Macroprolactinomas: longitudinal assessment of biochemical and imaging therapeutic responses

Abstract

Purpose: To assess biochemical and imaging therapeutic response rates, when these occur and their predictive factors in patients with macroprolactinomas treated with dopamine agonists (DA).

Methods: Retrospective, longitudinal study of patients with macroprolactinomas treated with DA for ≥12 months.

Outcomes: prolactin normalization, reduction in maximum tumor diameter ≥50% and time until therapeutic responses.

Results: We included 67 patients; 49.3% females, with median age at diagnosis of 43 years, 61.2% only treated with bromocriptine, 10.4% only with cabergoline, and 28.4% with both DA. Median follow-up time was 73 months. Prolactin levels normalized in 87%, mostly during the first 2 years. Prolactin levels after 6 months (HR 0.994, p = 0.012), 1 year (HR 0.970, p = 0.003), and 2 years (HR 0.970, p = 0.015) predicted its normalization time. Only 62% of the patients achieved a ≥50% reduction in maximum tumor diameter. Percent tumor diameter reduction after 1 year (OR 1.098, p = 0.022) and 2 years (OR 1.102, p = 0.008) predicted a ≥50% size reduction. Size reduction occurred later than prolactin normalization. Initial tumor diameter (HR 1.050, p = 0.032) and its percent reduction at 6 months (HR 1.110, p = 0.002), 1 (HR 1.060, p < 0.001), 2 (HR 1.045, p < 0.001), 3 (HR 1.048, p = 0.002), and 4 years (HR 1.074, p = 0.042) predicted the time until imaging response.

Conclusion: A significant number of patients did not obtain an imaging response. Biochemical and imaging responses were asynchronous and occurred mainly in the first 4 years of treatment. This may allow an earlier identification of partially resistant and resistant macroprolactinomas, with consequent change in the therapeutic approach.

Keywords: Bromocriptine; Cabergoline; Dopamine agonists; Hyperprolactinemia; Prolactinoma; Tumor burden.