Department of Neurosurgery, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands.
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands.
Trials. 2021 Sep 25;22(1):653. doi: 10.1186/s13063-021-05604-y.
First-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.
We 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.
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 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.
US National Library of Medicine registry (ClinicalTrials.gov) NCT04107480 . Registered on 27 September 2019, registered retrospectively (by 2 months).
催乳素瘤的一线治疗是使用多巴胺激动剂（DAs）的药物治疗，这种治疗方法能有效控制大多数患者的高催乳素血症，尽管停药后的缓解率约为 34%。因此，许多患者需要长期接受 DA 治疗，而副作用会对健康相关生活质量（HRQoL）产生负面影响。对于有严重副作用或 DA 抵抗性催乳素瘤的患者，保留内镜经蝶窦切除术。手术具有良好的安全性和高缓解率，因此在催乳素瘤治疗中应占有更重要的地位。本研究的假设是，对于局限性小的非侵袭性催乳素瘤患者，早期或 upfront 手术切除在 HRQoL 和缓解率方面优于 DA 治疗。
我们提出了一项联合随机临床试验和观察性队列研究设计，其中包括三项非盲随机对照试验（PRolaCT-1、PRolaCT-2、PRolaCT-3）和一个观察性研究臂（PRolaCT-O），比较神经外科咨询和潜在的随后内镜经蝶窦腺瘤切除术与当前的标准治疗。符合条件的患者为非侵袭性催乳素瘤（<25mm），根据 DA 治疗前的持续时间，他们将有资格参加三项 RCT 中的一项：PRolaCT-1：新诊断，无治疗史的患者；PRolaCT-2：DA 治疗时间有限（4-6 个月）的患者；PRolaCT-3：DA 治疗>2 年后催乳素瘤仍持续存在的患者。PRolaCT-O 将包括由于明显的治疗偏好而拒绝随机分组的患者。主要结局是 36 个月后的疾病缓解率和 12 个月后的 HRQoL。
对于局限性小的催乳素瘤患者，早期或 upfront 手术切除可能是当前 DA 治疗标准的合理替代方案，我们将通过三项 RCT 和一项观察性队列研究进行研究。在三项 RCT 中，患者将在神经外科咨询和标准护理之间进行随机分组。观察性研究臂将招募拒绝随机分组且治疗偏好明显的患者。PRolaCT 将收集随机和观察数据，这可能有助于更个体化地实践循证医学。
美国国立医学图书馆注册处（ClinicalTrials.gov）NCT04107480。于 2019 年 9 月 27 日注册，回顾性注册（提前 2 个月）。
