Epithelial ovarian cancer — structured SAQ (15 marks)

(a) FIGO 2021 Stage I and Stage III staging (4 marks)

Half a mark per verbatim line, maximum four. ^[1]

• Stage I: tumour confined to ovaries or fallopian tube(s).^[1]
• IA: tumour limited to one ovary (capsule intact) or fallopian tube; no tumour on surface; no malignant cells in ascites or peritoneal washings.
• IC1: surgical spill.
• IC2: capsule ruptured before surgery or tumour on ovarian or fallopian tube surface.
• IC3: malignant cells in the ascites or peritoneal washings.
• Stage III: tumour involves one or both ovaries or fallopian tubes with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph nodes.
• IIIA1: positive retroperitoneal lymph nodes only (cytologically or histologically proven).
• IIIA1(i): metastasis up to 10 mm in greatest dimension; IIIA1(ii): metastasis more than 10 mm.
• IIIA2: microscopic extrapelvic peritoneal involvement with or without positive retroperitoneal lymph nodes.
• IIIB: macroscopic peritoneal metastasis beyond the pelvis up to 2 cm, with or without nodal metastasis.
• IIIC: macroscopic peritoneal metastasis beyond the pelvis more than 2 cm, with or without nodal metastasis (includes extension to capsule of liver/spleen without parenchymal involvement).

(b) Primary debulking vs NACT — the trials and the decision (5 marks)

One mark per point, maximum five. ^[2][3]

• EORTC 55971 (Vergote 2010): of 670 women with stage IIIC or IV disease randomly assigned to primary debulking followed by platinum chemotherapy or neoadjuvant platinum chemotherapy followed by interval debulking, 632 were eligible and started treatment. HR for death 0.98 (90 percent CI 0.84 to 1.13), non-inferior. Complete resection of all macroscopic disease was the strongest independent variable predicting overall survival.^[2]
• CHORUS (Kehoe 2015): 552 women with suspected stage III or IV disease. Median OS 24.1 vs 22.6 months; HR for death 0.87 (upper bound of one-sided 90 percent CI 0.98), non-inferior. Grade 3/4 postoperative adverse events 14 percent vs 24 percent (p = 0.0007); 28-day postoperative mortality under 1 percent vs 6 percent (p = 0.001).^[3]
• FIGO position: in selected patients with cytologically proven Stage IIIC and IV disease who may not be good surgical candidates, 3 to 4 cycles of neoadjuvant chemotherapy may be given, followed by interval debulking; this may be particularly useful with poor performance status, significant comorbidities, visceral metastases, or large pleural effusions and/or gross ascites.^[1]

(c) BRCA testing and PARP maintenance (4 marks)

One mark per point, maximum four.

• All women with high-grade nonmucinous invasive ovarian cancers should be offered genetic testing (Berek 2021): at least 15% of women with high-grade nonmucinous ovarian cancers have germline mutations in BRCA1/2, and almost 40% of these women do not have a family history of breast/ovarian cancer.^[1]
• PARP benefit by biomarker: patients with BRCA mutations, germline and somatic, have the greatest benefit from PARP inhibitors, and a subset with homologous recombination deficient tumours also benefit.^[1]
• SOLO-1: olaparib maintenance vs placebo in newly diagnosed BRCA-mutated advanced disease after response to platinum. 3-year PFS 60 percent vs 27 percent; HR for progression or death 0.30 (95 percent CI 0.23 to 0.41).^[4]
• PRIMA: niraparib maintenance vs placebo after first-line platinum. Overall population median PFS 13.8 vs 8.2 months (HR 0.62); HRD subgroup 21.9 vs 10.4 months (HR 0.43).^[5]

(d) Screening and prevention (2 marks)

One mark per point.

• USPSTF: recommends against screening for ovarian cancer in asymptomatic women not known to have a high-risk hereditary cancer syndrome; screening does not reduce ovarian cancer mortality, and harms include unnecessary surgery.^[6]
• Prevention: as many as 80% of tumors that were classified as high-grade serous carcinomas of the ovary or peritoneum may have originated in the fimbrial end of the fallopian tube. The American College of Obstetricians and Gynecologists (ACOG) has recommended that opportunistic (at the time of a clinically indicated hysterectomy) bilateral salpingectomy be considered in women not at genetic risk who wish to retain their ovaries.^[1]