• If patient is medically inoperable or wishes to preserve fertility, observation after conization or cone biopsy may be appropriate if:
  • Depth of invasion is shown to be <3 mm
  • There are clear margins
    • If margins are positive, repeat cone biopsy or do trachelectomy
    • If margins are still positive on repeat cone biopsy, treat as stage IB
  • No vascular or lymphatic invasion is noted
• If with lymphovascular invasion, surgical option is cone biopsy or trachelectomy with pelvic lymph node dissection with or without para-aortic lymph node sampling

Surgery vs Radiotherapy (RT) in Patients with Stage IB1 or Stage IIA1

• Treatment of choice will depend on many factors including the following:
  
  • Patient preference
  • Desire for preservation of vaginal and ovarian functions
  • Psychological and medical conditions
  • Age
  • Local clinician expertise
  • Size of primary tumor; radiotherapy should be primary treatment for adenocarcinomas that expand the cervix >3 cm
• Both treatments result in equivalent cure rates

Negative Lymph Nodes

• The following are options in patients with negative lymph nodes after radical hysterectomy:
  
  • Observation
  • Pelvic EBRT with or without concurrent Cisplatin-containing chemotherapy in patients with high-risk factors (ie lymphovascular invasion, deep stromal invasion, and large primary tumor)
    
    • Based on a trial that after 2 years, the recurrence-free rate for surgically treated patients on pelvic radiotherapy was 88%; after a 12-year follow-up, an increase in the progression-free survival was noted

Positive Pelvic Lymph Nodes, and/or Parametrial Involvement and/or Surgical Margins

• Patients should be treated with postoperative pelvic EBRT with concurrent Cisplatin-containing chemotherapy with or without vaginal brachytherapy
• Based on a study, it showed that pelvic radiation with 5-Fluorouracil and Cisplatin has a statistically significant benefit in patients

Positive Para-aortic Lymph Nodes

• Further screening with computed tomography (CT) or combined positron emission tomography-computed tomography (PET-CT) scan is required
• Biopsy of suspicious areas is recommended in patients with positive distant metastases
• Patients with negative findings should undergo para-aortic lymph node EBRT with concurrent Cisplatin-based chemotherapy and pelvic EBRT
  
  • Brachytherapy is recommended
• Patients with positive findings should be treated with chemotherapy and individualized EBRT

• Patients who develop distant metastasis are rarely curable
• The following measures, such as surgical resection with or without individualized EBRT, may be done in highly selected patients with isolated distant metastases
• Palliative measures, in pelvic recurrences with heavily irradiated sites not amenable to surgical resection or local pain control techniques, are unresolved clinical issues
  • Patients may occasionally benefit from radiotherapy to a localized recurrence (eg supraclavicular, bone metastases, or painful para-aortic nodal recurrences)
    • If with limited resources and if feasible, short or single courses of radiotherapy can be utilized with retreatments for recurrent or persistent symptoms

Relapse and Metastases

Chemotherapy

• Has a limited role in prolonging survival or improving quality of life
• Recommended in patients with extrapelvic metastases or patients with recurrent disease who are not candidates for radiotherapy or exenteration
• Combination platinum-based regimens are preferred over single agents, if Cisplatin has been previously used as a radiosensitizer
• Cisplatin is the preferred 1st-line single agent for recurrent or metastatic cervical cancer
  • Response rates of approximately 20-30% and overall survival of about 6-9 months
• Other first-line single agents include Carboplatin and Paclitaxel
  • Carboplatin may also be preferred over Cisplatin due to tolerability, ease of administration, and preservation of renal function
    • In basic-resource settings, single-agent chemotherapy with either Carboplatin or Cisplatin is recommended
  • Paclitaxel has also been reported to be effective and tolerable
• The following are first-line combination therapies: Cisplatin/Paclitaxel, Cisplatin/Gemcitabine, Cisplatin/Topotecan, Paclitaxel/Carboplatin, Cisplatin/Paclitaxel/Bevacizumab, Topotecan/Paclitaxel, Topotecan/Paclitaxel/Bevacizumab, and Carboplatin/Paclitaxel/Bevacizumab
  • Cisplatin/Paclitaxel or Carboplatin/Paclitaxel is less toxic and provides easier administration
  • Cisplatin/Topotecan has been approved for advanced cervical cancer
    • The combination was shown to be superior compared to single-agent Cisplatin based on overall response rate of 27%, progression-free survival of 4.6 months, and median survival of 9.4 months
  • Cisplatin/Gemcitabine may be useful in patients with neuropathy who cannot tolerate other drug combinations
• Second-line therapies include Bevacizumab, Docetaxel, Gemcitabine, Ifosfamide, Irinotecan, Mitomycin, Pemetrexed, Topotecan, Vinorelbine, Fluorouracil (5-FU), and albumin-bound Paclitaxel