02/02/22 20.

17 Cervical Cancer Treatment Protocols: Treatment Protocols

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Cervical Cancer Treatment

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

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
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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
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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] :

 
Docetaxel
Ifosfamide
5-FU
Mitomycin 
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Irinotecan 
Pemetrexed 
Gemcitabine
Albumin-bound paclitaxel
Vinorelbine 
Topotecan
Nivolumab
Larotrectinib or entrectinib
Tisotumab vedotin-tftv

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