Cervical%20cancer%20-%20treatment Treatment

Stage IA1

• Recommended therapies depend on cone biopsy results and if patients want to preserve fertility, are medically operable and have lymphovascular space invasion (LVSI)

Stage IB1, IB2 or Stage IIA1 

Surgery Versus Chemoradiotherapy

• Treatment of choice will depend on many factors including the following:
  • Patient preference
  • Medical conditions
  • Age
• Both treatments result in equivalent cure rates

Stage IVB or Distant Metastases

• After radical surgery, factors that increase risk of early cervical cancer recurrence include high grade tumor, >4-cm tumor, non-squamous histology, lymphovascular space or deep stromal invasion, and involvement of lymph nodes, lower uterine segment, or parametrial or vaginal margin 

• 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 
• The Sedlis criteria, which identify patients belonging to the intermediate-risk group based on pathologic risk factors, may be used to guide adjuvant treatment decisions
  • Include >1/3 stromal invasion, capillary lymphatic space involvement, and tumor >4 cm in diameter
  • Increase the risk for disease recurrence and influence patient survival rate

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  
• 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
  • Recommended radiosensitizing agents include Cisplatin (preferred), Carboplatin for Cisplatin-intolerant patients or Cisplatin/5-FU combination

Systemic Therapy for Relapse and Metastases 

• 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  
• Preferred 1st-line combination therapies include:
  • Cisplatin/Paclitaxel/Bevacizumab 
  • Carboplatin/Paclitaxel/Bevacizumab
  • Pembrolizumab + Carboplatin/Paclitaxel +/- Bevacizumab for PD-L1-positive tumors
  • Pembrolizumab + Cisplatin/Paclitaxel +/- Bevacizumab for PD-L1-positive tumors
• Other recommended 1st-line combination therapies include:
  • Cisplatin/Paclitaxel (if not previously given Cisplatin)
  • Carboplatin/Paclitaxel for patients previously treated with Cisplatin
  • Cisplatin/Topotecan: Has been approved for advanced cervical cancer and an 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 
• Single-agent therapy options include:
  • Cisplatin
  • Carboplatin
• Preferred 2nd-line or subsequent-line agents include:
  • Pembrolizumab for patients with PD-L1-positive or MSI-H/dMMR tumors 
    • Pembrolizumab is also recommended in patients with unresectable or metastatic TMB-H (≥10 mutations/megabase) which have progressed after previous treatment and without alternative options
  • Tisotumab vedotin-tftv
• Other recommended 2nd-line therapies include Bevacizumab, Docetaxel, Gemcitabine, Irinotecan, Paclitaxel, Pemetrexed, Topotecan, Vinorelbine, 5-FU and albumin-bound Paclitaxel 
  • Larotrectinib or Entrectinib is recommended for NRTK gene fusion-positive tumors
  • Nivolumab for patients with PD-L1-positive tumors
  • Selpercatinib for RET gene fusion-positive tumors