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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
Last Revision Date – September 2019 5
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.
Last Revision Date – September 2019 6
5 Management Algorithms
Early stage cervical cancer
Last Revision Date – September 2019 7
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
Last Revision Date – September 2019 9
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
Last Revision Date – September 2019 10
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
Last Revision Date – September 2019 11
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
Last Revision Date – September 2019 12
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.
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