What are the options for a fertility-sparing approach in young women with early-stage ovarian cancer who wish to preserve their fertility?

Fertility-Sparing Approach in Ovarian Cancer

Young women with early-stage ovarian cancer who desire fertility preservation should undergo unilateral salpingo-oophorectomy with comprehensive surgical staging, but only for highly selected cases: stage IA low-grade (serous, endometrioid, or mucinous expansile subtype) and selected IC1 disease. 1

Patient Selection Criteria

Appropriate candidates for fertility-sparing surgery include: 1

• Stage IA low-grade serous, endometrioid, or mucinous (expansile subtype) carcinoma 1
• Selected stage IC1 disease with unilateral ovarian involvement and favorable histology 1
• Borderline ovarian tumors at any stage, even with peritoneal implants 1, 2
• Malignant germ cell tumors at any stage 1
• Unilateral stage I sex cord-stromal tumors 1

Fertility-sparing surgery is NOT appropriate for: 1, 3

• High-grade serous carcinoma (any stage) 1
• Clear cell carcinoma (controversial, see below) 1, 4
• Stage IB, II, III, or IV epithelial ovarian cancer 1
• Mucinous infiltrative subtype 5

Pre-Operative Assessment

All young women desiring fertility preservation must be managed in an oncofertility clinic to coordinate surgical and reproductive planning. 1

Pre-operative imaging and tumor markers: 1

• Expert ultrasound assessment is the first-line imaging modality 1
• If expert ultrasound unavailable, use IOTA ADNEX model combined with CA-125 1
• Measure AFP and beta-hCG in women <35 years to assess for germ cell tumors 1
• For mucinous histology, perform gastrointestinal tract evaluation to exclude metastatic disease from GI primary 1, 5
• Intraoperative frozen section evaluation is mandatory to confirm histology and guide surgical extent 1

Surgical Technique

The standard fertility-sparing procedure consists of: 1

• Unilateral salpingo-oophorectomy (removing only the affected ovary and fallopian tube) 1
• Comprehensive surgical staging including:
  • Peritoneal washings for cytology 1
  • Biopsies from all visible lesions and peritoneal surfaces 1
  • Omentectomy 1
  • Appendectomy (mandatory for mucinous tumors) 1, 5
  • Systematic pelvic and para-aortic lymphadenectomy for high-grade histologies 1

Critical surgical principles: 1

• Minimally invasive surgery (laparoscopy) is acceptable if tumor rupture can be avoided 1
• However, midline laparotomy remains standard due to lower capsule rupture risk 1
• Do NOT biopsy the contralateral normal-appearing ovary unless there is visible suspicion of involvement 1
• Lymphadenectomy can be omitted in low-grade endometrioid or expansile mucinous carcinoma with radiologically negative nodes (lymph node metastasis rate <1%) 1

Fertility Preservation Strategies

Gamete cryopreservation is recommended over ovarian tissue cryopreservation for patients requiring adjuvant chemotherapy. 1

Timing considerations: 3, 2

• Oocyte or embryo cryopreservation should occur before initiating chemotherapy if time permits 3
• GnRH agonists during chemotherapy may reduce gonadotoxicity 3
• Assisted reproductive technology can be initiated after completion of treatment 2

Adjuvant Chemotherapy Decisions

Adjuvant chemotherapy is generally recommended for FIGO stage I-IIB disease, with specific exceptions: 1

Chemotherapy can be OMITTED in: 1

• Stage IA low-grade serous carcinoma 1
• Stage IA grade 1-2 endometrioid carcinoma 1
• Stage IA-IC1 clear cell carcinoma (based on Asian data) 1
• Stage I mucinous expansile subtype or grade 1 infiltrative 1

Chemotherapy IS RECOMMENDED for: 1

• High-grade serous carcinoma (any stage I) 1
• Stage IC-II disease (any histotype) 1
• High-grade endometrioid carcinoma 1

Standard regimen: Six cycles of carboplatin-paclitaxel or carboplatin alone. 1 For high-grade serous or high-grade endometrioid carcinoma, six cycles are preferred; for other histologies, minimum three cycles may suffice. 1

Special Histologic Considerations

Clear Cell Carcinoma

Clear cell carcinoma presents a controversial scenario. 1, 4

• Most guidelines consider clear cell carcinoma high-grade and recommend against fertility-sparing surgery 1
• However, retrospective data suggests stage IA clear cell carcinoma treated with fertility-sparing surgery has comparable survival to radical surgery 4
• Recurrence rates for clear cell carcinoma with fertility-sparing surgery (13.2%) are similar to non-clear cell histologies (10.9%) 4
• If fertility-sparing surgery is pursued for stage IA clear cell carcinoma, comprehensive staging with lymphadenectomy is mandatory 1

Mucinous Carcinoma

Only the expansile subtype of mucinous carcinoma is appropriate for fertility-sparing surgery. 5

• The infiltrative subtype has worse prognosis and should undergo radical surgery 5
• Always perform appendectomy to rule out appendiceal primary 5
• Stage IA low-grade expansile mucinous carcinoma has excellent prognosis with fertility-sparing surgery 5

Germ Cell Tumors

Fertility-sparing surgery should be offered regardless of stage for malignant germ cell tumors. 1

• Excellent prognosis with 5-year survival >85% 1
• Postoperative chemotherapy with BEP (bleomycin, etoposide, cisplatin) for 3-4 cycles is standard for advanced stages 1
• Stage I dysgerminoma and stage I grade 1 immature teratoma can be observed without chemotherapy 1

Oncologic Outcomes

Fertility-sparing surgery in appropriately selected patients demonstrates: 6, 3, 2

• Overall recurrence rate: 10-13% (comparable to radical surgery) 6, 3
• 5-year disease-free survival: >90% 6, 3
• Recurrences after fertility-sparing surgery tend to occur earlier (mean 10 months vs 53 months) but are more likely to be localized with favorable prognosis 6
• No difference in overall survival between fertility-sparing and radical surgery in stage I disease 6, 4

Reproductive Outcomes

Pregnancy success rates after fertility-sparing surgery: 3, 2

• Approximately 72-80% of patients attempting pregnancy will succeed 6, 3
• Pregnancy and miscarriage rates resemble the general population 3
• Regular menstrual cycles typically resume after surgery 6
• Assisted reproductive technology can be utilized if spontaneous pregnancy does not occur 2

Critical Pitfalls to Avoid

Common errors that compromise outcomes: 1, 5

• Performing fertility-sparing surgery without comprehensive surgical staging (incomplete staging leads to understaging and inadequate treatment) 1
• Failing to obtain intraoperative frozen section before deciding on fertility-sparing approach 1
• Biopsy of normal-appearing contralateral ovary (unnecessary and potentially harmful) 1
• Missing occult gastrointestinal primary in mucinous tumors (always evaluate GI tract) 5
• Attempting fertility-sparing surgery in high-grade serous carcinoma (unacceptably high recurrence risk) 1
• Omitting lymphadenectomy in high-grade histologies (understaging risk) 1

Post-Treatment Surveillance

After fertility-sparing surgery, patients require: 1

• Regular ultrasound monitoring of the retained ovary 1
• Tumor marker surveillance (CA-125, AFP, beta-hCG as appropriate for histology) 1
• Completion surgery (bilateral salpingo-oophorectomy with hysterectomy) should be considered after childbearing is complete 1