Oncology Frontier：At oral abstract session of gynecologic cancer， you are the discussant of abstract 5500， 5501， 5502. Would you please share your opinion on the three studies?


Dr. Salani: I had the opportunity to discuss three abstracts at this meeting. All the abstracts were randomized controlled trials， which is very exciting. Two were surgical trials and I will start with the ovarian cancer trials.

The first trial was the LION study， Lymphadenectomy in Ovarian Neoplasms， looking at systematic lymph node dissection versus no dissection or omitting the lymph node dissection in patients who had advanced ovarian cancer but no evidence of bulky lymph nodes. This was detected both clinically in the surgery as well as radiographically prior to the surgery. The authors did stipulate that patients would undergo complete resection (the complete resection rate was approximately 100%). What the authors found that was really interesting is that there is no difference in overall survival or progression-free survival when you omit lymph node dissection compared to patients who have a systematic lymph node dissection. This result was surprising because there had been prior studies that had tended to suggest that patients who had lymph node dissections had an improved progression-free survival. One of the interesting things from the study is that we are probably harming our patients by adding lymph node dissection in this group. These patients had higher perioperative morbidity (such as infections， re-operations， bleeding requiring transfusions)， and also a higher mortality rate of 3.1% compared to 0.9%. I agree with the authors’ conclusions that we can safely omit lymph node dissections in patients who have no evidence of disease both radiographically and clinically and who are otherwise able to undergo complete macroscopic resection. I think this finding is really going to change the management of ovarian cancer， and I commend the authors on the study.

The other surgical study in ovarian cancer was looking at secondary cytoreductive surgery in patients who are platinum-sensitive and who had a positive AGO score. These were patients who had no ascites who underwent complete resection at the time of primary surgery and who had a favorable performance status. The authors methodically evaluated their study approach. They first did assessments to look at what the scoring system should be based on， and then they validated the scoring system. At this year’s meeting， they presented their progression-free survival outcomes. This is the DESKTOP III study. They found that secondary cytoreductive surgery was associated with a progression-free survival benefit when compared to patients who didn’t undergo surgery， but chemotherapy only. They had a complete resection rate of >70%， which is very impressive. One of things to note is that the authors reported comparable morbidity or complications from surgery as well as mortality rates. This is a reassuring finding. The most surprising finding was that compared to prior retrospective studies， which have suggested optimal resection was superior to no surgery， these authors were able to demonstrate that complete resection was really the key. Patients who had any residual disease， even if it were optimal， did not benefit from secondary cytoreductive surgery. The progression-free survival of 5.6 months was really limited to those patients who had complete resection. The study was designed to look at overall survival， but those results are not matured yet， so we are still waiting for those results. The authors are a little surprised that the results are taking longer than anticipated， but this may be because this is a really favorable group. These patients had a platinum-free interval of >12 months， so this is a really optimal group of patients. We look forward to the overall survival rates. I don’t think these changes clinical practice just yet， but I think these results are really promising. As we wait for these data， I think we have to continue with our current practices， but we can hopefully look forward to seeing that secondary cytoreductive surgery plays a role.

The last study was PORTEC-3. This was a study looking at radiation therapy in patients with high-risk early stage or advanced endometrial cancer versus chemoradiation with cisplatin followed by four cycles of carboplatin and paclitaxel. Both of these regimens were very well tolerated but there was no difference in both progression-free and overall survival. I think these results were a little surprising to many of us， as we were hoping to be able to improve on our current progression-free and overall survival rates in this group of patients. There are a couple of points I want to highlight though. In stage 3 disease， the authors did note that there was some possible benefit with the progression-free or the failure-free survival rate being superior in patients who did receive the chemotherapy in addition to radiotherapy. However， this has not translated into an overall survival benefit. I think we need to use caution when adding therapies to our patients that add toxicity as well. The other takeaway point is that we have to question whether the radiation preceding chemotherapy is really the right sequence of therapy. We know that when you have radiotherapy， the vascularity changes and that may affect the role of chemotherapy. So， I challenge the authors and our community to consider chemotherapy prior to radiation and there are ongoing studies looking at this. At this time， whether it is radiation， chemotherapy or chemotherapy and radiation combined， this is still a question we have not answered. This group of patients remain a center of debate for us.

Ritu Salani教授：临床评价（术前影像学检查及术中探查）无淋巴结转移的晚期卵巢癌（AOC）在获得肉眼完全切除后，是否需要行盆腔及腹主动脉旁淋巴结清扫术（LNE）？2017 ASCO报告的随机、前瞻LION研究发现， 这些卵巢癌患者行盆腔及腹主动脉旁淋巴结清扫未能改善生存且风险增加（摘要号5500）。研究者规定患者手术必须是完全切除（完全切除率为100%）。未行淋巴结清扫的患者和接受系统淋巴结清扫的患者相比，PFS和OS没有差异。研究结果与既往预期相反，让人惊讶。淋巴结清扫甚至会给患者增加伤害，造成围手术期并发症增加（比如感染、再次手术、增加出血量、增加输血比例等），增加60天内死亡率（3.1% vs. 0.9%）。


我同意研究者的结论，临床和影像学评估无淋巴结转移且获得肉眼完全切除的晚期卵巢癌患者，没有必要接受系统性盆腔及腹主动脉旁淋巴结清扫术。我认为这项研究可以改变临床实践。

AGO DESKTOP III/ENGOTov20试验是评价复发卵巢癌二次减瘤术意义的随机、对照、Ⅲ期研究。研究者在2017 ASCO会议上报告了PFS结果。研究共入组407例首次复发、且无铂治疗间隔（TFIp）6个月以上、AGO评分好（ECOG 0分、腹水≤500 ml、第一次手术完全切除）的患者，随机分为单纯二线化疗组（非手术组）和手术+化疗组。非手术组与手术+化疗组的中位PFS分别为14个月和19.6个月。中位至首次后续治疗时间（TFST）分别为13.9个月和21个月。相比单纯二线化疗组，二次减瘤术增加了患者的PFS获益。

手术切除率＞70%，令人印象深刻。值得注意的一点是，两组的死亡率和并发症发生率相当。最令人惊讶的是，这项研究发现“完全切除”是关键，有任何残留的患者（即使是最佳切除）没有从二次肿瘤细胞减灭术中获益。5.6个月的PFS获益仅限于完全切除的患者。

首要研究终点OS数据尚不成熟，研究者也惊讶OS结果花费时间比预期长。这项研究目前还不能改变临床实践，我们期待OS数据成熟，以验证二次减瘤术在复发卵巢癌的作用。

ASCO 2017发布了对比辅助放化疗和单纯放疗治疗高危子宫内膜癌(HREC)的PORTEC-3最终结果。入组患者1:1随机分入放疗组（RT，48.6 Gy盆腔外照射，每次 1.8 Gy）或放化疗组[CCRT，上述放疗方案基础上给予2周期顺铂（50 mg/m²），序贯四周期卡铂（AUC5 ）联合紫杉醇（175 mg/m²），顺铂在放疗第一周和第四周给药，接下来每间隔21天给予一次卡铂+紫杉醇]。首要共同研究终点是总生存（OS）和无失败生存时间（FFS）。CCRT组（n=330）和RT组（n=330）的5年总生存率分别为82% vs. 77%；5年FFS率分别为76% vs. 69%。

这两个方案的耐受性都很好，但是两个治疗组的PFS和OS没有差异。研究结果让人有点吃惊，因为我们本来预期CCRT组能改善PFS和OS。值得注意的一点是，接受放疗联合化疗的III期患者的PFS和FFS的确有一些获益，但是没有转化为OS获益。因此在治疗方案中纳入会增加毒性的治疗选择时应谨慎。另一点是，我们要考虑研究中所用的放化疗顺序是否合理，因为放疗会引起血管变化，从而影响化疗的作用。我向研究者以及其他学术界人士提出：能否在放疗前使用化疗（这方面的研究正在进行）。