1. Ganesh Kumar M

2. Cervical Cancer
Most common gynecologic malignancy
worldwide and the second most common
cancer in women in the world
Since the advent of cytologic screening in
the 1940s, the incidence of cervical cancer
has been decreasing
However, a steady increase in the
incidence of preinvasive and locally
invasive disease of the cervix has occurred

3. FIGO Staging
Stage Description
0 Carcinoma in situ
I Strictly confined to cervix
IA Micro-invasive carcinoma
IA1 Invasion of stroma ≤ 3mm depth; ≤ 7mm width
IA2 Invasion of stroma ≤ 5mm depth; ≤ 7 mm width
IB Clinical lesions confined to cervix
IB1 Clinical lesion </= 4 cm
IB2 Clinical lesion > 4 cm
II Clinical lesions extending beyond cervix, but not to the pelvic wall
IIA No obvious parametrial involvment
IIB Obvious parametrial involvment
III No extension to pelvic wall, involvment lower 1/3 of vagina
IIIA Extension to pelvic wall or hydronephrosis or nonfunctioning kidney
IIIB Beyond true pelvis/clinically involving mucosa of bladder or rectum
IVA invades mucosa of the bladder or rectum, and/or extends beyond true pelvis
IVB Distant metastases

4. Lymphatic Drainage

5. Management of cervical cancer
determined primarily by the stage and
extent of disease
0, IA1: conservative surgery (excisional
conization or extrafascial/simple
hysterectomy)
IA2: Modified radical hysterectomy
IB1: -radical surgery (radical/modified
radical hysterectomy)
-radiation alone
-chemoradiation

6. Management of LACC??
Controversy still surrounds the optimal
management of these bulky tumors at
the primary site
Triple modality treatment often
employed
Metastatic disease in the regional
nodes: important factor for tumor
recurrence

8. Introduction
Incidence of extrapelvic disease at the
time of initial management of locally
advanced cervical cancer (LACC) is
high
10 to 30%
para-aortic (PA) nodes and/or the chest

9. Introduction(contd)
Chemoradiotherapy(CRT) is considered
the standard treatment for LACC
Newer radiotherapy modalities have
been useful for local control
However, rate of nodal and/or distant
failure remains a major problem, raising
the question of the early detection of
such potentially occult disease missed
on conventional imaging

10. Introduction(contd)
PET/CT : improves the rate of detection
of extracervical disease; but carries a
false-negative results of upto 12%
Purpose of the study: evaluate the
survival of patients with LACC without
uptake in PA nodes on PET-CT who
were thus submitted to PA staging
surgery

11. Aim of the study
to evaluate the therapeutic impact of
laparoscopic PA lymph node staging in
patients with locally advanced cervical
cancer with negative PET imaging
outside the pelvic area

12. Patients and Methods
Prospective Multicenter Series
Three French comprehensive cancer
centers
Similar strategy employed at all these
centers for the staging procedures and
treatment of LACC

13. Eligibility Criteria
Stages IB2 to IVA cervical cancer (as
per the FIGO 2009 classification)
Adenocarcinoma, squamous cell
carcinoma, or adenosquamous subtypes
No extrapelvic disease on conventional
imaging(abdominopelvic MRI or CT
scan and pelvic MRI)
No PA (or extrapelvic) uptake on initial
PET-CT imaging

14. Additional Criteria
First, PA staging surgery performed
using a laparoscopic extraperitoneal or
transperitoneal approach
removal of PA nodes from the aortic
bifurcation to the left renal vein(PA,
preaortic, superficial intercavoaortic and
precaval groups)
Pelvic nodes not resected, because they
will subsequently be included in the RT
field

15. Additional Criteria(contd)
Second, no macroscopic extrapelvic
disease should be present during the
laparoscopic peritoneal exploration
Patients with limited pelvic peritoneal
carcinomatosis and/or ovarian
metastasis were excluded from the
study

16. Additional Criteria(contd)
Third, the cervical tumor was treated (if
no PA node involvement after staging
laparoscopy) with pelvic external
radiation therapy (45 to 50 Gy)
Concomitant platinum-based
chemotherapy( Cisplatin @ 40
mg/m2/week)

17. Few patients at the end of this study underwent
IMRT, subsequently completely by uterovaginal
brachytherapy
In patients with initial parametrial and/or suspicious
pelvic nodes on PET/CT imaging, an additional boost
EBRT of upto 60 Gy given optionally
Completion surgery only if -brachytherapy not
technically feasible or
-in clinical and radiologic
(using MRI exam) residual disease 6 to 8 weeks
after the end of brachytherapy

18. Additional Criteria(contd)
Finally, patients with histologic PA node
metastasis after staging laparoscopic
surgery were treated using pelvic and
PA CRT (45 to 60 Gy) with concomitant
cisplatin chemotherapy (40 mg/m2 per
week)

21. Morbidities
Patients were evaluated weekly with a clinical
examination, a blood count, and renal function tests
during treatment
Morbidities related to the laparoscopic surgical procedure
(within 60 days after the staging surgery) - Clavien-Dindo
classification
Morbidities during and/or after CRT - National Cancer
Institute Common Terminology Criteria for Adverse Events
(CTCAE) classification (version 4; revised in October
2009)
To have the most reliable reports on morbidities, grade 1
complications not evaluated

23. Statistical Analysis and End
Points of the Study
Descriptive data were compared using the
Chi-square test or Fisher’s exact test for
proportions
primary end point – overall survival (OS):
time from the beginning of CRT to death
from any cause
secondary end point - event-free survival
(EFS): time from the beginning of CRT to
recurrence or disease progression or death

24. Patients with no event at the time of
analysis: censored at date of last follow-up
OS and EFS curves were calculated
using the Kaplan-Meier method
Median follow-up was estimated using
the Schemper method

25. All qualitative variables tested using the
log-rank test (univariate procedure)
Continuous variables (delays between
procedures) tested using a Cox
proportional hazards regression model
The hazard ratio (HR) and its 95% CI
were provided.
P=0.05 was set as the threshold for
statistical significance

26. Statistically significant factors
the presence and size of metastatic PA
nodes
a delay of 45 days between PET-CT and
the beginning of CRT

30. Discussion
Addresses two important questions
Q1: accuracy of PET-CT imaging in LACC?
False-negative rate between 9% and 22%
Half of this group had a nodal metastasis
<5mm
5 mm cutoff: limit of PET-CT imaging for
accurately detecting tumor tissue is
approximately 5mm

31. Q2: impact of the PA node staging on survival in
LACC?
prognosis of patients with small PA metastasis
( ≤ 5 mm) after laparoscopic staging surgery
and were then treated with extended-field
CRT, was similar to that of patients without PA
metastasis
majority (10 of 13) of these patients also had a
single nodal metastasis
it is unclear whether the good prognosis
among these patients could be owed to the
solitary nature or the small size

32. The risk of distant metastasis was lower in this
subgroup compared with those with a PA node
measuring more than 5 mm.
The survival of this subgroup of patients
(lesion < 5 mm) was excellent and again
similar to that of patients without PA nodal
spread.
If nodal metastasis had not been detected
initially, this patient subgroup would have been
undertreated

33. Patients with PA nodal mets ≥ 5 mm?
Prognosis after laparoscopic staging
surgery remains poor, despite treatment
with extended-field CRT

34. Review of Literature:
PET/CT vs conventional
imaging
Yildirim et al, Gynecol Oncol. 2008 Jan:
Integrated PET/CT for the evaluation of para-aortic
nodal metastasis in locally advanced
cervical cancer patients with negative
conventional CT findings
The accuracy, sensitivity, specificity, PPV and
NPV of the PET/CT were 75%, 50%, 83.3%,
50% and 83.3%, respectively
The treatment was modified in four of sixteen
(25%) patients(EFRT in combination with
cisplatin chemotherapy instead of standard
pelvic field radiotherapy in combination with
cisplatin chemotherapy)

35. Chao A et al, Gynecol Oncol. 2008 Aug:
PET in evaluating the feasibility of curative
intent in cervical cancer patients with
limited distant lymph node metastases
Additional PET or PET/CT had positive
clinical impact in 21 (44.7%) of the 47
study patients, 23 had no impact, and three
had negative impact
Positive Clinical Impact: disclosing additional
curable sites (n=8), down-staging (n=6),
offering metabolic biopsy (n=4) or change
to palliation

36. Review of Literature:
Surgery vs conventional
imaging
Gold et al, Cancer. 2008 May:
Surgical versus radiographic determination of
para-aortic lymph node metastases before
chemoradiation for locally advanced
cervical carcinoma: a Gynecologic
Oncology Group Study
550 patients: S Group; 130 patients: R Group
R group was associated independently with a
poorer prognosis compared with the S
group(HR for progression – 1.35 and for
death – 1.46)

37. Delpech et al, Gynecol Obstet Fertil 2010
Jan:
Lymph node surgical staging for locally
advanced cervical cancer
Even if recent studies have reported
promising results with FDG PET/CT,
surgical staging remains the most accurate
procedure for evaluating LN metastases
Although laparoscopy allows an early start of
adjuvant treatment, due to doubts over its
survival benefits, needs to be validated
through randomized trials

38. Review of Literature:
Staging laporoscopy vs PET/CT
Mortier et al, Int J Gynecol Cancer. 2008
Jul-Aug:
Laparoscopic para-aortic lymphadenectomy
and PET scan as staging procedures in
patients with cervical carcinoma stage IB2-
IIIB (90 pts)
Lymphadenectomy showed metastases in
13% of the patients. In the subgroup with
negative PET scan, 11%(5 of 44) had
metastases

39. Conclusion
Staging laparoscopy has better
sensitivity to detect para-aortic nodal
metastases, owing to the poor spatial
resolution of PET/CT in identifying
metastases < 5mm in size
Staging laparoscopy fraught with peri-operative
and post-operative
morbidities(29/237, 12.2%)