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