SLN & Lymphadenectomy in early stage cervical cancer Lcuru F, - - PowerPoint PPT Presentation

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SLN & Lymphadenectomy in early stage cervical cancer Lcuru F, - - PowerPoint PPT Presentation

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Gynecologic Cancer InterGroup Cervix Cancer Research Network SLN & Lymphadenectomy in early stage cervical cancer Lcuru F, Mathevet P, Balaya V, Ng C, Delomnie M, Bonsang Kitzis H, Bats AS, Gosset M, Mimouni M, Nos C. Gynecologic

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Lécuru F, Mathevet P, Balaya V, Ngô C, Deloménie M, Bonsang Kitzis H, Bats AS, Gosset M, Mimouni M, Nos C.

Gynecologic and Breast Oncologic surgical Dept, Georges Pompidou European Hospital, Paris, France Faculté de Médecine, Paris Descartes University, Paris, France Lausanne University Hospital.

www.cancerologiegynecologique.eu

SLN & Lymphadenectomy in early stage cervical cancer

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

ECC: Risk factors of recurrence

– Large cervical tumor (>4cm) – Parametrial extension – Non squamous histology – Deep (>75%) stromal invasion – LVSI

Fuller A & al 1989 Schorge J & al 1997 Landoni F & al 1997 Lennox G & al 2017

–Lymph node metastases

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Prognosis = Nodes

  • Prognosis is different between N0 et N1 patients (macrometastases)*
  • Better prognosis in “occult” metastases vs macroscopic
  • Poorer prognosis with increasing number of nodes, if ≥ 2 (10% 5-year

DFS / node)

  • Prognosis linked to location of nodes (the highest the worst)
  • Prognosis of N+ depends of parametrial invasion
  • Ib – IIa (IIb), RH + PLN + RT(CT)

van Bommel P & al 1987 Delgado G & al 1990 Inoue T & al 1990 Suprasert P & al 2013 Tinga D & al 1990 Tsai C & al 1999

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Inoue 1990 Cancer Benedetti Panici 1996 GynOncol Lee K 2006 JOGR Horn 2008 GynOncol Gortzak Uzan 2010 GynOncol Achouri 2013 EJSO

Prognosis = nodes

  • 5 to 20% patients from Ia1 to IIa have metastatic lymph

nodes.

  • Only ONE node is invaded in 35-54.8% of patients pN1
  • Small size of the metastasis

➢ Median size of metastasis is 1.5 mm ➢ 22 to 38% measure less than 2mm ➢100% of metastases measure less than 8 mm

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

The SLN concept

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Check list

Reiffenstuhl G & al

  • Lymphatic drainage ?
  • Main pathway + variations ?
  • Accessible tumor ?
  • Tracer ?
  • Nodes accessible ?
  • Impact on patients treatment ?
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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Assessment

❖ Feasibility  ❖ Reproducibility  ❖ Diagnostic accuracy  * ❖ Anatomical information  ❖ Histological information (prognosis?)  ❖ Reduced morbidity  ❖ Similar prognosis ? ❖ Useful data ?

Altgassen G & al 2008 Lécuru F & al 2011 Plante M,Roy M & al 2011 Cormier B & al 2011

*: high NPV in case of bilateral detection

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

To maximize the Detection Rate

  • Selection of patients
  • Training cervical injection
  • Combined technique
  • SPECT-CT if isotope
  • Use of ICG
  • Training operative

detection

  • ≤4cm diameter
  • 20 cases***
  • No blue dye only
  • No planar LS
  • Be precise and patient

≥95% detection rate

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

≥95% detection rate

  • Location of the SN:

Senticol1 Senticol2 – External iliac/ obturator: 83,5% 85,8% – Para-aortic + presacral: 5,1% 2,6% – Common iliac: 8,5% 9,5% – Parametrium : 2,7% 1,1%

UPP: most of SLN IPP: less frequent

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

≥95% detection rate

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

≥95% detection rate

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

To Lower the FN rate

  • Stage Ia1 – IIa
  • No suspicious lymph node on pre-operative imaging and

per-operative assessment

  • Tumour size <40mm
  • Bilateral detection

FN rate: 1/1257 (0.08%)

Tax C & al 2015

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

MSKCC SLN algorithm

  • 8/122 (6.6%) : failed detection

= bilat LND

  • 23/122 (18.9%) : unilat

detection = unilat LND

  • 91/122 (94.6%) : bilat

detection.

  • NPV 100%

Cormier B & al 2011

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Quality assurance (SENTICOL)

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Blue Dye Isotope ICG Learning curve 10 - 15 10 - 15 <10 DR, bilat DR + ++ +++ Cost 25€ 373€ 45€ Regulatory No Complex No Risk ++ (<2%) + (<2/1000) Easy handling Yes Moderate Yes * Detection ergonomy Yes § Moderate $ Yes £ Delay inj- detection Short (15 min) Long Short (<10min) Obese patients + +++ +++ Control Ex vivo Imaging, ex vivo Ex vivo Leakage Yes No No Parametrium Risk FN Risk FN Good

  • * Possibility of re-injection
  • $ coordination with nuclear medicine
  • § Blue on the cervix and surrounding tissue
  • £ non visible without IR light
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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Imboden S & al 2015

ICG enhances DR and bilateral DR

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

SLN better than PLN

  • Well differentiated
  • LVSI neg
  • Histologic size < 13mm
  • LN met prevalence: 0.75%

Fagotti A & al 2016 Ferrandina G & al 2017

  • No node on preop MRI
  • SCC or aSCC
  • Histologic size < 20mm
  • LN met prevalence: 0.31%

pN1 pN0 ≤ 20mm 10% 90% > 20mm 12% 88%

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Cibula D et al. 2012

ITC and micrometastases

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

  • Location of the SN:

Senticol1 Senticol2 – External iliac/ obturator: 83,5% 85,8% – Para-aortic + presacral: 5,1% 2,6% – Common iliac: 8,5% 9,5% – Parametrium : 2,7% 1,1%

  • Unxecpected location = 16-18% patients
  • Senticol 1: 2 patients had a metastatic aberrant SN with all pelvic

nodes negative including after serial-sectioning and immunohistochemistry

Unexpected locations of the SN in the Senticol studies (139 and 206 patients)

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Senticol 2: PRIMARY END-POINT = MORBIDITY

related to the LYMPHATIC DISSECTION

Arm A (SLN) Arm B (CONTROL) P

Nb % Nb % Total Patients 105 100,0 101 100,0

Global lymphatic morbidity

33

31,4 52 51,5 0,0046

Major morbidity (grade 3 – 4)

1

1 6 5,9 0,061 Minor morbidity (grade 1 – 2)

32

30,5 50 49,5 0.0068

Mathevet P & al

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Mathevet P & al

Senticol 2: neurological symptoms

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Mathevet P & al

Senticol2: quality of life (SF36)

Physical score Psychic score

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Survival ?

  • SENTIX:

– Prospective observational study – on going

  • SENTICOL III

– International randomized controlled trial – starting

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Still indications for lymphadenectomy ?

  • Is there a place for patients with Ib2 or IIb

stages ?

  • Is there a place after neo-adjuvant

chemotherapy ?

  • Patients with pos SLN
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Gynecologic Cancer InterGroup Cervix Cancer Research Network

De-escalation in ECC

  • Laparoscopy, Trachelectomy, Radicality,

Neoadjuvant chemo, NSRH, SLN

  • N0 patients

– Maintain a good prognosis – Improve long term QoL

  • N1 patients

– More accurate information for a personalized treatment

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

Thank you

www.cancerologiegynecologique.eu fabrice.lecuru@aphp.fr patrice.mathevet@chuv.ch

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018

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Gynecologic Cancer InterGroup Cervix Cancer Research Network

Cervix Cancer Education Symposium, February 2018