La « désescalade » thérapeutique dans le cancer du col · PDF fileLa...
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La « désescalade » thérapeutique
dans le cancer du col utérin
Dr Marie Plante
Gynécologue Oncologue
L’Hôtel-Dieu de Québec
Université Laval, Canada
Paris, 10 Mars 2016
Erablière Plante-D’Amboise !
Erablière Plante-D’Amboise !
Désescalade thérapeutique
Je n’ai pas de conflits… d’intérêt
Désescalade thérapeutique
Plan de la présentation
Revoir l’évolution de la trachélectomie radicale
au cours des 30 dernières années
Options thérapeutiques pour patientes avec
• Lésions de petit volume (faible risque) (< 2 cm)
• Lésions de plus grand volume (> 2 cm)
La désescalade thérapeutique dans le
cancer du col utérin
1900 1990 2000 1980 2010
Wertheim
Abd Rad Hyst
TP LN
dissection
Schauta
Vag Rad Hyst
Vaginal Rad
Trachelectomy
Abdominal Rad
Trachelectomy
RP LN
dissection
SLN
mapping
Cone &
SN ?
Neoadjuvant
Chemotx ?
Simple
Trach
& SN ?
Robotic Rad
Trachelectomy
Laparoscopic Rad
Trachelectomy
Radical Trachelectomy
VAGINAL approach
Professor Daniel Dargent
Vaginal Radical Trachelectomy
N Fertility not
preserved
Recurrences Death
Lanowska, 2011 225 13 (6%) 8 (3.8%) 4 (1.9%)
Shepherd, 2012 208 24 (11.5%) 8 (3.8%) 5 (2.4%)
Covens, 2013*
Helpman, 2011
180 17 (9.4%) 9 (2.7%) 2 (1.1%)
Plante, 2011 140 15 (10.7%) 6 (4.8%) 2 (1.6%)
Marchiole, 2007 135 17 (12.6%) 7 (5.7%) 5 (4.2%)
Kim, 2012 51 9 (17.6%) 2 (3.9%) 1 (1.9%)
Total 924 95 (10.2%) 40 (4.4%) 19 (2.1%)
Plante M. Int J Gynecol Cancer 23:982, 2013
Vaginal Radical Trachelectomy N T1 T2 T3
Shepherd, 2012 125 27 (22%) 18 (14%) 73 (58%)
Plante, 2011 106 21 (20%) 3 (3%) 77 (73%)
Covens, 2013*
Helpman, 2011
86 14 (16%) 7 (8%) 65 (76%)
Speiser, 2011 60 5 (8%) 3 (5%) 45 (75%)
Mathevet, 2003 56 9 (16%) 8 (14%) 34 (61%)
Kim, 2012 19 1 (5%) 0 15 (78%)
Total 452 77 (17%) 39 (8.6%) 309 (68%)
Plante M. Int J Gynecol Cancer 23:982, 2013
< 32 wks 32-37 wks > 37 wks
14 (11%) 26 (21%) 33 (26%); 45%
4 (4%) 15 (14%) 58 (55%); 75%
11 (13%) 11 (13%) 43 (50%); 66%
12 (20%) 6 (10%) 27 (45%); 60%
2 (4%) 3 (5%) 29 (52%); 85%
0 6 (31%) 9 (47%); 60%
43 (9.5%) 67 (15%) 199 (44%); 64%
Oncologic Outcome
125 VRT
Recurrences: 6/125 (4.8%)
Deaths: 2/110 (1.6%)
Risk factor associated with recurrence
Size of the lesion > 2 cm (p=0.001)
• 10% of ptes had lesions > 2 cm
• Represent 50% of the recurrences
Plante et al. Gynecol Oncol 121:290-7, 2011
Gynecologic Oncology 138 (2015) 304–310
N=120
6 recurrences (5.1%); 2 deaths (1.7%)
7 patients had lesions >2 cm (5.8 %)
3 recurrences (50%)
Hauerberg et al. Gynecologic Oncology 138 (2015) 304–310
Vaginal Radical Trachelectomy
Over 1200 cases published
Consistent low recurrence rate
< 5%
Best obstetrical outcome
Limitations
Skills in vaginal surgery
Advantages
More familiar to gyn oncologists
Similar to a radical hysterectomy
Shorter learning curve
Wider parametrial resection
Does not require skills in vaginal or
laparoscopic surgery
No special instrumentation or training
Abdominal Trachelectomy
Abdominal Trachelectomy
Easier to implement in developing
countries
Series from Argentina (30 cases)
Good oncologic and obstetrical outcome
Testa R et al. J Low Genit Tract Dis: 2013;17(4):378-84
Abdominal Trachelectomy
International series of ART (n=101)
Consortium:
• MSKCC, Czech Republic and Mass General
4% recurrence
70% preserved fertility (no hyst, no adj tx)
74% who attempted preg conceived
31 pregnancies
• 6 (19%) delivered T2 (8.8% VRT)
• 16 (52%) delivered T3
Wethington S et al. Int J Gynecol Cancer. 2012 Sep;22(7):1251-7.
(Int J Gynecol Cancer 2016;26: 163-168
172 ART
6 recurrences (3.5%)
(5 > 2 cm)
61 pregnancies
42 (69%): IUI/IVF
22-27
Kasuga et al. Int J Gynecol Cancer 2016;26: 163-168
33%
Abdominal Trachelectomy
The most “popular” approach
> 800 cases published
Surgical morbidity higher
Abscess, blood loss
Recurrence rate < 5%
Obstetrical outcome (>150)
? Higher T2 losses
Laparoscopic Trachelectomy
Less “popular” approach
Technically challenging
> 200 cases published
Morbidity low
Recurrence rate 6%
Half in lesions > 2 cm
Obstetrical outcome (< 60)
J Surg Oncol 2014;110:252–257
N=88; 9 converted to LRH (LN+) + CRT
79 completed LRT
9 recurrences (11.4%), 1 death
Curr Opin Obstet Gynecol 2014, 26:302–307
Gynecologic Oncology 131 (2013) 83–86
Robotic Trachelectomy
“A la mode” approach
About 100 cases published
Morbidity low
Few recurrence
Higher rates of positive/close margins
Limited obstetrical data
N =49
2 local recurrences (4%)
17 pregnancies
12 (71%) delivered at term
Gynecol Oncol, 2016 (in press)
Gynecologic Oncology 138 (2015) 585–589
MIS
- Less blood loss
- Shorter hospital stay
Open
- Better fertility rate
Int J Gynecol Cancer 2015;25: 681-687
Conclusion
Surgical approach does not matter
Careful patient selection
Procedure well done / low morbidity
Oncologic outcome good
Fertility is preserved
Matter of preference / skills / training
Access to equipment
Conclusion
Considerable evolution in the radical
trachelectomy technique (last 30 years)
Radical Trachelectomy now considered
« standard of care » in young women who
wish to preserve fertility
Radical Trachelectomy
Is radical surgery necessary in low risk
small volume disease (< 2 cm) ?
Less radical surgery
IA2 IB1
FIGO Staging
Less radical surgery
IA2 IB1, 3 cm
Less radical surgery
IA2 IB1, 3 cm
Less radical surgery
Standard treatment for stage IA2-IB1
Radical hysterectomy
Pelvic lymph node dissection
To rule out
Parametrial spread
Lymph node metastasis
Less radical surgery
Morbidity of the rad hyst comes from
Parametrectomy
• Damage to autonomic nerve fibers a/w bladder,
bowel and sexual dysfunction
• Late urological/rectal dysfunctions: 20-30%
Magrina 1995, Sood 2002, Benedetti-Panici 2005
Less radical surgery
What are the chances of parametrial
spread in early-stage cervical cancer
< 2 cm
Does it justify the morbidity of the
radical surgery ?
Less radical surgery
Schmeler K et al. Gynecol Oncol 120:321, 2011
N=1117 < 1% All retrospective data
( Int J Gynecol Cancer 2016 Feb;26(2):416-21
Conclusions: Our data show a risk of parametrial
spread of 0.45% for tumors less than
20 mm in diameter, no LVSI, and a depth of
invasion within the inner third.
Triage patients
Size < 2 cm, LVSI- : PI 1.8% (2/112)
Size < 2 cm, LVSI- , node -: PI 0% (0/107)
“ Patients with early small lesions, no LVSI and
no nodal involvement may be spared radical
surgical procedures and parametrectomy “
Gemer O, Eur J Surg Oncol. 2013 Jan;39(1):76-80.
Less radical surgery
All retrospective data
No prospective randomized trials
Cochrane Review
The 2014 Cochrane Review of Surgical treatment of
stage IA2 cervical cancer has reviewed 982
references
They were ALL rejected as NONE met the review
criteria (ie randomized controlled trial)
Authors identified the SHAPE study as the only
relevant, randomized trial that can answer the
question about lesser surgery for IA2 patients.
Cochrane Database Syst Rev. 2014 May 29;5:CD010870
Cochrane Review
This review acknowledged that “Surgical trials
often present a greater challenge than trials
examining other treatment modalities, but this
should not be cited as a reason for not conducting
one
Trialists need to be pro-active in this area as there
is currently a substantial gap in the evidence“
Cochrane Database Syst Rev. 2014 May 29;5:CD010870
The SHAPE Trial
Comparing radical hysterectomy and pelvic
node dissection against simple hysterectomy
and pelvic node dissection in patients with
low risk cervical cancer
Chair: Marie Plante Laval University, Quebec City
An NCIC Clinical Trials Group proposal for the Gynecological Cancer Inter Group (GCIG)
Trial Schema
Current Status
Country # Sites Activated
Canada 17
France 29
South Korea 1
The Netherlands 3
Belgium 8
Austria 7
Ireland 1
United Kingdom 16
China 1
Total 83
Country # Patients
Accrued
Canada 81
France 16
South Korea 7
The Netherlands 8
Belgium 10
Austria 7
Ireland 4
United Kingdom 10
China 2
Total 145 (20%)
Current Status
Less radical surgery
Hard to justify the morbidity of a radical hysterectomy and parametrectomy in low risk patients
Risk of PI < 1%
Less radical surgery
Perhaps radical surgery is NOT
necessary is small volume lesions…
Less radical surgery
Simple trachelectomy and nodes
Goals of less radical surgery
Provide adequate oncologic outcome
Preserve fertility potential
Reduce surgical morbidity
Fertility
Cancer
Simple trachelectomy
60183-04
60183-05
60183-07
60183-02
25 year old woman G0
Very early cervical cancer
Minimal endocervical involvement
Simple trachelectomy
Less radical fertility-preserving sx
N Procedure Stage Follow-up
(mo)
LN
mets
Recurrence Adjuvant
treatment
Plante, 2013 16 SVT (14)
Cone (2)
IA1 LVSI
IA2-IB1
27 (1-65) 0 0 0
Maneo, 2012 36 Cone IB1 66 (18-168) 0 1 (PN) 0
Biliatis 2012 35 LLETZ IB1
(< 500mm3)
56 (13-132) 0 0 0
Palaia, 2012 14 SVT IA2-IB1 38 (18-96) 0 0 0
Raju, 2011 15 SVT IA2-IB1 96 (12-120) 0 0 0
Fagotti, 2011 17 Cone IA2-IB1 16 (1-101) 1 0 62 (RH in 4; CT in 2)
Ditto, 2009 16 Cone IA2-IB1 25 (4-71) 2 0 2 (RH)
Rob, 2008 40 SVT (27)
Cone (13)
IA1 LVSI
IA2-IB1
47 (12-102) 6 1 (central) 3 6 (RH)
189 9 (4.8%) 2 (1.0%) 14 (7.4%)
Plante M et al. Int J Gynecol Cancer. 2013 Jun;23(5):916-22.
Less radical fertility-preserving sx
# pregnancies /
# attempting
Term
Delivery
Preterm
Delivery
2nd Trimester
Loss
1st Trimester
Loss2
Ongoing
Pregnancy
Plante, 2013 8/8 (4 completed) 4 (100%) 0 0 0 4
Maneo, 2012 21/? 12 (57%) 3 (15%) 1 (5%) 5 (24%) 0
Biliatis, 2012 7/? 7 (100%) 0 0 0 0
Palaia, 2012 8/14 3 (37.5%) 5 (62.5%) 0 0 0
Raju, 2011 4/5 4 (100%) 0 0 0 0
Fagotti, 2011 2/5 2 (100%) 0 0 0 0
Ditto, 2009 3/10 1 (33%) 1 (33%) 1 (33%) 0 0
Rob, 2008 23/24 (20 completed) 9 (45%) 3 (15%) 3 (15%) 5 (25%) 3
76 (69 completed) 42 (61%) 12 (17%) 5 (7%) 10 (14%) 7
Plante M et al. Int J Gynecol Cancer. 2013 Jun;23(5):916-22.
• Conservative surgery (n = 247)
• Positive nodes = 13 patients (5.2%)
• Recurrence = 2 patients (0.8%)
• Death due to disease = 1 patient (0.4%)
• 73 pregnancies reported to date
Ramirez et al., Gyn Onc, 2014 Ramirez P. Gynecol Oncol 132:254, 2014
Less radical surgery
Meticulous/careful patient selection is of
utmost importance
Preoperative pelvic MRI
Expert pathology review
Noel P and Plante M. RadioGraphics 2014;34:1099-1119
Preoperative pelvic MRI
Noel P and Plante M. RadioGraphics 2014;34:1099-1119
Preoperative pelvic MRI
Noel P and Plante M. RadioGraphics 2014;34:1099-1119
In subcentimetre cervical cancers,
endovaginal MRI correlates with
pathology and is invaluable in assessing
patients for fertility-sparing surgery
Downey K. Gynecologic Oncology 133 (2014) 326–332
Expert pathological assessment
Diagnostic LEEP and cone
Margins status
Several pieces
Is the lesion truly < 2cm and < 10mm deep
Danger is to perform conservative
treatment in more extensive cervical
cancer and end-up with cancer recurrence
43 cases
37 IB1
15 births
Int J Gynecol Cancer 2014;24: 118- 123
Conclusion
Change FIGO classification?
Sub-divide stage IB1
• a: < 2 cm
• b: ≥ 2 cm
< 4 cm
NACT and Fertility Sparing
Radical trachelectomy
Recognized option for the management of
young women with IA2/IB1 cervical cancer
Mostly validated
• Lesions < 2 cm
NACT and Fertility Sparing
How to best manage young women with
larger size lesions/bulky IB1-IB2 (2-4 cm)
Preservation of fertility and ovarian function
Oncologic outcome
Obstetrical outcome
NACT and Fertility Sparing
27 y.o woman G0P0
Stage IB1
3.5 cm adenoca
Upfront Trach ?
NACT + FPS ?
NACT and Fertility Sparing
Management options for patients with
larger size lesions
• Upfront Radical Trachelectomy
• NACT followed by fertility-preserving
surgery (FPS)
NACT and Fertility Sparing
Upfront radical trachelectomy
Abdominal Trachelectomy
MSKCC
Comparison between 28 VRT and 15 ART
Length of parametrial excision statistically
wider with ART c/w VRT
• 3.97 cm vs 1.45 cm
ART can be performed
in patients with
larger size lesions
Einstein MH et al. Gynecol Oncol 2009; 112: 73
Abdominal Trachelectomy
MSKCC n=15
2/15 (13%) underwent conversion rad hyst
7/15 (47%) received adj RT or CT/RT
• Positives nodes
• Other intermediate risk factors
9/15 (60%) permanent loss of fertility and
ovarian function
Einstein MH et al. Gynecol Oncol 2009; 112: 73
Indications for adjuvant RT
LVSI Stromal Invasion Tumor Size
Positive Deep 1/3 Any
Positive Middle 1/3 > 2
Negative Superficial 1/3 > 5
Negative Deep or Middle 1/3 > 4
Sedlis criteria : needing 2 or more of these factors
- LVSI involvement
- Deep stromal invasion (middle or deep third)
- Size > 4 cm
Upfront ART: lesions > 2 cm
N Fertility
spared
Node
Positivity Recurrences Pregnancies
Wethington
, 2013
29 9 (31%) 13 (45%) * 1/29 (11%) 1/3
Lintner,
2013
45 31 (69%) 13 (29%) 4/31 (13%) ** 4/8
Liu, 2013 62 55 (89%) 6 (9.8%)
0 3/9
136 95 (70%) 32 (24%)
5/122 (5.3%) 8/20 (40%)
8/95 (8.9%)
8/136 (5.8%)
MSKCC: SLN mapping and ultrastaging
Hungarian series: 14 ptes who had rad hyst excluded from analysis
Plante M. Internat J Gynecol Cancer 2015 May;25(4):722-8.
Abdominal Trachelectomy
Wider parametria and more radical surgery
can be obtained with ART
ART can be performed in larger size lesions
Oncologic outcome good
Obstetrical outcome limited
High rate of adjuvant Tx post
trachelectomy
Impact on fertility and ovarian function
Impact on QoL
NACT + FPS
NACT option followed by fertility-
preserving surgery (FPS)
NACT + fertility preserving surgery
Our experience : 3 cases
Chemotx x 3 cycles (TIP)
Rad trachelectomy / nodes
Complete path response
2 residual dysplasia
1 completely negative
No recurrences
Plante M, et al. Gynecol Oncol, 2006; 101: 367
Bulky IB1 lesion
Neoadjuvant chemotherapy
Pre-chemo Post-chemo
NACT + fertility preserving surgery
N Chemotherapy
Regimen
Procedure Optimal Response
to NACT
(CR + OPR)
Node
Positivity
Maneo 21 TIP x 3 LPLND +
cone
17/21 (81%) 2
Plante 3 TIP x 3 LPLND +
RVT
3/3 (100%) 0
Marchiole 7 TIP/TEP x 3 LPLND +
RVT
4/7 (57%) 0
Lanowska 18 TIP/TP x 2-3
LPLND +
RVT
14/18 (78%) 2
Robova 28 CI q 10d x 3
CA q 10d x 3
LPLND +
SVT
17/28 (61%) 2
Total 77 55/77 (71%) 6/77 (7.8%)
Plante M. Internat J Gynecol Cancer 2015 May;25(4):722-8.
Recurrences Death Fertility
Preserved
Pregnancy/
Attempted
Pregnancy
Outcome
Maneo 0 0 16/21 (76%) 10/9 1 FTM
5 preterm
2 SVD (term)
2 CS (term)
Plante 0 0 3/3 (100%) 4/3 1 FTM
1 preterm , 2 term
Marchiole 0 0 6/7 (86%) 1/1 1 ongoing
Lanowska 1/18 (5.5%) 0 17/18 (94%) 7/5 1 FTM
1 ectopic
1 ongoing
2 preterm, 2 term
Robova 4/20 (20%) 2/20 (10%) 20/28 (71%) 13/10 1 FTM
2 STM
2 ongoing
3 preterm, 5 term
Total 5/69 (7.2%) 2/69 (2.9%) 62/77 (80%) 35/28 11 FT loss (31%)
11 preterm (31%)
13 term (37%)
Plante M. Internat J Gynecol Cancer 2015 May;25(4):722-8.
Buda A, Int J Gynecol Cancer 2015;25: 1468-1475
Response to NACT is a good surrogate endpoint of survival
in patients with LACC.
NACT + fertility preserving surgery
Substantial response to NACT
CR/OPR: 71%
Recurrence rate / death
Higher in Sub Optimal PR
Node positivity is much lower post NACT
Fertility preservation high: 80%
Fertility/obstetrical outcome good
NACT + fertility preserving surgery
N Fertility spared Recurrences Pregnancies/
attempting
Wethington, 2013 29 9 (31%) 1/29 (11%) 1/3
Lintner, 2013 45 31 (69%) 4/31 (13%) 4/8
Liu, 2013 62 55 (89%) 0 3/9
136 95 (70%) 5/122 (4.1%) 8/95 (8.9%)
N Fertility spared Recurrences Pregnancies
NACT/FPS
literature summary
77 62 (80%) 5/69 (7.2%) 35/28
35/62 (56%)
NACT and Fertility Sparing
Sooooo ?
Upfront Trach ?
or
NACT + FPS ?
Unresolved issues
Staging LN dissection prior to NACT ?
Simple vs radical trachelect post NACT ?
What is best chemotherapy regimen ?
NACT + fertility preserving surgery
Should a staging lymph node evaluation
be done prior to NACT ?
NACT + fertility preserving surgery
Laparoscopic nodal staging: n=18
12 node + : CT/RT
• 25% recurrence ; one DOD
6 node - : NACT + VRT
• 3: complete response
• 3: > 50% tumor size reduction
• No recurrence ; one successful pregnancy
Nodal staging allows triaging between high
and low recurrence risk ptes
Vercellino GF et al. Gynecol Oncol 2012; 126;325
NACT + fertility preserving surgery
Advantage of LN staging
Rule out patients with metastatic disease
Offer non-surgical treatment (CT/RT)
Disadvantage of LN staging
Exclude some patients with minimal lymph
node involvement who might have cleared
the LN mets with the NACT
NACT + fertility preserving surgery
IB2-IIA2 (n=304 ptes)
Procedure Node positivity
Primary surgery (154) 25.6%
NACT + surgery (150) 8.1%
Li R et al. Gynecol Oncol 2013;128(3):524-9.
Response rate to NACT was 72%
NACT + fertility preserving surgery
Should a radical or a simple
trachelectomy or a cone be done post
NACT ?
NACT + fertility preserving surgery
Simple / radical trachelectomy / cone post NACT
Very little data available following NACT
Trend towards less radical surgery in small
volume cervical cancer (< 2 cm)
Extrapolate data from upfront SVT ??
NACT + fertility preserving surgery
In good chemotherapy responders
Node negative patients
Minimal / no residual disease post NACT
The chances of finding occult parametrial
infiltration are probably very low
Cone / SVT sufficient ??
NACT + fertility preserving surgery
Optimal chemotherapy regimen
Optimal chemotherapy regimen
Taxol / Ifosfamide / Platinum (TIP)
Most widely used regimen
Toxicity of triple chemo regimen
Ifosfamide (alkylating agent)
• gonadotoxicity
Optimal chemotherapy regimen
Can cisplatin be switched for carboplatin ?
Optimal chemotherapy regimen
Systematic review
17 studies / 1181 patients
Recurrent or metastatic cervical cancer
Comparing cisplatin and carbo + taxol
Conclusion: carboplatin represents a valid and
less toxic alternative compared to cisplatin
Lorusso D . Gynecol Oncol 2014;133(1):117-23.
Optimal chemotherapy regimen
A randomized, phase III trial of paclitaxel plus
carboplatin (TC) versus paclitaxel plus
cisplatin (TP) in stage IVb, persistent or
recurrent cervical cancer: Japan Clinical
Oncology Group study (JCOG0505) (n=253)
Taxol / Carbo q 3 weeks
• Non-inferior in terms of OS
• More feasible
• Less toxic
Kitagawa R et al. J Clin Oncol 2015;33(19):2129-35
Optimal chemotherapy regimen
How about dose-dense chemotherapy ?
Optimal chemotherapy regimen
Dose-dense chemo regimen
Weekly Taxol and Carbo
• Taxol 60-80 mg/m2 and Carbo AUC 2 x 6 cycles
Locally advanced cervical cancer
Objective response rate (complete & partial)
• Ranges from 68-87 %
McCormack M. Br J Cancer 2013;108(12):2464-9.
Singh RB. Gynecol Oncol 2013;129(1):124-8.
Dose dense Taxol-Carbo
After 3rd cycle Pre-chemoTx
Dose dense regimen
Dose dense regimen (Prague protocol)
Cisplatin 75mg/m2 / Ifosf 2g/m2 (squamous)
Cisplatin 75mg/m2 / Doxo 35mg/m2 (adeno)
Q 10 days x 3 cycles
Interval from chemo to surgery: < 45 days
Response rate: 61%
Robova H et al. Gynecol Oncol 2014 135(2):213-6.
Courtesy of Lukas Rob, Prague
Pre chemotherapy After one cycle of chemo After 3 cycles of chemo
Neoadjuvant chemotherapy
Dose-Dense Prague Protocol:
N = 11
7 had lesions < 2 cm (63%)
CR 64%, PR 27%, PD 9%
10 pregnancies
One recurrence
3 chemo regimen used
- Dose Dense
- Taxol 60 / Carbo AUC 2.7 weekly x 9
Gynecologic Oncology 139 (2015) 447–451
Chemotherapy regimen
Italian
Q 3 weeks x 3
Taxol 175 mg/m2
Ifosfamide 5g/m2 Cisplatin 75 mg/m2
“Ovarian”
Q 3 weeks x 3
Taxol 175 mg/m2
Carbo AUC 6
Dose dense
Weekly x 9
Taxol 80 mg/m2 Carbo AUC 2
“Belgian”
Dose dense
Weekly x 9
Taxol 60 mg/m2
Carbo AUC 2.7
Prague regimen
Q 10d x 3
Ifosfamide 2g/m2
Squamous
Cisplatin 75 mg/m2
Prague regimen
Q 10d x 3
Adriamycin 35mg/m2
Adenoca
Cisplatin 75 mg/m2
9 weeks = 63 days EORTC 55994 regimen
Stage IB1 (2-4 cm) Cervical cancer treated
with Neoadjuvant chemotherapy followed by
fertility Sparing Surgery (CoNteSSa)
Marie Plante (NCIC)
Jeffrey Goh & Vivek Arora (ANZGOG)
Radical hysterectomy
SUMMARY
Trachelectomy: The Future ?
Trachelectomy
Simple
Trachelectomy
NACT + Simple
Trachelectomy
< 2 cm
> 2 cm
Radical Trachelectomy
2-3 cm
Evolution in the management of
cervical cancer
1900 1990 2000 1980 2010
Wertheim
Abd Rad Hyst
TP LN
dissection
Schauta
Vag Rad Hyst
Vaginal Rad
Trachelectomy
Abdominal Rad
Trachelectomy
RP LN
dissection
SLN
mapping
Cone &
SN ?
Neoadjuvant
Chemotx ?
Simple
Trach
& SN ?
Robotic Rad
Trachelectomy
Laparoscopic Rad
Trachelectomy
Next big issues
Chemotherapy in N+ patients ??
SLN mapping
SLN mapping
Gynecologic Oncology 139 (2015) 559–567
DFS: SLN vs LND
Quality of Life
Quality Assurance
Prognosis of LVM
SLN Alone
SLN + LND
N = 900
Lecuru F, Abu-Rustum N, Mathevet P, Plante M.
SLN mapping
Logical / intelligent compromise
Between no nodes at all and complete LND
Endoscopy Unit
Endoscopy Unit
0 or 30o scope
“pinpoint” button
activates NIR mode
ICG SLN mapping
Normal mode
Spy mode
NIR mode
Maintains normal tissue color
Can switch mode as often as needed
ICG SLN mapping
ICG SLN mapping
ICG does not tend to “leak out”
Detection rate much better in obese patients
ICG SLN mapping
Detection rate much better in bloody surgical field
ICG – Color Segmented Fluorescence (CSF)
ICG – Color Segmented Fluorescence
ICG – Color Segmented Fluorescence
ICG SLN mapping: first 50 cases
No isolated paraaortic node metastasis
No isolated paraaortic node metastasis
Plante M. Gynecol Oncol;137(3):443-7, 2015
ICG SLN mapping: first 50 cases
Plante M. Gynecol Oncol. 2015;137:443–447
Final pathology :
SLN: only lymphatic tissue
One non-SLN was found to have metastasis
True side-specific false negative
ICG SLN mapping: first 50 cases
Plante M. Gynecol Oncol;137(3):443-7, 2015
ICG SLN mapping: first 50 cases
Table4.Sentinellymphnodemetastasis(n=11)
Typeofmetastasis Frequency(%)
Macrometastasis 1(9%)
Micrometastasis 2(18%)
IsolatedTumorCells(ITC) 8(73%)
Plante M. Gynecol Oncol;137(3):443-7, 2015
22%
ICG SLN mapping: literature review
Plante M. Gynecol Oncol;137(3):443-7, 2015
N=513 (pooled data)
Detection rate: 96%
Sensitivity: 87%
Specificity: 100%
Journal of Minimally Invasive Gynecology, 2015, in press
SLN mapping
ICG currently not FDA approved for
interstitial injection
Lymphatic mapping
FILM Study
A Randomized, Prospective, Open Label, Multicenter
Study Assessing the Safety and Utility of PINPOINT®
Near Infrared Fluorescence Imaging in the Identification
of Lymph Nodes in Subjects with Uterine and Cervical
Malignancies who are Undergoing Lymph Node Mapping
Blue Dye
ICG
FILM study
FILM study
ICG - Pinpoint system
Advantages
Excellent safety profile
Maintains normal colored anatomy
Switch on/off NIR mode easily
CSF mode very useful
System is versatile
• Laparoscopic, robotic and open surgery
Conclusion
SLN mapping using endoscopic NIR
fluorescence imaging with ICG
Simple, easy to learn
High overall / bilateral detection rate
Cervical injection works well
Most practical approach for large scale
worldwide implementation
N= 645
Micromets: 39%
FNR 1.3%
- Bilateral SLNs
- Ultastaging
Gynecologic Oncology 127 (2012) 462–466
Less radical surgery
Prospective series
Simple vag hyst and nodes
102 patients (IA1 +LVSI, IA2, IB1 < 2 cm)
• IB1: 74% of cases
7 positives nodes (6.9%)
95 node negative patients
• No recurrence so far…
• Value of parametrectomy…???
Rob et al. Presented at ESGO meeting, 2011
Lakhman Y. Radiology: 2013:269, 149-58
Abdominal Trachelectomy
N Fertility not
preserved
Recurrence # preg /
# attempting
Wethington, 2012
(MSKCC, CR, MG)
101 30 (30%) 4 (4%) 28/38 (74%)
T1: (10%) ; T2: (19%) ; T3: (52%)
Nishio, 2009 71 10 (14%) 6 (10%)
5 > 2 cm
4/29 (14%)
Li, 2011 64 12 (19%) 0 2/10 (20%)
Muraji, 2012 23 3 (13%) 0 1/10 (10%)
Saso, 2012 30 0 3 (10%) 3/10 (30%)
Pareja, 2008 15 1 (6%) 0 3/6 (50%)
Ungar, 2005 33 3 (10%) 0 3/10 (30%)
Total 337 59 (17%) 13 (3.7%) 44/113 (39%)
Plante M. Int J Gynecol Cancer 23:982, 2013
Laparoscopic RT
N Abandoned Recurrences # pregnancy/
# attemps
Park, 2012 71 9 (13%) 7 (10%) N/A
Kim, 2010 27 6 (22%) 1 (4.5%)
3/6
Chen, 2008 16 1 (6%) 0 5/?
Hong, 2010 3 1 0 0
Cibula, 2005 1 0 0 0
Lee, 2003 2 0 0 0
Total 120 17 (14%) 9 (7%) 8
Plante M. Int J Gynecol Cancer 23:982, 2013
Robotic radical trachelectomy
n Fertility not
preserved
Recurrence Pregnancy
Nick, 2012 12 4* 0 1
Perrson, 2012 13 2 0 4/5
Hong, 2010 3 0 0 0
Burnett, 2009 6 1 0 0
Chuang, 2008 1 0 0 0
Geissler, 2008 1 0 0 0
Total 36 7 (19%) 0 5
* Conversion to rad hyst: + margin
Plante M. Int J Gynecol Cancer 23:982, 2013
NCCN Guidelines
NACT + fertility preserving surgery
Fertility preservation and obstetrical
outcome appear superior with NACT/FPS
Oncologic outcome comparable to ART
Patients with suboptimal response to NACT
have a higher rate of recurrences
Upfront ART: lesions > 2 cm
Wide variation in node positivity
9.5 to 45%
Variation in the Tx of node positive patients
CT/RT
Chemo alone
Cone/Trachelectomy and lymph node
Courtesy of Lukas Rob, Prague
Prague protocol (LAP-1): 2 steps procedure
- Laparoscopy, SN mapping and pelvic lymphadenectomy
- One week later, LN- : simple trachelectomy or large cone