Download Fertility Preservation in Gynaecological Oncology Patients: How

Conservative Surgery to Preserve
Fertility in Gynaecological Cancers.
Sean Kehoe
Oxford Gynaecological Cancer Centre
Churchill Hospital
Oxford
Malignancies
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Cervical
Endometrial
Ovarian
Vulval Cancer ?
Counselling
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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
20
85+
80-84
75-79
70-74
65-69
60-64
55-59
50-54
45-49
40-44
0
35-39
0
30-34
5
25-29
100
20-24
10
15-19
200
10-14
15
5-9
300
0-4
Number of cases
Female cases
Female rates
Rate per 100,000 population
400
Age at diagnosis
About 33% of cervical carcinomas occur in women <40 years
Cervical Carcinoma

Severe Dyskaryosis ? Invasion

? Invasion on Colposcopy
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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
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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?
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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.
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Histopathology
Imaging
Both of these are paramount in decision
making.
Endometrial Cancer
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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: Metaanalysis
Contrast enhanced MRI best – BUT of
note myometrial invasion detected
correctly in 90% of cases – i.e. 10%
false negative rate.
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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
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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
Curettage at 6/12
If Attempt
pregnancy
If +
Offer
Hysterectomy
Intervene
If
Any
concerns
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
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Ushijima et al. J. Clinical Oncology 2007
28 Stage 1 A, 17 Atypical hyperplasia, all < 40 years
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600mgs MPA with low dose aspirin
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Continued for 28 weeks once responding
Endometrium checked 8 and 16 weeks
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CR 55% Endometrial CA, and 82% AH
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In responders– either oestrogen/progesterone therapy or Fertility
therapy.
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36 months follow-up – 12 pregnancies and 7 deliveries
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However 47% recurrence rate – need careful monitoring
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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)
Age at pregnancy, yr (mean SD)
Histology type
Adenocarcinoma
Adenosquamous
Grade of differentiation
Well
Moderate and poor
Hysterectomy after childbearing
Yes
No
Metastasis/recurrence
Yes
No
50
43
45
44
1
41
38
3
50
9
41
50
4
46
32.8 , 4.1 (n = 14)
34.3, 4.0 (n = 13)
14
14
0
14
13
1
14
3
11
14
0
14
29.5, 5.3 (n = 36)
30.9 , 5.3 (n = 30)
31
30
1
27
25
2
36
6
30
36
4
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
0.05
0.05
1.0
1.0
0.70
0.57
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)
Preterm labor
Cesarean rate
Primigravida
Multiple pregnancy
Group 1 (n=15)
Group 2 (n=50)
p
7 (46.7)
14 (93.3)
14 (93.3)
6 (40.0)
3 (6.0)
11 (22.0)
36 (72.0) 0.160
3 (6.0) 0.003
0.001
<0.001
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?
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Numbers are too small to make any
dogmatic statements.
We can preserve fertility
After single delivery – most
recommend hysterectomy.
Ovarian Cancer
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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
Grade 1 = 35
Grade 2= 9
10 stage 1C
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
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What if Cystectomy performed ?
A. If malignant – proceed to
oophorectomy and full staging
B. If borderline – oophorectomy –
reduces recurrence rates
Ovarian Cancer
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Must Monitor the Contra-lateral
ovary.
Ultrasound/tumour markers.
Borderline Ovarian Cancer
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Boran 2005
Fertility Sparing
62
Radical
80
Recurrence
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
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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
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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