PRINCESS MARGARET CANCER CENTRE

CLINICAL PRACTICE GUIDELINES

GYNECOLOGIC CANCER

CERVIX

Last Revision Date – September 2019 2

Site Group: Gynecology – Cervix

Original Author: Dr. Stephane Laframboise

Reviewer: Dr. Stephanie Lheureux

1. INTRODUCTION 3

2. PREVENTION 3

3. SCREENING AND EARLY DETECTION 3

4. DIAGNOSIS 4

5. PATHOLOGY 5

6. MANAGEMENT 6

6.1 MANAGEMENT ALGORITHMS 6 6.2 SURGERY 9 6.3 CHEMOTHERAPY 9 6.4 RADIATION THERAPY 9 6.5 ONCOLOGY NURSING PRACTICE 10

7. SUPPORTIVE CARE 11

7.1 PATIENT EDUCATION 11 7.2 PSYCHOSOCIAL CARE 11 7.3 SYMPTOM MANAGEMENT 11 7.4 CLINICAL NUTRITION 11 7.5 PALLIATIVE CARE 11

8. FOLLOW-UP CARE 12

Last Revision Date – September 2019 3

1. Introduction

Cancer of the cervix is the third most common gynecologic cancer diagnosis and cause of

death among gynecologic cancers in North America. In 2018, an estimated 569 847 new

cases of cervical cancer were diagnosed and 311 365 deaths occurred worldwide due to

this malignancy,1 although incidence and mortality vary widely with geographic location.

In high-income countries, cervical cancer incidence and mortality have decreased by

more than half over the past 30 years since the introduction of formalised screening

programmes.Prevention

Prevention of cervical carcinoma can be achieved by primary or secondary measures.

Primary prevention: Primary prevention of cervical cancer is done through

avoidance of HPV infection. Vaccines have been developed that can protect women

from

HPV infections. So far, a vaccine that protects against HPV types 6, 11, 16 and 18

(Gardasil®) and one that protects against types 16 and 18 (Cervarix®) have been

studied and approved for use. Both vaccines require a series of 3 injections over a 6-

month period. In 2018, a nine-valent vaccine has shown efficacy at 6 years in young

women aged 16 to 26 years and is being rolled out.

Secondary prevention: PAP smear screening may detect premalignant cells on

cytology. This can be followed by a colposcopic examination where pathological

diagnosis can be made. Pre-cancerous lesions may be treated using ablative or

excisional procedures to prevent them from developing into invasive carcinoma.

2. Screening and Early Detection

Screening for cervical cancer can be achieved with a pap smear and/or an HPV test.

Pap smear: The Papanicolaou test (pap test) is performed at time of a pelvic

examination to collect cells from the cervix for cytological evaluation.

HPV testing: An HPV test can be done along with a Pap test or as a separate test.

Like a Pap test, the HPV test is done during a pelvic exam, using a small brush to

collect a sample from the cervix. Women who are under age 30 are not usually tested

for HPV because many women in this age group have transient HPV infections,

which will resolve without treatment.

Regular screening is essential to the prevention and early detection of cervical cancer.

The Ontario Cervical Cancer Screening Guidelines provide recommendations for

screening schedule.

https://www.cancercare.on.ca/pcs/screening/cervscreening/

Last Revision Date – September 2019 4

3. Diagnosis

Initial Evaluation

Physical examination: Complete physical examination including weight and height

(Body Mass Index), abdominal, pelvic and rectovaginal examination.

Colposcopy may also be helpful to define the lesion.

Biopsy

Laboratory testing: CBC, electrolytes, creatinine, liver functions, as indicated

Imaging: CT Thorax or CXR, CT abdomen/pelvis, Pelvic MRI

Expert pathology review

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4. Pathology

The human papillomavirus (HPV) is central to the development of cervical neoplasia and

can be detected in 99.7% of cervical cancers. The most common histologic types of

cervical cancer are squamous cell carcinoma, 69% and adenocarcinoma, 25%. Other rare

histological types include serous, clear cell, endometrioid, small cell, undifferentiated and

metastatic.

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5 Management Algorithms

Early stage cervical cancer

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Advanced stage cervical cancer

Chemo and radiation therapy

for early stage cervical cancer

Last Revision Date – September 2019 8

For stage 4B and recurrent disease, chemotherapy is doublet platinum based

chemotherapy with the addition of bevacizumab if no contre indication.

Clinical trial can be an option at different times of the treatment.

Recurrent cervical cancer

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6.2 Surgery

Radical Hysterectomy

Laparotomy or minimal invasive surgery: Surgery is aimed at removal of the uterus, parametria

and paracervical tissue with an adequate vaginal cuff. In addition a bilateral pelvic

lymphadenectomy is required. Removal of the tubes and ovaries will depend on patient’s age and

risk factors.

Identification of positive lymph nodes at radical hysterectomy: if the nodes and primary

tumour can be removed with an adequate margin it is recommended to complete the radical

hysterectomy. If the nodes cannot be removed, it is recommended to abandon the surgical

procedure in favour of chemotherapy, EBRT and intracavitary radiation.

Fertility sparing surgery

A radical trachelectomy and pelvic lymph node dissection may be considered in women who

wish to preserve their fertility and who present with a small tumor (<2cm) and a negative

metastatic work up.

6.3 Chemotherapy

Weekly cisplatin in conjunction with radiation therapy (EBRT).

Early stage disease (Stage 1b1 and 1b2)

• Concurrent cisplatin chemotherapy 40 mg/m2 weekly x 5 courses

Locally advanced disease (Stage 2, 3, and 4a)

Cisplatin chemotherapy (40mg/m2 weekly x 5 courses during external beam radiotherapy)

Stage 4b - Patients with metastatic disease will be assessed for suitable palliative

treatment. This may involve radiation, chemotherapy with or without bevacizumab or,

in some cases, no active treatment until symptoms arise.

6.4 Radiation Therapy

Locally advanced cervical cancer

• Stage 1b - 4A: Radical external beam radiotherapy to the pelvis ± paraaortics (45 Gy) plus

concurrent cisplatin chemotherapy, and intracavitary/interstitial brachytherapy (28 Gy in four 7

Gy fractions or 24 Gy in three 8 Gy fractions) towards the end or shortly after completion of

external beam RT

• Stage 4b - Patients with metastatic disease will be assessed for suitable palliative treatment.

This may involve radiation, chemotherapy or, in some cases, no active treatment until

symptoms arise.

Post-op treatment for high risk tumors following Rad hyst and LND:

Positive nodes and/or margins and/or parametrium

o Adjuvant RT with concurrent chemotherapy

Tumor size > 4 cm and/or deep invasion and/or lymphovascular-space involvement (LVI)

o Sedlis criteria: LVI+, deep 1/3 stromal invasion, any size

LVI+, middle 1/3 invasion, size ≥ 2cm

LVI+, superficial 1/3 invasion, size ≥ 5cm

LVI-, deep or middle 1/3 invasion, size ≥ 4cm

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o Adjuvant RT +/- concurrent chemotherapy

Simple hysterectomy for unrecognized cervical cancer

o Adjuvant RT +/- concurrent chemotherapy, followed by vaginal vault

brachytherapy

External Beam Radiotherapy

CT/MRI simulation for intact cervix:

Planning images include a primary CT (full bladder) and two secondary MR images

(empty and full bladder).

Rectum and sigmoid should be empty with cross-sectional diameter ≤ 4cm

Diagnostic MRI, CT, ± PET images may also be fused to planning CT images to help

define individualized ITV

Radical External Beam Radiotherapy Volumes

GTVp (GTVinit): macroscopic tumor extension at diagnosis detected by clinical exam or

MRI

GTVn: gross nodal disease on imaging

CTVp (CTVLR): GTVp, cervix, uterus, vagina (2 cm margin) and parametria

CTVn: GTVn, pelvic lymph nodes including the pre-sacral lymph nodes anterior to S1-

S3 +/-para-aortic nodes

ITVp: individualized margin based on internal target motions on planning ± diagnostic

images

Adjuvant External Beam Radiotherapy Volumes

CTVp: vagina and parametria

CTVn: pelvic lymph nodes including the pre-sacral lymph nodes anterior to S1-S3 +/-

para-aortic nodes

Organs at risk

Bladder, rectum, sigmoid, small bowel, vagina, femoral heads +/- kidneys

Dose

Pelvic dose:

o 45 Gy in 1.8 Gy daily fractions

Para-aortic dose:

o 45 Gy in 1.8 Gy daily fractions

Nodal dose to grossly enlarged nodes:

o Consider total cumulative dose 54-60 Gy EQD2 via sequential or simultaneous

integrated boost, taking into account dose received from brachytherapy

Brachytherapy

MR-guided brachytherapy

MR scans in the final week of external beam radiotherapy and after intrauterine/

interstitial applicator insertion to define target volumes and normal tissues

Target and normal tissue contours as per GEC-ESTRO/ICRU89 guidelines

o GTVres : residual tumor at the time of brachytherapy

o CTVHR: GTVres, cervix, grey zones/residual pathologic tissue

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o CTVIR: GTVinit, CTVHR with 5-15 mm margin

o OARs: bladder, rectum, sigmoid, small bowel, vagina, femoral heads +/- kidneys,

duodenum

Plan optimization as per GEC-ESTRO/EMBRACE II guidelines

HDR dose:

o 28 Gy in four 7 Gy fractions or 24 Gy in three 8 Gy fractions beginning towards

the end or shortly after completion of external beam RT.

o The external beam fraction is omitted on days when HDR brachytherapy is

administered.

o Chemotherapy should not be given on days of brachytherapy.

6.5 Oncology Nursing

Refer to general oncology nursing practices

7 Supportive Care

7.1 Patient Education

Cancer Care Ontario patient education link:

https://www.cancercare.on.ca/pcs/screening/cervscreening/patient_education/

Also refer to general patient education practices

7.2 Psychosocial Care

Refer to general psychosocial oncology care guidelines

7.3 Symptom Management

Refer to general symptom management care guidelines

7.4 Clinical Nutrition

Refer to general clinical nutrition care guidelines

7.5 Palliative Care

Refer to general oncology palliative care guidelines

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8 Follow-up Care

Surgically treated patients:

Follow-up should be every 3-4 months for two years after surgery, then every 6 months

for 3 years, then yearly. It should include a pap smear and pelvic examination. When

indicated a CT scan of the abdomen and pelvis should be ordered. Hormone replacement

therapy should be considered for patients who were pre-menopausal prior to treatment of

cervical cancer and were rendered menopausal with surgery.

Radiation treated patients:

Every 3 to 4 months for 2 yrs after competing treatment, then every 6 months for 3 years.

MRI pelvis 3-6 months after completing treatment.

Cervical/vaginal cytology at the discretion of the oncologist beginning 1 year after

competing RT.

Vaginal dilators three times a week for six months after the completion of brachytherapy

to prevent vaginal stenosis. Some patients may require ongoing use of dilators.

Consider hormone replacement therapy for patients who were pre-menopausal prior to

treatment for cervix cancer.

Recurrence:

Cervix cancers that recur centrally can be cured. All recurrences require metastatic

workup including a CT scans of thorax, abdomen and pelvis, possibly pelvic MRI. When

the recurrence is thought to be central, with no evidence of other disease, consider pelvic

exenteration (anterior and/or posterior). A PET scan can also be helpful to rule out distant

metastatic disease.

At the time of exenterative surgery, efforts need to be made to rule out metastatic disease

by sampling lymph nodes that are in and above the previously radiated fields. When

disease is proven to be central and margins at resection can be cleared, this surgical

procedure has the potential of curing 50-60% of those with a central recurrence.

At the time of first recurrence, doublet chemotherapy with bevacizumab is considered. At

the second recurrence, standard mono-chemotherapy is offered. Recent data showed

potential benefit of pembrolizumab for PD-L1 positive tumors.

Clinical trials remain an option at the time of recurrence.

References

https://www.cancercareontario.ca/en/types-of-cancer/cervical/screening

Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019 Jan

12;393(10167):169-182.