1. Treatment of advanced stage of carcinoma cervix: Radiotherapy (including brachytherapy, teletherapy and adjuvant radiotherapy), Chemotherapy and Chemoradiotherapy; 2. Ca Cervix in Pregnancy: Includes flowchart for screening and management

1. Treatment of Advanced stage
of Invasive Carcinoma Cervix
and Ca Cervix in Pregnancy
K. Muthu Raman
Unit-5 IOG
Madras Medical College

2. FIGO Staging of Ca Cervix (2018)
Early stage
(IA1 to IIA)
Late stage
(IIB to IV)

3. Treatment options
1. Radiotherapy
2. Chemotherapy
3. Chemoradiotherap
y

4. ● Radiotherapy can be used to treat all stages of cervical cancer,
with cure rates of about 70% for stage I, 60% for stage II, 45%
for stage III, and 18% for stage IV.
● Primary radiation treatment plans consist of a combination of
External beam radiation therapy (Teletherapy) to treat the
regional lymph nodes and to decrease the tumor volume, and
Brachytherapy delivered by intracavitary applicators.
Radiotherapy

5. ● Brachytherapy means “treatment at a short distance”
● During this therapy, radioisotopes are inserted into the cancer or its
immediate vicinity.
● As radiation doses fall sharply with increasing distances from the
radioactive source, it is indicated only for small tumor volumes {less
than 3 to 4 cm) . For this reason, brachytherapy is done after external
beam radiation therapy has decreased a large tumor volume.
● Iridium-192 isotope (Radiation energy - 0.4 MeV; Half life - 74 days)
and Cobalt-60 (Radiation energy - 1.2 MeV; Half life - 5 years) are
used in our hospital.
1. Brachytherapy:

6. ● Brachytherapy may be intracavitary or interstitial. During Intracavitary
brachytherapy, applicators that hold sealed radioactive sources are
inserted into a body cavity such as the uterus. This is used in our hospital.
● Alternatively, Interstitial brachytherapy requires the placement of
catheters or needles directly into the cancer and surrounding tissues, but is
not used nowadays.
● Low dose-rate (LDR) (0.4 to 2 Gy/hr) and Medium dose-rate (MDR) (2 to
12 Gy/hr) brachytherapy are delivered over the course of many days.
However, with High-dose-rate (HDR) brachytherapy (>12 Gy/hr)
technique, treatment is shortened to a few minutes (3 to 5 weekly fractions
with 5 to 7 Gy/fraction given in 10 to 20 minutes)
● Unlike LDR & MDR, HDR avoids lengthy inpatient hospitalization and
minimizes patient immobility and thromboembolic events.

7. ● In classical 2D cervix brachytherapy, usual doses delivered are
-70 to 80 Gy to point A (defined as 2 cm superior and lateral
to the external cervical os, point where uterine artery and ureter
cross) and
-60 Gy to point B (defined as 3 cm lateral to point A,
corresponding to obturator lymph node), limiting the bladder and
rectal dosage to less than 6,000 cGy
● In modern 3D Image-guided adaptive brachytherapy [IGABT],
cumulative radiation doses delivered are 80 to 90Gy, with the dose
shaped to the patient’s individual tumor geometry as defined on 3D
MRI or CT imaging

8. Equipments
Tandem and Ovoid
(T&O) Device

9. Brachytherapy High dose rate
Remote Afterloader (in IOG)

10. Brachytherapy techniques
● In Paris and Manchester techniques, the source strength is smaller but
exposure time is increased. The vaginal source is away from the cervix
● In Stockholm technique, large high intensity source with less exposure
time is given, but the vaginal source is closer to the cervix. This is
being followed in our hospital.

11. ● External beam radiation therapy (EBRT) or teletherapy is the treatment
with beams of ionizing radiation produced from a source external to the
patient.
● Cobalt-60 (Radiation energy - 1.2 MeV; Half life - 5 years) is the
teletherapy source for EBRT in our hospital. Caesium-137 (Radiation
energy - 0.6 MeV; Half life - 30 years) can also be used
● External beam radiation is commonly administered from Monday to
Friday for 5 weeks (40 to 50 Gy) - Total 25 fractions. 1.8 Gy/fraction is
administered in our hospital
● Commonly involved lymph nodes in EBRT are Internal iliac, External
iliac, Hypogastric, Obturator and Presacral group of nodes
2. Teletherapy:

12. ● Older 3D conformal radiation therapy (3D-CRT) is capable of projecting
polygonal or box shaped radiation into target tumors that deliver full
external beam prescription dose. This is used in our hospital
● The 3-D anatomical areas that will receive a tumoricidal dose are defined
with the help of CT, MRI and PET scan
● Newer Intensity-modulated radiation therapy (IMRT) is capable of
projecting curved, even concave radiation that is shaped to the target
tumor space with sparing of nearby normal organs, with the help of a
dedicated computer software.
● In the treatment of cervical cancer, use of IMRT could reduce radiation
dose to multiple organs at risk including bone marrow, rectum, bladder,
small bowel, and femurs.

13. Despite the technical sophistication of IMRT, in the
field of radiation oncology, IMRT is considered
complementary to brachytherapy and not a
replacement for brachytherapy.

14. Equipments
Linear accelerator
(Linac)

15. The working of a linear accelerator:
Skin source distance
(SSD): The distance
between the radiation
source and skin is kept
80 cm in our hospital

16. LINAC (in
IOG)

17. In case surgey was the first line of treatment of early stage cancer
cervix, postoperative radiotherapy, (3 to 6 weeks following surgery) will
be needed for the following indications:
• Positive lymph nodes for metastasis
• Positive resected margin of vagina or parametrium
• Evidence of lymphovascular invasion or deep stromal invasion
• Poorly differentiated tumour
In stages Ib3 and IIa2, preoperative radiotherapy may be used to
reduce the tumor size, following which surgery can be performed
3. Adjuvant Radiotherapy:

18. Complications of Radiotherapy
● Perforation of the uterus (upto 9%) with the insertion of the tandem
● Acute morbidity - diarrhea, abdominal cramps, nausea, frequent
urination, and occasional bleeding from the bladder or bowel
mucosa
● Chronic morbidity - Radiation induced vasculitis and fibrosis, bowel
bleeding, stricture, stenosis, or obstruction (6.4 to 8.1%)
● Vesicovaginal fistula (1 to 5%)
● Rectovaginal fistula (<2%)
● Small bowel - Crampy abdominal pain, intestinal rushes, partial small
bowel obstruction, low-grade fever, anemia and small bowel fistulas

19. ● Stenosis of vagina leading to sexual dysfunction
● Radiation induced secondary carcinogenesis:
● The ovaries are destroyed in radiotherapy, however they can be
conserved during surgery

20. Chemotherapy
● There is no evidence that neoadjuvant chemotherapy offers superior
results or a survival advantage over standard therapy.
● For advanced diseases, Doublet therapy compared four cisplatin-
containing doublets (gemcitabine, paclitaxel, topotecan,
vinorelbine), and Cisplatin + Paclitaxel doublet had the best
overall survival (OS)
● Studies also showed comparable survival and lower toxicity with
carboplatin and paclitaxel compared with cisplatin and paclitaxel
● A survival benefit was demonstrated when Bevacizumab, an anti-
VEGF-A monoclonal antibody, was added to the combination of
platinum-based chemotherapy. However, the addition of
bevacizumab to the combination increased the risk of fistula
formation

21. Chemoradiotherapy
● Chemoradiation is the treatment of choice for stages IB3 and IIA2 to
IVA disease
● Studies have shown addition of chemotherapy with cisplatin 40
mg/m² weekly to radiotherapy improves the radiation effect (as
cisplatin acts as a radiosensitizer agent) and thus significantly
improves overall and disease-free survival rates in women with
cervical cancer
● Current Standard of radiation therapy is to combine it with weekly
cisplatin for 5 weeks when the patient is undergoing external beam
radiation with or without Brachytherapy

22. Tumoricidal action of Cisplatin based
Chemoradiotherapy:

23. Stage IVA Disease:
● If extension to bladder, then bladder removed after EBRT
● If extension to rectum (rare), then diversion of fecal stream before
EBRT
● Pelvic exenteration may also be performed, but rare
Stage IVB Disease:
● Palliative treatment is the mainstay
● Pelvic radiation is administered to control vaginal bleeding and
pain
● Systemic chemotherapy is offered to palliate symptoms and
prolong overall survival
● Control of symptoms with the least morbidity is the primary
concern

24. Stage wise management of Ca Cervix
1. Early stage:

25. 2. Advanced stage:

26. Ca Cervix in pregnancy
● Incidence: 1.2 in 10,000 pregnancies
● The woman presents with antepartum haemorrhage, which may
be a sign of early stage carcinoma cervix
● Diagnosis may be delayed because of symptoms mistaken for
pregnancy complications
● A Pap test should be performed on all pregnant patients at the
initial prenatal visit and any grossly suspicious lesions should
be biopsied
● The clinical stage is the most important prognostic factor for
Ca Cervix during pregnancy

27. Normal
CIN/Stage Ia1
Vaginal/ Cesarean
delivery (at term)
Follow up with
repeat smear 6
weeks Postpartum
Stage 1a2
Cesarean delivery
(at term),
immediately
followed by Type 2
hysterectomy and
pelvic
lymphadenectomy
Abnormal pap smear in pregnancy
Colposcopy and
biopsy
Unsatisfactory
Multiple
biopsies/LLETZ/LEEP (no
cone biopsy)
Stage Ib and above
Terminate in
early pregnancy
(1st trimester)
with EBRT
Near term, wait
for viability
Classical CS with
chemoradiation after
uterine involution
(4 weeks later)
Repeat 2-3
monthly
Normal cytology
Vaginal delivery
Repeat Pap smear
in 3-6 months

28. Question Answer
Session

29. 1. A 65 year old woman with cervical carcinoma
was found to have lung metastasis on imaging.
What is the preferred treatment option?
A. Pelvic exenteration
B. Extended Radical hysterectomy
C. Palliative radiotherapy
D. Neoadjuvant chemotherapy

30. Answer:
C. Palliative radiotherapy

31. 2. A 45 year old woman undergoes radical
hysterectomy for stage IB Ca cervix. It was found
that cancer extends to lower part of body of uterus,
next step of management will be:
A. Chemotherapy
B. Radiotherapy
C. Chemoradiation
D. Follow-up

32. Answer:
D. Follow-up
Postoperatively it was found that carcinoma extends to the
lower part of uterus, but uterine extension has no
significance in cancer cervix and does not change the
staging.

33. 3. A 55 year old woman came with complaints of
continuous vaginal urinary discharge. She is currently
undergoing Chemoradiotherapy for stage IIIB Ca
cervix. What is the most probable Diagnosis and it's
management?
A. Vesicovaginal fistula; Percutaneous nephrostomy
B. Vesicovaginal fistula; Supravesicular urinary diversion
C. Urethrovaginal fistula; Percutaneous nephrostomy
D. Ureterovaginal fistula; Supravesicular urinary diversion

34. Answer:
B. Vesicovaginal fistula; Supravesicular urinary diversion
Vesicovaginal fistula (1 to 5% incidence) - Most common urinary tract
complication of radiotherapy
Treatment: Supravesical diversion involves the external diversion of the
urine stream without use of the bladder. While percutaneous
nephrostomy offers a short-term alternative to operative diversion (mainly
palliative), problems with frequent tube changes, infection, and external
appliances make surgical diversion the preferred method in those
needing long-term supravesical diversion

35. References:
1. Williams Gynecology - 4th Edition
2. Berek & Novak’s Gynecology - 16th Edition
3. D C Dutta’s Textbook of Gynecology - 7th Edition
4. Undergraduate Manual of Clinical Cases in Obstetrics &
Gynecology - 2nd Edition - N. Hephzibah Kirubamani
5. Self Assessment & Review Gynecology - 13th Edition - Sakshi
Arora Hans
6. Howkins & Bourne Shaw’s Textbook of Gynecology - 18th
Edition

36. Thank You