This document discusses treatment approaches for early stage cervical cancer. It notes that for invasive cervical cancers measuring less than 2 cm, removal of the parametrium may be omitted. For some very small tumors, pelvic lymphadenectomy can also be omitted as the risk of lymph node metastasis is limited. It also discusses outcomes from vaginal trachelectomy and laparoscopic pelvic lymphadenectomy for early stage cancers. The document considers conservative treatment approaches for stage IA2-IB1 cancers less than 3 cm in size, including a proposed study design stratifying patients based on tumor diameter.

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Mario Sideri
Ginecologia Preventiva
IEO
Microinvasive and
early invasive
cervical cancer

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Standard treatment for invasive cervical
cancer traditionally includes radical
hysterectomy and pelvic limphoadenectomy.
The rationale of the treatment is the
extirpation of the tumour, with clear
margins, and of the lumphatic vessels.

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There are early tumours with a small
volume in wihich the removal of the
parametrium can be omitted;
in addition in some instances the tumour
volume can be so small that the risk of
lymphnode metastasis is limited, and
pelvic lymphadenectomy can also be
omitted

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Volume  is expressed as lenght and
depth of infiltration of the neoplasia
Categories where conservative approach
is feasible:
IA1 3 mm in depth, 7 mm in lenght, no LVSI
IA2 5 mm in depth, 7 mm in lenght, neg. nodes
IB1< 2 cm in largest diameter neg. nodes
IB1 >2<3 cm in largest diameter, neg. nodes

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Volume  is expressed as lenght and
depth of infiltration of the neoplasia
The measures that define “micoinvasive”
cervical cancer can only be obtained from a
surgical specimen containing the whole lesion.
Colposcopy is critical to help excise all the
lesion in order to define the diagnosis

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Main reasons for cervical cancer
declining mortality:
• Cervical cancer screening programs
• Intraepithelial lesions (CIN) detection
• CIN therapy

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Conservative therapy
Accurate pre-surgical
evaluation of the lesion
Chappatte, Gynecol. Oncol. 1991

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Citology,Colposcopy,Histology
Key role in:
• Grading
• Size definition of the lesion
• Identification of early invasive
disease

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Failure after excisional CIN
treatment
Incorrect assessment of
the lesion
Luesley, Br. J. Obstet. Gynecol. 1985
Buxton, Br. J. Obstet. Gynecol. 1991

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END POINT
To verify the predictive value of
multiple tests in CIN pre-surgical
assessment
• avoid under/over treatment
• schedule proper follow-up
• prevent risk for disease persistence

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Clinical characteristic of the 1000
patients treated by cone biopsy
Referral Pap smear
• LG SIL or less
• HG SIL
• Susp. Cancer
Punch biopsy
• Neg/CIN 1
• CIN 2-3
• Cancer (early invasion)
n %
262 26.2
722 72.2
16 1.6
107 11.9
786 87.5
5 0.6
Costa et al. 2001

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Clinical characteristic of the 1000
patients treated by cone biopsy
Colposcopic features
Neg
AnTZ 1
AnTZ 2
Visible SCJ
Not visible SCJ
n %
131 13.1
313 31.3
556 55.6
271 27.1
729 72.9
86,9%
Costa et al. 2001

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Clinical characteristic of the 1000
patients treated by cone biopsy
Colposcopic features
Involved quadrants°
1
2
3
4
°869 positive colposcopy
n %
222 25.5
394 45.3
174 20
79 9.1
Costa et al. 2001

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Histology on 1000 cone biopsies
CONE Histology N°
Negative 148
CIN 1 176
CIN 2-3 607
Cancer° 69
°Including 54 Stage IA1, 9 Stage IA2, 3 Stage IB
carcinomas, and 3 Adenocarcinomas
Costa et al. 2001

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Pap smear by Cone Biopsy
Pap smear Cone biopsy Total
Neg/CIN 1
N %
CIN 2-3
N %
Cancer
N %
LG SIL or less 130 49.6 128 49 4 1.4 262
HG SIL 194 26.9 470 65.1 58 8 722
Cancer 0 9 56 7 44 16
Costa et al. 2001

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CAUTION !!!
PAP SMEAR Vs CONE BIOPSY
LG SIL 50.4% CIN 2-3/Cancer
HG SIL 26.9% Neg/CIN 1
Costa et al. 2001

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CAUTION !!!
• > 25 % HSIL in persistent ASCUS/LSIL
Gerber S et al., Int J Gynaecol Obstet, 2001; 75:251-5
• > 25% CIN III/Ca. in CIN I-II directed Bx
Petry KU et al., Am J Obstet Gynecol, 2002;186:28-34

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Lesion size related to cone
biopsy findings
Cone biopsy % Lesion
Involved quadrants
Negative 67.8 1
CIN 1 50.3 1-2
CIN 2-3 78.8 2-3
Cancer 66.2 3-4
Costa et al. 2001

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Cone Punch
biopsy biopsy
Neg/CIN 1 CIN 2-3
264/201 76.1%
Small lesion removed by biopsy
Rate of over-estimation of punch biopsy
Costa et al. 2001

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Colposcopy by cone biopsy
Colposcopy
15 SCJ vis.
131 Neg
116 SCJ not vis.
313 AnTZ 1
869 Pos
556 AnTZ 2
Cone biopsy
CIN 2-3 Cancer Total
4 0 4 (0.6%)
37 4 41 (6 %)
163 6 169 (25.1%)
403 59 462 (68.3%)
607 69 676 (100%)
Costa et al. 2001

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Punch biopsy by Cone biopsy
Punch biopsy*
Neg/CIN 1
Neg/CIN 1 63
CIN 2-3 201
Cancer 0
264
Cone biopsy
CIN 2-3 Cancer Total
39 5 44 (6.9%)
527 58 585 (92.3%)
3 2 5 (0.8%)
569 65 634 (100%)
Costa et al. 2001

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Conclusions 1
No Gold Standard in diagnosis !!!
• LG SIL on Pap smear or punch biopsy
may hide a HG SIL or Cancer
• Punch biopsy may be an inadequate end
point by which to judge the severity of the
lesion

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Conclusions 2
Limits of colposcopy in Presurgical
HG lesion assessment
• SCJ not entirely visible 70%
• Misleading target biopsy 40%
• No lesion 7%

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H-SIL and microinvasive
cervical cancers

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Open Question
In stage Ib1 cervical cancer is
the removal of parametria
always necessary even in case
of minimal involvement?

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HSG experience in Cervical Cancer
(1982 - 1986)
Stage Ib1, Class I vs Class III
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10years
%
Class I
Class III p: 0.1
Landoni et all. I.G.C.S. 1989

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0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10years
%
Class I Class
III p: 0.9
Landoni et all. I.G.C.S. 1989
HSG experience in Cervical Cancer
(1982 - 1986)
Stage Ib1 < 3 cm, Class I vs Class III

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German Experience
Surgery* Pts 5yrs
Wertheim - Meigs 108 72.3 %
Galvin – Te Linde 102 78.5 %
* adjuvant RT ~ 50% in both groups
Stark G.:Geburt. und Frauen. 47(1), 45-8,1987

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Pts N+(%) P+(%)
Landoni ’89 189 32 (17) 20 (10)
Covens ‘01 842 45 ( 6) 33 ( 4)
(8 PMLN & 25 PT)
tumor size < 2cm/nodesNeg/depth inv.< 10mm (0.6)
Winter ’01 (N-) 351 44 (12)
Steed ’06 110 13(12) 5 ( 5)
Benedetti ‘00 49 15 (31)
Parametrial involvement in
Early Stage Cervical Cancer

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Recurrences 2%

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Recurrences 30%

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Recurrences
 Size < 2 cm 1.9%
 Size > 2 cm 20%

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26 patients with stage IA2 (6) - IB1 (20) cervical cancer
 4 patients had radical surgery due to nodes pos.(16.7%)
 1/22 conservative surgery patients had a pelvic recurrence
(isthmic part of the uterus) 14 mts after initial treatment (NED at
30 mts after CT/RT)
 No Deaths
 Conception rate 71%
 Term Deliveries 42%
OUTCOMES from VAGINAL TRACHELECTOMY
and LAPAROSCOPIC PLND
Robb L. et all. Int. J.Gyn. Cancer, 2006

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Simple
trachelectomy
Leep

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IEO Study Design
Conservative treatment for Stage IA2-IB1
cervical cancer patients

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IEO Study design
Patients will be stratified in two categories based
on the tumor diameter
Patients with tumor diameter < 2cm
Patients with tumor diameter >2cm<3cm

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 Histologically confirmed diagnosis FIGO stage IA2-IB1
squamous/adenosquamous/adeno
 Cervical tumor diameter < 3 cm on MRI or on cervical specimen after
cone
 Distance between OUI and tumor > 1 cm on MRI
 No evidence of pelvic lymph nodes involvement and distant metastasis
on CT scan/PET
Adequate hematological, liver and renal function
 Absence of any psycological, familial, sociological, condition potentially
hampering compliance with the study protocol and follow-up schedule
 Signed informed consent
INCLUSION CRITERIA

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 First step: cone biopsy and laparoscopically pelvic lymphadenectomy
 No evidence of RISK FACTORS on the cervical specimen and
negative pelvic lymph nodes: FOLLOW-UP
 Presence of RISK FACTORS on the cervical specimen:
LVS Involvement & invasion > 10mm – CT
Free Margins < 3mm – SURGERY
 Presence of pelvic lymph nodes metastases: RADICAL TREATMENT
Treatment A ( < 2 cm)

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 36 patients IB1 < 2 cm
 Conization & LND
 66 months follow up (range 18 -168)
Single case of pelvic recurrence 34 months after treatment
- squamous
- G3
- LVSI

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21 preganacies in 17 patients
 3 preterm (27-32 and 33 weeks)
 3 first trimester abortions
 1 second trimester abortion
 1 ectopic pregnancy; 1 FID genetic anomalies
Obsterical Outcomes
Cervical conization is a possible conservative
management in stage FIGO IB1< 2 cm, in very selected
patients with negative lymphnodes

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 First step: laparoscopic pelvic lymphadenectomy
NEGATIVE NODES
 Second step: NACHT for 3 cycles every 21 days
 Third step: cone biopsy after clinical and radiologic
evaluations
Treatment B (> 2 < 3 cm)

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BEFORE

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AFTER