carcinoma cervix, incidence, pathogenesis preinvasive stages, histology, ajcc 8, stage, examination, management, surgery,radiotherapy, nccn guideline,update,

1. Management of CARCINOMA CERVIX –
A Review
Dr. MUNEER . A
DNB Radiotherapy

2. INTRODUCTION
 Cervical cancer is the fourth most common cancer in women.
 Most common gynaecological cancer in the world.
 More than 85% of Global burden occurs in developing countries,
where cervical cancer is the leading cause of death in women.

3. india
 most common cancer in Indian women
 cervical cancer had increased from 0.11 million in
2000 to 0.16 million in 2010
 Over 80% of the cervical cancer present at a fairly
advanced stage and annually around 80,000 deaths
are reported in India.
 India, the second most populous country in the
world, accounts for 27% (77,100) of the total cervical
cancer deaths6

4. PRE DISPOSING FACTORS
 coitus before the age of 18 years.
 multiple sexual partners.
 Delivery of the first baby before the age of 20
years.
 multiparity with poor birth spacing between
pregnancies.
 History of smoking

5.  poor personal hygiene.
 poor socioeconomic status.
 women with-
 HPV (16,18,31,33)
 HIV
 HSV 2 infection
 condylomata , have an increased
risk.

6.  women with pre invasive lesion
 immunocompromised women(following
transplant).
 women on combined oral contraceptives and
progesterone have doubled the risk of
ADENOCARCINOMA ENDOCERVIX
 5% of women who received diethylstilbestrol in
utero developed cancer of vagina and cervix.
withdrawal of this hormone has reduced the
incidence.

7. HPV and Ca Cervix
 Persistent HPV infection - most important cause.
 Incidence of Cervical Ca is related to prevelance of HPV in population.
 In countries with high incidence of Ca Cervix, prevlence of HPV is 10-20%.
 In countries with low incidence of Ca Cervix ,prevlence of HPV is 5-10%.
 Immunization against HPV will prevent persistent infection with HPV and thus
carcinoma.
 In developed countries , the substantial decline in incidence and mortality of
Squamous cell carcinoma is presumed due to result of effective screening.
NCCN 2017

8. •Avoidance of Human Papillomavirus Infection
(abstinence, or condoms (lower risk by 60%)
•HPV16/18 vaccination will lower the risk by
92%
•Screening (pap smear) will lower incidence and
mortality by 80%
•Smoking cessation (smoking cigarettes
increases the risk in HPV+ women by 2 to 3
times)

9. CERVICAL SCREENING PROTOCOL
joint recommendations of the American Cancer Society (ACS), the American Society for Colposcopy
and Cervical Pathology (ASCCP) and the American Society for Clinical Pathology (ASCP) in 2012, and
later accepted and promoted by the American Congress of Obstetricians and Gynecologists (ACOG)
Starting women age 21
Women ages 21-29 Screen with cytology every 3 years
Women Ages 30-65 Screen with cytology cotesting with
HPV every 5 years. OR cytology
alone every 3 year
Women<21 Do not screen
Women>65, had adequate prior
screening and are not at high risk
Do not screen
Women after hysterectomy with
removal of cervix ,no h/o high grade
precancer or cervical cancer
Do not screen
Women<30yrs Do not screen with HPV testing

10. Clinical Presentation
 Asymptomatic - Most common presentation in western
countries due high rate of screening (Intraepithelial or
early invasive carcinoma of the cervix may be detected
by cytological smears before symptoms appear )
 Abnormal vaginal bleeding– >80 % earliest symptom of
invasive cervical cancer (most commonly post coital
bleeding)
 Spotting
 Menorrhagia – Heavier than usual flow
 Fowl smelling discharge – May or may not be mixed
with blood
 Exophytic/ulceroproliferative mass visible on
examination

11. Symptoms of Advanced Carcinoma Cervix
 Anemia,Fatigue – Due to chronic blood loss
 Anuria -- Renal failure – due to pressure effect on
ureter leading to back pressure on kidney
 Rectal bleeding- venous engorgement due to
pressure effect
 Constipation
 Dysuria
 Hematuria

12. Contd…
 Triad
1) Sciatic pain(from lumbosacral plexus
involvement / compression by tumor/ PID)
2) Lower extremity edema (from extensive pelvic
lymph node involvement / lymphatic obstruction)
3) Hydronephrosis ( ureteral obstruction)

13. Contd…
Ascites- Due to peritoneal deposits
Dribbling of urine per vaginum –Due to vesico
vaginal fistula formation
Fecal matter per vaginum- Rectovaginal fistula
• Metastasis as Cervical Malignancy
• Metastasis of distant tumors to the uterine cervix is
rare (about 4% of all tumors) and should be
considered in the differential diagnosis.
• Metastases to the cervix from the breast, ovary, and
kidney have been reported.

14. Histologic Subtypes
 Squamous-Cell Carcinoma(>90%)
 Large cell-Keratinizing or Nonkeratinizing
or small cell carcinomas
 Verrucous-
 very well differentiated scc, tendency to recur locally
but not metastasize
 Papillary transitional
 Lymphoepithelioma-like
 Adenocarcinoma (7-10%)
 (arises from the cylindrical mucosa of the
endocervix or the mucus secreting
endocervical glands
 Mucinous
 Endometrioid- MC Endocervical adeno ca
 Clear Cell
 Serous
 Mesonephric
 Well differentiated villoglandular
 Minimal deviation (adenoma malignum)-
associated with Peutz-Jeghers,ominous
natural history
 Other epithelial
 Adenosquamous
 Glassy Cell
 Carcinoid Tumor
 Neuroendocrine
 Small-cell
 Undifferentiated
 Basaloid Ca
 Primary Sarcoma of cervix

15. STAGING

16. FIGO STAGING
 International Federation of Gynecology and
Obstetrics has put forth a staging system that
depends mainly on clinical examination
 It includes– Inspection
Palpation
Colposcopy
Endo cervical curettage ,conization
Hysteroscopy
Cystoscopy
Proctoscopy
Intravenous urography, barium
enema

17. STAGING
 Clinical rather than surgical staging
 This allows staging to occur in low resource
setting
 Stage should be assigned before any definitive
therapy is administered.
 The clinical stage should never be changed on
the basis of subsequent findings.
 When the stage to which a particular case should be allotted is in doubt,
the case should be assigned to the lesser stage
 Not included in the FIGO Staging are-
 Lymphangiography ,FNAC or Biopsy of LN
,MRI,CT,PET
,Laparoscopy & Laparotomy

18. UPDATE ( AJCC 8 TH EDN)

19. AJCC
8
FIGO
Tx primary tumour cannot be assesed
T0
No evidence of primary tumour
T1
I CERVICAL CARCINOMA CONFINED TO UTERUS
T1 a
IA
Invasive carcinoma diagnosed only by microscopy.
T1 a1
IA1
Measured stromal invasion 3 mm or less in depth and 7mm or less in
horizontal spread.
T1 a2
IA2
Measured stromal invasion more than 3 mm and <5mm, and 7mm in
horizontal spread.

21. AJCC
8
FIGO
T1 b
I B
Clinically visible lesion confined to cervix or microscopic disease greater
than IA1,2
T1 b1
I B1
Clinically visible lesion <= 4cm in greatest dimension
T1 b2
I B2
Clinically visible lesion > 4cm in greatest dimension

22. AJCC
8
FIGO
II
Cervical carcinoma invade beyond the uterus but not to the pelvic
sidewall or lower third of vagina
T1 b
II A
Cervical lesion w/o parametrial involvement
T1 b1
II a1
Clinically visible lesion <= 4cm in greatest dimension
T1 b2
II a2
Clinically visible lesion > 4cm in greatest dimension
II B
Cervical lesion with parametrial involvment but not upto LPW

23. AJCC
8
FIGO
T 3a
III A Tumor involving lower third of vagina, no extension to LPW
T 3b
III B
Tumor extending to LPW and/or causing hydronephrosis or nonfunctioning
kidney
Pelvic side wall is defined as the muscle, fascia, neurovascular
structure, and skeletal portions of the bony pelvis. On rectal
examination there is no cancer free space between the tumour and
pelvic side wall

24. AJC
C 8
FIGO
N x
Regional lymphnode cannot be assessed
N 0 No Regional lymph node metastasis
N 0
(i+)
Isolated tumour cell in regional lymphnode(s) . No greater than
0.2 cm
N 1 Regional lymphnode metastasis
REGIONAL LYMPHNODES
Para-metrial, obturator , internal iliac (hypogastric),
external iliac, sacral , presacral, commmon iliac , para-
aortic

25. AJCC
8
FIGO
IV A Tumor invades mucosa of bladder or rectum and/or extends beyond true
pelvis (bullous edema is not sufficient to classify a tumour as T4

27. AJC
C 8
FIGO
M 0 No distant metastasis
M 1
IV B Distant metastasis ( including peritoneal
spread or involvement of supraclavicular
,mediastinal , or distant lymph node : lung ;
liver ; or bone.

28. Patterns of Spread
 Local Invasion
 Lymphatic
 Risk relates to depth of invasion
 Pelvic nodes before paraaortic or supraclavicular
 Hematogenous
 More likely in adenocarcinoma, neuroendocrine or
small cell tumors
 Intraperitoneal
 Unknown incidence
 Poor prognosis

29. Patterns of spread
 Direct Invasion
Corpus 10-30% Urinary Bladder
Cervical Epithelium Cervical Stroma Parametrium
Vagina Rectum

30. LYMPH NODE METASTASIS
Perez CA,dIsAIA pj,Knapp RC,et al.Gynecologic tumors.In:Devita VT Jr,Hellman S,Rosenberg SA,eds.Cancer:Principles and Practice
of Oncology,2nd edition Philadelphia:jb Lippincott,1985;1013-1041.
STAGE PELVIC LN(%) PARA-AORTIC LN(%)
IA1 0.5 0
IA2 4.8 <1
IB 15.9 2.2
IIA 24.5 11
IIB 31.4 19
III 44.8 30
IVA 55 40

31.  CARCINOMA OF THE UTERINE CERVIX (MALLINCKRODT
INSTITUTE OF RADIOLOGY 1959–1986): ANATOMIC SITE OF FIRST
METASTASIS

32. Prognosis
1. TUMOR-size, depth of invasion, LN status, histology
,vascularity , oncogenes , receptors
2. PATIENT - Age, S/E condition ,immune status
3. MEDICAL CONDITION- anemia, hypertension and the
t/t factors
4. TREATMENT RELATED FACTORS -dose, no of
intra-cavitary

33.  Lymph node metastasis is one of the most
important predictors of prognosis.
 Survival rates for patients treated with
radical hysterectomy with or without
postoperative radiotherapy for stage IB
disease were usually reported as 85% to
95% for patients with negative nodes and
45% to 55% for those with lymph node
metastases.
 {“Averette HE, Lichtinger M, Sevin BU, et al. Pelvic exenteration: a 150-year experience in a general
hospital. Am J Obstet Gynecol 1970;150:179.
 Delgado G, Bundy B, Zaino R, et al. Prospective surgical-pathological study of disease-free interval in
patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.
Gynecol Oncol 1990;38:352”}

34.  Roman et al reported a correlation between
the percentage of histopathologic sections
containing LVSI and the incidence of lymph
node metastases.
 Uterine-body involvement has been
associated with an increased rate of distant
metastases[Noguchi H, Shiozawa I, Kitahara T, et al. Uterine body invasion of
carcinoma of the uterine cervix as seen from surgical specimens. Gynecol Oncol 1988;30:173.]
 Most investigators have concluded that
adenocarcinomas confer a poorer
prognosis [Shingleton HM, Bell MC, Fremgen A, et al. Is there really a difference in
survival of women with squamous cell carcinoma, adenocarcinoma, and adenosquamous cell
carcinoma of the cervix? Cancer 1995;76:1948.]

35. DIAGNOSTIC AND METASTATIC
WORK UP
HISTORY AND
PHYSICAL
EXAMINATION:
• Pelvic and recto v
aginal examination:
• Tumor extension
• SCF LN
PROCEDURES:
• Colposcopy
• Pap smear if no
bleeding
• 4 Quadrant punch
biopsy
• Cold knife conization
if no gross lesion
visible or microscopic
carcinoma suspected
LAB
• Cbc
• Blood
chemistries
• Urinalalysis
RADIOLOGY
• Chest xray
• CT or MRI of
abdomen and
pelvis
• PET/PET-CT

36. Examination
 There are three steps:
1. The External Genital Exam
2. The Speculum Exam
3. The Bimanual Exam
Prerequisites :
• Patient must be counselled properly regarding the procedures to be done.
• A female attendant should be present by the side(nurse/or relative).
• A light source should be available.
• Sterile gloves,swabs,speculum,sponge holding forceps required.
1.Shaws’s Gynaecology,The gynaecology
examination

37. Step 1. The External Genital Exam
• Visually examine the soft folds of the vulva and the
opening of the vagina to check for signs of irritation,
discharge, cysts, genital warts, or other conditions.
• Note character of visible
vaginal discharge if any.
• Elicit the signs of Stress
incontinence and Genital
prolapse.
• Look for hemorrhoids,any
other palpable pathology
over the area.

38. Step 2. The Speculum Exam
 Speculum examination
should preferably be done
prior to bimanual
examination.
 Advantages :
 Cervical scrape cytology and
endocervical sampling can be
taken as screening in the same
sitting.
 Discharge P/V can be sent for
examination if need be
 Cervical lesion may bleed
during bimanual examination
which makes the lesion difficult
to visualise
• Anterior vaginal wall is to be visualized by
Sim’s speculum

39. Step 2. The Speculum Exam
• Insert a speculum into the
vagina usually in lithotomy
position .
• When opened, it separates the
anterior and posterior lip of the
vagina, which normally are
closed and touch each other,
so that the cervix can be seen.
• Patient may feel some degree
of pressure or mild discomfort
when the speculum is inserted
and opened.
• so it is essential that patient
must be advised to relax

40. Contd..
• The position of the cervix
or uterus may affect the
comfort as well.
• May feel the chill of the
metal, if a metal speculum
is used
• Lubricate the speculum
and warm it to body
temperature for more
comfort.
PER SPECULUM

41. BIMANUAL DIGITAL EXAMINATION
1) Assessing the cervix:
Vaginal fingers locate the cervix and
the external cervical os:
- Determine whether it is open or
closed
 Directed posteriorly when the uterus
is anteverted
 Consistency
 usually firm when normal,
 but hard due to fibrosis or carcinoma,
 soft in pregnancy
 Note any mass its
 size,
 shape,
 consistency,
 position,
 mobility ,
 extension

42. BIMANUAL DIGITAL EXAMINATION
2 Assessing the anae:
 The vaginal fingers are now
moved into one of the lateral
fornices with the abdominal
hand moving to the
corresponding iliac fossa.
 Assess for any adnexal
masses (ovaries and
fallopian tubes) on both sides
- size, shape, tenderness,
etc.

43. BIMANUAL DIGITAL EXAMINATION
3 Assessing the Pouch of
Douglas (recto-uterine
pouch):
-The vaginal fingers now placed
into the posterior fornix of
the vagina and its shape is
assessed (normally concave
away from the fingers, but
may be convex towards the
fingers if there is a mass in
the Pouch of Douglas).

44. Combined PR and PV Examination
 It is done with one finger inserted per vaginally and
the second finger of same hand per rectally
 Aim of the examination is to evaluate the extension
of tumor up to lateral pelvic wall
 Both the fingers are moved towards lateral pelvic
wall
 If tumor extends to pelvic wall the 2 fingers do not
converge

45. PAP Smear
 Insert the spatula with the
endocervical tip ( the longest
part), into the endocervical
canal and turn 360 degrees.
 Apply the smear onto the slide –
2 strokes.
 The Craigbrush is superior to
the spatula if the transition
zone is high and you cannot see
it.
 Turn it gently in five complete
circles and apply the smear to
the slide in gentle strokes.
 Within 20 seconds of taking it,
apply the smear onto the glass
slide with a light sweeping
motions.
• Conventional
• Liquid based cytology

46. Liquid Based Cytology:
•Taken using plasctic spatula
•Rinsed in a buffered methanol solution
•Sepatrated by centrifugation
Advantages :
• avoids false positive,false negative
• reduces number of unstaisfactory
smears

47. Pap tests can detect
• The presence of
abnormal cells in the
cervix
• Infections and
inflammations of the
cervix
• Symptoms of STDs
(With the exception of
trichomoniasis, Pap
tests cannot identify
specific STDs, )

48. Categories for Pap test results:
 Normal results:
 If no abnormal cells are seen, then the test result is normal.
 If only benign changes are seen, usually resulting from inflammation
or irritation, then the test result is normal.
 Abnormal results:
 Atypical cells of undetermined significance (ASCUS, AGUS).
 Low-grade squamous intraepithelial lesions (LSIL) or cervical
intraepithelial neoplasia (CIN) 1. These are mild, subtle cell
changes, and most go away without treatment.
 High-grade squamous intraepithelial lesions (HSIL) or CIN 2 or 3.
Moderate and severe cell changes which require further testing or
treatment.
 Carcinoma.

49. Pap test performance:
 Sensitivity = 51% for CIN I or higher
 Range of 37% to 84%
 Specificity = 98% for CIN I or higher
 Range of 86% to 100%
• meta-analyses of cross-sectional studies (AHCPR
• Historical success in developed countries.
• High specificity, meaning women with no cervical
abnormalities are correctly identified by the test
with normal test results.
• be cost-effective in middle-income countries.
Strengths of cytology:

50. Limitations of cytology:
 Moderate to low sensitivity:
 High rate of false-negative test results
 Women must be screened frequently
 Results are not immediately available
 Requires multiple visits
 Likely to be less accurate among post-menopausal
women
ACCP. Pap smears: An important but imperfect method.
Cervical Cancer Prevention Fact Sheet. (October 2002).

51. ENDOCERVICAL CURETTAGE: scraping of
mucus membrane by endocervical brush or
curettage.

52. Punch Biopsy
 Multiple punch biopsy of the grossly visible lesion
should be adequate to diagnose invasive carcinoma
 It is advised that the specimen be taken from all the four
quadrant
 Important thing is to obtain specimen from periphery of
lesion with some normal tissue
 Biopsy specimen from central area of necrosis or
ulceration may not be sufficient for diagnosis
 Dilatation and curettage

53. Colposcopy

54. COLPOSCOPY
 Binocular stereoscope giving 10-20 times
magnification
 To study cervix when pap smear detect abnormal cells
 To locate the abnormal areas and take biopsy
 Conservative surgery under colposcopic guidence
 Follow up
• Visual inspection of acetowhite areas;
• Applying 5% acetic acid
• Acid coagulates protein of nucleus and
cytoplasm and makes the protein opaque
and white
• Dull white plaque with faint border: LSIL
• Thick plaque with sharp border: HSIL

55. CT
 CT provides diagnostic information about the
 presence of metastases,
 enlarged lymph nodes, and
 the primary tumor.
 On a CT scan,
 cervical tumor seen as
 an enlarged, irregular, hypoechoic mass with ill-defined margins.
 Parametrial regions
 appear dense when involved, and uterosacral involvement may be
seen.
 Lymph nodes appear
 enlarged, with most >1 cm on axial dimension considered
pathologic.
 The overall accuracy of CT scanning in staging cervical
cancer ranges from 63% to 88%.50,52
 Sensitivity - 44%

56. MRI
 MRI is frequently used for the
 initial assessment of
 the cervical tumor and
 of extracervical tumor extension
T1W: isointense
T2W:
hyperintense
CE-T1W:
hyperintense

57.  MRI is significantly better than clinical examination or
CT for detecting uterine-body involvement or
measuring tumor size, but no method was accurate at
evaluating the cervical stroma.
 MRI was significantly better at detecting the tumor
and parametrial involvement.
 MRI also increased detection of involved lymph
nodes.
 The tumor is less likely to be as visible on MRI for
adenocarcinoma cases, compared to squamous cell
cancer.
Perez &Brady,6th edition

58. CT vs
MRI$
Sensitivity Specificity Accuracy
*
CT MRI CT MRI CT MRI
Parametrial
invasion
55%
[44-66 %]
74%
[68-79 %]
- - 76
%
94
%
Lymph nodes 43%
[37-57 %]
60%
[52-68 %]
- - 86
%
86
%
Bladder invasion - - 73%
[52-87 %]
91%
[83-95 %]
- -
Bladder and
rectal invasion
71% 75% - - - -
Stromal invasion - - - - 78
%
88
%
Staging - - - - 65
%
90
%
$ Bipat S,et al, Gynecol Oncol. 2003 Oct;91(1):59-66
*Obs&Gyn,1995;86(1):43-5

59. Positron Emission Tomography
 PET scanning is increasingly used in the evaluation of patients
with invasive cervical cancer, using 2-[18F]-fluoro-2-deoxy-D-
glucose (FDG).
 Rose et al.
 observed uptake in 91% of the primary tumors in 32 patients with
locally advanced carcinoma of the cervix.
 Compared with surgical staging, PET scanning has a
 sensitivity of 75% &
 specificity of 92% in detecting para-aortic metastasis.
 PET-CT –
 highly accurate localization of focal radiotracer uptake
 significantly improved diagnostic accuracy when compared with PET or
CT alone.
 The most significant prognostic factor for progression-free survival was
the presence of positive para-aortic lymph nodes on PET imaging.
Grisby et al, JCO 2001

60.  Maximum standardized uptake value (SUV max) is
an independent predictor of death from cervical
cancer and is associated with persistent disease.
 The SUV of the pelvic node predicts pelvic
disease recurrence.
 Squamous cell carcinoma is more often FDG avid
than is adenocarcinoma.
Perez & Brady,6 th edition

61. Therapeutic Modalities
Surgery

62. Principles of treatment
 Both the primary lesion and the potential sites of spread
should be evaluated and treated
 Optimal therapy consists of radiation or surgery
ALONE - Morbidity is higher when both are combined

63. PRE INVASIVE
 CIN part or the full thickness of the stratified
squamous epithelium is replaced by cells showing
varying degree of dysplasia, but the BASEMENT
MEMBRANE IS INTACT.
 These pre invasive lesions end up as invasive lesions over a period of
time.
 4% - at the end of first year
 11%- by the end of 3 years
 22%- by 5 years
 30%- by 10 years

64. DYSPLASIA
 Dysplasia in term literally means disordered growth.It is
characterised by a constellation of changes that include a loss of
uniformity of the individual cells as well as a loss
in their architectural orientation.
 dysplasia is graded as
 mild (CIN I)
 moderate (CIN II)
 severe (CIN III)
 tadpole cells as seen in invasive cancer

65.  MILD DYSPLASIA(CIN I)- undifferentiated cells are
confined to lower third of epithelium.
 aka low grade squamous intraepithelial
neoplasia(LSIL)[Bethseda classification].
 MODERATE DYSPLASIA(CIN II)- undifferentiated cells
occupy lower 50-75% of thickness.
 SEVERE DYSPLASIA(CIN III)- entire thickness of
epithelium is filled with abnormal cells. basement
membrane is still intact.
 CIN II and CIN III are together considered as high grade
squamous intra-epithelial lesion HSIL.

68. Conization
 Removes the cervical lesion, the transformation zone
& the endocervical canal in the shape of a cone along
with endocervical curettage
 Indications: both diagnostic & therapeutic
 To assess correctly the depth and the linear extent when
microinvasion suspected
 Inconclusive colposcopy
 TZ not fully visualized
 A visible lesion extending to endocx canal
 Dysplastic fragments in ECC
 Discordance of >1 grade among the diagnostic evaluation
 Treatment of Stage Ia1

69. Types of surgeries
in
CARCINOMA
CERVIX

70. Surgical procedures in Carcinoma Cervix
 Fertility sparing surgeries
 Conization
 Trachelectomy
 Radical hysterectomy
 Laparoscopic assisted radical vaginal
hysterectomy
 LEER
 Lymphadenectomy &Staging
lymphadenectomy
 Exentration
 Oophoropexy

71. Conization
 Removes the cervical
lesion, the transformation
zone & the endocervical
canal in the SHAPE OF A
CONE along with
endocervical curettage
 Is both diagnostic &
therapeutic

72. Radical trachelectomy
 Tricky and difficult to master: the surgeon removes
the CERVIX, PARAMETRIUM,
SURROUNDING LYMPH NODES, AND UPPER
2 CM OF THE VAGINA. The uterus is then
attached to the remaining vagina. A cerclage is placed
where the Neocervix used to be to allow the patient
to carry a pregnancy
 Transvaginally /transabdominally/laparoscopic with
lymphadenectomy
 Selection criteria
 Lesion size < 2 cm
 Absence of overt LN metastases
 Absence of LVSI.

73. SIMPLE RADICAL
INDICATION HSIL , 1A1 IA2 & IB1 ,IF <2 cm , SQUAMOUS
Intent CURATIVE, FERTILITY
PRESERVED
CURATIVE, FERTILITY PRESERVED
Uterus SPARED SPARED
Ovaries SPARED SPARED
Cervix REMOVED REMOVED
Vaginal margin NONE UPPER ¼ TO 1/3
Ureters NOT MOBILIZED TUNNELED THROUGH BROAD
LIGAMENT
Cardinal l RESECTED AT CERVICAL
BORDER
DIVIDED AT PELVIC SIDEWALL
Utero sacral l DIVIDED AT CERVICAL
BORDER
DIVIDED NEAR SACRAL ORGIN
Surgical
approach
VAGINAL VAGINAL/LAP/ROBOTIC
LAPROSCOPY

74.  RVT is a safe and feasible procedure to perform in women with small
cervical carcinomas who wish to preserve fertility
 Complications : cervical stenosis, vaginal discharge, or
dysmenorrhea and reduced fertility , 2nd trimester miscarriage or
premature delivery, deep dyspareunia and recurrent candidiasis
 Lesion size >2 cm is probably the most important risk factor in terms of
tumor recurrence
 Pregnancy rates following RVT range between 41% -79%, and term
delivery ( 37 weeks) is reached in 38% of the pregnancies
 In-appropriate in gastric type adeno carcinoma and adenoma malignum
 For 1B1 ART is considered than VRT , because it provide broader
resection of parametrium
 However miscarriage and pre term labour rates were elevated among
women who underwent radical trachelectomy

75. Type I hysterectomy(simple) type A
 Extrafascial hysterectomy-The
fascia of the CERVIX AND
LOWER UTERINE SEGMENT,
which is rich in lymphatic, is
removed with the uterus
 No pelvic LND

76. Type II radical hysterectomy(wertheim’s) type B
 The uterine artery is ligated where
it crosses over the ureter and the
uterosacral and cardinal ligaments
are divided midway towards their
attachment to the sacrum and
pelvic sidewall, respectively. The
upper one-third of the vagina is
resected.
 Less extensive
 Selective removal of enlarged LNs
UTERINE
ARTERY
URETER

77. Type III radical hysterectomy (Meig’s) type C
 The uterine artery is ligated at its
origin from the superior vesical or
internal iliac artery. Uterosacral and
cardinal ligaments are resected at their
attachments to the sacrum and pelvic
sidewall. The upper one-half of the
vagina is resected.
 Pelvic LND

79. Extended radical hysterectomy
 TYPE IV - The ureter is completely dissected from the
vesicouterine ligament, the superior vesical artery is
sacrificed, and three-fourths of the vagina is resected
 TYPE V - There is additional resection of a portion of the
bladder or distal ureter with ureteral reimplantation into the
bladder.
 Rarely used

80. Type-II Vs Type III -Hysterectomy
 The therapeutic efficacy of a type II comparable to that of a type
III but with lower morbidity
 THE TYPE II OPERATION WAS ASSOCIATED WITH
 Shorter mean operative time
 Less late urologic morbidity
 Similar recurrence rates & Cause-specific mortality
 5year OS & DFS
 Type II procedure appears preferable as long as appropriate
tumor clearance can be achieved

81. Laparoscopy-assisted radical vaginal
hysterectomy (LARVH)
 Procedure :
 laparoscopic visualization of the abdominal cavity to exclude
macroscopic disease
 Laparoscopic lymphadenectomy
 Radical vaginal hysterectomy (type II or III)
 Advantages :
 Less blood loss
 Better cosmetic results
 Faster recovery, shorter hospitalization
 Complications
 Similar to those seen with abdominal surgery

82. Staging lymphadenectomy
 Aim- To discovers positive lymph nodes as clinical staging is
imprecise
 Clinical stage fails to identify para-aortic involvement
 Stage IIa- 10 %
 Stage IIb -20%
 Pelvic LN dissection
 PA LN dissection-
 Bulky cx ca
 Grossly positive LNs
 For whom frozen section evaluation will be performed

83. Staging lymphadenectomy
 Arguments in favor
 Surgical staging is the most accurate method of
determining lymph node involvement.
 Therapeutic survival benefit of resecting bulky lymph
nodes prior to chemo radiation
 Arguments against
 Delay in the institution of primary CRT
 Increased risk of morbidity (especially late bowel
obstructions) with the combined modality approach.
 Methods
 Transperitoneal approach-radiotherapy induced bowel
complications – 30%
 Extraperitoneal dissection-postradiotherapy bowel
complications-<5%
 Laparoscopic lymphadenectomy

84. LEER, LATERALLY EXTENDED
ENDOPELVIC RESECTION
 For recurrent disease involving pelvic side walls
 Extended lateral resection plane
 Internal iliac vessels, endopelvic part of obturaror
internus, coccygeus, iliococcygeus,
pubococcygeus are removed

85. EXENTERATION
 An ultraradical surgical procedure consisting of an en bloc
resection of the FEMALE REPRODUCTIVE ORGANS,
LOWER URINARY TRACT, AND A PORTION OF
THE RECTOSIGMOID.
 Indications
 Recurrent or advanced gynecologic cancer
 Extensive central pelvic disease that cannot be resected with a lesser
procedure
 Has received Radiation before
 Contraindications
 Presence of distant metastasis - 50%
 Unresectable or extrapelvic disease - 30-50%
 Disease extending to pelvic side walls

87. OOPHOROPEXY
 Aim: To shield the normal
premenopausal ovary from the
damaging effects of radiation
 PROCEDURE: The ovaries and
their vascular supply are brought
out of the pelvis and sutured
lateral and above the psoas
muscle
 Ovarian failure can result despite
oophoropexy because of scatter
radiation and surgically induced
changes in ovarian blood supply&
innervation

88.  CRITERIA FOR CONSERVATIVE
PROCEDURE
 The entire area must be visible within the
squamocolumnar junction.
 No evidence of macro or micro metastasis as
proven by histopathological study.
 No evidence of endocervical involvement.
 Young women desirous of child bearing.

89.  Hysterectomy is desirable in-
 old and parous women,
 when a women cannot comply with
followup.
 if uterus is associated with
fibroids/DUB/prolapse.
 if micro invasion exists.
 if recurrence occurs following conservative
therapy or persistence of lesion.

90.  SURGERY
 Best role, only option : Preinvasive disease
 Definite role, alternate option : Early
invasive disease
 Controversial role : Bulky disease
 Some role, only option : recurrent disease
(RT failure)

91. STAGE
&
MANAGEMENT

92. FERTILITY SPARING IA1, IA2, IB1
CLINICAL STAGE PRIMARY TREATMENT
 I A1 ( No LVSI ) CONE BIOPSY with negative margin ( preferably
a non fragmented specimen with 3 mm -ve
margin)
If +VE margin >> repeat CONE
BIOPSY/TRACHELECTOMY
 I A1 ( With LVSI)
 I A2
CONE BIOPSY with negative margin ( preferably
a non fragmented specimen with 3 mm -ve
margin)
If +VE margin >> repeat CONE
BIOPSY/TRACHELECTOMY
+ PELVIC LYMPH NODE DISSECTION+/- Para-
aortic ln sampling
OR
RADICAL TRACHELECTOMY+ PLND +/- Para-
aortic ln sampling
I B1
RADICAL TRACHELECTOMY+ PLND
+/- Para-aortic ln sampling
NCCN 2017

93. NON FERTILITY SPARING IA1, IA2,
CLINICAL STAGE PRIMARY TREATMENT
 I A1 (No LVSI )
 I A1 ( With
LVSI)
 I A2
MODIFIED RADICAL HYSTERECTOMY + PELVIC
LYMPH NODE DISSECTION+/- Para-aortic ln
sampling
OR
PELVIC EBRT+ BRACHYTHERAPY
NCCN 2017
CONEBIOPSY
-VE MARGIN ,
IN OPERABLE
-VE MARGIN,
OPERABLE
+VE MARGIN
OBSERVE
TYPE1/II
HYSTERECTOMY
TYPE 1-
HYSTERECTOMY

94. IB1, IIA1,
CLINICAL STAGE PRIMARY TREATMENT
 I B1
 II A1
MODIFIED RADICAL HYSTERECTOMY +
PELVIC LYMPH NODE DISSECTION+/- Para-
aortic ln sampling
OR
PELVIC EBRT+ BRACHYTHERAPY +/-
CONCURRENT CISPLATIN CONTAINING
CHEMOTHERAPY
NCCN 2017

95. IB2, IIA2,
CLINICAL STAGE PRIMARY TREATMENT
 I B2
 II A2
DEFINITIVE PELVIC EBRT+ CONCURRENT
CISPLATIN CONTAINING CHEMOTHERAPY+
BRACHYTHERAPY (Cat 1)
OR
RADICAL HYSTERECTOMY+ PLND +/-PA
LN(cat 2)
OR
PELVIC EBRT+CONCURRENT CISPLATIN
CONTAINING CHEMOTHERAPY+
BRACHYTHERAPY+ Adj HYSTERECTOMY ( Cat
3)
NCCN 2017

96. Stage IIB, III, and IVA Disease
Radiotherapy (EBRT+CC+BT) is the primary
treatment for locoregionally advanced cervical
carcinoma.
 The success of radiotherapy depends on a careful
balance between external-beam radiotherapy and
brachytherapy, optimizing the dose to tumor and
normal tissues and the overall duration of treatment.

97. Randomized study of radical surgery v/s
radiotherapy for stage Ib-IIa cervical cancer:
Lancet 1997
 Only prospective trial comparing radical surgery with
radiotherapy
 Design
Surgery
EBRT+ICR
pT2b , <3
mm
margins,
positive
margins,
positive
pelvic
node,
parametrial
extn.
Post op RT
IB and
IIA
343

98. Results
Median follow-up of 87 months
Worse morbidity seen in combined modality
Treatment
modality
5-year
overall
and
disease-
free
survival
Toxicity
Surgery 83% & 74
%
25% 28%
Radiotherap
y
83 % &
74%
26% 12%
Local
recurren
ce
P=0.004

100.  For patients treated with radiotherapy alone for stage
IIB, IIIB, and IV disease,
 5-year survival rates of 65% to 75%,
 35% to 50%,
 and 15% to 20%,
 respectively, have been reported.
 “Benedet J, Odicino F, Maisonneuve P, et al.
Carcinoma of the cervix uteri. J Epidemiol Biostat
1998;3:5.
 Logsdon MD, Eifel PJ. FIGO IIIB squamous cell
carcinoma of the cervix: an analysis of prognostic
factors emphasizing the balance between external
beam and intracavitary radiation therapy. Int J Radiat
Oncol Biol Phys 1999;43:763.”

101. FAILURE RATE FOLLOWING RADICAL
RADIATION IN CARCINOMA CERVIX
STAGE PELVIC
FAILURE
DISTANT
METS
IB 10% 16%
IIA 17% 30%
II B 23% 28%
III 42% 45%
IVA 74% 65%
Mallinckrotd Institute of Radiology, 1959-89

103.  Therefore, there is need to use some
additional modality of treatment with radiation
to improve results of locally advanced
carcinoma cervix.

104. CHEMORADIATION
IN
CARCINOMA CERVIX
?????

105. NATIONAL CANCER INSTITUTE CLINICAL
ANNOUNCEMENT
 Concurrent chemoradiation for cervical cancer
 FEBRUARY 1999

106. 106
improve survival by
 1. Increasing control of the
primary cervical tumor
(Radiosensitization)
A) Additivity : increased
killing,
B) Synergism
inhibition of repair of RT
induced damage,
promoting cells into radio
sensitive phase, intiate
proliferation in non-
proliferating cells., reducing
fraction of hypoxic cells
 2. Decreasing the rate of
distant metastases
STEEL PARADIGM

107. 107
Major Trials
Author Trial No. Investigational
Arm
Control Arm Tumor Comment
Keys
1999
GOG
123
369 RT+ Cisplatin
Surgery
RT alone
Surgery
Stage IB
(≥ 4cm)
Combined with
Surgery
Peters
2000
SWOG
8797
243 Surgery
RT+Cisplatin+5F
U
Surgery
RT alone
IA2, IB, IIA
(with postop
high risk)
Combined with
Surgery
Morris &
Eifel 1999
&.2004
RTOG
9001
388 RT+Cisplatin+5F
U
Extended -
field RT
IB or IIA
(≥5cmorPLN+)
IIB, III, IVA
Surgical staging
for PALN
Whitney
1999
GOG
85
368 RT+Cisplatin+5F
U
RT+
Hydroxyurea
IIB, III, IVA Surgical staging
for PALN
Rose
1999
GOG
120
526 RT+Cisplatin
RT+Cisplatin +
5FU
+Hydroxyurea
RT+
Hydroxyurea
IIB, III, IVA Surgical staging
for PALN
Pearcey
2002
NCIC 253 RT+Cisplatin RT alone IB2, IIA(≥5cm),
IIB, III, IVA
No surgical
staging for
PALN

109. 109
Randomized controlled trials of
concurrent chemotherapy

110. GOG 80
GOG
120
GOG
123
RTOG
9001

111. 111
Reduction in the risk of death by cisplatin-
based CRT: 6 major trials

112. 112
Locally advanced cervix cancer
Concurrent chemoradiation:
Results of RCTs
 Significant reduction (43-46%) in the risk of
recurrence & death.
 Reduction in relative risk of recurrence &
death remarkably similar in all studies.
 Compelling evidence of survival benefit (10-15%)
with concurrent cisplat chemo.

113. 113
Concurrent Chemoradiation
Results of Meta-analyses
 19 RCTs between 1981 and 2000 : 4580
randomized patients
 Increase in OAS by 12% & RFS by 16%
(absolute benefit) (p=0.0001)
 Greater benefit in patients in stages IB2 and IIB
 Decrease in local and systemic recurrence
(p=0.0001)
Cochrane Collaborative Group (19 Trials) (4580
patients)
Green JA et al Lancet 358;781 (Sept. 2001)
“Grade A”
Update in July 2005: 21 trials and 4921
pts
• Similar findings (absolute benefit:
10%)
• Test for Heterogeneity : Positive
• No data on late toxicities
Cochrane Database Syst Rev. 2005 Jul 20;(3):CD002225.

114.  Breaks during or between external-beam and
intracavitary therapy should be discouraged, and every
effort should be made to complete the entire radiation
treatment in less than 7 to 8 weeks.
 Several studies have suggested that treatment courses
longer than 8 weeks are associated with decreased pelvic
disease control and survival rates.
 “Fyles A, Keane TJ, Barton M, et al. The effect of treatment duration in the local control of cervix
cancer. Radiother Oncol 1992;25:273.
 Perez CA, Grigsby PW, Castro-Vita H, et al. Carcinoma of the uterine cervix. I. Impact of
prolongation of overall treatment time and timing of brachytherapy on outcome of radiation
therapy. Int J Radiat Oncol Biol Phys 1995;32:1275.
 Petereit DG, Sarkaria JN, Chappell R, et al. The adverse effect of treatment prolongation in
cervical carcinoma. Int J Radiat Oncol Biol Phys 1995;32:1301.”

115. 115
Impact of RT delay on survival
(GOG 120&165)
(Monk BJ,et al: J Clin Oncol
2007)
P=0.012

116. 116
Optimal timing of intervention for acute
toxicity
(Ohno T. et al, Gynecol. Oncol. 2006)

117. 117
Criteria for modification of
chemotherapy
 Cisplatin is suspended in
 -Grade 2 hematological toxicities
 (WBC < 3000, Plt < 75000)
 -Fever > 38ºC
 -PS 3-4
 -Grade >3 non-hematological toxicities
 (e.g. diarrhea, loss of appetite, fatigue)
 -Serum creatinine > 2.0 mg/dl
 -Cases that are judged to be difficult to administer cisplatin by
responsible physician.
 Cisplatin is resumed when the hematological and
nonhematological toxicities are recovered to grade 1.

118. FIGO GUIDELINE IN 2000
 For Advanced Cervical cancer (Stage IIb , III, IVA)
Benedet et al Int J of Gynecol Oncol 2000
Addition of concurrent cisplatin-containing chemotherapy to standard
radiotherapy reduces the risk of disease recurrence by as much as 50%.

119.  NEOADJUVANT CHEMOTHERAPY
 NEO ADJUVANT CT followed by surgery has been used in areas
where RT is not available , data suggest NO
IMPROVEMENT in survival when compared with
surgery alone for early –stage cervical cancer or
locally advanced cervical cancer.
 A meta analysis of data on pts with stage IB1 to IIA
cervical cancer found that NACT may reduce the need
of adj RT by decreasing tumour size and metastases ,
but indicated no OS benefit.
 Second meta analysis suggested that response to
NACT was a strong prognostic factor for PFS and OS

120. Indications for adjuvant therapy
 High-risk disease
 Positive or close resection margins
 Positive lymph nodes
 positive parametrial involvement
 Intermediate-risk disease
 Lymphovascular space invasion
 Large tumor size (>4 cm)
 Deep cervical stromal invasion (to the middle or deep one-
third)
 low-risk disease
 Negative margins
 Negative lymph nodes
 Negative parametrial involvement

121. Adjuvant RT/ RT+CT

123. POSITIVE ADENOPATHY IB2,
IIA2,IIIA,IIIB,IV A

124. POSITIVE ADENOPATHY IB2,
IIA2,IIIA,IIIB,IV A
Work up for metastasis

125. RECURRENCE

126. SURVEILLANCE(NCCN Guidelines 2017)
Interval H& P 3-6 monthly 2yrs
6-12 monthly 3-5 yrs
>5 yrs annually
Cervical and vaginal cytology
as indicated for lower genital
tract neoplasia
Annual
Imaging as indicated CT, PET ,MRI
Lab Assessment as indicated CBC ,BUN, Creatinine
Patient education Symptoms of potential recurrence
Lifestyle
Obesity
Exercise
Nutrition
Sexual health and vaginal dilator use.

127. OVERALL SURVIVAL BY STAGE
SURVIVAL
(5YR)
Last Revised:
02/26/2015
IA 93%
IB1 83%
IB2 80%
IIA 63%
IIB 38%
IIIA 35%
IIIB 32%
IVA 16%
IVB 15%
 The rates below were published in
2010 in the 7th edition of the AJCC
staging manual.
 They are based on data collected by
the National Cancer Data Base from
people diagnosed between 2000 and
2002.
 These are the most recent statistics
available for survival by the current
staging system

128. Targets for EBRT
 Entire cervix
 Uterus and tubes
 Upper third of vagina
 Entire vagina in selected cases
 Parametrial tissues (cardinal,
uterosacral and pubocervical ligaments)
 Pelvic nodes (external and internal iliac,
in selected cases up to common iliac)
 Inguinal nodes in selected cases.
 Para-aortic nodes in selected cases.

129. Principles of radiotherapy
 volume : Gross disease, parametria, us ligaments,
sufficient vaginal margin (atleast 3mm), Presacral and
other Nodes at risk
 Nodes at risk -
Negative node on surgical or radiology ( EIL,IIL,O) ;
High risk/suspected node – cover common iliac also ;
CIL /para aortic – EX EBRT( upto the
level of renal vessels or even more according to the
nodal station)

130. Dose
 For coverage of microscopic/ nodal disease
 45-50 GY (1.8 to 2 gy/#)
 BOOST : 10-15 gy for gross unresected adenopathy

131. Brachytherapy
 Critical component of definitive therapy
 Usually performed using an intracavitory
approach
 When combined with EBRT , BT intiated
towards the latter part of traetment.
 In highly selected very early disease (STAGE I
A2) BT alone may be an option.

132. THANK YOU