Sayers Ian, Joao Carvalho Sara, Davidson Jennifer, Elster Naomi, Heer Rakesh, Raja Mohammad, Higgs Kate, Nolan Andrew, Sassmann Jelena
Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom.
CorEvitas, London, United Kingdom.
PLoS One. 2025 Mar 21;20(3):e0315208. doi: 10.1371/journal.pone.0315208. eCollection 2025.
This study aims to assess adherence to luteinising hormone-releasing hormone (LHRH) agonist treatment for prostate cancer (PC) in England, considering formulation-related differences, their impact on overall survival, and the association with changes in prostate-specific antigen (PSA) levels over time.
In this retrospective cohort study, utilising primary care data from the Clinical Practice Research Datalink (CPRD) Aurum database linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) death registrations, we assessed male patients aged 40 and above diagnosed with PC and prescribed 1-, 3-, or 6-monthly LHRH agonist injections between January 2007 and December 2019. The primary objectives were to measure adherence through proportion of days covered (PDC) and characterize delayed injections, while secondary objectives included assessment of patient demographics, comorbidities, overall survival, and PSA levels. Descriptive statistics were employed, with follow-up restricted to one year for PSA and testosterone measurements due to data availability constraints.
The study included 32,777 patients with PC receiving LHRH agonists. Most patients (67%) were prescribed 3-monthly formulations, while only 2% received 6-monthly formulations. The mean age of the study population was 74.1 years. Over 80% of patients had at least one comorbidity, with hypertension being the most common. 94% of patients initially prescribed the 3-monthly or 6-monthly regimen remained on their original treatment, in contrast to only 38% for the 1-monthly formulation. Adherence analysis showed that 41.1% of 6-monthly injections were received without delay, compared with 67.9% for the 3-monthly and 77.3% for 1-monthly formulations. A large proportion of patients experienced delays of 14-27 days (32.0%, 33.4%, 54.2%) and over 27 days (39.6%, 48.3%, 46.6%) across the 1-, 3- and 6-monthly formulations respectively. The mean PDC ranged from 90-91% across the three formulation groups, with 89.9%, 84%, and 88.2% achieving ≥ 80% adherence for 3-monthly, 1-monthly, and 6-monthly respectively.
This study revealed substantial and consistent dosing delays in LHRH agonist prescriptions across all formulations within primary care settings in England. These delays can negatively affect the control of PC, potentially hindering disease management for affected patients. Future research with a larger population, encompassing a larger cohort using the 6-monthly formulation, is essential for a comprehensive evaluation of the impact of LHRH agonist injection delays on PC progression.
本研究旨在评估英格兰前列腺癌（PC）患者对促黄体生成素释放激素（LHRH）激动剂治疗的依从性，考虑剂型相关差异、其对总生存期的影响以及与前列腺特异性抗原（PSA）水平随时间变化的关联。
在这项回顾性队列研究中，利用来自临床实践研究数据链（CPRD）Aurum数据库的初级保健数据，该数据库与医院 Episode 统计（HES）和国家统计局（ONS）死亡登记相关联，我们评估了2007年1月至2019年12月期间年龄在40岁及以上、被诊断为PC并被处方1个月、3个月或6个月注射一次LHRH激动剂的男性患者。主要目标是通过覆盖天数比例（PDC）来衡量依从性并描述延迟注射情况，次要目标包括评估患者人口统计学、合并症、总生存期和PSA水平。采用描述性统计，由于数据可用性限制，PSA和睾酮测量的随访限于一年。
该研究纳入了32777例接受LHRH激动剂治疗的PC患者。大多数患者（67%）被处方3个月剂型，而只有2%接受6个月剂型。研究人群的平均年龄为74.1岁。超过80%的患者至少有一种合并症，高血压最为常见。最初被处方3个月或6个月方案的患者中，94%仍采用原治疗方案，而1个月剂型的这一比例仅为38%。依从性分析显示，6个月注射剂型中41.1%的注射未延迟，3个月剂型为67.9%，1个月剂型为77.3%。很大一部分患者分别在1个月、3个月和6个月剂型中经历了14 - 27天（32.0%、33.4%、54.2%）和超过27天（39.6%、48.3%、46.6%）的延迟。三个剂型组的平均PDC在90 - 91%之间，3个月、1个月和6个月剂型分别有89.9%、84%和88.2%的患者依从性≥80%。
本研究揭示了英格兰初级保健机构中所有LHRH激动剂剂型处方均存在显著且持续的给药延迟。这些延迟可能对PC的控制产生负面影响，潜在地阻碍受影响患者的疾病管理。未来对更大人群进行研究，包括使用6个月剂型的更大队列，对于全面评估LHRH激动剂注射延迟对PC进展的影响至关重要。
