Conservative Surgery to Preserve

Fertility in Gynaecological Cancers.

Sean Kehoe
Oxford Gynaecological Cancer Centre
Churchill Hospital
Oxford
 Malignancies
 Cervical
 Endometrial
 Ovarian
 Vulval Cancer ?
 Counselling
 Counselling is very important

 Often we are deviating from what

could be considered the ‘Standard
Recommendations’

 In essence – experimentation with

the patient taking the risk.
 Cervical Carcinoma

Occurs not uncommonly in younger patients [33% < 40 years]

A real increase in adenocarcinomas

An impression of more cases occurring in nulliparous women –

probably due to women delaying pregnancies as compared to
previous times.
Figure 1.1: Numbers of new cases and age specific incidence
rates, cervical cancer, UK 2004
400 20
Female cases

Rate per 100,000 population

Female rates

300 15
Number of cases

200 10

100 5

0 0

85+
0-4
5-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
Age at diagnosis

About 33% of cervical carcinomas occur in women <40 years

 Cervical Carcinoma
 Severe Dyskaryosis ? Invasion

 ? Invasion on Colposcopy

 Requires some form of biopsy

Stage 1A1 – Squamous Carcinoma

A loop cone excision of the cervix is sufficient treatment

Once all pre-invasive and invasive disease cleared.

Stage 1A1 Adenocarcinoma

Problem with ‘definition’

Now staging as 1A1 is acceptable

Skip lesions can occur : ? Just Pre-invasive

For lesions 3 -5 mm x 7 mm, 141 women – only 1 case of

lymph node disease [0.73%]
 Cervical Cancer:
Trachelectomy
 Rules
 Nulliparous [?] – family incomplete
 Careful clinical staging
 MRI scan to evaluate tumour extent.
 Ib1 [2cms] or less.
 Adenocarcinomas ?
 ? Poorly Differentiated
 ?Lymph Vascular Space Invasion
 Trachelectomy

Excise to
Isthmus

Insert Cervical Circlage

 Cervical Cancer
Cervical
Circlage

Parametrial Tissue

But will surgery be further modified?

Why parametrial tissue which addresses only 2 of 4 planes ?

In tumour <10mm invasion and <2cms diameter – incidence of

parametrial involvement is estimates at 0.6%
Cervical Cancer

Single or 2 stage procedure ?

If single – depending on Frozen Section Histology

Extra-peritoneal or Intra-peritoneal Lymphadenectomy?

If the procedure is about preserving fertility – it seems

logical to prevent intra-peritoneal surgery when an alternative is available.
Patients and tumor characteristics for the seven clinical studies of radical vaginal
trachelectomy

Beiner ME and Covens A (2007) Surgery Insight: radical vaginal trachelectomy as a method of fertility
preservation for cervical cancer Nat Clin Pract Oncol 4: 353–361 doi:10.1038/ncponc0822
Table 2 Operative data and complications in the seven clinical studies of radical
vaginal trachelectomy

Beiner ME and Covens A (2007) Surgery Insight: radical vaginal trachelectomy as a method of fertility
preservation for cervical cancer Nat Clin Pract Oncol 4: 353–361 doi:10.1038/ncponc0822
Table 7 Number of obstetric outcomes in patients who underwent trachelectomy

Beiner ME and Covens A (2007) Surgery Insight: radical vaginal trachelectomy as a method of fertility
preservation for cervical cancer Nat Clin Pract Oncol 4: 353–361 doi:10.1038/ncponc0822
 Counselling
 Pregnancy:
If achieved –
30% miscarriage rate
Assume – Premature delivery
Assume – Operative Delivery
Recurrence Rates

To date the recurrence rates at about 4% are not in excess of that expected
with a radical hysterectomy.

The application of this procedure to large tumours is less frequent now.

 How Safe: Trachelectomy?
 Case selection very important
 Probably as safe as Radical
Procedures
 Avoid in Large tumours [>2cms ?]
 Avoid in rare/high risk tumours
 For nulliparous women only?
ENDOMETRIAL CANCER
 Endometrial Cancer
A Rare issue in women where fertility
is a factor.

 Histopathology
 Imaging
Both of these are paramount in decision
making.
 Endometrial Cancer
 Histology: Differentiation between Atypical
Hyperplasia and Frank Carcinoma

 Remember – when tissue confirms

Atypical Hyperplasia – Frank Malignancy is
found in the Hysterectomy specimen in
40-50% of cases [Cancer 2006,GOG
study]

 Most would agree that fertility

preservation should be limited to those
with well differentiated tumours [stage
1A]
 Endometrial Cancer
 Imaging:
This is important for the ‘staging’
process.
CT/MTI/Ultrasound?
Kinkel et al,Radiology 1999: Meta-
analysis
Contrast enhanced MRI best – BUT of
note myometrial invasion detected
correctly in 90% of cases – i.e. 10%
false negative rate.
 Endometrial Cancer

In the main – progestagens used as therapy.

Treatment time to regression ranges from 3.5 – 9 months

Recurrence occurs in about 20% of responders

This approach requires careful surveillance – and repeated

endometrial curettage.
 Endometrial Cancer
 How to manage??

Mirena IUCD

Progestogens:

GnRH analogues

All the above have been used with reasonable success

[responses about 70%].

Tamoxifen can increase the PR, and hence potentially enhance

the efficacy of progestagenic agents
 Endometrial Cancer
Stage 1a
Treatment
Curettage at 3/12
Intervene
Curettage at 6/12 If
Any
concerns
If - If +

Attempt Offer
pregnancy Hysterectomy
 Endometrial Cancer
Ref Cases Response Pregnancies

Kaku 2001 12 75% 2

Imai 2001 15 50% 2

Randall 1997 14 75% ?

Gotlieb 2003 13 100% 9 babies

Signorelli, 2009 21 57% 13 pregnancies

Laurelli 2011 14 90% 1 baby

Miniq, 2011 14 57% 11 pregnancies

 Endometrial Cancer
 Ushijima et al. J. Clinical Oncology 2007
 28 Stage 1 A, 17 Atypical hyperplasia, all < 40 years

 600mgs MPA with low dose aspirin

 Continued for 28 weeks once responding

 Endometrium checked 8 and 16 weeks

 CR 55% Endometrial CA, and 82% AH

 In responders– either oestrogen/progesterone therapy or Fertility

therapy.

 36 months follow-up – 12 pregnancies and 7 deliveries

 However 47% recurrence rate – need careful monitoring

Distribution of clinicopathological characteristics in the endometrial cancer patients with conception in
the meta-analysis
Characteristics Patients no. Group 1 Group 2 p

Age at diagnosis, yr (mean SD) 50 32.8 , 4.1 (n = 14) 29.5, 5.3 (n = 36) 0.05
Age at pregnancy, yr (mean SD) 43 34.3, 4.0 (n = 13) 30.9 , 5.3 (n = 30) 0.05
Histology type 45 14 31 1.0
Adenocarcinoma 44 14 30
Adenosquamous 1 0 1
Grade of differentiation 41 14 27 1.0
Well 38 13 25
Moderate and poor 3 1 2
Hysterectomy after childbearing 50 14 36 0.70
Yes 9 3 6
No 41 11 30
Metastasis/recurrence 50 14 36 0.57
Yes 4 0 4
No 46 14 32

Taiwan J Obstet Gynecol. 2011 Mar;50(1):62-6.

Obstetric outcomes of pregnancy after conservative treatment of endometrial cancer: case series and literature review.
Chao AS, Chao A, Wang CJ, Lai CH, Wang HS
author
platform+m
yes

Analyses of obstetric outcomes according to undergoing:

IVF, ICSI, gamete intrafallopian transfer, or zygote intrafallopian transfer (Group 1)
and spontaneous conception/intrauterine insemination (Group 2)

Group 1 (n=15) Group 2 (n=50) p

Preterm labor 7 (46.7) 3 (6.0) 0.001

Cesarean rate 14 (93.3) 11 (22.0) <0.001
Primigravida 14 (93.3) 36 (72.0) 0.160
Multiple pregnancy 6 (40.0) 3 (6.0) 0.003

Taiwan J Obstet Gynecol. 2011 Mar;50(1):62-6.

Obstetric outcomes of pregnancy after conservative treatment of endometrial cancer: case series and literature review.
Chao AS, Chao A, Wang CJ, Lai CH, Wang HS
How safe : Endometrial cancer?
 Numbers are too small to make any
dogmatic statements.

 We can preserve fertility

 After single delivery – most

recommend hysterectomy.
 Ovarian Cancer
 Agreed fertility preservation in all young
patients [?<40 years]- as:

 1. Germ cell tumours very chemosensitive

 2. Borderline tumours – normally cured
with local excision [ if early stage]
 3. If advanced ovarian cancer – then can
always re-operate.
 4. May be another condition – eg
Hodgkins !!
Invasive Early stage disease
Schilder et al, Gynecol Oncol, 2002

N = 52
42 stage 1A 10 stage 1C
Grade 1 = 35 Grade 2= 9 Grade 3 = 5

20 had adjuvant chemotherapy

5 recurrences [8-78 months after first surgery]

Sites : Contralateral ovary – 3 , peritoneum 1 and lung 1.

2 deaths

24 attempted pregnancies – 71% conceived.

Survival at 5 years 98% and 10 years 93%
 Fertility-sparing surgery in young women with mucinous adenocarcinoma
of the ovary.
Gynecol Oncol. 2011 Aug;122(2):334-8. Kajiyama H et al,Japan

N=148,The median follow-up time of all mEOC patients was 71.6 (4.8-448.3)
months

41 patients with Fertility Sparing, 27 = Stage 1a, 14 Stage 1c

5 year overall survival was 97.3%

Compared with 101 women who underwent Radical surgery for the
Same disease – there was no difference in outcome.
 Germ Cell Tumours

Ref Cases Chemo Preg Survival

Perrin 1999 45 29 7 babies 2 deaths

Sagae 2003 26 23 4 pregnancies – no deaths

Zanetta 2001 138 81 40 babies 95% 5 year

For Germ cell tumours – outcome excellent. Most problems

were in the more advanced stage diseases.

Fertility can be retained.

 Borderline Ovarian Tumours

Ref Cases Recurrence Pregnancies

Gotlieb, 2003 39 8% 22 in 15 women

Zanetta,2001 189 18% 41in 21 women

Demeter, 2002 12 ? 50%

Donnez,2003 16 18.7% 64%

Boran 2004 62 6.5% 13 in 10 women

Rao , 2005 38 16% 6 in 5 women

 Ovarian Cancer
 What if Cystectomy performed ?

 A. If malignant – proceed to
oophorectomy and full staging

 B. If borderline – oophorectomy –
reduces recurrence rates
 Ovarian Cancer
 Must Monitor the Contra-lateral
ovary.

 Ultrasound/tumour markers.
 Borderline Ovarian Cancer
 Fertility Sparing Radical Recurrence

Boran 2005 62 80 6.5% vs 0.0%

Zanetta 2001 189* 150 18.5 % vs 4.6%

• 7 cases progressed to ‘invasive’ carcinoma

Important to counsel the patient and is this evidence to

support routine pelvic clearance after completion of the
family ??
 Ovarian Cancer
 Fertility conservation safe for Borderline
tumours.
 In invasive tumours – probably best to
restrict fertility preservation surgery to
properly staged, Stage 1 disease.
 Following completion of family – pelvic
clearance seems a logical approach to
reduce recurrences, and considering the
limitations of screening such women.
 Conclusions
 Yes it can be done – but always the
question is :Should it be done?

 Need the full Multidisciplinary Team

– Oncological and Fertility Working
together. [?Obstetric/Neonatal?]

 Counsell– Counsell and Counsell

A Healthy Mother and Child