Conservative Surgery to Preserve Fertility in Gynaecological Cancers.ppt by hcj

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									 Conservative Surgery to Preserve
Fertility in Gynaecological Cancers.

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

n   Often we are deviating from what
    could be considered the ‘Standard
    Recommendations’

n   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.
About 33% of cervical carcinomas occur in women <40 years
         Cervical Carcinoma
n   Severe Dyskaryosis ? Invasion

n   ? Invasion on Colposcopy

n   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
n   Rules
n   Nulliparous [?] – family incomplete
n   Careful clinical staging
n   MRI scan to evaluate tumour extent.
n   Ib1 [2cms] or less.
n   Adenocarcinomas ?
n   ? Poorly Differentiated
n   ?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
n 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?
n   Case selection very important
n   Probably as safe as Radical
    Procedures
n   Avoid in Large tumours [>2cms ?]
n   Avoid in rare/high risk tumours
n   For nulliparous women only?
ENDOMETRIAL CANCER
         Endometrial Cancer
A Rare issue in women where fertility
 is a factor.

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

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

n   Most would agree that fertility
    preservation should be limited to those
    with well differentiated tumours [stage
    1A]
       Endometrial Cancer
n 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
n   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
n   Ushijima et al. J. Clinical Oncology 2007
n   28 Stage 1 A, 17 Atypical hyperplasia, all < 40 years

n   600mgs MPA with low dose aspirin

n   Continued for 28 weeks once responding
n   Endometrium checked 8 and 16 weeks

n   CR 55% Endometrial CA, and 82% AH

n   In responders– either oestrogen/progesterone therapy or Fertility
    therapy.

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

n   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
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?
n   Numbers are too small to make any
    dogmatic statements.

n   We can preserve fertility

n   After single delivery – most
    recommend hysterectomy.
             Ovarian Cancer
n   Agreed fertility preservation in all young
    patients [?<40 years]- as:

n   1. Germ cell tumours very chemosensitive
n   2. Borderline tumours – normally cured
    with local excision [ if early stage]
n   3. If advanced ovarian cancer – then can
    always re-operate.
n   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
n   What if Cystectomy performed ?

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

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

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

n   Need the full Multidisciplinary Team –
    Oncological and Fertility Working
    together. [?Obstetric/Neonatal?]

n   Counsell– Counsell and Counsell
A Healthy Mother and Child

								
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