编者按：前列腺癌是一种雄激素依赖性肿瘤，但大多数患者最终会进展为去势抵抗性前列腺癌（CRPC），此时的临床治疗仍是目前面临的重大挑战。对于晚期前列腺癌患者的早期诊断、疗效评估和复发监测等方面的相关研究就显得尤为重要，今年ESMO大会中Silke Gillessen教授作为主持，与多位专家共同探讨了晚期前列腺癌领域生物标志物方面的研究。在大会现场，《肿瘤瞭望》有幸邀请Silke Gillessen教授就相关内容进行深度分享。

 

 

Silke Gillessen教授：很高兴见到你。晚期前列腺癌是一个相当大的定义，包括转移性前列腺癌，也包括局部晚期前列腺癌。

 

回答生物标志物相关的问题时，我们更多地于转移性前列腺癌领域进行讨论。因为现在这类前列腺癌的治疗中使用了大量生物标志物，特别是对于CRPC患者。正如相关专家讨论的那样，很长一段时间以来，我们并没有前列腺癌的生物标志物进行指导以使治疗决策变得更为容易。但PARP抑制剂的出现，让我们发现存在DNA修复缺陷（特别是BRCA突变）的患者，对PARP抑制剂反应良好。目前生物标志物有益于治疗转移性前列腺癌治疗并已经应用于CRPC患者，同时也有研究探索激素敏感性患者的治疗方案。

 

目前的下一个生物标志物是PSMA。在PSMA PET扫描中发现PSMA阳性并且通过血清诊断的患者，现在可以使用PSMA定向放疗。这同样适用于CRPC；而对于激素敏感性患者，也正在进行研究。

 

Oncology Frontier:Hi Dr.Silke Gillessen.Our first question is，can you briefly explain what advanced prostate cancer is?What are the primary challenges in treating advanced prostate cancer?How have biomarkers improved the treatment of this?

 

Dr.Silke Gillessen:Yes，very nice meeting you.And advanced prostate cancer is a quite big definition.So it includes metastatic prostate cancer，but it also includes locally advanced prostate cancer.

 

So when you ask this question，I guess we are going more into the field of metastatic prostate cancer now.Because that is the field where we now using a lot of biomarkers，specifically in the castration resistance setting.So as we heard today also in the expert，we had for a long time that we didn’t have biomarkers in prostate cancer to make easier the treatment decision.but it started with the PARP inhibitors where we found that patients with DNA repair defects，specifically with BRCA mutations respond well to PARP inhibitors.So this is now going to help us，and this is for the moment we use them in the metastatic castration resistance setting.But their studies ongoing also in the hormone sensitive disease.

 

And then the next biomarker that we have is the PSMA.So we find PSMA positivity in PSMA PET scans and with the serognostics，we can now treat these patients who are positive on the scans with a PSMA-directed radioligine therapy.Again，this is for patients in the moment with metastatic castration resistant disease，but there is also studies ongoing in the hormone sensitive setting.

 

Silke Gillessen教授：正如我们之前讨论的下一代成像技术那样，PSMA PET主要基于镓（68 Ga），有时也基于氟化物（18 F）。这种技术有助于我们筛选适合接受PSMA定向放疗的患者。目前主要是常规配体联合镥（177 Lu）进行治疗，但也有即将推出的新型疗法。我认为目前可为患者提供基于生物标志物的治疗方法，这是一件非常好的事情。而对于不表达生物标志物或PSMA扫描呈阴性的患者，他们一般不会接受这种具有一定毒性且无法从中受益的治疗方案。

 

Oncology Frontier:So this is also about your research discusses the use of next-generation imaging for prostate cancer.How does next-generation imaging enhance the detection of biomarkers in advanced prostate cancer?

 

Dr.Silke Gillessen:So the next generation imaging，we’re speaking here specifically about，as I said also before，the PSMA PET that is mostly done with gallium，sometimes with fluoride.And that’s helping us to select the patients for the PSMA-directed therapies.Mostly for the moment it’s regular-ligand with lutecium，but there’s also new therapies upcoming.And it’s quite a nice thing I think that we now have these nice biomarker driven treatments for our patients.So patients who don’t express the biomarkers or negative on the PSMA scans，they don’t receive treatments that have some toxicity and they cannot benefit from them.

 

Silke Gillessen教授：未来的生物标志物，可能会有更多。正如前面讨论过，DNA修复缺陷患者已经开始使用生物标志物，并且我们也会在早期治疗中使用，我认为这非常令人振奋。目前PSMA是应用于在CRPC患者的另一种方案，但也计划用于早期诊疗。显然MSI-H比例较低，仅约为5%的前列腺癌患者。这是一种泛肿瘤标志物；如果患者为MSI-H，则免疫检查点抑制剂疗效较好。虽然已在其他领域使用过这种生物标志物，但对于前列腺癌而言，其仍为一种新型生物标志物。并且我们将在CRPC患者进行使用，或者说已经在CRPC患者中进行了应用；同样，在前线治疗中进行的试验可能也会非常有趣。

 

Oncology Frontier:Based on your research and the consensus from APCCC 2022，what do you see as the future of biomarker use in treating advanced prostate cancer?

 

Dr.Silke Gillessen:So the future biomarkers，there will probably be more coming.So we said already the DNA，the repair defects is one of the biomarkers we’re already using.But we will use it also in earlier lines.And I think this is quite exciting.And then as we said，the PSMA is another one that we are using in the moment in the castration resistance setting，but also here，planned for early lines.And then obviously also the MSI high that is a very small percentage，about 5%of prostate cancer patients who have that.And as you know，this is a pan-tumor marker.So if someone is MSI high，has a good response to immune checkpoint inhibitors.Let’s say，it’s not a new biomarker because we used it also before，but in prostate cancer it’s a quite new biomarker that in the moment again，we will use or we are using in the moment already currently for the castration resistance setting.But also there，it could be interesting to do trials in earlier lines.

Silke Gillessen教授：上述所有感兴趣的问题同样将在APCCC 2024与来自世界各地的专家进行非常深入的讨论，该会议将在明年4月底于卢加诺举行。想要参加的读者现在就可以报名，报名渠道对所有人开放，没有限制；每个对前列腺癌、治疗方案感兴趣的读者都可以注册。我也希望看到更多的中国同事来瑞士参加会议。还有一个名为www.apccc.org的晚期前列腺癌共识会议网站，我希望能与大家相见。

 

Oncology Frontier:What’s your opinion about APCCC 2024?

 

Dr.Silke Gillessen:Yes，and all your interesting questions that you just gave to me，we will discuss that very，very profoundly with all world experts at the APCCC 2024 in Lugano end of April.and everyone who wants to come can register now.So the registration is open，it’s not restricted.Everyone who is interested in prostate cancer，treating prostate cancer can register there.So I hope to see a lot of Chinese colleagues coming to the to the conference and to Switzerland.That would be really nice.And there is a website that’s called www.apccc.org for advanced prostate cancer consensus conference.So I hope I see a lot of you there.

 

Dr.Silke Gillessen

医学肿瘤学家，专注于泌尿生殖系统癌症。

她在巴塞尔、圣加仑和波士顿丹娜-法伯癌症研究所完成了专业培训。返回瑞士后，她在圣加仑州立医院建立了泌尿生殖系统肿瘤内科，并领导肿瘤学/血液学临床研究室。

她曾担任两届SAKK GU小组主席，担任EORTC泌尿生殖系统癌症小组主席，并创立了晚期前列腺癌共识会议（APCCC）。

自2018年以来，Gillessen教授一直担任曼彻斯特大学泌尿生殖系统癌症系统治疗研究主席和克里斯蒂医院名誉顾问，同时继续担任瑞士圣加仑州立医院肿瘤科/血液科顾问。

2020年1月，Gillessen教授被任命为卢加诺提契诺大学（USI）肿瘤内科主任、教授以及瑞士贝林佐纳的瑞士南部肿瘤研究所（IOSI）所长。