Cervical Cancer Protocol

A. Screening:

Please refer to existing national guidelines; the details of screening options are beyond the
scope of this clinical protocol.

B. Common findings at presentation are:

Note: most early stage cervical cancer is asymptomatic.

1. Symptoms
• Localized disease
o Vaginal bleeding
o Post coital bleeding
o Foul smelling discharge
• Advanced or metastatic disease
o Pain (especially back or kidney)
o Symptoms and signs from metastasis to lung (e.g. dyspnea, pleuritic
chest pain), liver (hepatomegaly, jaundice), and bone (bone pain,
fracture)

2. Physical exam and laboratory findings

• Localized Disease
o Cervical mass
o Pelvic mass
• Advanced or metastatic disease
o Renal failure
o Supraclavicular and/or cervical lymphadenopathy

C. Diagnosis:

1. Patient with post-coital spotting or intermenstrual bleeding in the absence of cervicitis

or a grossly visualized mass should be referred for VIA or colposcopy

2. Diagnostic biopsy of cervical mass should be done with Tishler or Kevorkian cervical
biopsy forceps, if the mass is large enough to be visualized grossly or if the cervix shows
hypervascularity or other abnormal findings even without a gross lesion. Pathology
should be obtained in ALL cases in which you suspect cervical cancer.

3. LEEP or CONE BIOPSY: Only use for very small lesions. These procedures remove a cone
shaped piece of the cervix, and can be used for both diagnosis and treatment of very
early cancer (stage 1A1). Ideally these procedures remove adequate tissue to ensure
negative margins in one piece. All specimens should be sent for pathologic diagnosis.

Since cervical biopsies can cause substantial hemorrhage, biopsies should be taken by
experienced doctors in a setting in which hemorrhage could be safely managed.

Cervical Cancer Protocol 1 Version Date 10-FEB-2017

D. Staging:

* Note: Patients are staged at the time of initial diagnosis. If more than 4 weeks pass without
treatment, staging should be repeated prior to initiation of treatment.

Imaging:
o Ultrasound of pelvis and abdomen including kidneys (assessing for hydronephrosis)
o Chest x-ray
o CT chest/abdomen/pelvis with IV and PO contrast is required if patient is being
considered for neo-adjuvant chemo and surgery (in order to rule out nodal disease).

Recommended laboratory tests:

CBC (NFS), urea/creatinine, HIV test, pregnancy test for women of reproductive age

Carcinoma of the Cervix Uteri - FIGO staging

• Stage I - The carcinoma is strictly confined to the cervix (extension to the corpus would be
disregarded).
o Stage IA - Invasive carcinoma, which can be diagnosed only by microscopy with deepest
invasion ≤5 mm and largest extension ≥7 mm.
▪ Stage IA1 - Satisfies IA criteria AND measured stromal invasion of ≤3.0 mm in depth
and extension of ≤7.0 mm.
▪ Stage 1A2 - Satisfies IA criteria AND measured stromal invasion of >3.0 mm and not
>5.0 mm with an extension of not >7.0 mm.
o Stage IB - Clinically visible lesions limited to the cervix uteri or preclinical cancers greater
than stage IA.
▪ Stage IB1 - Satisfies IB criteria AND clinically visible lesion ≤4.0 cm in greatest
dimension.
▪ Stage IB2 - Satisfies IB criteria AND clinically visible lesion >4.0 cm in greatest
dimension.
• Stage II - Cervical carcinoma invades beyond the uterus but not to the pelvic wall or to the lower
third of the vagina.
o Stage IIA - Involves upper 2/3 of the vagina without parametrial invasion.
▪ Stage IIA1 - Satisfies IIA criteria AND clinically visible lesion ≤4.0 cm in greatest
dimension.
▪ Stage IIA2 - Satisfies IIA criteria AND clinically visible lesion >4.0 cm in greatest
dimension.
o Stage IIB - With obvious parametrial invasion.
• Stage III - The tumor extends to the pelvic wall and/or involves lower third of the vagina and/or
causes hydronephrosis or nonfunctioning kidney.
o Stage IIIA - Tumor involves lower third of the vagina with no extension to the pelvic wall.
o Stage IIIB - Extension to the pelvic wall and/or hydronephrosis or nonfunctioning kidney.
• Stage IV - The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the
mucosa of the bladder or rectum. A bullous edema, as such, does not permit a case to be allotted to
stage IV.
o Stage IVA - Spread of the growth to adjacent organs.
o Stage IVB - Spread to distant organs.

Cervical Cancer Protocol 2 Version Date 10-FEB-2017

E. Treatment:

Stage IA1 (microscopic lesion <3mm depth and <7 mm width)

1. Cone biopsy, LEEP or simple hysterectomy.

Stage IA2 - IB1 (lesion confined to the cervix >= 3mm depth but less than 4cm)

1. Primary chemoradiation; OR

2. Radical hysterectomy with bilateral pelvic lymph node dissection (if gynecologic
oncologist available); OR

3. Neoadjuvant chemotherapy, followed by modified radical hysterectomy (if gynecologic

oncologist if available) or simple hysterectomy. If a simple hysterectomy is performed, a
surgeon should join to perform a lymph node dissection at the time of hysterectomy.

If none of the above options are available, a simple hysterectomy alone may be
performed, which may still be curative, though the chance of cure is less.

Stage IB2 (lesion confined to the cervix, but greater than 4 cm)

1. Primary chemoradiation is the preferred treatment; OR

2. Neoadjuvant chemotherapy with 3 cycles of carboplatin/paclitaxel followed by radical

hysterectomy and bilateral lymph node dissection is an option if available. (If inoperable
after neoadjuvant chemotherapy, patient should be referred for chemoradiation.)

Simple hysterectomy alone is unlikely to be curative and increases the risks of

subsequent chemoradiation, and should only be performed if there are no other options.

Stage IIA (involves upper 2/3 of the vagina without parametrial invasion)

1. Primary chemoradiation is the preferred treatment; OR

2. Neoadjuvant chemotherapy with 3 cycles of carboplatin/paclitaxel followed by radical

hysterectomy and bilateral lymph node dissection is an option if available. (If inoperable
after neoadjuvant chemotherapy, patient should be referred for chemoradiation.)

Stage IIB (invades parametrium but not lower third of the vagina or pelvic side wall)

1. Primary chemoradiation is the preferred treatment.

2. If radiotherapy is planned but there will be a delay of greater than 1 month, temporizing
chemotherapy with 3 cycles of carboplatin/paclitaxel may be considered.

Stage III (lesion extending to sidewall, lower 1/3 vagina, or causing hydronephrosis)

Cervical Cancer Protocol 3 Version Date 10-FEB-2017

 1. Primary chemoradiation is the preferred first choice of treatment.

2. If radiotherapy is planned but there will be a delay of greater than 1 month, temporizing
chemotherapy with 3 cycles of carboplatin/paclitaxel may be considered. In the setting
of renal failure, paclitaxel alone may be used until renal recovery.

Stage IV (lesion involving mucosa of bowel or bladder, or distant metastasis) OR

RECURRENT disease after definitive treatment

1. Palliative care is indicated, including medications for pain, constipation, nausea, and
blood transfusions as needed.

2. Chemoradiation may provide palliative benefit (and small chance of cure in stage IVA
disease) and may be considered in the setting of available resources.

NOTE: All surgical specimens should be sent for pathologic diagnosis

F. Pregnancy

• Treatment during pregnancy:

o Stage by stage, the treatment of cervical cancer is the same for pregnant
women as for non-pregnant patients.
o For pregnant women diagnosed with cervical cancer before 16 weeks of
gestation, immediate treatment is recommended (and entails termination of
the pregnancy).
o For pregnant women with early stage disease (IA1, IA2, IB) diagnosed after 16
weeks of gestation, treatment may be delayed to allow fetal maturity to occur.
o For pregnant women with advanced disease (IB2 or greater) diagnosed after 16
weeks of gestation, consideration for delay must be based on gestational age at
time of diagnosis. Temporizing single agent carboplatin (which is safe in
pregnancy) may be considered.
• Family planning:
o Following treatment of cervical cancer, women are generally infertile and do not
require family planning.

G. Drug regimens

• Concurrent chemoradiation:
o Cisplatin 40 mg/m2 every week at the same time as radiotherapy
• Neo-adjuvant (or temporizing) carboplatin/paclitaxel:
o Carboplatin AUC 6 and paclitaxel 175 mg/m2 IV Q 3 weeks

H. Radiotherapy

• External beam radiotherapy is typically given daily on weekdays for 5 – 8 weeks

Cervical Cancer Protocol 4 Version Date 10-FEB-2017

 • Brachytherapy (local application of radiation to the vagina) is given during external
beam radiotherapy once optimal tumor reduction is achieved (within 8 weeks from
the start of treatment).
• Common side effects of radiotherapy:
o Excoriation
o Skin desquamation
o Vaginal stenosis
o Pelvic pain; neurologic pain is a late side effect and may last for over a year

NOTE: Bleeding should stop before completion of treatment. Any residual mass should
resolve within 3 months.

I. Follow up:

For Stage I or II disease after curative chemotherapy and surgery:

• Pelvic exam every 4 – 6 months for 2 years; if disease recurs, patient may be
eligible for curative chemoradiation.
• After 2 years, pelvic exam every 6 – 12 months for the next 3 years
For any stage disease after curative chemoradiation:
• Pelvic exam every 6 months for 2 years (more frequent visits may be required
for treatment of toxicities), then annual follow-up thereafter.
• No routine blood work or x-rays unless clinically indicated
For metastatic disease: as clinically indicated for palliative care

Cervical Cancer Protocol 5 Version Date 10-FEB-2017