What is the recommended management for a patient with T1B1 cervical cancer (ca Cervix) post-operatively, with high-grade squamous cell carcinoma and multifocal lymphovascular invasion?

Management of T1B1 Cervical Cancer with High-Grade Squamous Cell Carcinoma and Multifocal Lymphovascular Invasion Post-Operatively

This patient requires adjuvant pelvic external beam radiotherapy (EBRT) with concurrent cisplatin-based chemotherapy, as multifocal lymphovascular space invasion (LVSI) represents an intermediate-risk factor that significantly increases recurrence risk and warrants combined modality treatment. 1

Risk Stratification

This patient falls into the intermediate-risk category based on the presence of multifocal LVSI, which is an independent predictor of recurrence in node-negative early-stage cervical cancer. 1 The Sedlis criteria from GOG-92 established that LVSI, along with deep stromal invasion and large tumor size, defines intermediate-risk disease requiring adjuvant therapy. 2

Recommended Treatment Algorithm

Primary Recommendation: Adjuvant Chemoradiation

Administer pelvic EBRT with concurrent cisplatin-based chemotherapy (Category 1 for radiation, Category 2B for adding chemotherapy). 2, 1

The treatment regimen should consist of:

• Pelvic external beam radiotherapy (not extended-field unless para-aortic nodes are involved) 1
• Concurrent weekly cisplatin 40 mg/m² intravenously administered during external beam radiation only 1
• Vaginal brachytherapy may be considered as a boost if surgical margins were close 1

Evidence Supporting This Approach

The GOG-92 trial demonstrated that adjuvant pelvic RT reduced recurrence risk by 47% in intermediate-risk patients, with recurrence-free rates of 88% versus 79% with observation at 2 years. 2, 1 Long-term follow-up at 12 years confirmed improved progression-free survival with a clear trend toward improved overall survival (P=0.07). 2

The addition of concurrent chemotherapy to radiation is recommended based on the Intergroup trial 0107, which showed significantly better 4-year overall survival (81% versus 71%) and progression-free survival (80% versus 63%) when cisplatin-based chemotherapy was added to radiation in high-risk patients. 2 While this trial focused on high-risk factors, the presence of multifocal LVSI strengthens the indication for adding chemotherapy to radiation. 1

Treatment Delivery Specifications

• Radiation field: Pelvic EBRT only (unless para-aortic nodes are involved) 1
• Chemotherapy timing: Concurrent with external beam radiation only, NOT during brachytherapy 1
• Cisplatin dosing: 40 mg/m² weekly during external beam radiation 1
• Alternative regimens: Carboplatin may be substituted if cisplatin is not tolerated 2

Important Clinical Considerations and Pitfalls

What NOT to Do

• Do not use observation alone - The GOG-92 trial clearly demonstrated inferior outcomes with observation in intermediate-risk patients 2, 1
• Do not use chemotherapy alone without radiation - While some retrospective studies suggest chemotherapy alone may have a role 3, the standard of care based on prospective randomized trials is radiation-based therapy 2
• Do not administer systemic consolidation chemotherapy after chemoradiation - This approach should only be used in clinical trials 2
• Do not give chemotherapy during brachytherapy - Concurrent chemotherapy is administered only during external beam radiation 1

Monitoring and Toxicity Management

• Acute toxicity: Expect increased hematological and gastrointestinal toxicity with chemoradiation compared to radiation alone 2
• Vaginal stenosis prevention: Strongly recommend vaginal dilators after pelvic radiation to preserve sexual function 4
• Follow-up schedule: Interval history and physical examination with cervical/vaginal cytology every 3-6 months for 2 years, then every 6 months for years 3-5, then annually 2

Nuances and Controversies

There is ongoing debate regarding whether all intermediate-risk patients require adjuvant therapy, with some recent retrospective data challenging the prospective GOG-92 findings. 1 However, the presence of multifocal LVSI (rather than focal LVSI) strengthens the indication for treatment in this case. 1

A recent 2025 retrospective study 5 suggested that adding chemotherapy to radiotherapy may not improve survival in patients with a single high-risk factor, but this study has limitations and contradicts the prospective randomized Intergroup 0107 trial. 2 Given the Level I evidence from prospective trials showing survival benefit with chemoradiation in high-risk patients, and the intermediate-risk status with multifocal LVSI, the addition of concurrent chemotherapy to radiation is justified. 2, 1

Evidence Quality Assessment

• Radiation for intermediate-risk disease: Level II evidence, Grade B recommendation (GOG-92 randomized trial) 2, 1
• Chemoradiation for high-risk disease: Level I evidence, Grade A recommendation (Intergroup 0107 trial) 2
• Multifocal LVSI as intermediate-risk factor: Established by GOG-92 criteria 1