Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

nonpregnant stage IA1 without LVSI: desiring fertility

1st line – surveillance (following cone biopsy)

Back
ACUTE
|
nonpregnant stage IA1 without LVSI: desiring fertility
|
with negative biopsy margins
1st line – 

surveillance (following cone biopsy)

Primary treatment options for patients with stage IA1 disease without lymphovascular space invasion (LVSI) who want to maintain fertility include cone biopsy (with negative margins) followed by surveillance.[90]

1st line – repeat cone biopsy or simple trachelectomy

Back
ACUTE
|
nonpregnant stage IA1 without LVSI: desiring fertility
|
with positive biopsy margins
1st line – 

repeat cone biopsy or simple trachelectomy

If cone biopsy reveals positive margins, options include repeat cone biopsy (to reevaluate depth of invasion and rule out more advanced disease), or trachelectomy.

Trachelectomy is a fertility-sparing option for carefully selected patients with early stage disease.[90]​ Simple trachelectomy may be considered for microinvasive disease (stage IA1). Minimally invasive procedures may be considered for cervical cancer patients with preoperative tumor size of ≤2 cm, but there is a lack of data on oncologic outcomes.[90][128]

nonpregnant stage IA1 without LVSI: not desiring fertility

1st line – simple (type A) hysterectomy (following cone biopsy)

Back
ACUTE
|
nonpregnant stage IA1 without LVSI: not desiring fertility
|
with negative biopsy margins; surgical candidate
1st line – 

simple (type A) hysterectomy (following cone biopsy)

Primary treatment options for patients with stage IA1 disease without lymphovascular space invasion (LVSI) not desiring fertility include cone biopsy (with negative margins) followed by simple (type A) hysterectomy (if surgical candidate).

Hysterectomy is the preferred treatment for early stage disease when fertility preservation is not desired; resection may limit the need for adjuvant treatment.[114][115]​​ The type of hysterectomy performed varies depending on disease stage, treatment intent (e.g., curative), and patient preference. The Querleu and Morrow classification system describes degree of resection and nerve preservation.[116][117]

Simple (extrafascial) hysterectomy (Querleu-Morrow type A) and modified radical hysterectomy (type B) are curative options for microinvasive disease and small lesions (stage IA1-IB1 disease).[90][118][120]

1st line – repeat cone biopsy or simple (type A) hysterectomy

Back
ACUTE
|
nonpregnant stage IA1 without LVSI: not desiring fertility
|
with positive biopsy margins (dysplasia); surgical candidate
1st line – 

repeat cone biopsy or simple (type A) hysterectomy

If cone biopsy reveals positive margins for dysplasia, options include repeat cone biopsy (to reevaluate depth of invasion and rule out more advanced disease), or simple (type A) hysterectomy.

Hysterectomy is the preferred treatment for early stage disease when fertility preservation is not desired; resection may limit the need for adjuvant treatment.[114][115]​ The type of hysterectomy performed varies depending on disease stage, treatment intent (e.g., curative), and patient preference. The Querleu and Morrow classification system describes degree of resection and nerve preservation.[116][117]

Simple (extrafascial) hysterectomy (Querleu-Morrow type A) and modified radical hysterectomy (type B) are curative options for microinvasive disease and small lesions (stage IA1-IB1 disease).[90][118][120]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

1st line – repeat cone biopsy or modified radical (type B) hysterectomy plus SLN mapping/pelvic lymphadenectomy

Back
ACUTE
|
nonpregnant stage IA1 without LVSI: not desiring fertility
|
with positive biopsy margins (carcinoma); surgical candidate
1st line – 

repeat cone biopsy or modified radical (type B) hysterectomy plus SLN mapping/pelvic lymphadenectomy

If cone biopsy reveals positive margins for carcinoma, options include repeat cone biopsy (to reevaluate depth of invasion and rule out more advanced disease), or modified radical (type B) hysterectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy.

Hysterectomy is the preferred treatment for early stage disease when fertility preservation is not desired; resection may limit the need for adjuvant treatment.[114][115]​​ The type of hysterectomy performed varies depending on disease stage, treatment intent (e.g., curative), and patient preference. The Querleu and Morrow classification system describes degree of resection and nerve preservation.[116][117]

Simple (extrafascial) hysterectomy (Querleu-Morrow type A) and modified radical hysterectomy (type B) are curative options for microinvasive disease and small lesions (stage IA1-IB1 disease).[90][118][120]

Open surgery is preferred for radical hysterectomy; minimally invasive radical hysterectomy (i.e., laparoscopic or robot-assisted) is associated with lower disease-free and overall survival compared with open abdominal surgery.[121][122][123]​​ Clinicians should assess the risks and potential benefits of each surgical approach for the individual patient, and counsel accordingly.[90][181] Studies are ongoing to identify which patients might safely benefit from minimally invasive surgery.[124][125]

Age does not appear to be a significant contraindication to radical hysterectomy. Class III obesity (i.e., body mass index ≥40) is a relative contraindication to surgery, and operative risk may need to be weighed against the risks of alternative treatment options.[126][127]​​​​

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[158]​[182]​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90]​ Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

1st line – surveillance (following cone biopsy)

Back
ACUTE
|
nonpregnant stage IA1 without LVSI: not desiring fertility
|
with negative biopsy margins; nonsurgical candidate
1st line – 

surveillance (following cone biopsy)

Primary treatment options for patients with stage IA1 disease without LVSI not desiring fertility include cone biopsy (with negative margins) followed by surveillance (nonsurgical candidate).[90]

1st line – brachytherapy ± pelvic EBRT

Back
ACUTE
|
nonpregnant stage IA1 without LVSI: not desiring fertility
|
with positive biopsy margins; nonsurgical candidate
1st line – 

brachytherapy ± pelvic EBRT

If cone biopsy reveals positive margins, options include brachytherapy with or without pelvic external beam radiation therapy (EBRT) (if nonsurgical candidate).

Radiation therapy alone is an effective option for patients with early stage disease or for those who are not candidates for surgery.[90][138][139]

Radiation therapy may be given using EBRT and/or brachytherapy. EBRT delivers radiation directly to the tumor site. Intensity-modulated radiation therapy (IMRT) should be considered to reduce acute and chronic toxicity in definitive treatment of the pelvis (with or without para-aortic treatment).[138]

Brachytherapy is an integral component of definitive radiation therapy for patients with primary cervical cancer, performed using an intracavitary and/or an interstitial approach. Brachytherapy is usually given following EBRT, as a radiation boost to the primary tumor. Brachytherapy has been shown to decrease recurrence rates and improve survival in combination with EBRT compared with EBRT alone.[140][141][142][143] In highly selected, very early stage disease, brachytherapy alone (without EBRT) may be an option. Image-guided brachytherapy is recommended; magnetic resonance imaging (MRI)-guided adaptive brachytherapy is the gold standard brachytherapy technique.​[138][144][145][146]

nonpregnant, stage IA1 with LVSI: desiring fertility

1st line – SLN mapping or pelvic lymphadenectomy (following cone biopsy)

Back
ACUTE
|
nonpregnant, stage IA1 with LVSI: desiring fertility
|
with negative biopsy margins
1st line – 

SLN mapping or pelvic lymphadenectomy (following cone biopsy)

Primary treatment options for patients with stage IA1 disease with LVSI who want to maintain fertility include cone biopsy (with negative margins) plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy.

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

1st line – radical trachelectomy + SLN mapping/pelvic lymphadenectomy

Back
ACUTE
|
nonpregnant, stage IA1 with LVSI: desiring fertility
|
with negative biopsy margins
1st line – 

radical trachelectomy + SLN mapping/pelvic lymphadenectomy

Primary treatment options for patients with stage IA1 disease with LVSI who want to maintain fertility include radical trachelectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy.

Trachelectomy is a fertility-sparing option for carefully selected patients with early stage disease. Simple trachelectomy may be considered for microinvasive disease (stage IA1); radical trachelectomy for stages IA1, IA2, IB1, and for select IB2 cases.[90] Minimally invasive procedures may be considered for cervical cancer patients with preoperative tumor size of ≤2 cm, but there is a lack of data on oncologic outcomes.[90][128]

Retrospective studies suggest that radical trachelectomy may be associated with an increased but acceptable risk of recurrence compared with radical hysterectomy.[129] Risk of recurrence may be increased in patients with tumor size >2 cm after any type of fertility-sparing procedures.[130]​ Patients with tumor size >2 cm who undergo radical abdominal trachelectomy may require adjuvant therapy, which will affect their fertility.[90][112][131][132][133][134]

Radical trachelectomy using a vaginal approach is typically recommended for tumors <2 cm.[90] An abdominal approach allows greater resection of parametrial tissue than the vaginal approach and is favored for larger tumors.

Risk of loss of pregnancy and preterm labor is increased in patients following radical trachelectomy due to cervical weakness. Systematic reviews suggest that oncologic outcomes are similar for different fertility-sparing techniques, but that vaginal radical trachelectomy may achieve improved reproductive outcomes.[135][136][137]​​ Further research is needed to determine fertility and pregnancy outcomes for different procedures.

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​​​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

1st line – repeat cone biopsy or radical trachelectomy + SLN mapping/pelvic lymphadenectomy

Back
ACUTE
|
nonpregnant, stage IA1 with LVSI: desiring fertility
|
with positive biopsy margins
1st line – 

repeat cone biopsy or radical trachelectomy + SLN mapping/pelvic lymphadenectomy

If cone biopsy reveals positive margins, options include repeat cone biopsy (to reevaluate depth of invasion and rule out more advanced disease), or radical trachelectomy plus SLN mapping or pelvic lymphadenectomy.

Trachelectomy is a fertility-sparing option for carefully selected patients with early stage disease. Simple trachelectomy may be considered for microinvasive disease (stage IA1); radical trachelectomy for stages IA1, IA2, IB1, and for select IB2 cases.[90] Minimally invasive procedures may be considered for cervical cancer patients with preoperative tumor size of ≤2 cm, but there is a lack of data on oncologic outcomes.[90][128]

Retrospective studies suggest that radical trachelectomy may be associated with an increased but acceptable risk of recurrence compared with radical hysterectomy.[129] Risk of recurrence may be increased in patients with tumor size >2 cm after any type of fertility-sparing procedures.[130]​ Patients with tumor size >2 cm who undergo radical abdominal trachelectomy may require adjuvant therapy, which will affect their fertility.[90][112][131][132][133][134]

Radical trachelectomy using a vaginal approach is typically recommended for tumors <2 cm.[90] An abdominal approach allows greater resection of parametrial tissue than the vaginal approach and is favored for larger tumors. 

Risk of loss of pregnancy and preterm labor is increased in patients following radical trachelectomy due to cervical weakness. Systematic reviews suggest that oncologic outcomes are similar for different fertility-sparing techniques, but that vaginal radical trachelectomy may achieve improved reproductive outcomes.[135][136][137]​ Further research is needed to determine fertility and pregnancy outcomes for different procedures.

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​​​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

nonpregnant, stage IA1 with LVSI: not desiring fertility

1st line – modified radical (type B) hysterectomy + SLN mapping/pelvic lymphadenectomy

Back
ACUTE
|
nonpregnant, stage IA1 with LVSI: not desiring fertility
|
surgical candidate
1st line – 

modified radical (type B) hysterectomy + SLN mapping/pelvic lymphadenectomy

Primary treatment options for patients with stage IA1 disease with lymphovascular space invasion (LVSI) not desiring fertility include modified radical (type B) hysterectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy (if surgical candidate).

Hysterectomy is the preferred treatment for early stage disease when fertility preservation is not desired; resection may limit the need for adjuvant treatment.[114][115]​​​​ The type of hysterectomy performed varies depending on disease stage, treatment intent (e.g., curative), and patient preference. The Querleu and Morrow classification system describes degree of resection and nerve preservation.[116][117]​​

Simple (extrafascial) hysterectomy (Querleu-Morrow type A) and modified radical hysterectomy (type B) are curative options for microinvasive disease and small lesions (stage IA1-IB1 disease).[90][118][120]

Open surgery is preferred for radical hysterectomy; minimally invasive radical hysterectomy (i.e., laparoscopic or robot-assisted) is associated with lower disease-free and overall survival compared with open abdominal surgery.[121][122][123]​​​​ Clinicians should assess the risks and potential benefits of each surgical approach for the individual patient, and counsel accordingly.[90][181]​​ Studies are ongoing to identify which patients might safely benefit from minimally invasive surgery.[124][125]

Age does not appear to be a significant contraindication to radical hysterectomy. Class III obesity (i.e., body mass index ≥40) is a relative contraindication to surgery, and operative risk may need to be weighed against the risks of alternative treatment options.[126][127]

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[158][157]​​​​​​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​​​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

Consider – postoperative radiation ± chemotherapy

Back
ACUTE
|
nonpregnant, stage IA1 with LVSI: not desiring fertility
|
surgical candidate
Consider – 

postoperative radiation ± chemotherapy

Treatment recommended for SOME patients in selected patient group

Postoperative chemoradiation is required if surgical pathology reveals positive nodes, involvement of the parametrium, or positive margins in patients with stage IA2, IB, or IIA disease.[90][159][173] Cisplatin plus external beam radiation therapy (EBRT) with or without brachytherapy is the standard regimen for postoperative chemoradiation.[159]

Adjuvant treatment should also be considered in patients with negative nodes, no parametrial involvement, and negative margins, if they have two or more of the following intermediate-risk factors (i.e., the Sedlis criteria): LVSI, deep stromal invasion, and/or large tumor size.[174] Postoperative EBRT with or without concurrent platinum-containing chemotherapy may be considered.[174][175]​ Optimal adjuvant treatment for intermediate-risk disease has not been determined[138][176]​​​

No further treatment is required for patients with negative nodes, no parametrial involvement, negative margins, and with one or no intermediate-risk factors. Patients should be monitored for recurrence.[90]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

1st line – pelvic EBRT + brachytherapy

Back
ACUTE
|
nonpregnant, stage IA1 with LVSI: not desiring fertility
|
nonsurgical candidate
1st line – 

pelvic EBRT + brachytherapy

Primary treatment options for patients with stage IA1 disease with LVSI not desiring fertility include pelvic EBRT plus brachytherapy (if nonsurgical candidate).

Radiation therapy alone is an effective option for patients with early stage disease or for those who are not candidates for surgery.[90][138][139]

Radiation therapy may be given using EBRT and/or brachytherapy. EBRT delivers radiation directly to the tumor site. Intensity-modulated radiation therapy (IMRT) should be considered to reduce acute and chronic toxicity in definitive treatment of the pelvis (with or without para-aortic treatment).[138]

Brachytherapy is an integral component of definitive radiation therapy for patients with primary cervical cancer, performed using an intracavitary and/or an interstitial approach. Brachytherapy is usually given following EBRT, as a radiation boost to the primary tumor. Brachytherapy has been shown to decrease recurrence rates and improve survival in combination with EBRT compared with EBRT alone.[140][141][142][143] In highly selected, very early stage disease, brachytherapy alone (without EBRT) may be an option. Image-guided brachytherapy is recommended; magnetic resonance imaging (MRI)-guided adaptive brachytherapy is the gold standard brachytherapy technique.[138][144][145][146]

nonpregnant stage IA2: desiring fertility

1st line – SLN mapping or pelvic lymphadenectomy (following cone biopsy)

Back
ACUTE
|
nonpregnant stage IA2: desiring fertility
|
conservative surgery candidate
1st line – 

SLN mapping or pelvic lymphadenectomy (following cone biopsy)

Patients with stage IA2 or IB1 disease may be considered for conservative surgical treatment if they meet all of the following criteria: no lymphovascular space invasion (LVSI); negative cone margins; squamous cell (any grade) or usual type adenocarcinoma (grade 1 or 2 only); tumor size ≤2 cm; depth of invasion ≤10 mm; and negative imaging for locoregional (for fertility-sparing treatment) disease.[90][118][120]

Conservative surgical treatment for patients who want to maintain fertility is cone biopsy (with negative margins) plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy.[90]

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

1st line – SLN mapping or pelvic lymphadenectomy (following cone biopsy)

Back
ACUTE
|
nonpregnant stage IA2: desiring fertility
|
nonconservative surgery candidate; with negative biopsy margins
1st line – 

SLN mapping or pelvic lymphadenectomy (following cone biopsy)

Primary treatment options for patients with stage IA2 disease who want to maintain fertility include cone biopsy (with negative margins) plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy.

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

1st line – radical trachelectomy + SLN mapping/pelvic lymphadenectomy

Back
ACUTE
|
nonpregnant stage IA2: desiring fertility
|
nonconservative surgery candidate; with negative biopsy margins
1st line – 

radical trachelectomy + SLN mapping/pelvic lymphadenectomy

Primary treatment options for patients with stage IA2 disease with LVSI who want to maintain fertility include radical trachelectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy.

Trachelectomy is a fertility-sparing option for carefully selected patients with early stage disease. Simple trachelectomy may be considered for microinvasive disease (IA1); radical trachelectomy for stages IA1, IA2, IB1, and for select IB2 cases.[90] Minimally invasive procedures may be considered for cervical cancer patients with preoperative tumor size of ≤2 cm, but there is a lack of data on oncologic outcomes.[90][128]

Retrospective studies suggest that radical trachelectomy may be associated with an increased but acceptable risk of recurrence compared with radical hysterectomy.[129] Risk of recurrence may be increased in patients with tumor size >2 cm after any type of fertility-sparing procedures.[130]​ Patients with tumor size >2 cm who undergo radical abdominal trachelectomy may require adjuvant therapy, which will affect their fertility.[90][112][131][132][133][134]

Radical trachelectomy using a vaginal approach is typically recommended for tumors <2 cm. An abdominal approach allows greater resection of parametrial tissue than the vaginal approach and is favored for larger tumors.

Risk of loss of pregnancy and preterm labor is increased in patients following radical trachelectomy due to cervical weakness. Systematic reviews suggest that oncologic outcomes are similar for different fertility-sparing techniques, but that vaginal radical trachelectomy may achieve improved reproductive outcomes.[135][136][137]​ Further research is needed to determine fertility and pregnancy outcomes for different procedures.

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%). 

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

1st line – repeat cone biopsy or radical trachelectomy + SLN mapping/pelvic lymphadenectomy

Back
ACUTE
|
nonpregnant stage IA2: desiring fertility
|
nonconservative surgery candidate; with positive biopsy margins
1st line – 

repeat cone biopsy or radical trachelectomy + SLN mapping/pelvic lymphadenectomy

Primary treatment options for patients with stage IA2 disease with LVSI who want to maintain fertility include repeat cone biopsy to reevaluate depth of invasion and rule out more advanced disease, or radical trachelectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy.

Trachelectomy is a fertility-sparing option for carefully selected patients with early stage disease. Simple trachelectomy may be considered for microinvasive disease (stage IA1); radical trachelectomy for stages IA1, IA2, IB1, and for select IB2 cases.[90][128]​ Minimally invasive procedures may be considered for cervical cancer patients with preoperative tumor size of ≤2 cm, but there is a lack of data on oncologic outcomes.[90][128]

Retrospective studies suggest that radical trachelectomy may be associated with an increased but acceptable risk of recurrence compared with radical hysterectomy.[129] Risk of recurrence may be increased in patients with tumor size >2 cm after any type of fertility-sparing procedures.[130]​ Patients with tumor size >2 cm who undergo radical abdominal trachelectomy may require adjuvant therapy, which will affect their fertility.[90][112][131][132][133][134]

Radical trachelectomy using a vaginal approach is typically recommended for tumors <2 cm. An abdominal approach allows greater resection of parametrial tissue than the vaginal approach and is favored for larger tumors.

Risk of loss of pregnancy and preterm labor is increased in patients following radical trachelectomy due to cervical weakness. Systematic reviews suggest that oncologic outcomes are similar for different fertility-sparing techniques, but that vaginal radical trachelectomy may achieve improved reproductive outcomes.[135][136][137]​ Further research is needed to determine fertility and pregnancy outcomes for different procedures.

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

nonpregnant stage IA2: not desiring fertility

1st line – simple (type A) hysterectomy + SLN mapping/pelvic lymphadenectomy

Back
ACUTE
|
nonpregnant stage IA2: not desiring fertility
|
conservative surgery candidate
1st line – 

simple (type A) hysterectomy + SLN mapping/pelvic lymphadenectomy

Patients with stage IA2 or IB1 disease may be considered for conservative surgical treatment if they meet all of the following criteria: no lymphovascular space invasion (LVSI); negative cone margins; squamous cell (any grade) or usual type adenocarcinoma (grade 1 or 2 only); tumor size ≤2 cm; depth of invasion ≤10 mm; and negative imaging for metastatic disease.[90][118][120]

Conservative surgical treatment for patients not desiring fertility is simple (type A) hysterectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy.

Hysterectomy is the preferred treatment for early stage disease when fertility preservation is not desired; resection may limit the need for adjuvant treatment.[114][115]​ The type of hysterectomy performed varies depending on disease stage, treatment intent (e.g., curative), and patient preference. The Querleu and Morrow classification system describes degree of resection and nerve preservation.[116][117]

Simple (extrafascial) hysterectomy (Querleu-Morrow type A) and modified radical hysterectomy (type B) are curative options for microinvasive disease and small lesions (stage IA1-IB1 disease).[90][118][120]

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis. Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156] If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

1st line – modified radical (type B) hysterectomy + SLN mapping/pelvic lymphadenectomy

Back
ACUTE
|
nonpregnant stage IA2: not desiring fertility
|
nonconservative surgery candidate
1st line – 

modified radical (type B) hysterectomy + SLN mapping/pelvic lymphadenectomy

Primary treatment options for patients with stage IA2 disease not desiring fertility include modified radical (type B) hysterectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy (if surgical candidate).

Hysterectomy is the preferred treatment for early stage disease when fertility preservation is not desired; resection may limit the need for adjuvant treatment.[114][115]​​ The type of hysterectomy performed varies depending on disease stage, treatment intent (e.g., curative), and patient preference. The Querleu and Morrow classification system describes degree of resection and nerve preservation.[116][117]​​

Simple (extrafascial) hysterectomy (Querleu-Morrow type A) and modified radical hysterectomy (type B) are curative options for microinvasive disease and small lesions (stage IA1-IB1 disease).[90][118][120]

Open surgery is preferred for radical hysterectomy; minimally invasive radical hysterectomy (i.e., laparoscopic or robot-assisted) is associated with lower disease-free and overall survival compared with open abdominal surgery.[121][122][123]​​ Clinicians should assess the risks and potential benefits of each surgical approach for the individual patient, and counsel accordingly.[90][181]​ Studies are ongoing to identify which patients might safely benefit from minimally invasive surgery.[124][125]

Age does not appear to be a significant contraindication to radical hysterectomy. Class III obesity (i.e., body mass index ≥40) is a relative contraindication to surgery, and operative risk may need to be weighed against the risks of alternative treatment options.[126][127]

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​​​​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​​​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

Consider – postoperative radiation ± chemotherapy

Back
ACUTE
|
nonpregnant stage IA2: not desiring fertility
|
nonconservative surgery candidate
Consider – 

postoperative radiation ± chemotherapy

Treatment recommended for SOME patients in selected patient group

Postoperative chemoradiation is required if surgical pathology reveals positive nodes, involvement of the parametrium, or positive margins in patients with stage IA2, IB, or IIA disease.[90][159][173] Cisplatin plus external beam radiation therapy (EBRT) with or without brachytherapy is the standard regimen for postoperative chemoradiation.[159]

Adjuvant treatment should also be considered in patients with negative nodes, no parametrial involvement, and negative margins, if they have two or more of the following intermediate-risk factors (i.e., the Sedlis criteria): LVSI, deep stromal invasion, and/or large tumor size.[174] Postoperative EBRT alone or with or without concurrent platinum-containing chemotherapy may be considered.[174][175]​ Optimal adjuvant treatment for intermediate-risk disease has not been determined.[138][176]​​​​

No further treatment is required for patients with negative nodes, no parametrial involvement, negative margins, and with one or no intermediate-risk factors. Patients should be monitored for recurrence.[90]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

1st line – pelvic EBRT + brachytherapy

Back
ACUTE
|
nonpregnant stage IA2: not desiring fertility
|
nonsurgical candidate
1st line – 

pelvic EBRT + brachytherapy

Primary treatment options for patients with stage IA2 disease not desiring fertility include pelvic EBRT plus brachytherapy (if nonsurgical candidate).

Radiation therapy alone is an effective option for patients with early stage disease or for those who are not candidates for surgery.[90][138][139]

Radiation therapy may be given EBRT and/or brachytherapy. EBRT delivers radiation directly to the tumor site. Intensity-modulated radiation therapy (IMRT) should be considered to reduce acute and chronic toxicity in definitive treatment of the pelvis (with or without para-aortic treatment).[138]

Brachytherapy is an integral component of definitive radiation therapy for patients with primary cervical cancer, performed using an intracavitary and/or an interstitial approach. Brachytherapy is usually given following EBRT, as a radiation boost to the primary tumor. Brachytherapy has been shown to decrease recurrence rates and improve survival in combination with EBRT compared with EBRT alone.[140][141][142][143] In highly selected, very early stage disease, brachytherapy alone (without EBRT) may be an option. Image-guided brachytherapy is recommended; magnetic resonance imaging (MRI)-guided adaptive brachytherapy is the gold standard brachytherapy technique.[138][144][145]​​[146]

nonpregnant stage IB1: desiring fertility

1st line – SLN mapping or pelvic lymphadenectomy (following cone biopsy)

Back
ACUTE
|
nonpregnant stage IB1: desiring fertility
|
conservative surgery candidate
1st line – 

SLN mapping or pelvic lymphadenectomy (following cone biopsy)

Patients with stage IA2 or IB1 disease may be considered for conservative surgical treatment if they meet all of the following criteria: no lymphovascular space invasion (LVSI); negative cone margins; squamous cell (any grade) or usual type adenocarcinoma (grade 1 or 2 only); tumor size ≤2 cm; depth of invasion ≤10 mm; and negative imaging for locoregional disease.[90][118]

Conservative surgical treatment for patients who want to maintain fertility is cone biopsy (with negative margins) plus pelvic lymphadenectomy or sentinel lymph node (SLN) mapping.

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​​​​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​​​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

1st line – radical trachelectomy + SLN mapping/pelvic lymphadenectomy ± para-aortic lymphadenectomy

Back
ACUTE
|
nonpregnant stage IB1: desiring fertility
|
nonconservative surgery candidate
1st line – 

radical trachelectomy + SLN mapping/pelvic lymphadenectomy ± para-aortic lymphadenectomy

Primary treatment option for patients with stage IB1 disease and select patients with IB2 disease who want to maintain fertility is radical trachelectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy, with or without para-aortic lymphadenectomy.

Trachelectomy is a fertility-sparing option for carefully selected patients with early stage disease. Simple trachelectomy may be considered for microinvasive disease (stage IA1); radical trachelectomy for stages IA1, IA2, IB1, and for select IB2 cases.[90] Minimally invasive procedures may be considered for cervical cancer patients with preoperative tumor size of ≤2 cm, but there is a lack of data on oncologic outcomes.[90][128]

Retrospective studies suggest that radical trachelectomy may be associated with an increased but acceptable risk of recurrence compared with radical hysterectomy.[129] Risk of recurrence may be increased in patients with tumor size >2 cm after any type of fertility-sparing procedures.[130]​ Patients with tumor size >2 cm who undergo radical abdominal trachelectomy may require adjuvant therapy, which will affect their fertility.[90][112][131][132][133][134]

Radical trachelectomy using a vaginal approach is typically recommended for tumors <2 cm. An abdominal approach allows greater resection of parametrial tissue than the vaginal approach and is favored for larger tumors.

Risk of loss of pregnancy and preterm labor is increased in patients following radical trachelectomy due to cervical weakness. Systematic reviews suggest that oncologic outcomes are similar for different fertility-sparing techniques, but that vaginal radical trachelectomy may achieve improved reproductive outcomes.[135][136][137] Further research is needed to determine fertility and pregnancy outcomes for different procedures.

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%). For patients w​ith large tumors, para-aortic node dissection may be performed if nodal involvement is suspected or confirmed.[90][154]

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[158][182]​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

nonpregnant stage IB1: not desiring fertility

1st line – simple (type A) hysterectomy + SLN mapping/pelvic lymphadenectomy

Back
ACUTE
|
nonpregnant stage IB1: not desiring fertility
|
conservative surgery candidate
1st line – 

simple (type A) hysterectomy + SLN mapping/pelvic lymphadenectomy

Patients with stage IA2 or IB1 disease may be considered for conservative surgical treatment if they meet all of the following criteria: no lymphovascular space invasion (LVSI); negative cone margins; squamous cell (any grade) or usual type adenocarcinoma (grade 1 or 2 only); tumor size ≤2 cm; depth of invasion ≤10 mm; and negative imaging for metastatic disease.[90][118][120]

Conservative surgical treatment for patients not desiring fertility is simple (type A) hysterectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy.

Hysterectomy is the preferred treatment for early stage disease when fertility preservation is not desired; resection may limit the need for adjuvant treatment.[114][115]​​​ The type of hysterectomy performed varies depending on disease stage, treatment intent (e.g., curative), and patient preference. The Querleu and Morrow classification system describes degree of resection and nerve preservation.[116][117]

Simple (extrafascial) hysterectomy (Querleu-Morrow type A) and modified radical hysterectomy (type B) are curative options for microinvasive disease and small lesions (stage IA1-IB1 disease).[90][118][120]

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%).

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​​​​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​​​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

1st line – radical (type C1) hysterectomy + SLN mapping/pelvic lymphadenectomy ± para-aortic lymphadenectomy

Back
ACUTE
|
nonpregnant stage IB1: not desiring fertility
|
nonconservative surgery candidate
1st line – 

radical (type C1) hysterectomy + SLN mapping/pelvic lymphadenectomy ± para-aortic lymphadenectomy

Primary treatment options for patients with stage IB1 or IB2 disease not desiring fertility include radical (type C1) hysterectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy, with or without para-aortic lymphadenectomy (if surgical candidate).[90]

Hysterectomy is the preferred treatment for early stage disease when fertility preservation is not desired; resection may limit the need for adjuvant treatment.[114][115]​​ The type of hysterectomy performed varies depending on disease stage, treatment intent (e.g., curative), and patient preference. The Querleu and Morrow classification system describes degree of resection and nerve preservation.[116][117]​​

For larger lesions (stage IB1), nerve-sparing radical hysterectomy (type C1) is typically recommended.[90][119] 

Open surgery is preferred for radical hysterectomy; minimally invasive radical hysterectomy (i.e., laparoscopic or robot-assisted) is associated with lower disease-free and overall survival compared with open abdominal surgery.[121][122][123]​ Clinicians should assess the risks and potential benefits of each surgical approach for the individual patient, and counsel accordingly.[90][181] Studies are ongoing to identify which patients might safely benefit from minimally invasive surgery.[124][125]

Age does not appear to be a significant contraindication to radical hysterectomy. Class III obesity (i.e., body mass index ≥40) is a relative contraindication to surgery, and operative risk may need to be weighed against the risks of alternative treatment options.[126][127]

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases. These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%). For patients with large tumors, para-aortic node dissection may be performed if nodal involvement is suspected or confirmed.[90][154]

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156] SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​​​​​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156] If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

Consider – postoperative radiation ± chemotherapy

Back
ACUTE
|
nonpregnant stage IB1: not desiring fertility
|
nonconservative surgery candidate
Consider – 

postoperative radiation ± chemotherapy

Treatment recommended for SOME patients in selected patient group

Postoperative chemoradiation is required if surgical pathology reveals positive nodes, involvement of the parametrium, or positive margins in patients with IA2, IB, or IIA disease.[90][159][173]​ Cisplatin plus external beam radiation therapy (EBRT) with or without brachytherapy is the standard regimen for postoperative chemoradiation.[159]

Adjuvant treatment should also be considered in patients with negative nodes, no parametrial involvement, and negative margins, if they have two or more of the following intermediate-risk factors (i.e., the Sedlis criteria): LVSI, deep stromal invasion, and/or large tumor size.[174] Postoperative EBRT alone or with or without concurrent platinum-containing chemotherapy may be considered.[174][175]​ Optimal adjuvant treatment for intermediate-risk disease has not been determined.[138][176]​​​

No further treatment is required for patients with negative nodes, no parametrial involvement, negative margins, and with one or no intermediate-risk factors. Patients should be monitored for recurrence.[90]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

1st line – pelvic EBRT + brachytherapy ± concurrent platinum-containing chemotherapy

Back
ACUTE
|
nonpregnant stage IB1: not desiring fertility
|
nonsurgical candidate
1st line – 

pelvic EBRT + brachytherapy ± concurrent platinum-containing chemotherapy

Primary treatment options for patients with stage IB1 or IB2 disease not desiring fertility include pelvic EBRT plus brachytherapy with or without concurrent platinum-containing chemotherapy (if nonsurgical candidate).

Radiation therapy may be given using EBRT and/or brachytherapy. EBRT delivers radiation directly to the tumor site. Intensity-modulated radiation therapy (IMRT) should be considered to reduce acute and chronic toxicity in definitive treatment of the pelvis (with or without para-aortic treatment).[138]

Brachytherapy is an integral component of definitive radiation therapy for patients with primary cervical cancer, performed using an intracavitary and/or an interstitial approach. Brachytherapy is usually given following EBRT, as a radiation boost to the primary tumor. Brachytherapy has been shown to decrease recurrence rates and improve survival in combination with EBRT compared with EBRT alone.[140][141][142][143] In highly selected, very early stage disease, brachytherapy alone (without EBRT) may be an option. Image-guided brachytherapy is recommended; magnetic resonance imaging (MRI)-guided adaptive brachytherapy is the gold standard brachytherapy technique.[138][144][145]​​[146]

Systematic reviews and meta-analyses confirm that chemoradiation is superior to radiation therapy alone in improving progression-free and overall survival, and reducing local and distant recurrence in locally advanced disease.[147][148] Cisplatin was the most commonly used chemotherapeutic agent.[147][148] Acute gastrointestinal toxicity was significantly more common in the chemoradiation groups; cisplatin-based chemoradiation was not associated with increased late toxicity in one randomized trial.[147][148][149]

Cisplatin plus EBRT and brachytherapy is the preferred regimen for patients with locally advanced disease. It may be an option for some patients with stage IB1, IB2, or IIA1 disease (e.g., if surgery is not suitable), with careful consideration of the risks and benefits. Carboplatin may be considered for patients who cannot tolerate cisplatin.[90] Other chemotherapy regimens may be effective, including two-drug regimens (e.g., cisplatin plus fluorouracil, cisplatin plus gemcitabine).[149][150][151]​​ However, chemotherapy regimens that incorporate multiple-drug regimens are not recommended because of increased toxicity.[151][152][153]​​​​

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

OR

carboplatin

nonpregnant stage IB2: desiring fertility

1st line – radical trachelectomy + SLN mapping/pelvic lymphadenectomy ± para-aortic lymphadenectomy

Back
ACUTE
|
nonpregnant stage IB2: desiring fertility
1st line – 

radical trachelectomy + SLN mapping/pelvic lymphadenectomy ± para-aortic lymphadenectomy

Primary treatment option for patients with stage IB1 disease and select patients with IB2 disease who want to maintain fertility is radical trachelectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy, with or without para-aortic lymphadenectomy.

Trachelectomy is a fertility-sparing option for carefully selected patients with early stage disease. Radical trachelectomy may be considered for select IB2 cases.[90]

Retrospective studies suggest that radical trachelectomy may be associated with an increased but acceptable risk of recurrence compared with radical hysterectomy.[129] Risk of recurrence may be increased in patients with tumor size >2 cm after any type of fertility-sparing procedures.[130] ​Patients with tumor size >2 cm who undergo radical abdominal trachelectomy may require adjuvant therapy, which will affect their fertility.[90][112][131][132][133][134]

Radical trachelectomy using a vaginal approach is typically recommended for tumors <2 cm. An abdominal approach allows greater resection of parametrial tissue than the vaginal approach and is favored for larger tumors.​

Risk of loss of pregnancy and preterm labor is increased in patients following radical trachelectomy due to cervical weakness. Systematic reviews suggest that oncologic outcomes are similar for different fertility-sparing techniques, but that vaginal radical trachelectomy may achieve improved reproductive outcomes.[135][136][137]​​​ Further research is needed to determine fertility and pregnancy outcomes for different procedures.

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without lymphovascular space invasion (LVSI), because the risk of nodal metastases is very small (less than 1%). For patients with large tumors, para-aortic node dissection may be performed if nodal involvement is suspected or confirmed.[90][154]

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[158][182]​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

nonpregnant, stage IB2: not desiring fertility

1st line – radical (type C1) hysterectomy + SLN mapping/pelvic lymphadenectomy ± para-aortic lymphadenectomy

Back
ACUTE
|
nonpregnant, stage IB2: not desiring fertility
|
surgical candidate
1st line – 

radical (type C1) hysterectomy + SLN mapping/pelvic lymphadenectomy ± para-aortic lymphadenectomy

Primary treatment options for patients with stage IB1 or IB2 disease not desiring fertility include radical (type C1) hysterectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy, with or without para-aortic lymphadenectomy (if surgical candidate).

Hysterectomy is the preferred treatment for early stage disease when fertility preservation is not desired; resection may limit the need for adjuvant treatment.[114][115]​​ The type of hysterectomy performed varies depending on disease stage, treatment intent (e.g., curative), and patient preference. The Querleu and Morrow classification system describes degree of resection and nerve preservation.[116][117]

For larger lesions (stage IB1-IIA1), nerve-sparing radical hysterectomy (type C) is typically recommended.[90][119]

Open surgery is preferred for radical hysterectomy; minimally invasive radical hysterectomy (i.e., laparoscopic or robot-assisted) is associated with lower disease-free and overall survival compared with open abdominal surgery.[121][122][123]​​ Clinicians should assess the risks and potential benefits of each surgical approach for the individual patient, and counsel accordingly.[90][181]​ Studies are ongoing to identify which patients might safely benefit from minimally invasive surgery.[124][125]

Age does not appear to be a significant contraindication to radical hysterectomy. Class III obesity (i.e., body mass index ≥40) is a relative contraindication to surgery, and operative risk may need to be weighed against the risks of alternative treatment options.[126][127]

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases.[90] These procedures are not generally required for patients with stage IA1 disease without LVSI, because the risk of nodal metastases is very small (less than 1%). For patients with large tumors, para-aortic node dissection may be performed if nodal involvement is suspected or confirmed.[90][154]

SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​​​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​​​​​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis.[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​​​​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

Consider – postoperative radiation ± chemotherapy

Back
ACUTE
|
nonpregnant, stage IB2: not desiring fertility
|
surgical candidate
Consider – 

postoperative radiation ± chemotherapy

Treatment recommended for SOME patients in selected patient group

Postoperative chemoradiation is required if surgical pathology reveals positive nodes, involvement of the parametrium, or positive margins in patients stage IA2, IB, or IIA disease.[90][159][173] Cisplatin plus external beam radiation therapy (EBRT) with or without brachytherapy is the standard regimen for postoperative chemoradiation.[159]

Adjuvant treatment should also be considered in patients with negative nodes, no parametrial involvement, and negative margins, if they have two or more of the following intermediate-risk factors (i.e., the Sedlis criteria): LVSI, deep stromal invasion, and/or large tumor size.[174] Postoperative EBRT with or without concurrent platinum-containing chemotherapy may be considered.[174][175]​Optimal adjuvant treatment for intermediate-risk disease has not been determined.[138][176]

​​No further treatment is required for patients with negative nodes, no parametrial involvement, negative margins, and with one or no intermediate-risk factors. Patients should be monitored for recurrence.[90]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

1st line – pelvic EBRT + brachytherapy ± concurrent platinum-containing chemotherapy

Back
ACUTE
|
nonpregnant, stage IB2: not desiring fertility
|
nonsurgical candidate
1st line – 

pelvic EBRT + brachytherapy ± concurrent platinum-containing chemotherapy

Primary treatment options for patients with stage IB1 or IB2 disease not desiring fertility include pelvic EBRT plus brachytherapy with or without concurrent platinum-containing chemotherapy (if nonsurgical candidate).

Radiation therapy may be given using EBRT and/or brachytherapy. EBRT delivers radiation directly to the tumor site. Intensity-modulated radiation therapy (IMRT) should be considered to reduce acute and chronic toxicity in definitive treatment of the pelvis (with or without para-aortic treatment).[138]

Brachytherapy is an integral component of definitive radiation therapy for patients with primary cervical cancer, performed using an intracavitary and/or an interstitial approach. Brachytherapy is usually given following EBRT, as a radiation boost to the primary tumor. Brachytherapy has been shown to decrease recurrence rates and improve survival in combination with EBRT compared with EBRT alone.[140][141][142][143] In highly selected, very early stage disease, brachytherapy alone (without EBRT) may be an option. Image-guided brachytherapy is recommended; magnetic resonance imaging (MRI)-guided adaptive brachytherapy is the gold standard brachytherapy technique.[138][144][145]​​[146]

Systematic reviews and meta-analyses confirm that chemoradiation is superior to radiation therapy alone in improving progression-free and overall survival, and reducing local and distant recurrence in locally advanced disease.[147][148] Cisplatin was the most commonly used chemotherapeutic agent.[147][148] Acute gastrointestinal toxicity was significantly more common in the chemoradiation groups; cisplatin-based chemoradiation was not associated with increased late toxicity in one randomized trial.[147][148][149]

Cisplatin plus EBRT and brachytherapy is the preferred regimen for patients with locally advanced disease. It may be an option for some patients with stage IB1, IB2, or IIA1 disease (e.g., if surgery is not suitable), with careful consideration of the risks and benefits. Carboplatin may be considered for patients who cannot tolerate cisplatin.[90] Other chemotherapy regimens may be effective, including two-drug regimens (e.g., cisplatin plus fluorouracil, cisplatin plus gemcitabine).[149][150][151] However, chemotherapy regimens that incorporate multiple-drug regimens are not recommended because of increased toxicity.[151][152][153]​​

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

OR

carboplatin

nonpregnant stage IIA1

1st line – radical (type C1) hysterectomy + SLN mapping/pelvic lymphadenectomy ± para-aortic lymphadenectomy

Back
ACUTE
|
nonpregnant stage IIA1
|
surgical candidate
1st line – 

radical (type C1) hysterectomy + SLN mapping/pelvic lymphadenectomy ± para-aortic lymphadenectomy

Primary treatment options for patients with stage IIA1 disease include radical (type C1) hysterectomy plus sentinel lymph node (SLN) mapping or pelvic lymphadenectomy, with or without para-aortic lymphadenectomy (if surgical candidate).

Hysterectomy is the preferred treatment for early stage disease when fertility preservation is not desired; resection may limit the need for adjuvant treatment.[114][115]​​ The type of hysterectomy performed varies depending on disease stage, treatment intent (e.g., curative), and patient preference. The Querleu and Morrow classification system describes degree of resection and nerve preservation.[116][117]

For larger lesions (stage IB1-IIA1), nerve-sparing radical hysterectomy (Querleu and Morrow type C1) is typically recommended.[90][119]​ 

Open surgery is preferred for radical hysterectomy; minimally invasive radical hysterectomy (i.e., laparoscopic or robot-assisted) is associated with lower disease-free and overall survival compared with open abdominal surgery.[121][122][123]​ Clinicians should assess the risks and potential benefits of each surgical approach for the individual patient, and counsel accordingly.[90][181] Studies are ongoing to identify which patients might safely benefit from minimally invasive surgery.[124][125]

Age does not appear to be a significant contraindication to radical hysterectomy. Class III obesity (i.e., body mass index ≥40) is a relative contraindication to surgery, and operative risk may need to be weighed against the risks of alternative treatment options.[126][127]

Pelvic lymphadenectomy or SLN mapping should be performed for most patients having surgical treatment for stage I and II disease to assess for lymph node metastases. These procedures are not generally required for patients with stage IA1 disease without lymphovascular space invasion (LVSI), because the risk of nodal metastases is very small (less than 1%). For patients with large tumors, para-aortic node dissection may be performed if nodal involvement is suspected or confirmed.[90][154]

​SLN mapping may safely reduce the need for extensive pelvic lymph node dissection in many patients with early stage disease.[155][156]​​ SLN mapping is associated with fewer complications than lymphadenectomy; however, long-term survival data comparing these techniques is lacking.[157][158]​​​​​​​​​ Detection rate for SLN is highest if the tumor is <2 cm, although SLN mapping has been used in tumors up to 4 cm in size.[59][90]

Ultrastaging should be carried out for increased detection of micrometastasis[90] Sentinel nodes should be detected on both sides, and all suspicious lymph nodes should be removed.[155][156]​ If SLN mapping fails, side-specific nodal dissection should be carried out.[90]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

Consider – postoperative radiation ± chemotherapy

Back
ACUTE
|
nonpregnant stage IIA1
|
surgical candidate
Consider – 

postoperative radiation ± chemotherapy

Treatment recommended for SOME patients in selected patient group

Postoperative chemoradiation is required if surgical pathology reveals positive nodes, involvement of the parametrium, or positive margins in patients with stage IA2, IB, or IIA disease.[90][159]​ [173] Cisplatin plus external beam radiation therapy (EBRT) with or without brachytherapy is the standard regimen for postoperative chemoradiation.[159]

Adjuvant treatment should also be considered in patients with negative nodes, no parametrial involvement, and negative margins, if they have two or more of the following intermediate-risk factors (i.e., the Sedlis criteria): LVSI, deep stromal invasion, and/or large tumor size.[174] Postoperative EBRT with or without concurrent platinum-containing chemotherapy may be considered.[174][175] O​ptimal adjuvant treatment for intermediate-risk disease has not been determined.[138][176]​​​

No further treatment is required for patients with negative nodes, no parametrial involvement, negative margins, and with one or no intermediate-risk factors. Patients should be monitored for recurrence.[90]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

1st line – pelvic EBRT + brachytherapy ± concurrent platinum-containing chemotherapy

Back
ACUTE
|
nonpregnant stage IIA1
|
nonsurgical candidate
1st line – 

pelvic EBRT + brachytherapy ± concurrent platinum-containing chemotherapy

Primary treatment options for patients with stage IIA1 disease include pelvic EBRT plus brachytherapy with or without concurrent platinum-containing chemotherapy (if nonsurgical candidate).

Radiation therapy may be given using EBRT and/or brachytherapy. EBRT delivers radiation directly to the tumor site. Intensity-modulated radiation therapy (IMRT) should be considered to reduce acute and chronic toxicity in definitive treatment of the pelvis (with or without para-aortic treatment).[138]

Brachytherapy is an integral component of definitive radiation therapy for patients with primary cervical cancer, performed using an intracavitary and/or an interstitial approach. Brachytherapy is usually given following EBRT, as a radiation boost to the primary tumor. Brachytherapy has been shown to decrease recurrence rates and improve survival in combination with EBRT compared with EBRT alone.[140][141][142][143] In highly selected, very early stage disease, brachytherapy alone (without EBRT) may be an option. Image-guided brachytherapy is recommended; magnetic resonance imaging (MRI)-guided adaptive brachytherapy is the gold standard brachytherapy technique.[138][144][145]​​[146]

Systematic reviews and meta-analyses confirm that chemoradiation is superior to radiation therapy alone in improving progression-free and overall survival, and reducing local and distant recurrence in locally advanced disease.[147][148] Cisplatin was the most commonly used chemotherapeutic agent.[147][148] Acute gastrointestinal toxicity was significantly more common in the chemoradiation groups; cisplatin-based chemoradiation was not associated with increased late toxicity in one randomized trial.[147][148][149]

Cisplatin plus EBRT and brachytherapy is the preferred regimen for patients with locally advanced disease. It may be an option for some patients with stage IB1, IB2, or IIA1 disease (e.g., if surgery is not suitable), with careful consideration of the risks and benefits. Carboplatin may be considered for patients who cannot tolerate cisplatin.[90] Other chemotherapy regimens may be effective, including two-drug regimens (e.g., cisplatin plus fluorouracil, cisplatin plus gemcitabine).[149][150][151] However, chemotherapy regimens that incorporate multiple-drug regimens are not recommended because of increased toxicity.[151][152][153]​​

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

OR

carboplatin

nonpregnant stage IB3 or IIA2

1st line – pelvic EBRT + concurrent platinum-containing chemotherapy + brachytherapy

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ACUTE
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nonpregnant stage IB3 or IIA2
1st line – 

pelvic EBRT + concurrent platinum-containing chemotherapy + brachytherapy

Primary treatment options for patients with stage IB3 or IIA2 disease include pelvic external beam radiation therapy (EBRT) plus concurrent platinum-containing chemotherapy plus brachytherapy (preferred treatment).[90]

Chemoradiation is preferred in patients with bulky tumors measuring ≥4 cm (stage IB3 and IIA2) given the high likelihood that postoperative chemoradiation will be required for adverse pathologic findings if hysterectomy is carried out initially.[147][159][160][161]​​

Systematic reviews and meta-analyses confirm that chemoradiation is superior to radiation therapy alone in improving progression-free and overall survival, and reducing local and distant recurrence in locally advanced disease.[147][148] Cisplatin was the most commonly used chemotherapeutic agent.[147][148] Acute gastrointestinal toxicity was significantly more common in the chemoradiation groups; cisplatin-based chemoradiation was not associated with increased late toxicity in one randomized trial.[147][148][149]

Cisplatin plus EBRT and brachytherapy is the preferred regimen for patients with locally advanced disease. It may be an option for some patients with stage IB1, IB2, or IIA1 disease (e.g., if surgery is not suitable), with careful consideration of the risks and benefits. Carboplatin may be considered for patients who cannot tolerate cisplatin.[90] Other chemotherapy regimens may be effective, including two-drug regimens (e.g., cisplatin plus fluorouracil, cisplatin plus gemcitabine).[149][150][151] However, chemotherapy regimens that incorporate multiple-drug regimens are not recommended because of increased toxicity.[151][152][153]​​

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

OR

carboplatin

Consider – selective completion hysterectomy

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ACUTE
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nonpregnant stage IB3 or IIA2
Consider – 

selective completion hysterectomy

Treatment recommended for SOME patients in selected patient group

Adjuvant (completion) hysterectomy may be considered if there is a poor response (with evidence of residual disease) after chemoradiation (including brachytherapy), or if brachytherapy is not feasible.[90][162]

1st line – radical (type C1) hysterectomy + pelvic lymphadenectomy ± para-aortic lymphadenectomy

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ACUTE
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nonpregnant stage IB3 or IIA2
1st line – 

radical (type C1) hysterectomy + pelvic lymphadenectomy ± para-aortic lymphadenectomy

Primary treatment options for patients with stage IB3 or IIA2 disease include radical (type C1) hysterectomy plus pelvic lymphadenectomy with or without para-aortic lymphadenectomy.[90]

Hysterectomy is the preferred treatment for early stage disease when fertility preservation is not desired; resection may limit the need for adjuvant treatment.[114][115]​​ The type of hysterectomy performed varies depending on disease stage, treatment intent (e.g., curative), and patient preference. The Querleu and Morrow classification system describes degree of resection and nerve preservation.[116][117]

For larger lesions, nerve-sparing radical hysterectomy (Querleu and Morrow type C1) is typically recommended.[90][119]

Open surgery is preferred for radical hysterectomy; minimally invasive radical hysterectomy (i.e., laparoscopic or robot-assisted) is associated with lower disease-free and overall survival compared with open abdominal surgery.[121][122][123]​ Clinicians should assess the risks and potential benefits of each surgical approach for the individual patient, and counsel accordingly.[90][181]​ Studies are ongoing to identify which patients might safely benefit from minimally invasive surgery.[124][125]

Age does not appear to be a significant contraindication to radical hysterectomy. Class III obesity (i.e., body mass index ≥40) is a relative contraindication to surgery, and operative risk may need to be weighed against the risks of alternative treatment options.[126][127]

Pelvic lymphadenectomy should be performed to assess for lymph node metastases.[90] For patients with large tumors, para-aortic node dissection may be performed if nodal involvement is suspected or confirmed.[90][154]

Following surgery, it is essential to evaluate surgical pathology to guide decisions on adjuvant therapy.

Consider – postoperative radiation ± chemotherapy

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ACUTE
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nonpregnant stage IB3 or IIA2
Consider – 

postoperative radiation ± chemotherapy

Treatment recommended for SOME patients in selected patient group

Postoperative chemoradiation is required if surgical pathology reveals positive nodes, involvement of the parametrium, or positive margins in patients with stage IA2, IB, or IIA disease.[90][159][173] Cisplatin plus external beam radiation therapy (EBRT) with or without brachytherapy is the standard regimen for postoperative chemoradiation.[159]

Adjuvant treatment should also be considered in patients with negative nodes, no parametrial involvement, and negative margins, if they have two or more of the following intermediate-risk factors (i.e., the Sedlis criteria): LVSI, deep stromal invasion, and/or large tumor size.[174] Postoperative EBRT with or without concurrent platinum-containing chemotherapy may be considered.[174][175]​Optimal adjuvant treatment for intermediate-risk disease has not been determined.[138][176]​​​

No further treatment is required for patients with negative nodes, no parametrial involvement, negative margins, and with one or no intermediate-risk factors. Patients should be monitored for recurrence.[90]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

nonpregnant stage IIB to IVA

1st line – pelvic EBRT + concurrent platinum-containing chemotherapy + brachytherapy

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ACUTE
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nonpregnant stage IIB to IVA
1st line – 

pelvic EBRT + concurrent platinum-containing chemotherapy + brachytherapy

Primary treatment for patients with stage IIB to IVA disease is pelvic external beam radiation therapy (EBRT) plus concurrent platinum-containing chemotherapy plus brachytherapy (if no lymph node involvement).

Imaging studies are recommended for evaluation of nodal or extrapelvic involvement and to guide treatment. Para-aortic lymph node EBRT or extended-field EBRT may be indicated depending on pelvic and para-aortic lymph node status on imaging or surgical staging.[90]

Chemoradiation is preferred in patients with bulky tumors measuring ≥4 cm (stage IB3 and IIA2) given the high likelihood that postoperative chemoradiation will be required for adverse pathologic findings if hysterectomy is carried out initially.[147][159][160][161]​​

Systematic reviews and meta-analyses confirm that chemoradiation is superior to radiation therapy alone in improving progression-free and overall survival, and reducing local and distant recurrence in locally advanced disease.[147][148] Cisplatin was the most commonly used chemotherapeutic agent.[147][148] Acute gastrointestinal toxicity was significantly more common in the chemoradiation groups; cisplatin-based chemoradiation was not associated with increased late toxicity in one randomized trial.[147][148][149]

Cisplatin plus EBRT and brachytherapy is the preferred regimen for patients with locally advanced disease. Carboplatin may be considered for patients who cannot tolerate cisplatin.[90] Other chemotherapy regimens may be effective, including two-drug regimens (e.g., cisplatin plus fluorouracil, cisplatin plus gemcitabine).[149][150][151]​ However, chemotherapy regimens that incorporate multiple-drug regimens are not recommended because of increased toxicity.[151][152][153]​​​

EBRT delivers radiation directly to the tumour site. Intensity-modulated radiation therapy (IMRT) should be considered to reduce acute and chronic toxicity in definitive treatment of the pelvis (with or without para-aortic treatment).[138]

Brachytherapy is an integral component of definitive radiation therapy for patients with primary cervical cancer, performed using an intracavitary and/or an interstitial approach. Brachytherapy is usually given following EBRT, as a radiation boost to the primary tumor. Brachytherapy has been shown to decrease recurrence rates and improve survival in combination with EBRT compared with EBRT alone.[140][141][142][143]​ Image-guided brachytherapy is recommended; magnetic resonance imaging (MRI)-guided adaptive brachytherapy is the gold standard brachytherapy technique.[138][144][145][146]

Extended-field pelvic and para-aortic EBRT are recommended in chemoradiation regimens for locally advanced disease with positive para-aortic and pelvic lymph nodes (stage IIIC, identified by imaging or surgical staging) without distant metastases.[90]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

OR

carboplatin

nonpregnant, stage IVB (metastatic disease)

1st line – chemotherapy ± immunotherapy ± bevacizumab

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ACUTE
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nonpregnant, stage IVB (metastatic disease)
1st line – 

chemotherapy ± immunotherapy ± bevacizumab

Molecular biomarker analysis, including programmed death ligand 1(PD-L1), human epidermal growth factor receptor 2 (HER2), and microsatellite instability/mismatch repair (MSI/MMR) status, is recommended for patients with metastatic disease to help guide targeted therapy options and/or eligibility for clinical trials.

Molecular profiling may be considered using an FDA-approved assay or validated test including at least HER2, MMR/MSI, tumor mutational burden (TMB), and NTRK and RET gene fusions.[90] If analysis of tissue is not possible, comprehensive genomic profiling (using a validated plasma circulating tumor DNA assay) may be an option.[90]

Combination chemotherapy plus bevacizumab (a vascular endothelial growth factor-directed monoclonal antibody) is a preferred first-line treatment option for metastatic disease.[90] Cisplatin plus paclitaxel is the preferred chemotherapy regimen. Carboplatin plus paclitaxel is a less toxic option, recommended for patients who have received previous cisplatin therapy. Cisplatin plus topotecan is an option if taxanes are not suitable.[90][163][164][165]​ The addition of bevacizumab has been shown to increase survival rate.[166]

The checkpoint inhibitor pembrolizumab (an antiprogrammed death 1 monoclonal antibody) may be combined with chemotherapy (with or without bevacizumab) in patients with PD-L1-positive metastatic disease.[90] The addition of pembrolizumab to chemotherapy (with or without bevacizumab) improves progression-free and overall survival in PD-L1-positive patients, without reducing patient-reported quality of life.[108][168][169]​​​​​​[170]

Further first-line options include combination chemotherapy regimens without bevacizumab (e.g., cisplatin plus paclitaxel, carboplatin plus paclitaxel, topotecan plus paclitaxel, cisplatin plus topotecan); or single-agent chemotherapy (e.g., cisplatin or carboplatin).

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

and

paclitaxel

and

bevacizumab

OR

carboplatin

and

paclitaxel

and

bevacizumab

OR

cisplatin

and

paclitaxel

and

pembrolizumab

and

bevacizumab

OR

cisplatin

and

paclitaxel

and

pembrolizumab

OR

carboplatin

and

paclitaxel

and

pembrolizumab

and

bevacizumab

OR

carboplatin

and

paclitaxel

and

pembrolizumab

Secondary options

cisplatin

and

paclitaxel

OR

carboplatin

and

paclitaxel

OR

topotecan

and

paclitaxel

and

bevacizumab

OR

topotecan

and

paclitaxel

OR

cisplatin

and

topotecan

OR

cisplatin

OR

carboplatin

Plus – supportive care

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nonpregnant, stage IVB (metastatic disease)
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be offered alongside treatment for metastatic disease or as an alternative to further chemotherapy in some patients.[90]

Best supportive care addresses physical, psychological, social, and spiritual issues. Common medical challenges include pain, nausea and vomiting, lymphedema, obstruction (genitourinary and gastrointestinal), and fistulae.

Consider – local treatment

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ACUTE
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nonpregnant, stage IVB (metastatic disease)
Consider – 

local treatment

Treatment recommended for SOME patients in selected patient group

In patients with isolated distant metastases that are amenable to local treatment, the following therapy options can be considered: surgical resection with or without external beam radiation therapy (EBRT); local ablative therapies with or without EBRT; EBRT with or without chemotherapy.[90]

Consideration may be given to adjuvant chemotherapy for these patient.

2nd line – single-agent chemotherapy, immunotherapy, targeted therapies, clinical trial enrollment, or supportive care

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ACUTE
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nonpregnant, stage IVB (metastatic disease)
2nd line – 

single-agent chemotherapy, immunotherapy, targeted therapies, clinical trial enrollment, or supportive care

If first-line combination chemotherapy-based regimens or local treatments fail or are not tolerated, individualized discussion between the oncology specialist, the patient, and the family regarding personal goals of treatment, perceived quality of life, and baseline performance status guides the decision on further therapy.

Second-line or subsequent options may include single-agent chemotherapy, immunotherapy, targeted therapies (including bevacizumab), enrollment in a clinical trial, or supportive care.

Preferred second-line treatments include pembrolizumab (for tumors positive for programmed death ligand 1 [PD-L1] or microsatellite instability/mismatch repair [MSI/MMR] deficiency, or with high mutational tumor burden) or tisotumab vedotin.[90][171]​​​[172]

The most active single-agent chemotherapy is cisplatin (response rate is approximately 20% to 30%).[90] If cisplatin has been used previously, or is contraindicated or not tolerated, alternative single agents include carboplatin or paclitaxel.

Targeted therapies may include fam-trastuzumab deruxtecan (a human epidermal growth factor receptor 2 [HER2]-directed antibody-conjugate) for HER2-positive tumors.[90]

Primary options

pembrolizumab

OR

tisotumab vedotin

Secondary options

cisplatin

OR

carboplatin

OR

paclitaxel

OR

bevacizumab

OR

fam-trastuzumab deruxtecan

nonpregnant local or regional recurrent disease

1st line – local treatment ± drug therapy

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ACUTE
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nonpregnant local or regional recurrent disease
1st line – 

local treatment ± drug therapy

In patients with local or regional recurrence who have not had previous radiation therapy, surgical resection (if possible) followed by tumor-directed external beam radiation therapy (EBRT) with chemotherapy and/or brachytherapy may be considered.

In patients with central pelvic recurrence after radiation therapy, the following options may be considered: pelvic exenteration with or without intraoperative radiation therapy; or, in carefully selected patients (with small central lesions <2 cm), radical hysterectomy, or brachytherapy, or EBRT with or without chemotherapy.

For patients with noncentral recurrence, options may include: EBRT with or without chemotherapy; or surgical resection with or without intraoperative radiation therapy; or chemotherapy; or supportive care.

The long-term survival for patients who undergo successful exenterative surgery (pathologic negative margins and no unresectable or extrapelvic disease) is approximately 50%, but treatment-related severe morbidity is high.[177] Rehabilitation programs should be provided following exenterative surgery.

Drug therapy (e.g., chemotherapy, immunotherapy, bevacizumab), a clinical trial, and supportive care are options for further recurrence (metastases).[90]

pregnant

1st line – multidisciplinary care

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ACUTE
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pregnant
1st line – 

multidisciplinary care

A positive screening test or acute presentation of cervical cancer during pregnancy is unusual. Most patients have stage I disease, but those with invasive disease may have to make difficult decisions, such as whether to delay treatment or terminate the pregnancy.

Surgery is typically avoided, and radiation therapy absolutely contraindicated as it would result in pregnancy termination and fetal death. Treatment options depend on the stage of cancer at diagnosis and the trimester of pregnancy.

When diagnosed in the first trimester, pregnancy termination is often discussed to allow for standard treatment that entails surgery or definitive chemoradiation.[178]

A cone biopsy (without endocervical sampling) may be used to treat stage IA1 tumors without lymphovascular space invasion (LVSI).[90] For stage IA1 tumors with LVSI, IA2 and IB1, staging lymphadenectomy may be performed up to 22 weeks.[179] Radical trachelectomy with successful pregnancy preservation has been reported in a few patients with early stage disease.[90] Termination of pregnancy is usually recommended if there are nodal metastases (including micrometastases).

In patients with node positive or locally advanced disease who wish to preserve their pregnancy, chemotherapy during the second or third trimester appears to be safe, but there are little data on the risk of late complications.[180] Alternatively, chemotherapy may be delayed until after delivery and the patient followed up regularly.[179]

Patients diagnosed with cervical cancer in the third trimester who proceed with pregnancy should have multidisciplinary care and delivery by cesarean section after 35 weeks.

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