编者按：对于前列腺癌的早期诊断，前列腺穿刺活检是前列腺癌检测的金标准；但穿刺活检造成创伤易引起并发症，为临床应用造成了极大的不便。而血清学肿瘤标志物检测具有自动化操作、无创、快速、灵敏等特点，在前列腺癌诊断和治疗中具有一定优势。近日举行的ESMO 2023大会公布了应用循环肿瘤DNA诊疗前列腺癌的研究结果，《肿瘤瞭望》有幸在现场邀请到Henrik Gro?nberg教授，请他深入分享该研究及参会感悟。

 

Henrik Gro?nberg教授：今天我在大会报告了ProBio研究的主要结果，该研究是一项针对男性转移性前列腺癌的研究。目前的一个现实问题是面临多种不同药物，该如何选择？因而ProBio研究使用了适应性设计随机临床试验，可以在这项平台型临床试验中同时比较多种不同药物的疗效。并且可以通过结果自适应设计，根据每个患者的结果更改研究设计的随机化情况。这意味着研究会更加智能，可以为合适的患者选择恰当的治疗方案。

 

我们也使用了循环肿瘤DNA这种生物标志物，这项分析只需要通过血液即可进行，包括了约75个前列腺癌相关基因。随后根据这些循环肿瘤DNA的生物标志物将患者随机分配至不同的治疗方案。研究将医生选择方案与雄激素受体抑制剂（阿比特龙、恩扎卢胺）和紫杉烷类药物进行了比较，发现雄激素受体抑制剂疗效优于紫杉烷类药物和医生选择方案，可增加5-6个月的无进展生存期（即疾病出现进展的时间）。我们还研究了总体生存期的次要终点，结果表明相对于紫杉烷类药物或医生选择方案，接受雄激素受体抑制剂治疗的患者生存期可延长约15个月。

 

这将对未来产生什么样的影响？我认为，如果患有转移性前列腺癌的男性既往未接受过雄激素受体抑制剂，那么他应该在接受紫杉烷类药物之前接受雄激素受体抑制剂。此外，这项研究也表明，可采用如ProBio研究的类似新颖研究设计，使用前瞻性生物标志物、自适应随机化设计，同时比较许多不同的治疗方案。

 

Oncology Frontier:Hi，Dr.Henrik Gro?nberg.Thank you so much for this interview.Our first question is about your study design of your recent research，can you elaborate for us?

 

Dr.Henrik Gro?nberg:Yeah，today I presented the first main result from the ProBio study，which is a study in men with metastatic prostate cancer.And one of the problems there is you have many different drugs at the same time and you don’t know which one to choose.So ProBio is what you call an outcome adaptive randomized clinical trial，a platform trial，in which you can compare many different drugs at the same time.But using what we call an outcome adaptive design is that you change the randomization probabilities over this study design based on the result from each patient.So that means the study becomes clever and clever to select the right treatment to the right patient.

 

But we also use biomarkers that are circulating tumor DNA.That’s a simple blood test that we measure about 75 genes，that are important for prostate cancer.And what we do is that use these circulating tumor DNA biomarkers to randomize patients to different treatments based on these biomarkers.The main results today that I show you is that we compare standard of care which is physician’s choice to androgen receptor inhibitors，that’s abiraterone and enzalutamide，and taxanes.And we showed that androgen receptor inhibitors were superior to both taxanes and physician’s choice.If you look at progression-free survival，which is the time to you have progression of your disease，and it increased between five and six months.But we also looked at the secondary endpoint at overall survival，which means that these patients treated with androgen receptor inhibitors lived about 15 months longer than those put on taxanes or physician’s choice.

 

And what kind of implications will this have in the future?I would say that，if a man with metastatic prostate cancer hasn’t received an androgen receptor inhibitor before，he should receive that before he receives taxanes.The other thing that this study shows is that you can actually have a novel study design like ProBio using prospective biomarkers，adaptive randomization，in comparing many different treatments at the same time.

 

Henrik Gro?nberg教授：我的主要研究领域是前列腺癌，因此会更为关注相关的研究及结果。例如，镥对部分转移性前列腺癌患者有效。此外，我认为本专场的关键进展之一是骨健康管理，这样转移性前列腺癌男性接受激素治疗期间同时进行骨健康管理，就可大大减少骨折风险。我认为这是本次大会的关键进展之一。

 

Oncology Frontier:That’s the final question，during ESMO 2023 congress，there are so many research and new discoveries，which one do you most interesting?Do you find anything like interesting discovery that could help the treatment for the future patient?

 

Dr.Henrik Gro?nberg:my main focus is prostate cancer.So of course I focused on these the results from these studies showing that，for example，Lutetium can work for a subset of men with metastatic prostate cancer.I think one of the key things today in the session I did my presentation，is that bone health agents，that means you should support bone health，so you don’t get fractures during treatment with hormones in men with metastatic prostate cancer.I think that’s one of the key home messages from this congress.

 

Henrik Gro?nberg教授

教授/主任医师

卡罗林斯卡学院癌症流行病学教授

斯德哥尔摩Capio St.Göran医院前列腺癌中心主任