What is the initial treatment approach for a young to middle-aged woman with a low-grade serous tumor, likely in the ovaries?

Low-Grade Serous Ovarian Tumor: Initial Treatment Approach

Primary Treatment Strategy

The initial treatment for a young to middle-aged woman with low-grade serous ovarian tumor is comprehensive surgical staging with maximal cytoreductive surgery performed by a gynecologic oncologist, followed by stage-specific postoperative management that differs fundamentally from high-grade disease due to relative chemotherapy resistance. 1

Critical Distinction from High-Grade Disease

Low-grade serous carcinoma represents a biologically distinct disease entity from high-grade serous carcinoma, presenting at younger ages with more indolent behavior but often more advanced stage at diagnosis. 1, 2 Neoadjuvant chemotherapy should NOT be recommended for low-grade serous carcinomas because these tumors respond poorly to standard chemotherapy regimens. 1

Surgical Management

Standard Surgical Approach

• Complete cytoreductive surgery with comprehensive staging is the cornerstone of treatment, as achieving no macroscopic residual disease is of pivotal importance given the low chemosensitivity of these tumors. 1, 2

• Comprehensive staging includes: peritoneal washings, peritoneal biopsies, omentectomy, bilateral salpingo-oophorectomy, hysterectomy, and lymph node evaluation. 1

• All patients must be evaluated by a gynecologic oncologist before treatment initiation to determine optimal surgical approach. 2, 3

Fertility-Sparing Options

• Fertility-sparing surgery (unilateral salpingo-oophorectomy with comprehensive staging) is appropriate for select patients with low-grade serous carcinoma who desire fertility preservation, specifically those with stage IA disease and unilateral involvement. 1, 4

• Fertility-sparing surgery is also an option for serous borderline tumors at any stage. 1, 4

• After childbearing completion, completion surgery (removal of remaining ovary, fallopian tube, and uterus) should be considered. 1, 4

Stage-Specific Postoperative Management

Stage IA or IB Disease

• Postoperative observation and monitoring are recommended, as these early-stage tumors have excellent prognosis without additional treatment. 1

Stage IC to II Disease

Postoperative options include (in order of preference): 1

1. Intravenous carboplatin with either paclitaxel or docetaxel (standard chemotherapy)
2. Observation (category 2B recommendation)
3. Hormone therapy including anastrozole, letrozole, leuprolide, or tamoxifen (category 2B for all hormone therapy options)

Stage III to IV Disease

Postoperative options include: 1

1. First-line chemotherapy regimens used for epithelial ovarian cancer (carboplatin plus paclitaxel for 6 cycles)
2. Hormone therapy (category 2B) as maintenance or alternative to chemotherapy given poor chemosensitivity

Chemotherapy Considerations

• Standard platinum-based chemotherapy (carboplatin plus paclitaxel) remains the adjuvant treatment when chemotherapy is indicated, despite lower response rates compared to high-grade disease. 1, 2

• Low-grade serous carcinomas have high rates of persistent disease at completion of primary treatment (approximately 67%), yet maintain prolonged overall survival with 5-year survival of 69%. 5

• The relatively chemotherapy-resistant nature of these tumors makes hormonal therapy an increasingly important consideration for maintenance treatment. 1, 2

Critical Pitfalls to Avoid

• Do not confuse low-grade serous with high-grade serous carcinoma—they are molecularly distinct diseases requiring different treatment approaches. 1, 2, 3

• Do not proceed with neoadjuvant chemotherapy without gynecologic oncologist evaluation, as primary surgery is superior for low-grade disease. 1, 2

• Do not perform incomplete surgical staging—approximately 30% of patients are upstaged with complete staging, significantly impacting treatment decisions. 2

• Do not assume chemotherapy will be highly effective—these tumors are relatively resistant to standard platinum-based regimens, making complete surgical cytoreduction even more critical. 1, 5

Molecular and Prognostic Features

• Low-grade serous carcinomas typically harbor mutations in the MAPK pathway (KRAS, BRAF, NRAS) and express strong hormone receptors, distinguishing them from high-grade disease. 6, 7

• These tumors present at younger ages (median age 51.7 years) with more indolent behavior but longer overall survival compared to high-grade serous carcinoma. 1, 5, 7

• Stage I low-grade serous tumors rarely recur after appropriate surgical management. 8