卵巢癌并不是常见的肿瘤，发病率在妇产科肿瘤中佔第三位。但由于它不易早期发现诊断，对根治带来一定的不利。下面4点可作为早期诊断作参考。
1）有卵巢癌的家属史。
2）临床上怀疑携带BRCA者。
3）40岁以上，有不明原因的腹胀，腹痛，便祕等症状。
4）其他因素，如個人的乳腺或结腸癌史，或从未妊娠者。
怀疑有卵巢肿瘤时，应做胸、腹和盆腔的CT増强造影。在准备开刀前，还应测血清的CA-125。
治疗的一個关键是手术须由妇产科肿瘤外科医生执行。另一個重要方面是对仅局限于盆腔的肿瘤，要考虑以下的手术范围 (NCCN 2013):
1）进入腹腔时，将已存在的腹水或把腹腔的灌洗液送去病理科作细胞学检查。
2）子宫切除，双侧卵巢和输卵管切除。要避免碰破囊肿。
3）网膜切除。
4）双侧盆腔淋巴结清扫。
5）腹主动脉旁淋巴结清扫。
6）仔细检查所有的腹膜，对可疑的结节和粘连的地方都要切除和活检。要是没有发现可疑之处，要对腹腔和盆腔的腹膜，结腸旁沟和膈肌的腹腔一侧随意抽样活检。
若肿瘤己扩展到上腹部，但术后残余的肿瘤能都在1公分以下，则称为最佳肿瘤减灭术。
术后化疗：
对病理分期为IC，II，III和IV期的病人，术后常用的化疗为紫杉醇（Taxol）和卡铂（Carboplatin），每三周一次，一共六次。最近有报告（lll期随机试验）提示每周一次紫杉醇，每三周一次卡铂，或每周同时使用两者，比传统的每三周一次，对推迟复发有利。对某些病人还可能延长生存。
对原发性腹膜转移癌，还可以考虑腹腔内化疗。
2015.9.26
卵巢癌术后化疗 紫杉醇（60毫克/平方米），每周一次，在一小时内注射完毕；卡铂（AUC＝2）每周一次，在30分钟内注射完毕，一共18次。这己成为2015年NCCN对第二和第三期卵巢癌术后所建议的化疗方案（第一类推荐）。而且这個化疗方案也适用于老年患者。
ASCO 关于PARP抑制剂对卵巢癌的治疗指南 (11/7/2020)
ASCO guideline about management of ovarian cancer using PARP Inhibitors
- 新诊断的卵巢癌（上皮性卵巢癌，输卵管癌或原发性腹膜癌）
- 不推荐在EOC的女性中重复PARPi治疗。 不建议将PARPis用于I-II期患者的初期治疗
- 对于刚诊断为III-IV期的女性, 对一线铂类化学疗法有完全或部分响应的，，应使用olaparib进行PARPi维持治疗（适用于具有BRCA1或BRCA2基因的种系变异, 或体细胞致病性或可能致病性变异的患者） 或niraparib用于患有高度浆液性或子宫内膜样卵巢癌（适用于所有女性）。
PARPi维持疗法应包括olaparib（口服，每12小时300毫克，持续2年）或niraparib（每日200-300毫克，持续3年）。 在选定的个别患者中可以考虑更长的持续时间。 - 对于患有III-IV期高度浆液性或子宫内膜样卵巢癌，BRCA1或BRCA2基因的种系或体细胞变异, 或具有可能致病的BRCA1/BRCA2基因变异或/和/基因组不稳定患者（通过Myriad myChoice CDx确定）, 对化疗加贝伐单抗联合治疗有部分或完全响应, 将olaparib添加至贝伐单抗维持治疗中。
- 目前不建议将PARPi veliparib与联合化疗并用veliparib维持治疗。
II.复发性卵巢癌, 第二线或更晚的维持和治疗
- 对尚未接受PARPi且对铂类疗法有响应的卵巢癌患者（无论BRCA突变状态如何）提供PARPi单药治疗（二线以上）。 治疗仍持续到疾病进展或尽管减少剂量和提供最佳支持治疗，毒性仍然存在。
可以选择：olaparib每12小时300毫克； 或rucaparib每12小时600毫克； 或niraparib 200-300毫克每天一次 - 对于尚未接受PARPi且在BRCA1或BRCA2基因中具有种系或体细胞致病性或可能致病性变异的复发性卵巢癌患者，应提供PARPi治疗。
选项包括：奥拉帕尼每12小时300毫克； 或rucaparib每12小时600毫克； 或niraparib 200-300毫克每天一次 - 对于尚未接受PARPi且肿瘤表现出基因组不稳定性（根据Myriad myChoice CDx而确定），且在铂类治疗后6个月内未复发的卵巢癌患者，应提供PARPi单药治疗。
- 不建议将PARPis用于治疗BRCA野生型或耐铂类复发性的卵巢癌。
- 不建议在复发的患者中, 在临床试验范围以外,，将PARPi与化疗，其他靶向药物或免疫肿瘤药物联合使用。
- III. 不良事件的管理
- 贫血: 需要输血以缓解症状和/或血红蛋白水平<8 克/分升的患者, 应当减少PARPi剂量，以避免多次输血。
- 中性粒细胞减少症：未表明它是接受PARPi患者使用生长因子的适应症。
但当发生4级中性粒细胞减少持续, 至少5-7天或伴有发烧, 应停药直至感染恢复和中性粒细胞计数恢复，然后减少剂量。在这种情况下，可以使用生长因子来支持患者的安全。 - 血小板：最常见于niraparib。应根据体重和血小板计数，使用Niraparib剂量指南降低起始剂量（200 毫克）。
对尽管剂量减少，但血小板仍持续性减少或明显出血者, 应中断PARPi。 - 恶心和心动过速: 在治疗的第一个周期中，许多患者会出现这些症状。
持续的恶心需要每天服用止吐药; 若工作状态降低，和/或体重减轻> 5％，应减少剂量。
- Newly diagnosed epithelial ovarian cancer (EOC) (ovarian, fallopian tube, or primary peritoneal cancer)
It is not recommended to repeat PARPi treatment in the treatment of women with EOC. It is not recommended to use PARPis for the initial treatment of patients with stage I-II
• For women who have just been diagnosed with stage III-IV, who have a complete or partial response to first-line platinum chemotherapy, olaparib should be used for PARPi maintenance therapy (for those with germline or somatic pathogenic or likely pathogenic variants in BRCA1 or BRCA2 genes) or niraparib (all women) for patients with high-grade serous or endometrioid ovarian cancer .
PARPi maintenance therapy should include olaparib (orally, 300 mg every 12 hours for 2 years) or niraparib (200-300 mg daily for 3 years). A longer duration can be considered in selected individual patients.
• The addition of olaparib to bevacizumab maintenance may be offered to patients who have stage III-IV high grade sersous or endometrioid ovarian cancer and germline or somatic pathogenic or likely pathogenic variants in BRCA1 or BRCA2 genes and/or genomic instability, as determined by Myriad myChoice CDx, and who have had a partial or complete response to chemotherapy plus bevacizumab combination
• It is not currently recommended to use PARPi veliparib and combination chemotherapy with veliparib for maintenance therapy.II. Recurrent ovarian cancer, second-line or later maintenance and treatment
• PARPi monotherapy (second-line or more) to ovarian cancer patients who have not yet received PARPi and who have responded to platinum therapy (regardless of BRCA mutation status). Treatment continues until disease progresses or toxicity despite dose reductions and best supportive care.
Options include: olaparib 300 mg every 12 hours; or rucaparib 600 mg every 12 hours; or niraparib 200-300 mg once a day
• For patients with recurrent ovarian cancer who have not received PARPi and have germline or somatic pathogenic or possibly pathogenic variants in the BRCA1 or BRCA2 gene, PARPi treatment should be provided.
Options include: olaparib 300 mg every 12 hours; or rucaparib 600 mg every 12 hours; or niraparib 200-300 mg once a day
• For patients with ovarian cancer who have not received PARPi and whose tumor demonstrates genomic instability, as determined by Myriad myChoice CDx, and has not recurred within 6 months of platinum-based therapy
- It is not recommended to use PARPis to treat BRCA wild-type or platinum-resistant recurrent EOC.
- It is not recommended to use PARPi in combination with chemotherapy, other targeted drugs or immuno-oncology drugs in patients
who have relapsed outside the context of clinical trials.
III. Management of Adverse Events
a) Anemia: Patients requiring a blood transfusion for symptom relief and/or hemoglobin level < 8 g/dL should be monitored. PARPi dose should be reduced with evidence of repeated anemia to avoid multiple transfusions.
b) Neutropenia: Growth factor is not indicated for use in patients receiving daily PARPi.
Neutropenia (grade 4 lasting at least 5-7 days or associated with fever) should result in dose hold until recovery of infection and granulocyte count, followed by dose reduction. Growth factor support may be used in this setting to support patient safety during the drug hold.
c) Platelets: Thrombocytopenia is most common with niraparib. Niraparib dosing guidelines should be used to lower starting dose (200 mg) based on weight and platelet count.
Discontinue PARPi for persistent thrombocytopenia or significant bleeding despite dose reduction.
d) Nausea and tachycardia: Many patients will have tachyphylaxis of nausea symptoms over the first cycle of therapy.
Persistent nausea requiring daily antiemetic intervention, causing a reduction in performance status, and/or resulting in > 5% weight loss should result in dose reduction.
参考文献 Reference
Tew WP et al. J Clin Onc 2020; 38:3468
晚期卵巢癌患者的细胞减灭手术+/-腹腔热腹化疗: 10 年随访的生存结果 (10/1/2023)
Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in advanced ovarian cancer: 10-year follow-up of overall survival
方法: 这是一项开放标签, 随机, 对照的 III 期试验(OVHIPEC-1, NCT00426257)，在荷兰和比利时的八个 HIPEC 中心招募了原发性上皮 III 期卵巢癌, 不适合初次细胞减灭术的患者, 患者年龄在 18-76 岁，在至少三个周期新辅助卡铂加紫杉醇内未出现进展，则符合入选资格。 患者被随机分配 (1:1) 接受间歇性细胞减灭术，不进行 HIPEC (腹腔热灌注化疗)（手术组）或进行 HIPEC（100 毫克/平方米 顺铂；手术加 HIPEC 组）。主要终点是无进展生存期，次要终点是总体生存期，在意向治疗人群（即所有随机分配的患者）中进行分析。
发现: 2007年4月1日至2016年4月30日期间，入组了245名患者，和10组患者，手术组（n =123）中位随访时间为10.1年（95% CI 8.4–12.9）, 手术加 HIPEC 组 (n =122) 中位随访时间为10.4 年 (95% CI 9.5–13.3)。 手术组有 114 名 (93%) 患者出现复发、进展或死亡（中位无进展生存期 10.7 个月 [95% CI 9.6–12.0]），而手术组有 109 名 (89%) 患者出现复发、进展或死亡。 手术加 HIPEC 组（中位无进展生存期14.3 个月 [12.0–18.5]；风险比 [HR] 0.63 [95% CI 0.48–0.83]，分层对数秩 p =0.0008）。 手术组有 108 名 (88%) 患者死亡（中位总生存期 33.3 个月 [95% CI 29.0–39.1]），手术加 HIPEC 组有 100 名 (82%) 患者死亡（中位总生存期 44.9 个月 [95% CI 38.6–55.1]；HR 0.70 [95% CI 0.53–0.92]，分层对数秩 p =0.011）。
解释: 这些更新的生存结果证实了 HIPEC 对接受细胞减灭术的原发性 III 期上皮性卵巢癌患者的长期生存益处。
Methods: This was an open-label, randomized, controlled phase III trial (OVHIPEC-1, NCT00426257) enrolling patients (age 18-76) with primary epithelial stage III ovarian cancer patients who were ineligible for primary cytoreduction. They were eligible if there was no progression upon at least three cycles of neoadjuvant carboplatin plus paclitaxel. Patients were randomly assigned (1:1) to undergo interval cytoreduction without HIPEC (hyperthermic intraperitoneal chemotherapy) (surgery group) or HIPEC (100 mg/m cisplatin; surgery plus HIPEC group). The primary endpoint was progression-free survival and the secondary endpoint was overall survival. The analysis was performed in the intention-to-treat population (i.e., all randomly assigned patients).
Findings: Between April 1, 2007 and April 30, 2016, 245 patients were enrolled. The median follow-up in the surgical group (n = 123) was 10.1 years (95% CI 8.4–12.9), and 10.4 years in the surgery plus HIPEC group (n =122) (95% CI 9.5–13.3). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival, 10.7 months [95% CI 9.6–12.0]), compared with 109 (89%) patients in the surgery plus HIPEC group (median progression-free survival 14.3 months ([12.0–18.5], hazard ratio [HR] 0.63 [95% CI 0.48–0.83], stratified log-rank p =0.0008). A total of 108 (88%) patients died in the surgery group (median overall survival 33.3 months [95% CI 29.0–39.1]) and 100 (82%) patients died in the surgery plus HIPEC group (median overall survival 44.9 months [95% CI 38.6–55.1]; HR 0.70 [95% CI 0.53–0.92], stratified log-rank p =0.011).
Interpretation: These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer who undergoing interval cytoreductive surgery.