Abstract-Relevance of FIGO in cervical cancer
K Narayan
Relevance of FIGO staging in the management of cervical cancer
Kailash Narayan
Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
Introduction
Classification of cervical cancer according to the extent of the growth was first published in 1929
(http://www.figo.org/) by the Cancer commission of Health Organization. Later when FIGO (International
Federation of Gynecology and Obstetrics), founded in 1957, adopted this classification in 1958. There after the
staging of cervical cancer became known as FIGO staging system. Neither the TNM System (developed by
Pierre Denoix between 1943 and 1952 and first published in 1953) nor AJCC staging system (published in
1977) had much influence on FIGO staging of cervical cancer.
FIGO staging was based on anatomical compartmental spread of cervical cancer. This was necessary. It
helped in evaluation of surgical resectabilty in each patient. Even if the surgical resection was not deemed
satisfactory, surgical findings and subsequent accurate anatomical pathology findings could be used to prescribe
tailored adjuvant therapies. Recently, in 2002 a collaborative effort between FIGO and International Society of
Gynecology Oncology (ISGO) resulted in the formulation of treatment guidelines of various gynecological
cancers(1). These guidelines were based on evidence gleaned from surgical-pathological; phase II and III
combined modality treatment trials for the management of cervical cancer(2-10). However, evidence cited in
these guidelines were based on clinical studies in which the selection criteria of patients were almost always
refined by modern medical imaging and surgical techniques not prescribed by FIGO staging system. These
guidelines would yield lower than expected survival results if applied to patients selected exclusively by FIGO
staging criteria thereby defeating the very purpose and philosophy of the staging system. Recent advances in
medical imaging had led to a non-invasive and yet better clinical staging of cervical cancer patients. It is the
purpose of this presentation to evaluate some of these advances in conjunction with FIGO staging system and
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Abstract-Relevance of FIGO in cervical cancer
K Narayan
propose a simple clinical staging system which can be used for selecting patients appropriately for a given
treatment package.
Aims
The aim of this discussion paper was to define cervical cancer staging criteria with maximum inter-group and
minimum intra-group prognostic variables, enabling uniform patient selection for various treatment modalities
and therapeutic investigations.
Methods
Published clinical studies exploring various prognostic variables in cervical cancer which formed the basis for
FIGO / ISGO treatment guidelines were explored in the light of recent publications reporting the results of
non-surgically, MRI and PET staged cervical cancer patients. A non invasive, MRI-FIGO clinical staging
system of greater intra-stage prognostically homogeneous groupings was fashioned.
Results
Conclusion from the published literature:
From the published literature it is clear that, FIGO stage Ia (consisting of occult primaries) and stage IVb
(disseminated cervical cancer) had been adequately staged on FIGO criteria alone. Stage Ia tumours can be
treated well by surgery alone. Present treatment policy yields 98-100% survival rates in these cancers. Stage IVb
cervical cancer is uniformly fatal. It can only be treated palliatively. A further refinement of this stage is unlikely
to improve survival.
Node negative, <4 cm Ib and IIa cervical cancer can be treated either by surgery or radiotherapy alone. If we
were to use Milan group’s(5) pre surgery patient selection criteria, about 60 to 70% patients staged Ib and IIa
with tumours <4 cm (would be node negative and) could either be treated with radiotherapy or surgery.
However, >50% of these patients will still require postoperative radiotherapy for deep tumour invasion, cut
through and / or Lympho-vascular space invasion (LVSI)(11)thereby experiencing higher treatment toxicity. If
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Abstract-Relevance of FIGO in cervical cancer
K Narayan
we were to include all cervical cancer patients (with unknown nodal status and) with < 4cm, Ib and IIa,
according to FIGO staging criteria, the proportion of patients treated by surgery alone and not requiring postoperative radiotherapy would shrink even further. Un-added FIGO staging in this group does not allow the
selection of ideal patients who can be treated by surgery alone. Clinical estimation of tumour extent, which
determines FIGO stage, can be inaccurate when compared with the surgical pathology findings. Lagasse et
al(12) have shown that staging according to EUA is incorrect in 25% of tumours designated stage I, and in
50% of tumours designated stage II.
In the remaining FIGO stages (bulky Ib to IVa) concurrent chemo-radiotherapy (CRT) is the undisputed
treatment of choice. However, over all survival in these patients remains unsatisfactory. In advanced cervical
cancer, increasing FIGO stage remains a very significant prognostic factor. However, each FIGO stage harbors
a prognostically heterogeneous group of patients. FIGO staging criteria does not include node positivity,
chemo-sensitivity, infiltrative or exophytic growth etc. etc. A large exophytic node negative stage III patient and
a small infiltrative node positive stage Ib illustrate the paradox of FIGO staging well. Such wide overlap of
prognostic factors across different stages makes the conduct of clinical trials exploring newer treatment options
difficult. It is true that surgical staging, (subjective variation in node sampling not withstanding) did provide
better prognostic information then clinical staging. Surgical staging was associated with increased treatment
related morbidity(13-15). It may therefore, be desirable to estimate tumour volume and the presence of lymph
node metastases before surgery so that the treatment plan for node positive and high risk node negative
patients could be changed to chemo-radiation alone, avoiding the potential high rate of complications
associated with a combination of radical surgery and postoperative radiotherapy(5).
MRI and PET scan:
Earlier efforts at non invasive staging methods such as lymphangiography proved to be cumbersome and its
interpretation too subjective. Medical imaging such as CT scan, by its inability to detect cancer in normal sized
lymph nodes and lack of discrimination between normal and neoplastic tissue did not prove useful. With the
advent of (magnetic resonance imaging) MRI, it was possible to estimate the local relations and volume of
primary cervical tumours more accurately than by clinical examination alone(16-19). Narayan et al(20) have
shown that EUA diameter plotted against the average MRI diameter correlated poorly. Whereas, MRI diameter
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Abstract-Relevance of FIGO in cervical cancer
K Narayan
plotted against the corresponding pathology diameter showed a strong linear relationship between the two
measurements (P < 0.001). Thus MRI provides a more accurate measure of the volume of disease. Indeed the
prognostic significance of the tumour volume as estimated by MRI has been studied by Kodaira et al(21) where
an arbitrarily chosen cut-off of 50 cm3
appeared to divide cervical cancer patients treated by radical
radiotherapy in two groups; <50 cm3 with better prognosis and >50 cm3 with poor prognosis.
The ability to detect the presence of lymph node metastasis prior to treatment would be clinically important
since this is the most important predictor of survival in loco-regionally advanced cervical cancer. In a surgically
staged locally advanced cervical cancer patients, the five-year survival in node negative patients was 57%. In
contrast, 5 year survival was 34% with involved pelvic nodes and 12% when para-aortic nodes were
involved(22). Indeed Hsu et al(23)reported 5-year survival of 88% in Ib cervical cancer with negative nodes
and only 40% for those with positive lymph nodes. Similarly La Polla et al(24)reported a three-year disease free
survival in stage Ib and 2a, node negative and node positive as 100% and 67% respectively. In stage 2b to 4a
corresponding figures were 56% and 24%.
Positron emission tomography (PET) scanning using a glucose analogue, fluorine-18 fluoro-2-deoxyglucose
(FDG) is a non-invasive test with high sensitivity for detecting metastatic lymph nodes in cervical cancer
patients(25-27). In particular, it appears to be able to detect neoplastic involvement in lymph nodes of normal
or borderline size, which is not detectable by structural imaging techniques. Survival according to nodal status
estimated by PET was reported by Grigsby et al(28). The 2-year progression-free survival, based solely on paraaortic lymph node status, was 64% in PET-negative patients and 18% in PET-positive patients (P< .0001). A
multivariate analysis demonstrated that the most significant prognostic factor for progression-free survival was
the presence of positive para-aortic lymph nodes as detected by PET imaging. Similar survival of 12%(22) and
16%(29) was observed in surgically staged, para-aortic node positive patient irrespective of FIGO stage.
A combined use of MRI and PET for pre-treatment staging of non-operable (>3 cm Ib and stage II to IVa)
cervical cancer has led to a better understanding of the relationship between FIGO stage, tumour volume,
tumour infiltration and nodal metastases(30). The presence or absence of tumour invasion in the uterus as a
dichotomous function (yes or no) was analyzed in 70 cervical cancer patients, along with FIGO stage (1, 2, 3,
4), and MRI tumour volume with respect to nodal involvement as detected by PET scan. There was a
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Abstract-Relevance of FIGO in cervical cancer
K Narayan
significant association between nodal involvement and both of FIGO stage (P= 0.018) and uterine body
involvement (P< 0.001) in univariable analysis. In multivariable analysis only uterine body extension, however,
was independently related to the risk of nodal involvement. FDG PET documented pelvic node positivity was
39/52(75%) in patients with uterine invasion by tumour as compared with 2/18 (11%) without. Since node
positivity is a strong indicator of poor survival, it might be expected that corpus invasion is associated with
poor survival. The prognostic significance of the involvement of uterine corpus has been studied in an as yet
unpublished retrospective study. In 190 cervical cancer patients with FIGO stages Ib to IVa and treated
radically, using pre-treatment MRI, Narayan et al(31) examined the prognostic effects, with respect to overall
survival, of FIGO stage, corpus invasion and MRI tumour volume, with the following results
Univariable analyses
Level
% of
patients
3-year
survival rate
FIGO stage
Ib
II
III
IVa
32%
42%
21%
6%
63%
72%
50%
27%
Corpus
invasion
No
Yes
38%
62%
84%
48%
 50 cm3
> 50 cm3
64%
36%
71%
46%
Factor
Tumour volume
95% CI for hazard
ratio
P
Hazard ratio
< 0.001
0.61
(per stage
increment)
0.48 to 0.78
0.23
0.13 to 0.43
0.40
0.25 to 0.62
< 0.001
< 0.001
Multivariable analyses
Factor
95% CI for hazard
ratio
Level
P
Hazard ratio
1
2
3
4
0.22
0.84
(per stage
increment)
0.63 to 1.11
Corpus invasion
No
Yes
< 0.001
0.29
0.15 to 0.56
Tumour volume
 50 cm3
> 50 cm3
0.12
0.67
0.40 to 1.10
FIGO stage
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Abstract-Relevance of FIGO in cervical cancer
K Narayan
In this data set, tumours with a volume of greater than 50 cm3 were associated with corpus invasion in 90%
of cases. (50 cm3 dichotomy was chosen to approximately match the cut-offs used by(21;32) and is used for
convenience of presentation.)
Discussion
Non-invasive investigations like MRI and PET can provide useful prognostic information related to tumour
volume and nodal spread in cervical cancer. Less infiltrative tumours not invading uterine corpus, irrespective
of their volume or FIGO stage had nodal metastases rate of 11% (or slightly higher, considering the possibility
of PET occult nodes)(27;30). A comparable rate of nodal metastases was found in selected FIGO stage I
patients treated in surgical series(33).
Since early stage cervical cancer managed either by surgery or
radiotherapy had identical survival; a uterine corpus negative patient regardless of FIGO stage, treated by
concurrent chemo-radiotherapy to pelvis would be expected to do as well as selected operable FIGO stage I
patients. This indeed was the case. Table (above) shows a three year survival rate of 84% in uterine corpus
negative patients treated by CRT. This also compared favorably with survival of 88%(23) and 85.6%(2) of
surgically staged node negative stage I cervical cancer. Three year survival of 48%, in corpus positive patients
reported here also fared well in comparison with 40%, in surgically staged node positive Ib patients(23) or with
67% in stage Ib and 2a and 24% in stage 2b to 4a patients(24).
In cervical carcinoma, information about the depth of invasion could only be obtained surgically. Surgical
staging of advanced staged tumour was not practical. Advent of CT scan proved only marginally better than
clinical staging except in those patients with grossly enlarged lymph nodes or ureteric obstruction. MRI, on the
other hand has provided the opportunity to study tumour infiltration non-invasively. MRI can be used to refine
FIGO staging of cervical cancer that may lead to improved prognostic categorization of these patients. It was
therefore necessary to formulate a clinical non invasive staging system for appropriate treatment selection,
better communication and comparing treatment results. The use of MRI can divide gross cervical cancer (Ib to
IVa) into two clear categories. Those patients with corpus negative tumours and those patients with corpus
positive tumours in any FIGO stage. The corpus negative patients when treated by standard treatment
modalities resulted in >80% survival rates. Corpus positive patients had relatively poor survival. These patients
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Abstract-Relevance of FIGO in cervical cancer
K Narayan
may benefit from enrolment in newer clinical trials with out having to first go through invasive selection
procedures.
Based on the above observations we suggest the following MRI assisted FIGO staging procedure for cervical
cancer. Suspected cases of cervical cancer should have a pelvic examination and a Pap smear. Patients with
positive Pap smear and an occult primary should be staged by cone biopsy. The patients with positive palpable
(inguinal and supra clavicular) nodes (FIGO stage IVb); should be investigated and treated according to their
individual palliative needs. Presently there is no need to alter disease classification of cervical cancer patients
staged as either Ia or IVb. The remaining patients (FIGO stage 1b to IVa, with clinically apparent lesion but
without cytologically proven palpable lymph nodes) should be further investigated with a pelvic MRI and
separated in just two categories. A corpus negative and a corpus positive group. This way all cervical cancer
patients could be accommodated in four distinct prognostic groups. Each group will contain prognostically
homogenous patients separated discretely from adjacent stages. It will then be possible to apply discrete
management package to all patients belonging to a particular stage. It will also allow for an objective
comparison of treatment results from different institution. This staging would be free from subjective errors
inherent in clinical estimation of tumour size, parametrial and pelvic side wall involvement.
MRI-FIGO clinical staging of cervical cancer
The suggested MRI enhanced FIGO stages and management options:
1.
Patients with occult lesion should have a cone biopsy. Most of these could be
managed by surgery alone.
2.
Patients with clinically apparent lesion (but not FIGO stage IVb) and MRI
corpus negative cases could be treated either by surgery or pelvic radiotherapy. If
surgery is employed as a primary treatment modality then the use of pre-operative
chemotherapy as cytoreduction modality in selected patients with large tumours in
this category is entirely justified. Being corpus negative tumours these patients are not
expected to have >15% incidence of node positivity requiring post operative
radiotherapy. Other indications of post-operative radiotherapy (in node negative high
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Abstract-Relevance of FIGO in cervical cancer
K Narayan
risk patients) will involve the use of low morbidity, small central pelvic field
radiotherapy(34).
3.
Patients with clinically apparent lesion (but not FIGO stage IVb) and MRI
corpus positive cases could only be treated by chemo-radiotherapy. If pelvic MRI
shows enlarge nodes then the radiotherapy fields could be individualized based on a
further, PET or abdominal CT or MRI scan indicating the para-aortic nodal status.
4.
Patients
with
cytologically
positive
palpable
(inguinal
and
/
or
supraclavicular) nodes; FIGO stage IVb patients. These patients should be
investigated and managed to their individual palliative needs.
Expected survival rates in each proposed stage based on the application of currently acceptable
treatment protocol would be 95 – 100% in stage 1, 80 – 85% in stage 2, 45 – 50% in stage 3 and 0 – 5%
in stage 4.
The proposed staging system would enable clinicians in appropriate patient selection for a given
treatment protocol and in assessing prognosis. It will also assist in the evaluation of the results of
treatment and facilitate a coherent exchange of information among various treatment centers.
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