What is the recommended treatment approach for a patient diagnosed with cervical cancer?

Treatment of Cervical Cancer

The recommended treatment for cervical cancer depends entirely on FIGO stage: early-stage disease (IA1-IB1) is treated with surgery or radiation, locally advanced disease (IB2-IVA) requires concurrent chemoradiation with weekly cisplatin, and metastatic disease (IVB) is managed with platinum-based chemotherapy plus bevacizumab. 1

Initial Staging and Diagnostic Workup

Before determining treatment, accurate staging is essential:

• MRI is superior to CT for tumor extension assessment and should be the preferred imaging modality for pelvic and abdominal evaluation 2, 1, 3
• Thoracic CT scan is recommended for metastasis assessment 1, 3
• PET imaging is useful for nodal assessment, particularly in advanced disease 1, 3
• Clinical gynecological examination remains fundamental for FIGO staging 1, 3
• Laboratory evaluation should include blood counts, renal and liver function tests 2, 3

Treatment Algorithm by FIGO Stage

Stage IA1 (Microinvasive Disease)

Without lymphovascular space invasion (LVSI):

• Conization with negative margins or simple hysterectomy based on patient age 2, 1, 3
• Conization is appropriate for fertility preservation in young patients 3

With lymphovascular space invasion:

• Add pelvic lymphadenectomy to the surgical approach 2, 1, 3
• If pelvic nodes are involved, proceed to complementary concurrent chemoradiation 2, 1, 3

Stage IA2

• Surgery is the standard treatment 2, 3
• Options include conization or trachelectomy for fertility preservation in young patients, or simple/radical hysterectomy in other patients 2, 3
• Pelvic lymphadenectomy is required in all cases 2, 1, 3
• If pelvic nodes are involved, add complementary concurrent chemoradiation 2, 1, 3

Stage IB1 and IIA1

Multiple equally effective treatment options exist 1, 3:

Option 1: Surgery

• Radical hysterectomy with pelvic lymphadenectomy 2, 1, 3
• Conservative surgery (conization or trachelectomy) can be considered for tumors with excellent prognostic factors in patients desiring fertility 2, 3
• If upfront surgery reveals pelvic node involvement, add complementary concurrent chemoradiation 2, 3

Option 2: Definitive Radiotherapy

• External beam radiation therapy plus high-dose-rate brachytherapy boost 3
• Total treatment time must be less than 8 weeks 3
• Total dose to target should be 80-90 Gy 3

Option 3: Combined Radio-Surgery

• Preoperative brachytherapy followed 6-8 weeks later by surgery 2
• If nodes are involved at surgery, add complementary concurrent chemoradiation 2

Stage IB2, IIA2, and IIB-IVA (Locally Advanced Disease)

Concurrent chemoradiation is the standard treatment for all locally advanced cervical cancer 1, 3:

• External beam radiation therapy to cover gross disease, parametria, and nodal volumes at risk 3
• Weekly cisplatin 40 mg/m² during external beam radiation therapy 1, 3
• Brachytherapy is an essential component of definitive treatment 1, 3
• The entire course of external beam and brachytherapy must be completed within 8 weeks, as treatment duration exceeding 8 weeks is associated with significantly worse outcomes 1, 3

This approach provides an absolute 5-year survival benefit of 8% compared to radiotherapy alone 1, 3

Stage IVB (Metastatic Disease)

Platinum-based combination chemotherapy with bevacizumab is the standard palliative treatment 1:

• Bevacizumab 15 mg/kg intravenously every 3 weeks in combination with paclitaxel and cisplatin, or in combination with paclitaxel and topotecan 4
• This is palliative treatment, not curative 1, 5
• Platinum-based combination chemotherapy has demonstrated potential benefit 2, 5

Management of Recurrent Disease

Locoregional Recurrence

For radiotherapy-naïve patients:

• Salvage chemoradiation with curative intent 1

For previously irradiated patients:

• Pelvic exenteration in highly selected cases 2, 1
• Exenteration can yield 5-year survival rates up to 82% in appropriately selected patients 6

Distant Metastatic Recurrence

• Platinum-based combination chemotherapy is the standard treatment 1, 5
• For most patients, palliative chemotherapy is the standard option 2, 5

Follow-Up Protocol

Surveillance schedule 1, 3:

• Every 3 months for the first 2 years
• Every 6 months for years 3-5
• Yearly after 5 years

Each visit should include 2, 1:

• Clinical and gynecological examination
• PAP smear (noting that cytology interpretation may be altered in previously irradiated patients) 2
• SCC antigen measurement may be useful in squamous cell carcinoma if initially elevated 2, 3

Critical Pitfalls to Avoid

• Do not exceed 8 weeks total treatment time for chemoradiation, as this significantly worsens outcomes 1, 3
• Do not attempt curative-intent extended-field chemoradiation for patients with paraaortic lymph node involvement and distant metastases 1, 5
• Do not delay systemic chemotherapy to pursue surgical staging or debulking in patients with radiologically confirmed distant metastases 5
• Do not use hysterectomy as primary treatment for CIN III or carcinoma in situ 6
• Withhold bevacizumab for at least 28 days prior to elective surgery and do not administer until at least 28 days following major surgery with adequate wound healing 4
• Discontinue bevacizumab permanently for gastrointestinal perforation, tracheoesophageal fistula, Grade 4 fistula, necrotizing fasciitis, Grade 3-4 hemorrhage, arterial thromboembolism, Grade 4 venous thromboembolism, hypertensive crisis, posterior reversible encephalopathy syndrome, nephrotic syndrome, severe infusion reactions, or congestive heart failure 4

Multidisciplinary Approach

Treatment planning must involve gynecologic oncologists, radiation oncologists, medical oncologists, radiologists, and pathologists 7, 8, 9. This multidisciplinary approach has led to marked improvement in outcomes and is mandatory for optimal treatment planning 2, 8, 9.