront adjuvant SRS in all patients with obvious residual tumor following TSR for atypical pituitary adenoma.

No conflict of interest has been declared by the author(s).