CERVICAL CANCER

MANAGEMENT
PROTOCOL
BY- HAYAT MOHAMMED R4(OBGYN
RESIDENT)
MODERATOR- MESERET OLANA(ONCO
FELLOW)

SPHMMC
2022
 Outline
 INTRODUCTION  DIAGNOSIS AND EVALUATION OF
 ANATOMICAL CONSIDERATIONS CERVICAL CANCER
 STAGING OF CERVICAL CANCER
 RISK FACTORS
 MANAGEMENT OF CERVICAL CANCER
 EARLY DETECTION &  PROGNOSIS
PREVENTION OF CERVICAL Ca  POST-TREATMENT FOLLOW-UP
 HISTOPATHOLOGY  RECURRENT DISEASE AND
PALLIATIVE CARE
 TUMOR SPREAD
 CERVICAL CANCER DURING
PREGNANCY
 INTRODUCTION
 Cervical cancer is the 3rd most common cancer in females after breast and colorectal- FIGO
2021
 ⁓ 604,00 new cases are diagnosed causing 342,00 deaths annually.

 It is the most common gynecologic malignancy in Ethiopia.

 Women have a 1 in 132 lifetime risk of developing this cancer

 High risk human papillomavirus (hrHPV) are the necessary cause.

 detected in 99.7 percent of cervical cancers.

 ANATOMICAL CONSIDERATIONS
 Cervix is a cylindrical structure which is the lowermost part of the uterus

 Composed of stroma and epithelium

 Ectocervix which projects into the vagina, is lined by squamous epithelium

 Endocervical canal is lined by columnar epithelium

 Transformation zone- between the old and new squamocolumnar junction

 Origin of almost all cervical carcinoma
 Risk Factors
 Lack of regular cervical cancer  Low socioeconomic status,
screening,  Parity ,
 Persistent HPV infection  Long-term COC use,
 Lower educational status,  Having > 6 lifetime sexual partners,
 Older age,  Coitarche before age 20,
 Smoking,  Immunosuppressed women.
 EARLY DETECTION AND PREVENTION OF CERVICAL
CANCER

 Two major strategies for prevention and early detection are

(1) HPV vaccination; and
(2) screening for precancerous lesions

 WHO’s 90%–70%–90% triple pillar intervention strategy before the year 2030
 90% of girls fully vaccinated with two doses of HPV vaccine by the age of 15 yrs.
 70% of women screened using a high-performance screening test at the age of 35-45 yrs.
 90% of women detected with cervical lesions to receive treatment and care
 HISTOPATHOLOGY
 Must be confirmed by microscopic examination

 Two most common histologic subtypes of cervical cancer

 Squamous cell - 70 % and arise from the ectocervix
 keratinizing and nonkeratinizing carcinomas

 Adenocarcinoma- 25 % and arise from the endocervical mucus-producing columnar cells

 Exhibit various histologic patterns, mucinous adenocarcinoma being the most common
 Tumor Spread

 Direct extension -the most common mode of spread.

 Lymphatic spread:
 Paracervical => obturator => internal iliac => external iliac => common iliac =>
paraaortic nodes.

 Left supraclavicular lymph nodes: echelon extrapelvic distant sites of lymphatic

spread.

 Hematogenous spread: Distant metastasis to lungs, liver, and skeleton is a late phenomenon
 Evaluation & Diagnosis of cervical cancer

 Symptoms :

 Early stage disease- asymptomatic,

 Watery, blood-tinged vaginal discharge,

 Intermittent vaginal bleeding that follows coitus or douching .

 Evaluation and Diagnosis…

 Uncontrolled hemorrhage:
 hemodynamic support of the patient,

 Combination of Monsel paste (ferric sub sulfate) and vaginal packing,

 Topical acetone if refractory to Monsel paste,

 Emergent radiation,

 Internal iliac artery Embolization or ligation.

 Evaluation and Diagnosis…

 Physical Examination
 Thorough external genital and vaginal examination- look for any lesion
 Speculum examination- normal/ varied appearance
 Bimanual examination- enlarged uterus, vaginal extension
 Rectovaginal examination- posterior spread
 PR examination- parametrial, uterosacral, pelvic side wall
 Cheek for enlarged supraclavicular or inguinal lymphadenopathy
 Lower extremity edema
 Evaluation and Diagnosis…

 Cervical Biopsy:
 Diagnosis of Stages IA1 and IA2 is made on microscopic examination of a cone
biopsy specimen, obtained by LEEP or cold knife conization or hysterectomy
specimen.

 In the case of visible lesions, a punch biopsy may generally suffice for
diagnosis, but if not satisfactory, a small loop biopsy or cone may be required.

 Biopsies are taken from the tumor periphery and include underlying stroma to
assess invasion.
 Radiologic Imaging
 Any of the imaging modalities can be used with consideration of available
resources and clinical findings -FIGO 2021.

 Ultrasound, CT scanning, MR imaging, or PET scanning are commonly used.

 MRI: best method of radiologic assessment of primary tumors >10 mm

outperformed CT in the ability to measure cervical cancer diameter,
superior detail of tumor-related anatomic invasion & parametrial invasion ,
affords best contour definition in brachytherapy radiation planning.

 PET-CT - detection of nodal metastasis greater than 10 mm.

 Radiologic Imaging…
 In patients with frank invasive carcinoma
• CXR
• Assessment of hydronephrosis (with renal ultrasound, CT, or MRI) should be done

 Sigmoidoscopy only if the patient is clinically symptomatic.

 Cystoscopy is also recommended in
• Symptomatic patient
• Barrel-shaped endocervical growth
• Growth has extended to the anterior vaginal wall

 Suspected bladder or rectal involvement should be confirmed by biopsy and histologic

evidence.
 Bullous edema alone does not warrant a case to be allocated to Stage IV.
 LYMPH NODE EVALUATION
 FNA or biopsy to exclude metastases in TB & HIV endemic areas

 Sentinel node biopsy can be considered in Stage IA2,IB1, IB2 and IIA1 with size smaller
tumor size ( <2 cm) and is now included in the NCC Guidelines in US

 LN DISSECTION of retroperitoneal pelvic and Para aortic LNs offers accurate metastasis
detection that is superior to radiologic imaging
 Tumor-laden nodes may be debulked
 Candidates include positive pelvic nodes undergoing chemo radiation treatment
Staging of Cervical Cancer

 The current staging system (FIGO 2021) allows incorporation of clinical,

radiological and pathologic findings.
 Stage is allocated after all imaging and pathology reports are available.
 It is not to be altered later, for example at recurrence.

 Early-stage disease refers to FIGO stages I through IIA.

 Advanced-stage disease refers to stages IIB and higher.
TABLE 1- FIGO STAGING OF CANCER OF THE CERVIX UTERI 2021
 Treatment of Cervical Cancer

• Treatment is primarily by:

Surgery or
Radiation therapy with Chemotherapy a valuable adjunct.

 Surgical management
 Surgery is suitable for early stages, where cervical conization, simple
hysterectomy, or radical hysterectomy may be selected according to
the stage of disease.
 In Stage IVA, selected cases may be suitable for pelvic exenteration.
 Fertility sparing surgery candidates
• Stage 1A1 with no LVSI- cone biopsy with negative margin
• Stage 1A2-1B1- cone biopsy with –ve margin + pelvic lymphadenectomy or SLN
mapping, conservative surgery criteria must be met
• Age <45
• No LVSI
• No extension beyond internal os
• -ve cone margin
• Squamous cell (any grade) & adeno ca( grade 1&2)
• Tumor size </=2cm
• Depth of invasion</=10mm
• Negative imaging for metastatic disease
• If LVSI or 1 of above criteria is not met- radical trachelectomy+ pelvic
lymphadenectomy+/- Para aortic lymphadenectomy
TABLE 2-2017 Querleu–Morrow Classification of Radical Hysterectomy
 Microinvasive cervical carcinoma: FIGO Stage IA

Stage IA1
 Type A hysterectomy- no LVSI & negative margin

 Type B hysterectomy + pelvic lymphadenectomy- LVSI or positive margin

Stage IA2
 Type A hysterectomy + Pelvic lymphadenectomy – conservative criteria met

 Type B radical hysterectomy + Pelvic lymphadenectomy- not met

Invasive cervical carcinoma: FIGO Stage IB1,IB2, IIA1
 Surgical treatment is the preferred modality- type C1 radical hysterectomy with pelvic
lymphadenectomy +/- para aortic lymphadenectomy

Stage IB1
 Type B1 radical hysterectomy may be considered in low risk with cervical stromal invasion
less than 50% and no suspicious lymph nodes on imaging
 Pelvic lymphadenectomy should always be included on account of the high frequency of
lymph node involvement
Stage IB2 and IIA1

 Surgery or radiotherapy have similar outcomes

 Preservation of ovarian and sexual function

 Precise postop staging
 Removal of radio-resistant cancer cells makes surgery the preferred mode

Stages IB3 and IIA2

 Concurrent platinum-based chemo radiation (CCRT) is the preferred treatment option.

 If radiotherapy facilities are scarce neoadjuvant chemotherapy (NACT)followed by

radical hysterectomy and pelvic lymphadenectomy can considered.
(1) down-staging of the tumor to improve the radical curability and safety of surgery
(2) inhibition of micro metastasis and distant metastasis
 NEOADJUVANT CHEMOTHERAPY
• Given every 3 week for 3 cycle
• Post NACT repeat imaging is not necessary
• Type c radical hysterectomy + pelvic lymphadenectomy is done after 3 weeks of the
last NACT

TABLE3- 1ST line NACT drug regimen

DRUG DOSE & ROUTE ADMINISTRATION GIVEN ON
PACLITAXEL 135MG/M2 IV DILUTE IN 1L OF NS DAY1
& ADMINISITER
OVER 3 HRS
CISPLATIN 75-100MG/M2 IV DILUTE WITH 25OML DAY1
OF NS &
ADMINISTER OVER 1
HR
Stage IVA or recurrence

 Rarely, if only central disease without involvement of the pelvic sidewall or distant spread
pelvic exenteration can be considered but usually has a poor prognosis
 Imaging to determine any sites of distant disease, and should be performed prior to
exenteration
Inadvertent incomplete surgery
 Assess the extent of the disease by appropriate imaging & plan subsequent treatment based
on finding

 CCRT is generally added after Inadvertent simple hysterectomy

 If expertise is available, some may be suitable for repeat laparotomy with parametrectomy
and pelvic lymphadenectomy
 Adjuvant Therapy
• Post surgery evaluate need of adjuvant therapy
 High-risk disease (Peter’s criteria) any 1 of
 Positive surgical margins or
 Positive lymph node metastases or
 Parametrial spread
 should be offered PORT with chemotherapy
 Intermediate-risk (Sedlis’ criteria) any 2 of
 Tumor size more than 4 cm
 Lymphovascular invasion
 Deep stromal invasion
require PORT and no chemotherapy should be offered
 All other patients following radical hysterectomy are termed as low-risk disease
patients and do not need any adjuvant therapy.
 Radiation management
 In LMICs, the majority of patients present with locally advanced disease, where surgery
plays a limited role.

 Apart from its curative role, radiotherapy can also be used as:-
 Adjuvant therapy; operated patients to prevent loco regional recurrence
 Palliative therapy; alleviating distressing symptoms in advanced incurable disease.

 For early stage disease in cases with contraindications for surgery or anesthesia, radiotherapy
provides equally good results in terms of local control and survival
 Micro invasive disease & <1cm 1B1- Intracavitary RT (ICRT) 60-65GY to point A
Radiation therapy for Stages IB3 and IIA2

 Surgery is not encouraged since 80% of them require PORT or CCRT

 Concurrent platinum-based chemo radiation (CCRT) is preferred

Radiation therapy for Stages IIB–IVA

 CCRT is considered the standard treatment

 CCRT
• Include external beam radiation(EBRT) + Intracavitary brachytherapy(ICRT)
• EBRT- 40-50GY to whole pelvis by 2 or 4 field box technique in 25 fractions in 5week
• ICRT- given to point A & Bwith
• LDR- 30-40GY IN ½ session
• HDR- 5.5-8GY BY 3-5 week fraction
• PDR
• Total combined dose- 80-90GY

 A once-weekly infusion of cisplatin (40 mg/m2weekly with appropriate hydration) for 5–6
cycles during external beam therapy is a commonly used

 For patients who are unable to receive platinum chemotherapy, 5-fluorouracil based
regimens are an acceptable alternative
 Should be completed with in 8 weeks
 Stage IVB/distant metastases

 A management plan should consider that the median duration of survival with distant
metastatic disease is approximately 7 months

 CCR may have a better response than systemic chemotherapy

 When para-aortic nodes are involved, extended field radiation therapy (EFRT) with
concurrent chemotherapy should be used

 Intensity modulated radiation therapy (IMRT) may be used in such patients to reduce the
toxicity.
 PROGNOSIS
 FIGO stage is the most significant prognostic factor
 Lymph node involvement, the number of nodal metastases, size of lymph node metastases
also worsen prognosis.
 Cervical Cancer Survival Rates According to Stage(Grigsby,1991;Komaki, 1995; Webb,
1980.)
Stage 5-Year Survival
IA 100%
IB 88%
llA 68%
IIB 44%
Ill 18-39%
IVA 18-34%
 Post-treatment follow-up
 Median time to recurrence- 7–36 months
 3-monthly Pap smears for 2 years, then 6-monthly for the next 3 years then if normal at 5
years return to routine schedule is recommended after fertility sparing surgery
 At each visit
 History taking
 Clinical examination
 Routine imaging is not indicated only if
 Abnormal pelvic mass
 Abnormal pelvic examination finding eg. cervical or vaginal lesion, rectovaginal
nodularity, and pain radiating down the posterior thigh
 New-onset lower extremity edema

 A cervical or vaginal cuff Pap test collected annually for 20 years after treatment completion.
 Recurrent disease
 The treatment plan depends on
 Patient's performance status
 Site
 Extent of recurrence and/or metastases
 Prior treatment received

 If there is extensive local disease or distant metastatic disease, the patient is assigned to
palliative therapy, with best supportive care.

 However, if the performance status is good and there is only limited metastatic disease, a trial
of platinum doublet chemotherapy along with bevacizumab is justified, after counseling
the patient and her family on the limited benefits in terms of response rate and progression-
free survival.
 Local recurrence

• Good prognostic factors are

 Isolated central pelvic recurrence- most common
 No involvement of the pelvic sidewall
 Long disease-free interval from previous therapy
 Largest diameter of the recurrent tumor is less than 3 cm

 Confirmation of recurrence with a pathologic specimen obtained by biopsy is

essential

 The second most common site of recurrence is in the para-aortic lymph nodes
 If isolated curative-intent radiation therapy or chemo radiation can achieve long-
term survival in approximately 30% of cases.
 Palliative care
 Symptom control is the essence
 Common CF include pain, ureteric obstruction causing renal failure, hemorrhage,
malodorous vaginal discharge, lymphedema, and fistula
 Support from the corresponding clinical services as well as psychosocial care and support for
their families and caregivers.
 Tiered approach to pain is practiced
 In terminal cases, some patients may also require the services of a hospice facility

Palliative radiotherapy

 Short-course radiotherapy is very effective in palliation of distressing symptoms

 Pain arising from enlarged para-aortic or supraclavicular nodes, skeletal metastases, and
symptoms associated with cerebral metastases
 Cervical cancer during pregnancy
 Multidisciplinary team

 The plan must be discussed with the patient, and ideally her partner too

 Same principles as in nonpregnant patients

 Before 16–20 weeks, patients are treated without delay depending on the stage of the
disease

 late second trimester onward, surgery and chemotherapy can be used in selected cases
while preserving the pregnancy
 Cervical cancer during pregnancy
 After 20 weeks, delaying definitive treatment is a valid option for Stages IA2 and IB1
and 1B2, which has not been shown to have any negative impact on the prognosis
compared with non pregnant patients

 Timing of delivery requires a balance between maternal and fetal health interests

 Delivery should be at a tertiary center with appropriate neonatal care, by classical CS and
radical hysterectomy at the same time is undertaken no later than 34 weeks of gestation.

 For more advanced disease, the impact of treatment delay on survival is not known

 Neoadjuvant chemotherapy may be administered to prevent disease progression in

women with locally advanced cervical cancer when a treatment delay is planned.
 References
1. International journal of gynecology & obstetrics, Volume 155 FIGO cancer report 2021,
Cancer of the cervix uteri: 2021 update
2. International journal of gynecology & obstetrics, FIGO cancer report 2021, Cancer of
the cervix uteri: 2021 update
3. Querleu–Morrow Classification of Radical Hysterectomy, Denis Querleu, David Cibula
and Nadeem R. Abu-Rustum: 2017 Update
4. NCCN guidelines version 1.2023, cervical cancer
5. Principles and practice of gynecologic oncology, 7th edition
6. Williams gynecology 4th edition
7. Berek and novak gynecology 16th edition
8. Up to date 2021
9. ACOG, 2018
THANK YOU!