Reproductive · PANCE / PANRE

Ovarian Cancer

'Silent' epithelial malignancy of the ovary/fallopian tube — vague abdominal symptoms; late diagnosis is the rule.

Also known as: ovarian cancer, epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, BRCA

Overview

Heterogeneous malignancy of the ovary, fallopian tube, or peritoneum. Epithelial subtypes (~90%) include high-grade serous (most common and aggressive), endometrioid, clear cell, mucinous, and low-grade serous. Non-epithelial tumors include germ cell (younger patients) and sex cord-stromal tumors. Most 'ovarian cancers' actually originate from the distal fallopian tube fimbriae.

Epidemiology

Fifth leading cause of cancer death in US women; ~20,000 new cases/year, ~13,000 deaths. Lifetime risk ~1.3% in general population; ~40% with BRCA1, ~15-25% with BRCA2. Median age at diagnosis ~63.

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Risk factors

  • Family history; BRCA1/BRCA2 mutations
  • Lynch syndrome (HNPCC)
  • Increased lifetime ovulations: nulliparity, early menarche, late menopause, infertility
  • Endometriosis (clear cell, endometrioid types)
  • Hormone therapy (modest)
  • Older age
  • Protective: multiparity, breastfeeding, combined OCP use (~50% reduction), tubal ligation, salpingectomy

Pathophysiology

High-grade serous carcinomas arise from serous tubal intraepithelial carcinoma (STIC) in fallopian tube fimbriae, with early peritoneal dissemination explaining late stage at diagnosis. TP53 mutations are nearly universal in HGSC. BRCA1/2 mutations impair homologous recombination DNA repair — confer hereditary risk and PARP inhibitor sensitivity.

Clinical presentation

Symptoms

  • Vague abdominal/pelvic discomfort, bloating
  • Early satiety, decreased appetite
  • Urinary urgency or frequency
  • Constipation or change in bowel habits
  • Symptoms persistent (>2 weeks) and new (within 12 months) — should prompt evaluation
  • Late: ascites, abdominal distension, weight loss, dyspnea (pleural effusion)

Signs / physical exam

  • Adnexal mass on bimanual or rectovaginal exam
  • Ascites, fluid wave
  • Sister Mary Joseph nodule (periumbilical lymph node metastasis)
  • Pleural effusion
  • Lymphadenopathy

Differential diagnosis

  • Benign ovarian cyst (functional, dermoid, endometrioma) — Simple cyst on ultrasound, normal CA-125; younger patients
  • Endometriosis / endometrioma — Cyclic pain, dysmenorrhea, dyspareunia; 'chocolate cyst'
  • Tubo-ovarian abscess — Fever, leukocytosis, sexually active; PID context
  • Diverticular abscess — LLQ pain, fever; CT diagnostic
  • GI malignancy with ovarian metastasis (Krukenberg) — Bilateral ovarian masses with signet-ring cells from gastric primary; EGD/colonoscopy
  • Primary peritoneal carcinomatosis — Diffuse peritoneal disease without primary ovarian mass
  • Ascites from cirrhosis or heart failure — Hepatic stigmata, cardiac history; SAAG calculation

Diagnostic workup

Diagnostic criteria

USPSTF 2018: Screening for ovarian cancer in asymptomatic average-risk women NOT recommended (Grade D). Genetic counseling/testing for women with personal or family history suggestive of BRCA/Lynch. FIGO 2014 staging: I (confined to ovaries/tubes), II (pelvic extension), III (peritoneal beyond pelvis ± nodes), IV (distant).

Labs

  • CA-125 — useful for postmenopausal women (better specificity); less reliable premenopausal due to other causes of elevation
  • HE4 (with CA-125 in ROMA algorithm)
  • Premenopausal mass: AFP, β-hCG, LDH (germ cell markers), inhibin (granulosa cell)
  • CEA, CA 19-9 if mucinous tumor suspected or to evaluate GI primary
  • CBC, BMP, LFTs
  • Genetic testing — BRCA1/BRCA2 and broader hereditary cancer panel recommended for ALL women with epithelial ovarian, fallopian tube, or primary peritoneal cancer

Imaging

  • Transvaginal ultrasound — characterizes adnexal mass (size, septations, solid components, vascularity, bilaterality, ascites)
  • CT abdomen/pelvis or MRI — staging, peritoneal disease
  • CT chest if suspicious findings
  • Surgical staging is required — laparotomy with comprehensive staging (peritoneal washings, omentectomy, lymphadenectomy)

Diagnostic algorithm

FeatureConcerning for MalignancyReassuring
Patient agePostmenopausalPremenopausal
Size>10 cm<5 cm
CompositionSolid or mixed; thick septationsSimple cystic
VascularityInternal flow on DopplerNo internal flow
BilateralityBilateral massesUnilateral
AscitesPresentAbsent
CA-125Elevated, especially postmenopausalNormal
Family historyBRCA, Lynch, ovarian/breastNone
ActionGyn-onc referral, surgical stagingSurveillance or simple cystectomy
Risk stratification of an adnexal mass — features pointing toward malignancy.

Treatment

First-line

  • Primary cytoreductive (debulking) surgery — TH/BSO, omentectomy, peritoneal biopsies, lymphadenectomy; goal complete or optimal (<1 cm residual) cytoreduction
  • Adjuvant chemotherapy — carboplatin + paclitaxel × 6 cycles
  • Stage IA grade 1 may not require chemotherapy
  • Neoadjuvant chemotherapy followed by interval debulking — for poor surgical candidates or unresectable disease

Maintenance therapy

  • PARP inhibitors — olaparib, niraparib, rucaparib — after response to platinum chemotherapy
  • Particularly effective in BRCA-mutated or HRD-positive tumors
  • Bevacizumab — angiogenesis inhibitor, used during and after chemo in advanced disease

Recurrent disease

  • Platinum-sensitive (>6 months since last platinum): retreat with platinum doublet
  • Platinum-resistant: single-agent chemotherapy (liposomal doxorubicin, topotecan, gemcitabine, weekly paclitaxel) ± bevacizumab
  • Targeted therapy based on molecular profile

Risk-reducing surgery

  • BRCA1: risk-reducing salpingo-oophorectomy by age 35-40 after childbearing
  • BRCA2: by age 40-45
  • Lynch syndrome: discuss after childbearing complete
  • Opportunistic salpingectomy at time of benign gyn surgery for average-risk women (ACOG recommends)

Germ cell tumors

  • Fertility-sparing unilateral salpingo-oophorectomy + staging often appropriate
  • BEP chemotherapy (bleomycin, etoposide, cisplatin) for most
  • Excellent cure rates

Complications

  • Bowel obstruction (peritoneal spread) — common in advanced disease
  • Malignant ascites, pleural effusion
  • Chemo toxicity (neuropathy, alopecia, cytopenias)
  • VTE — increased risk
  • Recurrence (~70% of advanced-stage cases)
  • Premature menopause from BSO

PANCE pearls

  • Screening with CA-125 and TVUS does NOT reduce mortality in average-risk women — not recommended (UKCTOCS and PLCO trials).
  • All women with epithelial ovarian, fallopian tube, or peritoneal cancer should be referred for genetic counseling and BRCA/HRD testing — affects family screening and PARP inhibitor eligibility.
  • The 'ovarian cancer triad' of bloating, early satiety, and urinary symptoms persisting >2 weeks warrants pelvic exam, TVUS, and CA-125.
  • Most ovarian cancers (~70%) present at advanced stage (III-IV) because of vague early symptoms — 5-year survival ~30%.
  • Krukenberg tumor: bilateral ovarian metastases with signet-ring cells from a GI primary (usually gastric) — always evaluate GI tract if histology suspicious.
  • Opportunistic salpingectomy during benign gyn surgery reduces future ovarian cancer risk and is now recommended by ACOG.

References

  • USPSTF 2018 — Screening for Ovarian Cancer: USPSTF Recommendation Statement (JAMA 2018)
  • NCCN Ovarian 2024 — NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer
  • ACOG PB 174 — ACOG Practice Bulletin No. 174: Evaluation and Management of Adnexal Masses
  • SGO 2019 — Genetic Testing for Ovarian Cancer: SGO Clinical Practice Statement

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