The document provides guidelines for the diagnosis, staging, and treatment of carcinoma of the cervix based on evidence and includes details on diagnostic workup, FIGO staging, pathologic classification, stage-wise management including surgery and radiotherapy, indications for adjuvant treatment, results of post-treatment, management of recurrent disease, techniques of radiotherapy including external beam radiotherapy and brachytherapy, and evolution of brachytherapy sources and applicators. Stages IA-IIA are generally treated with surgery or radiotherapy while stages IIB and higher involve concurrent chemoradiotherapy along with brachytherapy based on randomized controlled trial evidence showing improved outcomes.

1. CARCINOMA CERVIX-EVIDENCE
BASED MANAGEMENT AND
RADIOTHERAPY
DR. DEBARSHI LAHIRI, MD

2. INCIDENCE
Commonest cancer in Indian women.
Age adjusted incidence rates range from
19 – 44 per 100,000 women in various cancer
registries.

3. DIAGNOSTIC WORKUP
 HISTORY
 PHYSICAL EXAMINATION
 LAB STUDIES
 CYTOLOGY SMEARS (Pap)
 COLPOSCOPY and directed biopsies
 ENDOCERVICAL CURETTAGE
 CONIZATION

4. Diagnostic workup contd.
 PUNCH BIOPSIES
 CYSTOSCOPY AND
RECTOSIGMOIDOSCOPY

5. RADIOLOGIC STUDIES
 CHEST X-RAY
 IVP
 BARIUM ENEMA

6. COMPLEMENTARY PROCEDURES
 USG
 CT/MRI
 PET
 SURGICAL STAGING
(Aid in Tx Planning but can’t be used to
determine or change FIGO stage)

7. FIGO STAGING
 Stage 0 Preinvasive carcinoma / carcinoma in situ
 Stage I Tumour confined to cervix.
 IA Preclinical invasive ca, diagnosed by microscopy only.
 IA1 Measured Stromal Invasion 3mm or less in depth and 7 mm
or less in horizontal spread.
 IA2 Measured stromal invasion 3 to 5mm and 7 mm
or less in horizontal spread.
 IB Clinically visible lesion confined to the cervix or microscopic
lesion greater than IA2.
 IB1 4 cm or less in size.
 IB2 >4 cm in size.
contd.

8.  Stage II Tumour beyond uterus but not the lower 1/3 of vagina or up
to the pelvic side walls.
IIA without Parametrial invasion.(IIA1:<4 cm; IIA2:>4 cm)
IIB with Parametrial invasion.
 Stage III Tumour extending up to pelvic wall, lower 1/3 vagina,
hydronephrosis or non-functioning kidney.
 IIIA No extension to pelvic wall but involved lower 3rd vagina.
 IIIB Extension to pelvic side wall, hydronephrosis or non-
functioning kidney.
 Stage IV
 IVA Invasion of mucosa of bladder/rectum, and/or extends
beyond true pelvis (bullous edema is not sufficient to
classify a tumor as T4).
 IVB Distant Metastasis.

9. PATHOLOGIC CLASSIFICATION
 SQUAMOUS CELL CARCINOMA
- OVER 90%
 ADENOCARCINOMA
- 7 to 10%
 OTHERS
-1 to 2%

10. STAGE WISE MANAGEMENT
STAGE 0 (Carcinoma In Situ)
If FERTILITY PRESERVATION DESIRED
For Ectocervical Lesions:
 Loop electrosurgical excision procedure (LEEP).
 Laser therapy
 Cryotherapy
 Conization
If Endocervical Canal Involved:
 Conization

11. Treatment of stage 0 contd.
POST MENOPAUSAL PATIENTS
 Total abdominal or vaginal
hysterectomy
MEDICALLY INOPERABLE
 Intracavitary Irradiation Alone
- 45 to 50 Gy to Point A

12. STAGE I A
I A1 ( No LV Invasion)
 CONIZATION:
Adequate in those who desire fertility.
 TOTAL HYSTERECTOMY( Abdominal or
Vaginal)
(also in cone margin positive patients)

13. Treatment of Stage IA1 contd.
 INTRACAVITARY BRACHYTHERAPY
ALONE
Patients unfit for surgery.
Dose: 60 to 70 Gy to Point A
 LV Invasion- Treated Similar to IA2/IB1

14. STAGE IA2
 Radical Hysterectomy with
Pelvic Node Dissection
 Women not fit for surgery:
Brachytherapy plus External Pelvic
Irradiation( Point A dose: 75 to 80 Gy).

15. STAGE IB1 and IIA (<4 cm)
 Radical Hysterectomy plus Pelvic
Node Dissection
OR
 Pelvic RT plus Brachytherapy
(Point A Dose: up to 80 Gy)

16.  The ABS recommendation:
DEFINITIVE RT/RADICAL SURGERY
Results Equivalent.
The ABS recommends that primary therapy should
avoid routine use of both Radical Surgery and RT
to minimize morbidity related to multimodality
therapy.

17. STAGE IB2 and Bulky IIA(>4cm)
 Pelvic RT + Concurrent Cisplatin
containing Chemotherapy+ Brachytherapy
( Point A Dose: 85 Gy or more)
 Radical Hysterectomy + Pelvic Node
dissection (lower evidence)

18. INDICATIONS OF ADJUVANT TREATMENT
(Post Operative)

NODE NEGATIVE PATIENTS
PELVIC IRRADIATION in pts. with any 2 of the following:
> 1/3rd Stromal Invasion
LV space Invasion
Large (>4 cm) tumor

19. Adjuvant Treatment Contd.
 Positive Pelvic Nodes/Positive Surgical
margin/Positive Parametrium
Pelvic RT+ Concurrent Cisplatin
based chemotherapy and
vaginal brachytherapy if positive
vaginal margin.

20. STAGES IIB/IIIA/IIIB
 Pelvic RT + concurrent Cisplatin based chemotherapy +
Brachytherapy
( Total Point A Dose 85 Gy or more)
STAGE IVA
 Individualized Tx based on Extent of
Bladder/Rectal involvement/Renal
function/Parametrial involvement/performance
status.

21. Stage IVA Treatment Contd.
 Surgical Exenteration: Pts with no/minimal
parametrial invasion and good performance
status( anterior/posterior or total).
 Concurrent RT/CT: Selected pts with good general and renal
status and not suitable for surgical exenteration.
 Palliative RT: Majority have poor GC and extensive local
disease – best treated with Palliative RT alone.
A short regime of 30 Gy/10#/2 wks- few pts who respond
well-followed by intracavitary appl.

22. Stage IVB
 Palliative RT: Palliation of distant metastases in
Brain/Bone etc.
Palliation of symptoms like pain/bleeding/tenesmus
etc.
 Palliative CT: No standard CT regimen available.
Combinations like Cisplatin/Paclitaxel,
Cisplatin/Topotecan, Cisplatin/Ifosfamide have
been used with varying response rates.

23. CONCURRENT
CHEMORADIATION
 ABS/NCI Recommend the addition of
Cisplatin based CT during the course of
definitive RT for stage IB2 onwards.
5 Randomized Trials- significant improvement
in local control+ survival
(In women from affluent countries
with better performance/nutritional status and
renal parameters).

24.  CCRT IN INDIAN CONTEXT:
Our Patients- lower socioeconomic status/
more advanced disease/poor renal
parameters/doubtful compliance/doubtful
tolerance to CCRT
RADICAL RT ALONE CAN STILL BE
CONSIDERED AS AN ACCEPTABLE
TREATMENT APPROACH

25. POST TREATMENT RESULTS ( 5 year DFS )
IA: >95%
(With LV Invasion) up to 90%
IB 1 : 86-90%
IIA( Non bulky) : 75%
IB 2/IIA Bulky: 60-65%

26. Post treatment results contd.( 5 yr survival)
STAGE IIB: 60-65% with RT alone
STAGE III: 30-55% with RT alone
STAGE IVA:18-30% with Exenteration/RT

27. INVASIVE CANCER FOUND AFTER SIMPLE
HYSTERECTOMY
TWO TREATMENT OPTIONS:
1. Immediate Resurgery- Radical Parametrectomy and Pelvic LND.
2. Post op RT:
a) No disease/microscopic only at margins: Whole Pelvis RT 45-50 Gy
with Concurrent Cisplatin based Chemotherapy for Microscopic disease at
margins, followed by ICRT to boost the dose at vaginal apex to 60-65 Gy
(Total dose).
b) Gross Residual in vault: Whole Pelvis 40 Gy + parametrium additional
20 Gy, with Concurrent Cisplatin based Chemotherapy followed by ICRT up
to 65 Gy mucosal dose.

28. RECURRENT DISEASE
Post RT:
1. Central Disease
Small lesions
Radical Hysterectomy or Brachytherapy
Larger lesions, good PS
Pelvic Exenteration
2. Pelvic Side Wall Recurrence
Palliative CT/Symptomatic& supportive care.
Post Surgery:
Definitive Pelvic RT+ Cisplatin based chemotherapy
Extrapelvic/Distant Mets: Palliative Intent

29. RADIOTHERAPY
 EXTERNAL IRRADIATION- Treats Whole Pelvis+
Parametria
 ICRT- primarily irradiates central disease( cervix, vagina
and medial parametria)
EBRT delivered before ICRT If :
1) Bulky cervical lesions to improve the geometry
2)Exophytic, easily bleeding tumors
3)Tumors with necrosis or infection
4) Parametrial involvement

30. EBRT PORTAL: PELVIC AP/PA Borders:
Superior Border: L4-L5 Interspace
(up to common iliac nodes)
Inferior Border: Lower border of the Obturator Foramen.
Entire length down to introitus, if vaginal involvement.
Lateral Border: 2 cm lateral to bony pelvis on either side.

31. LATERAL PORTAL
Anterior Margin: Cortex of symphysis pubis
( cover ext. iliac nodes)
Posterior Margin: Covers atleast 50% of rectum
in stage IB and extends to Sacral hollow
in more advanced tumors.
LATERAL FIELDS ALLOW A DECREASE IN DOSE TO
THE SMALL BOWEL AND A PORTION OF THE
LOW RECTUM BUT CARE MUST BE TAKEN TO
INCLUDE ALL STRUCTURES OF INTEREST.

32. MIDLINE SHIELDING
May be used for Part of Pelvic RT to Shield Bladder
and Rectum to allow a higher dose to be given by
brachytherapy
 Simple Rectangular Block: 4 cm wide at midplane.
 Customized midline blocks based on radiographs.
 When inserted before 40 Gy, should not extend to top
of the pelvic field ( C. iliac& presacral nodes shielded).

33. BRACHYTHERAPY
ABS strongly recommends that:
1) Definitive Irradiation for cervical carcinoma must include
brachytherapy as a component.
2)Precise applicator placement is essential for improved local
control and reduced morbidity.
3)Interstitial brachytherapy should be considered for patients with
disease that can’t be optimally encompassed by intracavitary
brachytherapy.
4)Total treatment duration be less than 8 weeks when
possible( exceeding beyond 8 wks can reduce local control and
survival by about 1% per day of prolongation.

34. Treatments Classified with respect to Source
loading:
1) Preloading: The applicator is preloaded and
contains radioactive sources at the time of
placement into the patient.
2) Afterloading: The applicator is placed first into
the target position and the radioactive sources
are loaded later, either by hand (MANUAL) or
by a machine( REMOTE AFTERLOADING).

35. Treatments Classified with respect to Dose
Rate:
LDR: 0.4 – 2 Gy/hr
MDR: 2- 12 Gy/hr
HDR: > 12 Gy/hr ( practically much higher
dose rate used)

36. EVOLUTION OF BRACHYTHERAPY
IN CARCINOMA CERVIX
First application of Radium in treatment of
uterine cancer- 1908
Three Basic Systems evolved:
The Stockholm System
The Paris System
The Manchester System
Most systems used throughout the world are
derived from these three basic systems

37. Stockholm/Paris System- Applications reported in
terms of “mg.h”( milligram hours)- product of total
mass of Radium contained in the sources (in mg) and
duration of the application (in hours).
Manchester System: Designed to deliver a constant dose
rate to defined points near cervix, irrespective of variation
in size and shape of uterus/vagina.
Application specified in terms of “dose” in Roentgens delivered
at specific points( Point A, Point B, Bladder Point, Rectal Point).
Duration of implant based on the dose rate calculated at Point A.
Optimal dose taken as 8000 R (72.8 Gy) in two sessions of 72 hrs. each, 4-7 days
interval.

38. POINT A: Originally defined as 2 cm superior to
the lateral vaginal fornix and 2 cm lateral to the
cervical canal( later redefined as 2 cm superior to
the ext cervical os/cervical end of the tandem,
and 2 cm lateral to the cervical canal).
POINT B: Defined 3 cm lateral to Point A( intended
to quantify the dose delivered to the Obturator L.Ns.)
Dose to Bladder and Rectum: Localization of
bladder and rectum can be performed using radiographs
taken with contrast media in bladder/rectum.
Maximum dose to bladder/rectum: 80% or less than
the dose to point A.

39. MANCHESTER SYSTEM APPLICATORS:
 Two vaginal Ovoids- made of hard rubber
Locked in position by spacer or a washer
Ovoid Sizes: 2.0/2.5/3.0 cm
 Intrauterine Tubes- made of thin rubber
Three different lengths for 1/2/3 radium
tubes each about 2 cm long.
Each tube is closed at one end and has a flange at the
other.

40. Manchester System: Definition of
Points “A” and “B”

41.  Manchester ovoid dimensions and applicator
loadings were designed to ensure a dose rate of
about 0.52 Gy/hr , which remained constant for
all allowed applicator loadings and combinations.
Vaginal contribution to point A was limited to
40% of the total dose.
 Current Practice- Point A dose is used to
denote the average or minimum dose to the
tumor.

42. Modern Fletcher-Suit Applicator Systems
 Adhered to the basic Manchester design.
 After loading capability was added to the
Fletcher applicator by Suit and co-workers.
 Because of the similarity of Fletcher loadings
to the Manchester loadings, Point A dose rates
are nearly independent of the applicator
dimensions.
 Use of Cs-137 instead of radium.

43. VAGINAL CYLINDER
 Used in conjunction with an Intrauterine tandem
to irradiate the vagina when the disease extends
from the uterine cervix along the vaginal walls.
 Cylinder can be used alone after a radical
hysterectomy if there is a close or positive
vaginal margin.
 Also useful for a patient with a very narrow vagina.
 Available in various diameters(1-5 cm) and lengths to fit any
vaginal width or length.

44. CESIUM- 137
 Most LDR intracavitary systems use Cesium as
the implanted radioisotope.
 Similar in size and shape and have an output
similar to radium sources.
 Elimination of Radon gas leakage.
 Less required shielding for radiation protection
(lower energy, 0.662 Mev)

45. Characteristics of good insertion in brachytherapy
A-P View:
1) Tandem midline, unrotated
2) Tandem midway between colpostats
3) Colpostats high in the fornices along cervix
(approx 1/3rd of the ovoid should be superior
to the cervical collar and two-thirds should be
inferior.
Lateral View:
1) Tandem bisects the colpostats
2) Sufficient anterior and posterior packing
3) Foley baloon firmly tugged down

47. SIMULATION:
After insertion of the applicator, dummy sources
are loaded into the afterloading applicators and
an orthogonal pair of radiographs are taken.
The isocenter is set at the centre of the collar for
Fletcher-Suit tandem and ovoid applications.
ICRU BLADDER and RECTAL REF POINTS:
Bladder Point- Foley balloon is filled with 7 cc of
radiopaque fluid( Hypaque) and pulled down towards
the bladder neck. On Lat radiograph, obtained by drawing a
line through the center of the balloon and the posterior surface
of the balloon is used as the reference point.
On the anterior radiograph, the ref point is taken at centre of the balloon.

49. Rectal Ref Point:
Lat radiograph- An AP line drawn from the lower end
of the IU sources( or from the middle of the IV
sources). The Rectal point is taken at a depth of 0.5 cm,
posterior to the point where this line traverses the
posterior vaginal wall( identified by intravaginal
radiopaque gauge.
AP radiograph- the Rectal point is at the lower end of
the IU source or at the middle of thr IV sources at the
midline.

50. Advantages of HDR versus LDR :
1. Eliminates radiation exposure hazard for caregivers
and visitors.
2. Allows shorter treatment times.
3. Less risk of applicator movement during therapy.
4. Allows greater displacement of nearby normal tissues.
5. Possible to treat larger no. of patients.

51. 6. Allows use of smaller diameter sources than
are used in LDR
7. Reduces the need for dilatation of cervix and
therefore, reduces the need for heavy sedation
or GA every time.
8. Physically easier to insert applicator into the
cervix.
9. Makes treatment-dose-distribution optimization
possible.

52. HDR Equipment:
 Source most commonly used: Ir-192
 Half life- 74 days
 An encapsulated Ir-192 source is attached to the
end of a cable, which can be advanced or retracted
in precise increments using stepper
motors( stepping source).
 The ability to control the locations and dwell times
permits greater flexibility modifying the d ds.

53. The Ring Applicator:
 Particularly useful when the vaginal fornices are asymmetric or
absent.
 It is popular because it has a reproducible geometry and is easy
to insert.
 It is important that the plastic cap of the ring applicator be in
place with each insertion, because excessive vagina mucosal
doses would be delivered without them.
 Also important not to activate the entire ring circumference;
usually the lateral 4 – 6 dwell positions are activated on each side
of the ring, dependent on the ring diameter.

63. SEQUELAE OF RADIATION THERAPY
Acute:
 Diarrhea, abdominal cramping, rectal discomfort,
Occasionally, rectal bleeding.
 Dysuria, frequency, nocturia, rarely hematuria;
UTIs .
 Erythema, dry/moist desquamation in perineum
or intergluteal fold.
 Radiation vaginitis/superficial ulceration of vagina/
vaginal stenosis

64. Late:
 Rectovaginal/vesicovaginal fistula- 1to2%
 Proctitis/cystitis(3-5% stage I-IIA, 10-15%
for stage IIB-III).
 Vaginal stenosis,
 Anal Incontinence
 Femoral neck fractures/ lumbosacral plexopathy
(extremely rare)

65. Follow-up
Every month- For first 3 months.
Every 3 months- For remaining of the first year.
Every 4 months- The 2nd year.
Every 6 months- During the 3rd through 5th year.
And yearly thereafter.
Patients undergo Complete physical+ pelvic/rectal examination
with Pap smear taken from 3 months onwards.
(+ chest X-ray annually; CBC, Urea/creat. 6
monthly)
Other investigations( USG/CT) as clinically indicated.

66. THANK
YOU