12Ovarian
Snapshot. "Ovarian cancer" is really three families: (1) EPITHELIAL (~90%, older women) — high-grade serous (HGSC) dominates (p53/BRCA/HRD [homologous-recombination deficiency]-driven); also low-grade serous (indolent but chemo-RESISTANT, MAPK-driven → MEK inhibitor), endometrioid (Lynch-associated), clear cell (chemo-resistant, ↑VTE [venous thromboembolism]), and mucinous (exclude a GI primary — Krukenberg). (2) GERM-CELL (teens/20s, marker-driven — dysgerminoma↑LDH, yolk sac↑AFP, choriocarcinoma↑β-hCG — usually curable with BEP). (3) SEX-CORD STROMAL (granulosa↑inhibin/estrogen with LATE relapse; Sertoli-Leydig↑androgen) — indolent. ⚠ "Ovarian cancer" in a teenager is usually NOT epithelial — think germ-cell, or the rare aggressive SMARCA4-mutated SCCOHT (small-cell carcinoma of the ovary, hypercalcaemic type). BRCA/HRD is central in epithelial (opens PARP maintenance); CA125 tracks epithelial response.
Workup
CT chest/abdomen/pelvis · tissue (upfront surgery, or biopsy if neoadjuvant) · marker by suspected type — CA125 (epithelial) · AFP/β-hCG/LDH (germ-cell) · inhibin (granulosa) · calcium + SMARCA4 (SCCOHT) · germline + tumour BRCA + HRD testing for epithelial · surgically staged (FIGO — International Federation of Gynecology and Obstetrics).
Treatment by setting
| Setting | Treatment |
|---|
Epithelial
newly diagnosed | Cytoreductive surgery + chemo ± bevacizumab (GOG-0218) (ICON7)
primary, or interval after neoadjuvant carboplatin + paclitaxel ⚠ Low-grade serous is chemo-RESISTANT
a MEK inhibitor (trametinib) + hormonal therapy is preferred over chemo |
Epithelial
maintenance, after response | BRCA-mutated → PARP inhibitor monotherapy (olaparib) (SOLO-1)
or PARP + bevacizumab if bevacizumab was given with chemo (PAOLA-1) HRD-positive, BRCA wild-type → PARP + bevacizumab (PAOLA-1)
or niraparib monotherapy (PRIMA) HRD-negative / unknown → bevacizumab alone preferred
PARP benefit is minimal here ⚠ Niraparib's RECURRENT-setting label is BRCA-only
FDA restricted 2023 — the PRIMA all-comer label applies to FRONTLINE maintenance only |
Epithelial
recurrence | Platinum-SENSITIVE (relapse >6 months after last platinum) → re-challenge a platinum doublet ± bevacizumab Platinum-RESISTANT (<6 months) → sequential single-agent chemo FRα-positive → mirvetuximab soravtansine (MIRASOL)
folate-receptor-α-directed antibody-drug conjugate |
Germ-cell
any stage | Fertility-sparing surgery (unilateral salpingo-oophorectomy) + BEP
bleomycin / etoposide / cisplatin — highly curable even when advanced Surveillance alone for stage I dysgerminoma / grade-1 immature teratoma |
Sex-cord
granulosa / Sertoli-Leydig | Surgery Advanced / recurrent → platinum-based chemo ± hormonal therapy
carbo-taxane or BEP ⚠ Long follow-up mandatory — granulosa relapses LATE
years to decades out |
SCCOHT
young women, SMARCA4-mutated | Aggressive multimodal — surgery + platinum chemo + RT
± high-dose chemo / stem-cell rescue · consider immunotherapy or EZH2-inhibitor trials Poor prognosis despite intensive treatment |
Watch
Carboplatin (myelosuppression) + paclitaxel (neuropathy, hypersensitivity); bevacizumab → bowel perforation, hypertension, proteinuria; PARP inhibitors → cytopenias, rare secondary MDS/AML (myelodysplastic syndrome/acute myeloid leukaemia); BEP → bleomycin lung toxicity (germ-cell — baseline + serial pulmonary function). Track the right marker per type (CA125 / AFP-β-hCG-LDH / inhibin / calcium). Mucinous ovarian → always exclude a GI primary (Krukenberg).