Abstract
BackgroundFirst-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size.MethodsWe present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naïve patients; PRolaCT-2: patients with limited duration of DA treatment (4–6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months.DiscussionEarly or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine.Trial registrationUS National Library of Medicine registry (ClinicalTrials.gov) NCT04107480. Registered on 27 September 2019, registered retrospectively (by 2 months).
Highlights
First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, post-withdrawal remission rates are approximately 34%
Early or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three randomised controlled trial (RCT) and an observational cohort study
Study design This combined randomised clinical trial and observational cohort study design comprises three unblinded parallel superiority prolactinoma RCTs (PRolaCT-1, PRolaCT-2, PRolaCT-3) and an observational study arm (PRolaCT-O) that will compare counselling for endoscopic transsphenoidal adenoma resection to standard care (DA treatment) in patients with a prolactinoma of limited size (i.e. < 25 mm, no tissue invasion): 4. PRolaCT-O evaluates counselling for surgical resection as an valid second-line treatment and standard care in an observational study setting, aiming to include all patients eligible for PRolaCT1, PRolaCT-2, and PRolaCT-3 who do not participate in the RCTs because of a strong patient and/or physician treatment preference, and/or because the patient does not consent to randomisation
Summary
Study design This combined randomised clinical trial and observational cohort study design comprises three unblinded parallel superiority prolactinoma RCTs (PRolaCT-1, PRolaCT-2, PRolaCT-3) and an observational study arm (PRolaCT-O) that will compare counselling for endoscopic transsphenoidal adenoma resection to standard care (DA treatment) in patients with a prolactinoma of limited size (i.e. < 25 mm, no tissue invasion): 4. PRolaCT-O evaluates counselling for surgical resection as an valid second-line treatment and standard care in an observational study setting, aiming to include all patients eligible for PRolaCT1, PRolaCT-2, and PRolaCT-3 who do not participate in the RCTs because of a strong patient and/or physician treatment preference, and/or because the patient does not consent to randomisation. PRolaCT-O evaluates counselling for surgical resection as an valid second-line treatment and standard care in an observational study setting, aiming to include all patients eligible for PRolaCT1, PRolaCT-2, and PRolaCT-3 who do not participate in the RCTs because of a strong patient and/or physician treatment preference, and/or because the patient does not consent to randomisation. During these visits to the outpatient clinic, registration of prolactinoma treatment, physical symptoms, pregnancy, laboratory measurements (including prolactin level), and pituitary MRI (only at 12 and 36 months) takes place. Primary outcomes The two primary outcomes PRolaCT aims to evaluate are: 1. Health-related quality of life after 12 months of follow-up
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
