What is the staging and treatment of ovarian cancer?

Ovarian Cancer Staging

Ovarian cancer is staged surgically using the FIGO (International Federation of Gynecology and Obstetrics) system, which was most recently updated in 2014 to incorporate ovarian, fallopian tube, and primary peritoneal cancers into a unified classification system. 1, 2, 3

FIGO Staging System Overview

The staging system divides ovarian cancer into four main stages based on anatomic extent of disease:

Stage I: Disease Limited to Ovaries

• Stage IA: Tumor limited to one ovary; capsule intact, no tumor on ovarian surface, negative peritoneal washings 1
• Stage IB: Tumor limited to both ovaries; capsules intact, no tumor on ovarian surface, negative peritoneal washings 1
• Stage IC: Tumor limited to one or both ovaries with any of the following subdivisions 2, 3:
  • IC1: Surgical spill (intraoperative capsule rupture) 3, 4
  • IC2: Pre-operative capsule rupture or tumor on ovarian/fallopian tube surface 3, 4
  • IC3: Malignant cells in ascites or peritoneal washings 2, 3, 4

Stage II: Pelvic Extension

• Stage IIA: Extension and/or implants on uterus and/or fallopian tubes, negative peritoneal washings 1
• Stage IIB: Extension to other pelvic tissues (including sigmoid colon due to anatomic position), negative peritoneal washings 1, 3
• Note: Former stage IIC has been eliminated in the 2014 revision 2, 3

Stage III: Peritoneal Implants Outside Pelvis and/or Retroperitoneal Lymph Nodes

• Stage IIIA1(i): Positive retroperitoneal lymph nodes only, metastasis ≤10 mm in greatest dimension 2, 3, 4
• Stage IIIA1(ii): Positive retroperitoneal lymph nodes only, metastasis >10 mm in greatest dimension 2, 3, 4
• Stage IIIA2: Microscopic extrapelvic peritoneal involvement with or without positive retroperitoneal lymph nodes 2, 3, 4
• Stage IIIB: Macroscopic peritoneal metastasis beyond pelvis ≤2 cm in greatest dimension 1
• Stage IIIC: Peritoneal metastasis beyond pelvis >2 cm in greatest dimension and/or regional lymph node metastasis 1

Stage IV: Distant Metastases

• Stage IVA: Malignant pleural effusion with positive cytology 2, 3, 5
• Stage IVB: Parenchymal liver metastases, extra-abdominal metastases (including inguinal lymph nodes, umbilical deposits), and transmural bowel infiltration with mucosal involvement 2, 3, 5

Comprehensive Surgical Staging Requirements

All patients with suspected ovarian cancer must undergo comprehensive surgical staging via midline or para-median laparotomy performed by a trained gynecologic oncologist. 1, 6 This is a category 1 recommendation based on data showing improved survival when surgery is performed by experienced gynecologic oncologists. 1

Mandatory Staging Procedures

The following procedures are required for adequate staging 1, 6, 2:

• Peritoneal washings for cytological analysis (results recorded but no longer affect staging in the 2014 system) 2, 3
• Thorough visual and palpable examination of entire abdominal cavity including diaphragm, liver surface, paracolic gutters, and pelvis 1, 6
• Intact removal of ovarian tumor with frozen section analysis 1
• Bilateral salpingo-oophorectomy (may be unilateral in select fertility-sparing cases) 6, 2
• Total abdominal hysterectomy (except in fertility-sparing surgery) 6, 2
• Infracolic omentectomy 1, 6, 2
• Systematic peritoneal biopsies: diaphragmatic peritoneum, paracolic gutters, pelvic peritoneum, bladder peritoneum, and cul-de-sac 1, 6, 2
• Bilateral pelvic and para-aortic lymph node dissection or sampling 1, 6, 2
• Biopsy of any adhesions or suspicious lesions 1
• Appendectomy for mucinous tumors (8% have appendiceal involvement) 1

Critical Staging Pitfalls

Only 10% of American women with apparent early-stage ovarian cancer receive appropriate surgical staging and recommended postoperative therapy. 1 Common deficiencies include:

• Inadequate surgical incision (only 25% had appropriate incision before referral to specialized centers) 1
• Failure to perform bilateral lymph node dissection (15-19% of patients with disease confined to one ovary have microscopically positive lymph nodes, and 30% of these have contralateral nodal disease) 1
• Laparoscopic management of potentially malignant masses is not recommended 1

Treatment by Stage

Early-Stage Disease (Stage I-IIA)

For Stage IA/IB, well-differentiated (grade 1), non-clear cell histology: surgery alone is adequate. 1, 6

For Stage IA/IB poorly differentiated (grade 2-3), densely adherent, clear cell histology, AND all grades Stage IC and IIA: adjuvant chemotherapy is required after optimal surgical staging. 1, 6

The recommended adjuvant chemotherapy regimen is 6:

• Carboplatin AUC 5-7 mg/mL/min + paclitaxel 175 mg/m² IV every 3 weeks for 3-6 cycles 6, 7, 8

Restaging surgical procedures should be performed in patients with apparent intracystic and grade 1 tumors that were not adequately staged with initial surgery. 1

Advanced-Stage Disease (Stage IIB-IV)

Maximal upfront surgical cytoreduction with the goal of no residual disease (R0 resection) is the standard approach. 1, 6 Surgery should include total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and removal of all visible disease. 1, 6

Standard chemotherapy for advanced disease is carboplatin AUC 5-7.5 mg/mL/min + paclitaxel 175 mg/m² IV over 3 hours every 3 weeks for 6 cycles. 1, 6, 7, 8

Most patients with advanced-stage ovarian cancer receive maintenance therapy with bevacizumab (anti-angiogenesis monoclonal antibody) and/or PARP inhibitors after completing primary chemotherapy. 9

Fertility-Sparing Surgery

In younger patients with localized, unilateral tumors (stage I) and favorable histology (well-differentiated, non-clear cell), unilateral salpingo-oophorectomy with preservation of the contralateral ovary and uterus is acceptable. 1

Wedge biopsy of the contralateral ovary should be performed only if the contralateral ovary is not normal on inspection. 1 Systematic ovarian biopsy is not necessary when the contralateral ovary is macroscopically normal. 1

Prognostic Factors

Beyond surgical stage, established prognostic factors include 1:

• Small tumor volume (before and after surgery) 1
• Younger age 1
• Good performance status 1
• Histologic subtype: Non-mucinous and non-clear cell types have better prognosis 1
• Well-differentiated tumor (grade 1) 1
• Absence of ascites 1
• Complete surgical resection (no residual disease) 1, 6

Histologic grade is an important predictor of occult metastasis: 16% of grade 1 lesions, 34% of grade 2, and 46% of grade 3 tumors are upstaged after comprehensive surgical staging. 1

Survival Outcomes

• Early-stage ovarian cancer (Stage I-II): 5-year overall survival of 70-95% with appropriate treatment 9
• Advanced-stage ovarian cancer (Stage III-IV): 5-year overall survival of 10-40% with standard treatment 9
• BRCA-related ovarian cancer: 5-year overall survival of approximately 70% with PARP inhibitor maintenance therapy 9
• Recurrence: Despite 80% initial remission rate, approximately 75% of patients with advanced-stage disease experience relapse within 2 years 9

Preoperative Assessment

Before surgery and/or chemotherapy, patients should have 1:

• Abdominal/pelvic CT or MRI scan (CT preferred for metastases assessment, ultrasound for initial evaluation) 1, 2
• Chest imaging (chest X-ray or CT) 1
• Serum CA-125 (elevated in 85% of advanced disease, but not specific) 1
• Complete blood count and differential 1
• Renal and hepatic function tests 1
• Consider CEA and CA 19-9 if mucinous tumor or gastrointestinal origin suspected (CA-125/CEA ratio ≤25 suggests GI origin) 1