Chen Kenneth, Wong Ting Hong, Tan Yu Guang, Tay Kae Jack, Tan Wei Chong, Chan Johan, Ho Henry, Cheng Christopher, Teoh Jeremy Yuen-Chun, Chiu Peter Ka-Fung, Wang Hung Jen, Saad Marniza Binti, Kanesvaran Ravindran, Li You Quan, Ng Choon Ta, Tuan Jeffrey Kit Loong, Yuen John Shyi Peng
Department of Urology, Singapore General Hospital, Singapore, Singapore.
Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore.
Front Oncol. 2024 Jun 14;14:1386597. doi: 10.3389/fonc.2024.1386597. eCollection 2024.
Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.
雄激素剥夺疗法(ADT)和雄激素受体通路抑制剂(ARPi)强化治疗已使晚期前列腺癌患者的生存率提高。然而,ADT与显著的心血管毒性相关,ARPi也对心血管健康产生负面影响。加之在前列腺癌幸存者确诊时报告的基线心血管危险因素患病率较高,因此迫切需要在这一人群中优先考虑并优化心血管健康。首先,虽然没有专门的心血管毒性风险计算器,但其他工具如SCORE2可用于基线心血管风险评估。其次,接受联合治疗的部分患者可能会从降低ADT强度中获益,以在维持癌症控制的同时将其毒性降至最低。这些患者的特征可能是对激素治疗有异常的PSA反应、有利的疾病特征以及存在需要采取较不积极治疗方案的并存合并症。此外,新兴的分子和基因组生物标志物有可能识别出适合采用降低强度治疗方法的患者,无论是使用ADT还是ARPi。一种这样的生物标志物是AR-V7剪接变体,它可预测对ARPi的耐药性。最后,通过一个连贯的框架(ABCDE)和运动疗法来优化患者可改变的心血管危险因素同样重要。本文旨在全面综述激素操纵对转移性激素敏感性前列腺癌心血管的影响,提出减轻与激素治疗相关心血管毒性的总体策略,最重要的是,提高人们对我们目前涉及激素药物的管理策略中固有的有害心血管影响的认识。