Cervical%20cancer%20-%20treatment Treatment

Stage IA2

• For poor surgical risk patients
• Brachytherapy + pelvic EBRT (point A dose: 70-80 Gy)
  • Dose is based on summation of conventional external-beam fractionation and low-dose rate (40-70 cGy/hour) brachytherapy equivalents
  • Dose should be modified based on normal tissue tolerance, fractionation and size of target volume
  • In patients with lymphovascular invasion, concurrent platinum-containing chemotherapy may be added to pelvic EBRT
  • Brachytherapy/internal radiation therapy treats mainly the primary tumor
    • Delivery is through manual or remote after-loading techniques
    • If brachytherapy is not available in limited-resource settings, extrafascial hysterectomy or its modification may be performed in patients with residual tumor found 2-3 months after concurrent chemoradiotherapy and additional boost

Stage IB1, IB2 or IIA1 

• Patients with stage IB1, IB2 or stage IIA1 may be treated with pelvic EBRT plus brachytherapy (point A dose: 80-85 Gy) with concurrent platinum-containing chemotherapy
  • Should be modified based on normal tissue tolerance, fractionation and size of target volume
  • Cisplatin is the preferred radiosensitizing agent and Carboplatin may be used for Cisplatin-intolerant patients
    • Other recommended radiosensitizing regimen are the Cisplatin/5-FU and Paclitaxel-Cisplatin combinations
  • When using high dose-rate brachytherapy, define the doses according to biological equivalence

Advanced Tumors

• Concurrent chemoradiation represents the standard treatment for stages IB3 to IVA 
  • Concurrent chemoradiation with platinum-based chemotherapy (single-agent Cisplatin [preferred]) for stages IB3, II, III and IVA
    • Single-agent Carboplatin is the preferred radiosensitizing agent for patients intolerant to Cisplatin or with impaired renal function
  • Has been shown 30-50% decrease in the mortality risk compared to radiotherapy alone
  • Chemotherapy should be administered together with EBRT
• In patients undergoing primary chemoradiation, the volume of radiotherapy is critical and is guided by assessment of nodal involvement in the pelvic and para-aortic nodes
• Adjuvant hysterectomy after chemoradiation for stage IB3 and IIA2 tumors may be considered in patients after protracted chemoradiation with residual tumor after treatment
• Treatment of para-aortic lymph node disease using extended-field EBRT should be carefully planned so that adequate dose (45 Gy for microscopic disease) is given without exceeding bowel, spinal cord, or renal tolerances 
• Patients with positive para-aortic and pelvic lymph nodes should undergo extended-field EBRT with concurrent platinum-containing chemotherapy and brachytherapy after imaging work-up for metastatic disease
  • If positive for distant metastases, they should be treated with systemic therapy and with or without individualized radiotherapy 
• In basic-resource settings, neoadjuvant chemotherapy may be given to patients with larger tumors or advanced cancer to shrink the tumor prior to radical hysterectomy

Locoregional Therapy for Relapse and Metastases

• Determine whether radiotherapy and/or systemic therapy or surgery may be utilized for patients with local recurrence after initial treatment
  • Survival rates of approximately 40% have been reported
  • Tumor-directed EBRT with or without systemic therapy and/or brachytherapy may be offered to patients with recurrence outside of the previously treated radiotherapy field or radiotherapy-naive patients with local recurrence
    • Patients with relapse soon after completion of initial chemoradiation with Cisplatin or Carboplatin should be given 5-FU, Bevacizumab, Carboplatin, Docetaxel, Entrectinib (for patients with neurotrophic tyrosine receptor kinase [NTRK] gene fusion-positive tumors), Gemcitabine, Irinotecan, Larotrectinib (for patients with NTRK gene fusion-positive tumors), Nivolumab (for patients with PD-L1-positive tumors), Paclitaxel, albumin-bound Paclitaxel, Pembrolizumab (for patients with PD-L1-positive, MSI-H/dMMR or tumor mutational burden-high [TMB-H] tumors), Pemetrexed, Selpercatinib (for rearranged during transfection [RET] gene fusion-positive tumors), Tisotumab vedotin-tftv, Topotecan, and Vinorelbine
  •  Surgical resection may be considered for highly select localized lesions

Central Recurrence

• Patients with central recurrence after radiotherapy may benefit from pelvic exenteration, with or without intra-operative radiotherapy (IORT)
• Patients will benefit from pelvic exenteration if rehabilitation programs dealing with psychosocial and psychosexual issues are available
  • Reconstructive procedures should also be available
• Radical hysterectomy or brachytherapy may be an option in very few selected patients with small central lesions of <2 cm

Noncentral Recurrence

• The following options may be utilized:
  • Resection with or without IORT for close or positive margins
  • Individualized EBRT with or without concurrent chemotherapy
  • Systemic therapy
  • Participation in clinical trials
• Patients who recur after 2nd-line therapy, such as radiotherapy or surgery, have a poor prognosis
  • Systemic therapy (eg Cisplatin, Carboplatin, Bevacizumab, Carboplatin, Docetaxel, Entrectinib, 5-FU, Gemcitabine, Irinotecan, Larotrectinib, Nivolumab, Paclitaxel, albumin-bound Paclitaxel, Pembrolizumab, Pemetrexed, Selpercatinib, Tisotumab vedotin-tftv, Topotecan, and Vinorelbine), supportive care, or participation in clinical trials are the treatment options for these patients