Ovarian Cancer: Investigation, Staging Laparotomy, and Opportunistic Salpingectomy

Clinical Context

PART 1: Investigation

A. History and Physical Examination

• Detailed menstrual/postmenopausal history
• Family history of ovarian, breast, or colorectal cancer (BRCA1/2, Lynch syndrome)
• Abdominal and bimanual pelvic examination: assess mass characteristics (solid, irregular, bilateral, fixed)

B. Tumour Markers

Note: AFP, LDH, inhibin, and β-hCG are especially recommended in women <40 years with a suspected complex ovarian mass to exclude germ cell tumours.

• RMI = U × M × CA-125
  • U = ultrasound score (1 point each for: multilocular cyst, solid components, metastases, ascites, bilateral lesions); score = 0 if no features, 1 if 1 feature, 3 if 2-5 features
  • M = menopausal status: 1 (premenopausal), 3 (postmenopausal)
  • CA-125 in U/mL
• RMI >250 indicates high risk; refer to gynaecological oncologist

C. Imaging

• Combined transabdominal + transvaginal ultrasound (TVUS)
• Features suspicious for malignancy (IOTA criteria "M features"):
  • Irregular solid tumour
  • Ascites
  • ≥4 papillary structures
  • Irregular multilocular-solid tumour ≥100 mm
  • Strong blood flow on Doppler
• Thick septations (>3 mm), papillary projections, solid components, size >9 cm all raise suspicion

• Modality of choice for surgical planning and assessing resectability
• Evaluates: peritoneal deposits, omental cake, liver/splenic metastases, retroperitoneal lymphadenopathy, pleural effusion
• Identifies "difficult to resect" disease:
  • Pelvic side wall invasion, bladder involvement, ureteric obstruction
  • Upper abdominal deposits >1 cm in gastrosplenic ligament, porta hepatis, subphrenic space, small bowel mesentery
  • Retroperitoneal nodes above renal hila
• Stage IV disease: inguinal nodes, liver parenchymal metastases (not subcapsular implants), disease above diaphragm

• Better soft tissue characterisation when CT is equivocal
• Useful for local pelvic extent assessment

• Rule out pleural effusion (stage IVA) or pulmonary metastases (stage IVB)

• Recurrence assessment; occasionally for primary staging when CT is inconclusive

D. Other Investigations

• Full blood count, renal/liver function tests, coagulation profile - preoperative workup
• Ascitic fluid cytology - if peritoneal tap done (can confirm malignant cells, but surgery is still required for definitive staging)
• Tumour biopsy/omental biopsy - needed before neoadjuvant chemotherapy if primary surgery is not feasible (image-guided)
• Genetic testing - BRCA1/2, mismatch repair genes for all newly diagnosed epithelial OC patients (prognostic and therapeutic implications, especially for PARP inhibitor eligibility)
• Colonoscopy / upper GI endoscopy - if Krukenberg tumour (metastatic GI primary) is suspected based on CEA elevation or imaging

PART 2: Steps of Staging Laparotomy for Early Ovarian Cancer

Pre-operative

• Informed consent including potential bowel surgery
• Bowel preparation if bowel resection anticipated
• DVT prophylaxis, antibiotic prophylaxis
• Gynaecological oncologist involvement (studies show inferior outcomes when surgery is done by non-oncologists)

Steps of Staging Laparotomy

• Vertical midline incision from pubis, extended as needed to xiphisternum - allows complete peritoneal survey

• On entering the peritoneum, note any free fluid (ascites)
• If ascites is present: collect sample immediately for cytology
• If no free fluid: perform peritoneal washings with 50-100 mL saline

• Washings from four sites: right and left paracolic gutters, pelvis, and subdiaphragmatic space (right)
• Send for cytology - positive washings upgrade to Stage IC3

• Systematic exploration: pelvis, paracolic gutters, bowel mesentery, liver surface, diaphragm, omentum
• Document all suspicious lesions

• Remove omentum below the transverse colon
• Common site of occult metastasis (8.6% in apparent Stage I disease)

• Primary tumour removal
• For young women with Stage I disease wanting fertility preservation: unilateral salpingo-oophorectomy may be acceptable (borderline or Stage IA)
• Contralateral ovary carefully examined; peritoneal washings mandatory

• Pelvic lymph nodes (external iliac, internal iliac, obturator nodes)
• Para-aortic lymph nodes (up to renal vessels)
• Occult nodal metastases in apparent Stage I-II: pelvic nodes 5.9%, aortic nodes 18.1%
• Lymph node sampling upstages ~31% of patients thought to have early disease

• From normal-appearing peritoneal surfaces:
  • Undersurface of right hemidiaphragm
  • Bladder peritoneal reflection
  • Pouch of Douglas (cul-de-sac)
  • Right and left paracolic recesses
  • Both pelvic sidewalls

• Any suspicious nodules, masses, adhesions

• Performed for mucinous tumours (mucinous ovarian tumours may be metastatic from appendix)
• If intraoperative suspicion of mucinous tumour: take washings and biopsy from suspicious areas

• Intraoperative histology of tumour specimen guides extent of surgery
• If frozen section confirms malignancy: proceed with full staging
• If borderline tumour in a young woman: may limit to unilateral oophorectomy

Post-operative

• Results reviewed by multidisciplinary team
• Up to 31% of patients are upstaged after comprehensive staging
• 77% of upstaged patients reclassified as Stage III disease
• Adjuvant chemotherapy: indicated for Stage IC and above, and all Grade 3 / clear cell histology (carboplatin + paclitaxel, 3-6 cycles)
• Stage IA/IB Grade 1-2: surgery alone may be sufficient

PART 3: Opportunistic Salpingectomy

Definition

Rationale - The Fallopian Tube Origin Theory

• Careful microscopic examination using the "Sectioning and Extensively Examining the Fimbriated End" (SEE-FIM) protocol revealed occult tubal cancers and precancerous lesions in BRCA1/2 mutation carriers
• These lesions - designated Serous Tubal Intraepithelial Carcinoma (STIC) - are now recognised as the precursor to high-grade serous ovarian cancer (the most common and lethal subtype)
• STIC lesions are typically located at the fimbriated end of the fallopian tube, harbour TP53 mutations, and are histologically identical to the "ovarian" cancers they precede
• High-grade serous cancers of the ovary, fallopian tube, and peritoneum are now understood to share a common fallopian tubal precursor
• Scandinavian population-based cohort studies demonstrated a significant decrease in epithelial ovarian cancer following salpingectomy

Indications / When to Perform It

• At the time of hysterectomy for benign indications - now routinely recommended
• As a method of permanent sterilisation (in place of tubal ligation)
• Any other pelvic surgery where the fallopian tubes can be safely removed

Who Benefits?

• Average-risk women - preserves ovarian hormonal function while potentially reducing OC risk
• For high-risk women (BRCA1/2 mutations): risk-reducing bilateral salpingo-oophorectomy (BSO) is still the recommended strategy (reduces lifetime HGSOC risk to <3%)

Benefits

• Potential reduction in epithelial ovarian cancer incidence (particularly high-grade serous carcinoma)
• Preserves ovarian function (avoids complications of surgical menopause: cardiovascular, neurologic morbidity, bone density loss)
• No significant increase in operative morbidity when added to hysterectomy

Precautions

• Elective salpingo-oophorectomy (removing ovaries too) in women <50 years carries long-term cardiovascular and neurological morbidity - therefore routine oophorectomy at hysterectomy is not recommended unless there are specific indications
• Salpingectomy alone avoids these risks while potentially conferring cancer protection

Current Recommendations

• Sabiston, Schwartz's, Berek & Novak, and Goldman-Cecil all endorse routine opportunistic full salpingectomy at the time of hysterectomy
• A 2023 systematic review in JAMA Surgery (Kahn RM et al., PMID 37672283) evaluated salpingectomy for primary prevention of ovarian cancer, supporting this practice

Summary Table: Key Points