Oncology Frontier: Can you tell us about your presentation dealing with prognostic scoring including surgical implications?

　　《肿瘤瞭望》：请您介绍一下目前临床上使用的患者预后和疗效预测评估方法？

　　Dr. Sun Young Rha: For patient treatment decisions， we need to figure out the patient’s prognosis and how we can use that prognosis in our treatment decisions. Unfortunately， to-date， we don’t have biomarkers like molecular markers or specific markers to predict treatment efficacy. What we do is use prognostic risk groupings which have been used for more than twenty years.

　　The most common one is the Memorial Sloane-Kettering risk group based on six parameters. This was developed in the cytokine treatment era， so it is a little difficult to apply it to the current system where we are using a lot of VEGF TKIs.

　　But even in this era， when we apply those parameters， we can still group the patients. Then Heng’s group collected data from a few thousand patients from multiple sites to make the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium)， which includes patients treated in the molecular-targeted agents era. This IMDC score is similar to MSKCC but also includes neutrophil and platelet counts. We can categorize patients into three groups of varying prognosis.

　　There are several other prognostic scores but these are not validated externally and usually retrospective from institutional studies. Recently， we have received more data on second-line prognostic scoring where we use a modified Memorial Sloane-Kettering scoring system with three parameters. The IMDC also has six parameters to use to predict the outcome of second-line treatment， but again， that is not in standard use in the clinical setting. It is however useful for deciding further treatment options. For cytoreductive nephrectomy， when we use the IMDC scoring system， we can categorize patients who may benefit from the procedure and those who will not benefit from cytoreductive nephrectomy. That is based on tumor characteristics and also host characteristics including comorbidities.

　　So again， the prognostic scoring system provides support， but it is not the only determining factor and it is not mandatory in deciding patient treatment strategies. We still need more individualized biomarkers to predict outcomes and response to treatment.

　　Sun Young Rha教授：临床上，在为患者制定治疗方案前，需要先评估患者的预后。然而不幸的是，迄今为止，我们还没有发现可预测疗效的生物标记物，所以现在所能做的就是使用危险度分组预后模型（这种方法已使用了二十多年）。

　　纪念斯隆-凯特琳癌症中心（Memorial Sloan-Kettering Cancer Center， MSKCC）模型是最常用的基于六种参数的危险度分组预后模型。该方法最初是在细胞因子治疗领域发展起来的，所以将其应用于目前的治疗，尤其是使用最多的VEGF-TKI领域，还存在一定的困难。

　　国际转移性肾细胞癌联合数据库（International Metastatic Renal-Cell Carcinoma Database Consortium， IMDC）收集了来自全球多中心的几千例患者的信息，包括接受分子靶向治疗的患者。在此数据库基础上建立的IMDC模型能为肾细胞癌患者提供相关的预后信息。IMDC模型于MSKCC模型评分类似，同样也包括中性粒细胞和血小板计数，可以将患者分成3种不同的预后。

　　此外，也有其他的预后评分体系，但都没有获得验证，所以临床上通常不使用这些评分体系。最近，通过改良的MSKCC模型（基于三个参数），得到了更多的二线预后评估数据。IMDC模型也可以基于六个参数去预测二线治疗的疗效，对远期治疗方案的选择有很大帮助。例如，在行减瘤性肾切除术前，可以使用IMDC模型评估患者的手术获益情况，即区分可从手术中获益者和不能从手术中获益者。

　　总之，在制定患者治疗方案时，预后评分体系只是给予支持性的帮助，并非唯一的决定性因素，也没有强制性。希望在未来可以发现预测预后和疗效的个体化生物标记物。

　　Oncology Frontier: What are some of the important decision-making crossroads in the treatment of patients with RCC?

　　《肿瘤瞭望》：近年来，在晚期肾癌患者的治疗中，有哪些突破性的进展？

　　Dr Sun Young Rha: Until two or three years ago， we were in a plateau with regard to the efficacy of treatment including VEGF TKIs and mTOR inhibitors. Now we have more choices with immunotherapy. Immunotherapy today is different from the usual meaning seen previously with the cytokines and previous therapies. Now we have different mechanisms of immune inhibition through the immune checkpoint inhibitors. This provides very good efficacy increasing our chances to achieve cures using combinations of checkpoint inhibitors with other agents.

　　The problem is what is the proper partner. Some of the VEGF TKIs are being tested and we see increasing issues with toxicities. Another pathway is the inhibition of angiogenesis with bevacizumab and other monoclonal antibodies， which may prove to be efficacious and more tolerable. It is an exciting time to see more chances to treat patients with the possibility of cures.

　　The issue again is which patients to treat. We need biomarkers to select those patients who will benefit from these treatments. Currently， some of the markers (like PD-L1 expression in tumors) are being used but they are not yet standardized and validated and are not the only indicator. Renal cancer has been an important target for immunotherapy so from now on I think we have a good future in the treatment of metastatic renal cell carcinoma.

　　Sun Young Rha教授：直到两三年前，关于VEGF-TKIs和mTOR抑制剂的疗效才刚刚处于一个稳定期，而现在对于免疫治疗又有了更多的选择。如今的免疫治疗不同于传统的细胞因子治疗，主要是免疫检查点抑制剂治疗，在与其他药物的联合应用中显示出了很好的疗效，增加了患者治愈的可能。

　　哪些药物是联合免疫检查点抑制剂的最佳拍档？目前已有部分VEGF-TKI正在进行试验，但观察到的毒性反应问题令人担忧。此外，以贝伐单抗为代表的血管生成抑制剂和其他单克隆抗体，可能被证实有效并且患者更容易耐受。

　　看到患者有更多的治愈的可能是非常令人激动的。那么，究竟哪些患者适合接受免疫治疗呢？我们需要特定生物标记物，来筛选出可以从治疗中获益的人群。目前，已有一些标记物（如，肿瘤表达的PD-L1）被采用，但这些标记物并不是标准、未获得验证，也并非唯一的指标。肾癌是免疫治疗的一个重要领域，相信未来免疫治疗在转移性肾癌的治疗前景是非常好的。