IEO 2014

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. 1985Buxton, 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 0.6Costa 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 featuresInvolved 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 1No 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 parametriaalways 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