In cervical cancer, when is surgery indicated versus chemotherapy (with or without radiation) based on FIGO stage and high‑risk pathological features?

Surgery and Chemotherapy in Cervical Cancer: Treatment Selection by FIGO Stage

Surgery is the primary treatment for early-stage cervical cancer (FIGO IA-IIA1 without high-risk features), while concurrent chemoradiotherapy is the standard for locally advanced disease (FIGO IB2-IVA), with the critical principle being to avoid combined modality therapy (surgery followed by adjuvant chemoradiation) whenever possible, as this increases toxicity without improving survival. 1

Early-Stage Disease: Surgery as Primary Treatment

FIGO Stage IA1 (Microinvasive)

• Without lymphovascular space invasion (LVSI): Conization or simple trachelectomy for fertility preservation, or simple hysterectomy if fertility is not desired 1
• With LVSI: Add pelvic lymph node assessment including sentinel lymph node (SLN) mapping, as the risk of nodal metastasis increases 1

FIGO Stage IA2, IB1, and IIA1

• Radical hysterectomy with bilateral pelvic lymph node dissection is the standard surgical approach, achieving 5-year disease-free survival exceeding 85% in IB1 disease 2
• Surgery should only be performed in patients without risk factors that would necessitate adjuvant therapy, as combined surgery plus radiation increases toxicity without survival benefit 1
• Fertility-sparing radical trachelectomy with pelvic lymphadenectomy is an option for tumors ≤2 cm with negative lymph nodes 2, 3
• SLN mapping achieves 89-92% detection rates and 89-90% sensitivity, offering a potential alternative to complete lymphadenectomy 2, 3

Critical Surgical Decision Point

If positive lymph nodes are discovered intraoperatively, do not proceed with radical hysterectomy—these patients should receive primary chemoradiation instead to avoid the compounded morbidity of combined modality therapy. 2, 3

Locally Advanced Disease: Chemoradiotherapy as Primary Treatment

FIGO Stage IB2, IIA2, and IIB-IVA

• Concurrent chemoradiotherapy is the standard of care, demonstrating 30-50% reduction in risk of death compared to radiotherapy alone 3
• The regimen consists of weekly cisplatin 40 mg/m² during external beam radiotherapy (45-50 Gy) plus intracavitary brachytherapy, achieving total doses of 80-90 Gy delivered within 50-55 days 1, 3
• This approach provides an absolute 5-year survival benefit of 8% for overall survival and 9% for locoregional disease-free survival 1, 3
• Cisplatin is administered during external beam radiation but NOT during brachytherapy 3

Alternative Regimens

• For patients intolerant to cisplatin, carboplatin or non-platinum chemoradiation regimens are acceptable alternatives 1, 3
• The meta-analysis confirmed significant benefits even with non-platinum agents 1

Adjuvant Treatment After Surgery: Risk-Stratified Approach

Intermediate-Risk Features (Sedlis Criteria)

• Adjuvant pelvic radiotherapy alone (without chemotherapy) is recommended for patients with ≥2 of the following: deep stromal invasion (>1/3 depth), LVSI, or large tumor size (>4 cm) 1, 2
• This reduces disease progression (RR ≈ 0.6) but does not demonstrate clear overall survival benefit 3
• Patients with intermediate-risk disease do not need concurrent chemotherapy with radiation 1

High-Risk Features (Peters Criteria)

• Adjuvant concurrent chemoradiotherapy is mandatory for any of the following: positive pelvic lymph nodes, positive surgical margins, or parametrial involvement 1, 2
• The standard regimen is weekly cisplatin 40 mg/m² during external beam radiotherapy 2, 3
• This approach improves 4-year overall survival from 71% to 81% and progression-free survival from 63% to 80% 1

Neoadjuvant Chemotherapy: Investigational Role

NACT Followed by Surgery

• Meta-analysis shows NACT followed by radical surgery reduces risk of death by 35% (HR = 0.65) compared to radiotherapy alone, improving 5-year survival from ~50% to ~64% 3
• Major limitation: Control arms used radiotherapy without concurrent chemotherapy, which does not reflect current standard practice 3
• NACT may reduce the need for adjuvant radiotherapy in cervical cancer patients 1
• Two Phase III trials (EORTC 55994 and NCT00193739) comparing NACT + surgery versus definitive chemoradiation have completed enrollment; results are pending 3

NACT in Locally Advanced Disease

• The role of NACT in the era of concurrent chemoradiotherapy remains unclear and should be considered investigational 4, 5

Advanced/Metastatic Disease: Palliative Chemotherapy

First-Line Systemic Therapy

• Paclitaxel and cisplatin combined with bevacizumab is the preferred first-line regimen, based on superior efficacy and acceptable toxicity profile 1
• Cisplatin-based doublets with topotecan or paclitaxel demonstrate superiority to cisplatin monotherapy for response rate and progression-free survival 1
• Paclitaxel and carboplatin is an alternative for patients not candidates for cisplatin 1

Consolidation Chemotherapy After Chemoradiation

• Additional systemic chemotherapy after concurrent chemoradiation is NOT recommended outside clinical trials, as current evidence does not demonstrate survival benefit 3
• One study showed benefit for cisplatin-gemcitabine consolidation, but this approach should only be used within prospective trials 1

Common Pitfalls and Critical Caveats

1. Avoid multimodality therapy trap: Surgery followed by adjuvant chemoradiation results in increased toxicity without survival improvement compared to primary chemoradiation 1, 3

2. Complete treatment within timeframe: Radiation therapy must be completed within 50-55 days, as prolonged treatment duration significantly impacts outcomes 1, 3

3. Minimize invasive surgery concerns: Recent data challenge the oncologic equivalence of minimally invasive versus open radical hysterectomy, prompting re-evaluation of practice standards 3

4. Stage-appropriate treatment selection: Do not use concurrent chemoradiation as primary treatment for stage IB1 disease unless the patient is not a surgical candidate 2

5. Lymph node status is paramount: Lymph node status and number of involved nodes are the most important prognostic factors in cervical cancer 1