cervical%20cancer%20-%20treatment
CERVICAL CANCER - TREATMENT
Patients with abnormal Pap smear are referred for colposcopy to screen for presence of cervical cancer.
Colposcopic exam should include inspection of the transformation zone, definition of the extent of the lesion and biopsy of the most abnormal area for tissue diagnosis.
The earliest stages of cervical carcinoma are generally asymptomatic.
Watery vaginal discharge, postcoital or postmenopausal bleeding, intermittent spotting, or abdominal pain may be present and is usually unrecognized by the patient.

Radiotherapy

Stage IA2

  • 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
    • May be an option for medically inoperable patients or who refuse surgery
    • In patients with lymphovascular invasion, concurrent platinum-containing chemotherapy may be added to pelvic EBRT
  • Brachytherapy is an important part of radiotherapy for cervical carcinomas in patients who are not suitable for surgery
    • It treats mainly the primary tumor
    • The surrounding tissue can be relatively spared while high doses of radiation are delivered to the 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 or without 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 is the Cisplatin/5-FU combination
    • 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 using either single-agent Cisplatin (preferred) or Cisplatin/5-FU combination is the treatment of choice for stages IB3, II, III and IVA
      • Concurrent single-agent Cisplatin chemoradiation is preferred due to lesser toxicity
      • Concurrent Carboplatin chemoradiation is the preferred radiosensitizing agent for patients intolerant to Cisplatin 
    • 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
  • Chemoradiation is preferred over radical surgery in select patients with stage IB3 and most patients with stage IIA2
    • Has been shown to remarkably improve patient survival
    • EBRT with concurrent platinum-containing chemotherapy and brachytherapy is recommended
      • Should be modified based on normal tissue tolerance, fractionation and size of target volume
  • Adjuvant hysterectomy after radiation therapy for stage IB3 and IIA2 tumors may be considered in patients where adequate coverage by brachytherapy is hindered by extent of disease or uterine anatomy
  • Patients with IB2-IIA/B may benefit more from chemoradiotherapy than patients with stage III and IVA
    • Based on trials done, it translated to a 5-year survival benefit of 10% for patients with stage IB-IIA, 7% for patients with stage IIB and 3% for patients with stage IIIB-IVA
  • Patients with disease limited to the pelvis only or without nodal disease by surgical staging is recommended for EBRT with concurrent platinum-containing chemotherapy and brachytherapy
    • Concurrent platinum-containing chemotherapy using Cisplatin (preferred) or Carboplatin for Cisplatin-intolerant patients or Cisplatin/5-FU combination is given every 3-4 weeks during radiation therapy 
  • Patients with locally advanced cancer may benefit from initial pelvic EBRT of 40-45 Gy to obtain tumor shrinkage for optimal intracavitary placements
    • With low-dose rate intracavitary systems, total doses from brachytherapy and external beam radiation to point A of at least 80 Gy are recommended particularly for small tumors; whereas for larger tumors, doses of 85 Gy or higher is recommended
  • Inguinal lymph nodes should be treated in patients with lesions in the lower 1/3 of the vagina
    • Treatment of occult or macroscopic 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
  • Postoperative pelvic radiotherapy with or without Cisplatin-containing chemotherapy should be considered inpatients with at least 2 high-risk factors (ie lymphovascular invasion, >⅓ stromal invasion, primary tumor diameter >4 cm)
  • Patients with positive surgical margins, parametrial involvement or pelvic node involvement should be treated with post-op pelvic external beam radiation with concurrent Cisplatin-containing chemotherapy with or without vaginal brachytherapy
    • Concomitant chemoradiation may utilize Cisplatin as single agent or Cisplatin with 5-FU
  • Patients with positive para-aortic lymph nodes after surgical staging should undergo further screening with CT or PET scan
    • Extended-field EBRT with concurrent platinum-containing chemotherapy with or without brachytherapy is recommended if negative for metastases 
    • Once indicated, biopsy of suspected areas should be considered
    • If positive for distant metastases, they should be treated with systemic therapy with or without individualized radiotherapy  
  • Recommendations for patients with positive pelvic lymph nodes but negative para-aortic lymph nodes after imaging include:
    • Pelvic EBRT with concurrent platinum-containing chemotherapy and brachytherapy with or without para-aortic lymph node EBRT or
    • Surgical staging of para-aortic lymph nodes
      • If negative for para-aortic node involvement, pelvic EBRT with concurrent platinum-containing chemotherapyand brachytherapy is recommended
      • If positive for para-aortic node involvement, extended-field EBRT with concurrent platinum-containing chemotherapy and brachytherapy is recommended
  • Patients with positive para-aortic and pelvic lymph nodes after imaging should undergo extended-field EBRT withconcurrent 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 hysterectomy

Relapse and 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

Locoregional Therapy

  • Determine whether radiotherapy and/or chemotherapy 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 chemotherapy 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, Carboplatin or Cisplatin/5-FU maybe given Carboplatin, Paclitaxel and Gemcitabine
    •  Surgical resection may be considered

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 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, supportive care, or participation in clinical trials are the treatment options for these patients
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