Cervical%20cancer%20-%20treatment Treatment

Stage IA1

• Recommended therapies depend on cone biopsy results and if patients want to preserve fertility, are medically operable or have lymphovascular invasion
• Pelvic lymph node dissection extent will depend on the presence of pelvic nodal disease and/or lymphovascular invasion and size of the tumors

Surgery Versus Radiotherapy in Patients with Stage IB1, IB2 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 >4 cm
• Both treatments result in equivalent cure rates

Systemic Therapy for Metastatic Disease

• Patients who develop distant metastasis are rarely curable
• The following measures, such as surgical resection with or without individualized EBRT, local ablative therapies with or without individualized EBRT or individualized EBRT with or without systemic therapy, may be done in highly selected patients with isolated distant metastases
  • Systemic adjuvant chemotherapy may be considered
• 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

• Recommended after radical hysterectomy based on surgical findings and disease stage 

Negative Lymph Nodes, Margins and Parametria 

• The following are options in patients with negative lymph nodes after radical hysterectomy:
  
  • Observation
  • Pelvic EBRT with or without concurrent platinum-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
    • Recommended radiosensitizing agents include Cisplatin (preferred), Carboplatin for Cisplatin-intolerant patients or Cisplatin/5-Fluorouracil (5-FU) combination

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

• Patients should be treated with postoperative pelvic EBRT with concurrent platinum-containing chemotherapy with or without vaginal brachytherapy
  • Vaginal brachytherapy may be used as a boost in patients with positive vaginal mucosal margins
• Based on a study, it showed that pelvic radiation with 5-FU and Cisplatin has a statistically significant benefit in patients

Positive Para-aortic Lymph Nodes

• Further screening with CT or combined PET/CT scan is required
• Biopsy of suspicious areas is recommended in patients with positive distant metastases
  • Patients with positive findings should be treated with chemotherapy with or without individualized EBRT
• For patients negative for distant metastasis, extended-field EBRT with concurrent platinum-based chemotherapy with or without brachytherapy is recommended

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 recommended 1st-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
• Preferred 1st-line combination therapies include:
  • Carboplatin/Paclitaxel/Bevacizumab 
  • Cisplatin/Paclitaxel/Bevacizumab
• Other recommended 1st-line combination therapies include:
  • Carboplatin/Paclitaxel for patients previously treated with Cisplatin
  • Cisplatin/Paclitaxel
    • Cisplatin/Paclitaxel or Carboplatin/Paclitaxel is less toxic and provides easier administration
  • Cisplatin/Topotecan
    • Has been approved for advanced cervical cancer
    • Alternative for patients who cannot receive taxanes
    • 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
  • Topotecan/Paclitaxel/Bevacizumab
  • Topotecan/Paclitaxel 
• Second-line therapies include Bevacizumab, Docetaxel, Gemcitabine, Ifosfamide, Irinotecan, Mitomycin, Pemetrexed, Topotecan, Vinorelbine, 5-FU, Pembrolizumab (preferred for PD-L1-positive or MSI-H/dMMR tumors), and albumin-bound Paclitaxel
  • Pembrolizumab is also recommended in patients with unresectable or metastatic tumor mutational burden-high (≥10 mutations/megabase), which have progressed after previous treatment and without alternative options
  • Larotrectinib or Entrectinib is recommended for NRTK gene fusion-positive tumors