Cervical Cancer Treatment Protocols

Updated: Jan 04, 2022
  • Author: Mounika Gangireddy, MBBS; Chief Editor: Yukio Sonoda, MD  more...
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Treatment Protocols

Treatment protocols for cervical cancer are provided below, including treatment by stage, chemoradiation therapy, and chemotherapy.

Treatment recommendations for early-stage disease

Early-stage disease includes stages IA,IB1 and IB2.

Stage IA1 disease:

  • Primary treatment of stage 1A1 cervical cancer depends on the results of cone biopsy and whether the patient wishes to preserve her fertility. [1, 2, 3, 4, 5, 6, 7, 8]

  • For patients who desire fertility preservation and have negative margins on cone biopsy (3 mm) and no evidence of lymphovascular invasion, observation may be an option. [9, 10, 11]

  • Surgical options for all other individuals may include trachelectomy, pelvic lymph node dissection, sentinel lymph node mapping, and simple hysterectomy [12, 13, 14, 15]

Treatment recommendations for stage IA2

Stage IA2 disease:

  • Medically operable patients with stage IA2 tumors are treated with radical hysterectomy or radical trachelectomy with pelvic lymph node dissection.

  • For patients who wish to preserve their fertility, radical trachelectomy and pelvic lymph node dissection is recommended

  • For  patients who do not desire fertility preservation, radical hysterectomy and bilateral pelvic lymph node dissection with or without para-aortic lymph node sampling is recommended; radiation therapy may also be an option in select cases. [16]

  • For patients who are medically inoperable or who refuse surgery, pelvic external beam radiation with brachytherapy (generally dosed at 70-80 Gy to total point A dose) is a treatment option. [17]
  • If high-risk features are noted on final pathologic review (ie, lymphovascular invasion, positive margins, or involvement of pelvic nodes), adjuvant concurrent chemoradiation has improved overall survival. Cisplatin is the preferred agent. [16, 18, 19]

Treatment recommendations for stage IB (1,2,3) and IIA (1, 2)

Stage IB1, 2 or 3 and IIA1 or 2:

  • Patients with stage IB or IIA disease can be treated with surgery, radiation therapy, or concurrent chemoradiation, depending on the stage and bulk of their disease. [13, 20, 10, 21, 15, 22, 14, 23, 24, 25]
  • For IB1 or 2 or IIA1 disease, the preferred treatment is with radical hysterectomy. [7, 26, 27, 28, 29]
  • For IB3 or IIA2 disease, the preferred treatment is with concurrent chemoradiation with brachytherapy. [26, 27, 28, 29]
  • Primary surgery consists of radical hysterectomy plus bilateral pelvic lymph node dissection with or without para-aortic lymph node sampling (for tumors < 2 cm). [7, 30]
  • If lymph nodes are positive—clinically or after surgical staging—then a hysterectomy is not recommended; instead, the patient should receive chemoradiation.

  • Patients with stage IB or IIA may also be given pelvic radiotherapy and brachytherapy with (or without) concurrent cisplatin-based chemotherapy (category 1) . The addition of concurrent cisplatin-containing chemotherapy has been shown to improve survival [1, 31, 32, 7, 27, 18, 33, 19, 29, 34, 28, 16, 26]

  • Cisplatin 40 mg/m 2 IV once weekly plus  radiation therapy, 1.8-2 Gy daily per fraction, for six cycles or
  • Cisplatin 50-75 mg/m 2 IV on day 1 plus  5-flurouracil (5-FU) 1000 mg/m 2 continuous IV infusion over 24 h on days 1-4 (total dose 4000 mg/m 2 each cycle) every 3 wk plus radiation therapy, 1.8-2.0 Gy daily, for a total of three to four cycles

Treatment recommendations for advanced stage disease

Stage IIB, IIIA, IIIB, and IVA:

  • Traditionally, advanced disease includes stages IIB-IVA; however, many oncologists now also include patients with IB3 and IIA2 in the advanced disease category. [16]

  • Radiologic imaging studies (including PET/CT) are recommended for stage IB2 or greater disease, especially for evaluation of nodal or extrapelvic tumors. [35]
  • Treatment recommendations for advanced disease include concomitant chemoradiation and brachytherapy (category 1). [16, 31, 32, 27, 18, 33, 19, 29, 34, 28]

  • Cisplatin 40 mg/m2 IV once weekly (not to exceed 70 mg/wk) plus  radiation therapy 1.8-2 Gy per fraction (minimum 4 cycles; maximum 6 cycles) for a total of 45 Gy or

  • Cisplatin 50-75 mg/m2 IV on day 1 plus  5-fluorouracil (5-FU) 1000 mg/m2 continuous IV infusion over 24 h on days 1-4 (total dose 4000 mg/m2 each cycle) every 3 wk for a total of three or four cycles; plus radiation therapy, 1.8-2 Gy per day for a total for 45 Gy or

  • Cisplatin 40 mg/m2 IV once weekly and gemcitabine 125 mg/m2 weekly for 6 weeks with concurrent radiation therapy for total of 50.4 Gy in 28 fractions, followed by brachytherapy 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m2 on day 1, plus gemcitabine, 1000 mg/ m2 on days 1 and 8) [36]  

Treatment recommendations for metastatic disease

Stage IVB:

  • Patients with metastatic disease are primarily treated with cisplatin-based chemotherapy

  • Individualized radiation therapy can be considered for control of pelvic disease and other symptoms [1, 7, 16]

  • Tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) testing using a validated/US Food and Drug Administration– approved test  is recommended for all metastatic cervical cancers (category 2A). [16]

  • Pembrolizumab with cisplatin or carboplatin/paclitaxel with or without bevacizumab is approved in the first-line setting for treatment of tumors with PDL-1(combined positive score [CPS] > 1%)(category 1) [16, 37]
  • If cisplatin was previously used as a radiosensitizer, combination platinum-based regimens are preferred over single agents in the setting of metastatic disease [38, 39]

First-line therapy for stage IV recurrent or metastatic disease [16, 39, 40, 38, 41, 42] :

  • Bevacizumab 15 mg/kg IV over 30-90 min on dayt 1 plus  cisplatin 50 mg/m2 IV over 60 min on days 1 or 2 plus  paclitaxel 175 or 135 mg/m2 IV over 3 h or 24 h on day 1 every 3 wk (category 1) or

  • Bevacizumab 15 mg/kg IV over 30-90 min plus  paclitaxel 175 mg/m2 IV over 3 h on day 1 plus  topotecan 0.75 mg/m2 IV over 30 min on days 1-3 every 3 wk (category 1) or

  • Paclitaxel 135 mg/m2 IV over 24 h on day 1 (dosing at 175 mg/m2 IV over 3 h on same day as cisplatin is also acceptable) followed by  cisplatin 50 mg/m2 IV on day 2 every 3 wk (category 1) or

  • Paclitaxel 175 mg/m2 IV over 3 h followed by carboplatin area under the curve (AUC) 5 IV over 30 minutes on day 1 every 3 wk(category 1 for patients who received prior cisplatin therapy)

  • Other combinations—including cisplatin/topotecan, carboplatin/paclitaxel, and topotecan/paclitaxel—can also be considered for appropriate individuals (category 2A)
  • Cisplatin is generally the most active agent and may be used as first-line single-agent chemotherapy for recurrent or metastatic cervical cancer.

Second-line therapy for stage IV recurrent or metastatic disease:

Agents that the National Comprehensive Cancer Network (NCCN) recommends as useful in second-line therapy (category 2B) include the following [16] :