中国抗癌协会

概述
2022年，国家癌症中心发布的最新数据显示，中国妇科肿瘤的发病率呈上升趋势，以卵巢癌为例，年新发病例数为57 200例，粗发病率为8.47/10万，年死亡病例数为27200例，粗死亡率达4.04/10万，发病率和死亡率均高于世标率（分别为5.59/10万和2.45/10万），中国从事妇科肿瘤防治事业的医师面临更大的挑战。妇科肿瘤在早期经过规范性治疗后整体疗效较好，但对于晚期、复发转移的患者，有限的治疗模式及高复发率往往导致预后较差。近年来，靶向治疗、免疫治疗、抗体药物偶联物治疗等新兴治疗方式开创了妇科肿瘤治疗的新纪元，为妇科肿瘤患者带来了更多治疗希望。本文总结2022年度妇科肿瘤手术治疗、放疗、化疗、靶向治疗、免疫治疗和生物标志物检测等方面的重大进展，以期更好地指导妇科肿瘤个体化精准治疗。
1.宫颈癌免疫治疗提高疗效的探索

免疫治疗为宫颈癌患者的治疗开辟了新天地，但纵观各项研究的结果，免疫治疗单药疗效有限，获益人群整体较狭窄。目前除了国外的PD-1抑制剂，我国自主研发的免疫单抗联合小分子抗血管药物以及免疫双抗类药物，提示能够大大提高复发转移性宫颈癌的治疗效果。在局部晚期宫颈癌治疗方面，免疫治疗为患者的治疗获益带来更多选择，但免疫与同步放化疗的最佳组合模式仍在探索中，目前研究中的组合模式主要有三种：免疫+同步放化疗、免疫同步放化疗+免疫维持、免疫诱导+免疫同步放化疗±免疫维持。免疫联合同步放化疗可能有两大方向最为值得探索，一是如何精准筛选出可能获益的高危人群，以及哪些人群更可能从免疫治疗中获益；二是关于联合方案中免疫治疗使用的时机和时长，是与放化疗同步使用，还是在治疗就进行免疫诱导新辅助治疗，以及后续的免疫维持方案。这都值得未来进一步研究探索以及临床经验的总结来获得指导临床实践的医学证据。

2.卵巢癌PARP抑制剂耐药后治疗方式的选择

当前卵巢癌治疗手段层出不穷，但手术治疗依然是卵巢癌治疗的重要基石，其他疗法都需要建立在手术切除的基础上。化疗可作为疗效的保障，维持治疗、抗血管治疗以及靶向治疗则是锦上添花的多种治疗选择。我们作为妇科肿瘤医生，应该不断提高手术技巧，借助新兴的技术手段，让更多的患者实现真正R0切除，为后续的化疗和靶向治疗提供坚实基础。PRIME、ATHENA-MONO研究结果的公布，证实了PARPi对新诊断晚期卵巢癌BRCA野生型患者的生存获益，同时奠定了PARPi作为卵巢癌一线维持全人群标准治疗的地位。年末，SOLO1和PAOLA1两项研究的OS数据的公布，更是首次证实了PARPi单药在BRCA突变人群中、PARPi联合抗血管生成药物在HRD人群中能显著延长新诊断晚期卵巢癌患者总生存。由此引出的PARPi的最佳使用时机、PARPi治疗的后线治疗方案选择等新兴问题值得我们深思。尽早使用PARPi维持治疗似乎能给患者带来更多的生存获益。对于后线/铂耐药患者的联合治疗方案也值得进一步探索。

3. 子宫内膜癌免疫维持治疗模式的进一步探索与优化

近年来，晚期子宫内膜癌系统治疗迎来里程碑式进展，生物标志物指导下的免疫单药或联合治疗已成为晚期或复发性子宫内膜癌二线标准治疗，显著改善了患者的生存。而得益于目前正在进行的临床研究的结果，使得免疫联合化疗有望成为晚期或复发性子宫内膜癌的一线治疗新标准。然而我们也必须认识到现有治疗方案的局限性。例如，对于dMMR的晚期子宫内膜癌一线治疗的疗效，免疫联合化疗与免疫单药相比，仍有待进一步验证。此外，免疫联合化疗成为子宫内膜癌一线新标准治疗，并在临床广泛应用时，免疫治疗进展的患者该如何治疗，目前证据匮乏，也是在不久的将来我们须共同面对的问题。对于出现免疫治疗进展，暂无标准治疗，也没有明确的生物标志物可以参考，在临床实践中多数情况下会考虑更换化疗方案，在此基础上也会尝试联合抗血管生成药物或继续联合免疫治疗，或直接尝试靶免联合治疗等。

总结

2022年宫颈癌的研究进展主要聚焦于免疫治疗。免疫治疗处于飞速发展阶段，越来越多的新靶点、新药涌现，大量的临床试验得以开展。宫颈癌的免疫治疗已经从后线提至一线。从单抗治疗到双抗治疗，从单免疫治疗到双免疫治疗，从单药到联合，免疫治疗正在革新宫颈癌的诊治模式。然而并非所有患者均能从免疫治疗中获益，寻找新的生物标志物精准定位潜在获益人群至关重要；其次，免疫联合疗法尚在探索中，最佳的免疫联合方案、运用时机等尚需明确；免疫治疗中也存在耐药问题，探索肿瘤免疫治疗耐药的分子机制及其临床转化亟待解决。

2022年卵巢癌的研究进展主要仍是集中在PARPi相关研究，更新的数据基本符合预期。随着新药物的不断涌现，卵巢癌治疗将逐步慢病化，也给了临床医师更多的机会，能够开展更多研究改善患者预后，期待将来能有更多的创新成果用于卵巢癌治疗。

对于晚期子宫内膜癌，除传统治疗方法外，免疫单药及联合治疗方案已取得较大进展，如何最大化疗效，MSI-H/dMMR之外如何进一步扩大获益人群，需要更多研究探索，子宫内膜癌分型、检测、可靠预测生物标志物的选择等都值得重点关注。

外阴癌在2022年更新较少，随着早期筛查手段及HPV疫苗的发展，外阴癌得以早期发现、早期诊断和预防。对于晚期、转移或复发患者，个体化手术治疗、基因检测指导下的靶向治疗、免疫治疗是未来研究的重点。

【主编】

吴小华     复旦大学附属肿瘤医院

【副主编】

朱 俊     复旦大学附属肿瘤医院

【编委】（按姓氏拼音排序）

郭勤浩     复旦大学附属肿瘤医院

温 灏     复旦大学附属肿瘤医院

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