1. Heelkundige en Medicamenteuze Fertiliteitssparende Behandeling in de Gynaecologische oncologie
Ignace Vergote, MD PhD FACS
Voorzitter Leuvens Kanker Instituut (LKI)
Diensthoofd Gynaecologie-Verloskunde
Universitaire Ziekenhuizen Leuven

2. FER sparend in gyn oncologie
Cervix
- Conisatie
- Trachelectomie
- Portioamputatie
- Neoadjuvante chemotherapie + Conisatie
Ovarium
- Borderline
- Invasieve epitheliale tumoren
- Niet-epitheliale tumoren
Endometriumcarcinoom

3. FIGO 2009 Cervical Cancer Pecorelli, Int J Gynecol Obstet 2009;105:103-4

4. Incidence of pelvic lymph node metastasis in cervical carcinoma FIGO stage Ia1
LVSI <3mm mm
n= n=
% %
% %
IN CERVICAL CARCINOMA Ia1 WITHOUT LVSI
IS CONISATION SUFFICIENT Bellino 1994, Benedet 1996

5. Selection Criteria for Fertility Preserving Therapy in cervical cancer Ia2- IB1
PATIENTS’ CRITERIA 1. Strong desire to preserve fertility 2. Age limit ? (less than 35, 40, 45?) TUMOR CRITERIA 1. Tumor size (expert colposcopy / volume – NMR) 2. Preoperative biopsy (exclude neuroendocrine ca), LVSI, VSI
LVSI, lymphovascular space involvement

6. Fertility-sparing surgery
IB1 – less than 20 mm, less than ½ of stromal invasion
Optimal RADICALITY of SURGERY?

7. A: Conisation
B: Simple Trachelectomy or
Portioamputation
C: Proximal Radical Trachelectomy
D: Distal Radical Trachelectomy

8. How often is there parametrial involvement in IA2, IB1 < 2 cm with negative pelvic nodes?
Rob < ½ invas 0/125 0%
Covens < 10 mm invas 3/ ,6%
Steed / %
Plante / %
Stegeman < 10 mm invas 5/ %
Wright neg LVSI
Strnad /133 0%
Frumovitz neg LVSI 0/125 0%
Smith et al neg LVSI 0/53 0%
Parametrial involvement in patients wih tumors < 2cm and negative pelvic nodes is very rare (0-0.6%).

9. Radical Vaginal Trachelectomy
Recurrence (n)
Deaths (n)
Size < 2cm
Size > 2 cm
Shepherd NA 4
Sonoda
1/36 1
Pahisa
1/11
1/2
Chen
0/9
0/7
Hertel
3/105
1/1 2
Dargent
1/91
6/27 5
Plante
1/64
2/8
Covens
5/83
1/8
Burnett
Schlaerth
0/10
Total
12/409 (3%)
11/53 (21%)
20/683 (3%)

10. Radical Vaginal Trachelectomy
Pregnant women (n)
Conceptions (n)
First trimester loss (n)
Second Trimester loss (n)
Shepherd NA 88 22 12
Sonoda 11 3
Pahisa
Chen 5 2
Hertel 18
Dargent 33 56 14 8
Plante 51 90 23
Covens
Burnett 1
Schlaerth 4
Total
146/525 (28%)
300
68/300(23%)
31/300 (10%)

11. Radical Vaginal Trachelectomy
Delivery (n)
Ongoing pregnancy
Before week 32
Weeks 32-36
Term
Shepherd 10 35 NA 7
Sonoda 4
Pahisa 1 2
Chen
Hertel 12 3
Dargent 5 29
Plante 9 51
Covens
Burnett
Schlaerth
Total
34/300 (11%) 49
101 17
Pregnancy loss or delivery before 32 weeks in 44% of the patients!

12. Radical Abdominal Trachelectomy
Recurrence, n
Deaths, n
Size < 2 cm
Size > 2 cm
Abu Rustum NA
Pajera
Duska
Nishio
1/48
5/13
Cibula
1/14
0/3
Ungar
0/21
0/9
Total
2/83 (2%)
5/25 (20%)

13. Radical Abdominal Trachelectomy
Pregnant women (n)
Conceptions (n)
First trimester loss (n)
Second trimester loss (n)
Abu Rustum 2 1
Pajera 3
Duska 4
Nishio
Cibula 6
Ungar 13
Total
30/175 (17%) 32
7/32 (22%)

14. Radical Abdominal Trachelectomy
Delivery, n
Ongoing pregnancy
Before week 32
Weeks
32-36
Term
Abu Rustum 1
Pajera 2
Duska
Nishio
Cibula 3
Ungar 5
Total
5/32 (16%)
2/32
13/32
5/32
Pregnancy loss or delivery before 32 weeks in 38% of the patients!

15. Neoadjuvant chemotherapy followed by conisation or simple trachelectomy in patients with Ib1 < 3cm
Robova
Trach
Plante
Maneo
Conisation
Leuven
Total
Period
Chemotherapy
PI or PA every 10 days;
TIP or TEP every 21 days
TIP or TEP
TIP or TC weekly
Planned surgery (n) 9 3 21 11 44
Fertility spared (n) 7 16 10
36 (82%)
N1 (n) 2 1
3/44
Mean age (range), years
29(24-33)
32(26-36)
30(17-39)
32(27-37)
Nulliparous
women (n) 8 NA
20/23 (87%)

16. Neoadjuvant chemotherapy followed by conisation or simple trachelectomy in patients with Ib1 < 3cm
Robova
Trach
Plante
Maneo
Conisation
Leuven
Total
Histology
SCC AC
Others 7 2 3 9 12 5 6 24 20
Tumor Size
< 2 cm
> 2 cm 15
29 (66%)
LVSI, n NA 1 10
Recurrences
1/7*
0/3
0/16*
1/11
2/37 (5%)
* Only with fertility preservation included

17. Pregnancy loss or delivery before 32 weeks in 20% of the patients!
Neoadjuvant chemotherapy followed by conisation or simple trachelectomy in patients with Ib1 < 3cm
Robova
Trach
Plante
Maneo
Cone
Leuven
Total
Pregnant women, n
5/7*
2/3*
6/16*
5/9*
18/35 (51%)
Conceptions, n 5 3 10 6 24
1st trimester loss, n 1
2 (8%)
2nd trimester loss, n
Delivery
Before week 32
Weeks 32-36
Term 2 7 4
3 (12%) 16
Ongoing pregnancy, n NA
Pregnancy loss or delivery before 32 weeks in 20% of the patients!
* Only with fertility preservation included

18. Prague series: Simple Trachelectomy Cx ca Ia2 and Ib1 (< 2cm)
Less than 2 cm/less than ½ stromal invasion
Ia1 with LVSI (n= 3) , Ia2 (n = 10), Ib1 (n = 21)
All with negative pelvic lymph nodes
N = 34 , 32 fertility spared
One central recurrence
23 pregancies (17 patients pregnant)
5 first trimester and 3 second trimester losse
Rob L Gynecol Oncol 2008

19. Simple conization and lymphadenectomy for Stage IB1 CxCa Maneo et al, Gynecol Oncol 2011
Median age is 31 (range, 24-40)
Median tumor diameter is 11.7mm (median, 18-25mm)
LVSI 5%
Median FU is 66 months (range, months)
1 nodal relapse
21 pregnancies in 17 patients and 14 live babies
Simple cone is according to these authors a feasible option in tumors < 20 mm with negative pelvic nodes.

20. Conclusions (1) Fertility sparing in cervical cancer Ia2-Ib1
Patients should be very well selected:
Strong fertility wish
Ia2 or Ib1 (< 2cm) or < 3 cm ( only with neoadjuvant chemotherapy).
Negative pelvic lymph nodes
Abdominal, vaginal and laparoscopic (robotic) trachelectomies are options, however in patients with Ia2 with negative nodes these operations are an overtreatment.
In some series of radical trachelectomy up to 40% of the patients did not have residual tumor (after conisation).

21. Conclusions (2) Fertility sparing in cervical cancer Ia1-Ib1
4. Radical trachelectomy resulted in a about 40% pregnancy loss or delivery before week 32.
5. In some patients a simple trachelectomy or wide conisation might suffice when tumor < 1 (?) cm and negative nodes and:
no LVSI ?
< 10 mm invasion?

22. Conclusions (2) Fertility sparing in early cervical cancer.
6. Neoadjuvant chemotherapy followed by conisation seems to be a valuable alternative, especially in patients with larger tumors and/or LVSI. I personally prefer this option in all Ib1 tumors because:
7. NACT and conisation resulted in a pregnancy loss or delivery before week 32 of only 20%
8. and more patients (51%) seem to conceive than after radical trachelectomy (25%).
9. Paclitaxel-Carboplatin weekly seems to be a very effective and well tolerated regimen.

23. Fertility sparing in « early » ovarian cancer

24. Guidelines for treatment of Borderline tumors of the ovary
Cadron I et al JCO 2007

25. Fertility sparing versus radical surgery
in borderline tumors
FIGO Stages
Fertility sparing OP
Radical OP
Pts.
Relapse
all
Ovary only
all FIGO
2.868
439
303
3.735
182
(%)*
15,7 %
439 of 2.794
74,5 %
284 of 381
4,9 %
FIGO I
1.810
223
168
2.076 52
12,6 %
190 of 1.504
84,8 %
168 of 198
2,4 %
49 of 2.076
FIGO II-III
256 97 53
437 54
44,8 %
94 of 210
54,0 %
47 of 87
13,9 %
48 of 345
du Bois A Geburtsh Frauenheilk 2009; 69 :

26. Outcome relapsed BOT -> invasives (low grade) carcinoma?
Literature: 89 series
Pts.
Recurrence
deceased
invasive recurrence
of disease (DoD)
DID
all:
8.234 pts.
919
201
269
333
Recurrence rate: 11,0%
27,5%
of all recurrences
26,2%
All with >5 yrs.
follow-up: pts.
616
167
191
252
recurrence rate: 11,7%
33,3%
30,4%
Relation DoD : DID = 1 : 1,7
du Bois A, Ewald-Riegler N, du Bois O, Harter P, Borderline tumors of the ovary – a systematic review. Geburtsh Frauenheilk 2009; 69 :

27. AGO Retrospective study in Serous Borderline tumors
AGO Retrospective study in Serous Borderline tumors. Multivariate analysis for PFS (n = 644)
Factor HR
95% CI p
Post-OP Residual tumor
4.980
(2.131, )
0.0002
Implants present yes/no
2.743
(1.675; 4.494)
<0.0001
Organ preservation
2.363
(1.226; 4.554)
0.0102
Staging quality adequate
vs. incomplete
2.188
(1.315; 3.683)
0.0026
Age [years]
0.838
(0.726; 0.968)
0.0166
2.: Organerhalt bzw. Implants ausgeschlossen wegen Überlappung mit Fertiltitäserhaltung bzw. FIGO Stadium
PRESENTED BY: de Gregorio et al. ASCO 2012 Abstract ID:  5005

28. Guideline for treatment of Borderline tumors of the ovary
Adapted from Cadron I et al JCO 2007

29. OVARIAN INVASIVE CARCINOMA SURGERY
1. Initial Surgery : Surgical treatment
CONSERVATIVE TREATMENT :
Unilateral oophorectomy + infracolic omentectomy + staging
CONSIDER
2. Frequency of Occult Bilaterality in Apparently Stage Ia disease
Author Number Occult Bilaterality
Munnell (5%)
Williams* (7%)
*Includes only Stage Ia, well differentiated tumors

30. Conservative management in invasive Stage I epithelial ovarian carcinoma
Fertility preserving surgery should be reserved for G1 tumors, stage Ia (preferentially – expansile mucinous)
60% of the recurrences involve the contralateral ovary
Ritu and Bristow, Clin Obstet Gynecol 2012
Muyldermans K, Eur J Cancer 2013

31. Ovarian Germ cell tumors
Very rarely bilateral (1%) except in dysgerminoma (Stage Ib: 10-15%)
However, pure dysgerminoma is extremely chemosensitive and can almost always be cured at relapse with chemotherapy
IN YOUNG PATIENTS WITH GERM CELL TUMORS: TREAT (ALWAYS) CONSERVATIVE.
WHEN DOUBT ABOUT PATHOLOGY: WAIT FOR FINAL HISTOLOGY.

32. Fertility-Sparing Surgery in granulosacell tumors
134 young patients (≤50 years) with stage I
5 and 10 year survival of 97% and 94%
71 (54%) had a fertility-sparing surgery
There was no difference in the outcome of women who had a standard vs conservative surgery (97% vs 98%)
Zhang M, et al. Gynecol Oncol. 2007;104(2):

33. Fertility sparing in endometrial cancer

34. Progestagen treatment of endometrial cancer in patients wishing to preserve fertility
Literature review (n = 197):
Tangjitgamol Gynecol Obstet Invest 2009
104 with CR without recurrence 40 with progression or persistent disease
53 with recurrence after first CR

35. Progestagen treatment of endometrial cancer in patients wishing to preserve fertility
Korean series ( n= 148)
G1 endometrioid ca
No myometrial invasion
< 40 y
115 CR (78%) of which 35 recurred
33 progression or persistence (hence 54% of 148 remained in CR –med F-up 58 months)
All recurrences or persistence remained limited to the uterus and none died.
44 (38%) patients had at least one viable pregnancy
Park Eur J Cancer 2013

36. Progestagen treatment of endometrial cancer in patients wishing to preserve fertility
Park Eur J Cancer 2013

37. Progestagen treatment of endometrial cancer in patients wishing to preserve fertility.
Tangjitgamol Gynecol Obstet Invest 2009