surgical treatment of endometrial cancer...2014/03/05 · •in early stage ec,comprehensive...
TRANSCRIPT
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Fırat Ortaç,MD Ankara University Medical School,
Department of Gynecologic Oncology
Surgical Treatment of Endometrial Cancer
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Endometrial Cancer(EC)
The most common gynecologic malignancy
The 4th most common woman’s cancer (breast,lung,colorectal)
49,560 new cases → 8190 death (USA,2013)
Mostly early stage(75%)
Adenocancer(85%),USC(5-10%),Clear cell(5%)
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Types of EC
Type 1(80%)
Estrogen dependent
Endometroid adenocancer
63 y
70% stage I
5 y. surv.≈83%
Type 2
Estrogen unrelated
Non-endometrioid cancer
67y
50% advanced stage
5 y. surv.≈ 53% USC
57 % CC
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Revised FIGO Staging (2009)
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Mortality
Advanced stage disease (50% of all deaths)
High risk histology
Not comprehensive surgical staging?
Poor performance
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Prognostic Factors
Uterine
– MI
– LVSI
– Cervical
involvement
Extrauterine
– Adnexial
involvement
– Intraperitoneal
dissemination
– Peritoneal
cytology ??
– Lymph node
met.
Tumoral
- Histologic types
-Grade
-Tumor diameter
-Molecular
DNA ploidi
E , P
receptors
P53,PTEN
etc.
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Risk Definitions(GOG)
Risk Definition
Low Confined to uterus; MI (-) or ≤1/2
Intermediate
Confined to uterus MI >1/2, occult cx involvement One of poor prognostic factors (PPF) MI >1/3, G2-3, LVSI (+)
High-intermediate
50-69 Y; three of PPF ≥70 Y; two of PPF
High Stage II-IV, PSC or clear cell
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Endometrium CA : Lymphatic Drainage and Metastasis
• Primary => Pelvic lymph nodes • Pelvic lymph node (-) => isolated
paraaortic LN involvement 2% Onda. Br J Cancer 1977
Chen Gynecol Oncol 1985 Creasman. Cancer 1987
• Pelvik LN (+) • Advanced stage • MI >%50 • G3,High risk histology
Aortic LN met. risk
•Benedetti Panici. Int J Gynecol Cancer 1998
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Treatment
Surgery Adjuvant
Radiotx. Chemotx.
•Hormonal
•Debulking
•Before
•After
•Staging
•Cytotoxic
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Surgical Treatment
High risk factors
Comprehensive Surgical staging
Recurrence(local,dist.)
Adjuvant treatment
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Early Stage EC
•Peritoneal
cytology
•Exploration
Open Surgery
or
MIS
•TAH + BSO
•PPALND
Surgical Staging
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Topics of debate in surgical treatment of early stage EC
• LND to all patients?
• Type of LND ; sampling vs systematic?
• Only pelvic vs PABPLND?
• LND;therapeutic or diagnostic ?
• MIS vs Laparotomy ?
• Sentinel Lymph Node Concept?
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Topics of debate in surgical treatment of early stage EC
•LND to all patients? • Type of LND ; sampling vs systematic?
• Only pelvic vs PABPLND?
• LND;therapeutic or diagnostic ?
• MIS vs Laparotomy ?
• Sentinel Lymph Node Concept?
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LN Met. in EC
• # 422 • LND (-) (27%)
– Endometrioid (G1 ve G2), MI ≤1/2, PTD* ≤ 2cm
– Endometrioid and MI( -)(Grade ve PTD indepentendly)
• LN #; pelvik 36.5 ± 13.4, PA 17.4 ± 8.1 • LN Met (High risk group)
– Endometrioid 16%, nonedometrioid 40% – İzole pelvik 33%, izole PA 16%, pelvik+PA
51%
•*PTD: Primer tümör çapı
•Mariani A, Gynecol Oncol 2008
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No LND
Endometrioid (G1 ve G2), MI ≤1/2, PTD* ≤ 2cm
Endometrioid and MI(-) (independently from Grade ve PTD )
Mariani A, Gynecol Oncol, 2008
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Mayo 2010
If there is one of them; Extrauterine disease
Grade 3
Non endometrioid MI>50% Adnexiel met.
Yes No
BPPALND (non-endometrioid
omentectomy, appendectomy ,peritoneal biopsy)
One of them Tumor ≥ 2 cm and MI< 50% Cervical involv.
No
BPLND (frozen pelvic LN (+) PALND)
Operation
stop
EC
HYTERECTOMY (LS / LT / Robotic)
(cervical involv.; RH)
Yes
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G1
G2
G3
Myo>50% Myo≤50%
Mayo 2010
If ≤ 2 cm
If > 2 cm
Stop
Pelvic LND *
* PA LND, only if Pelvic Nodes Positive at FS
Orange Boxes
Black Boxes
Pelvic + PA LND
Black Boxes
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Frozen-Section(FS) and Fınal Pathology
• Grade: % 35
• MI : %28
• Cervical involvement:% 13
• LVSI :% 32
• Staging with intraoperative FS: 6.6 – 13% suboptimal
Kumar S, Cancer.(2011))
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Radiologic Examination
USG, CT, MRI
Sensitivity 29-90%
PET
Sensitivity 60%
•Horowitz NS, Gynecol Oncol, 2004; Kinkel K, Radiology, 1999; Rockall AG, J Clin Oncol, 2005
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Summary
LND to all patients
• Because of diagnostic inaccuracy of FS ,all patients with early stage EC should undergo comprehaensive surgical staging.
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Topics of debate in surgical treatment of early stage EC
• LND to all patients?
•Type of LND ; sampling vs systematic?
• Only pelvic vs PABPLND?
• LND;therapeutic or diagnostic
• MIS vs Laparotomy
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Type of LND
• Sampling
– Only 10% of LN : palpabl
– 37% of LN met. <2 mm
– Sufficient LN # ?
– 62% of PLN and 17% PALN mets. are missed out
• Systematic
– LN mets. and micromets. are taken out
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Therapeutic effect of LN counts
Chan JK, Cancer 2006 (SEER Data)
A: Low risk B: İntermediate C: High risk
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Topics of debate in surgical treatment of early stage EC
• LND to all patients?
• Type of LND ; sampling vs systematic?
• Only pelvic vs PAPLND? • LND;therapeutic or diagnostic
• MIS vs Laparotomy
![Page 25: Surgical Treatment of Endometrial Cancer...2014/03/05 · •In early stage EC,comprehensive surgical staging except low risk group •In advanced EC:Cytoreductive surgery •MIS](https://reader034.vdocuments.mx/reader034/viewer/2022042408/5f2490e0f315265d1630bc01/html5/thumbnails/25.jpg)
Only Pelvic or Pelvic+Paraaortic
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What is the incidence of isolated paraaortic nodal metastasis in patients with negative
pelvic nodes
•2-3%
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• Sol ovarian ven
•IMA
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Topics of debate in surgical treatment of early stage EC
• LND to all patients?
• Type of LND ; sampling vs systematic?
• Only pelvic vs PABPLND?
• LND;therapeutic or diagnostic ?
• MIS vs Laparotomy ?
• Sentinel Lymph Node Concept?
![Page 29: Surgical Treatment of Endometrial Cancer...2014/03/05 · •In early stage EC,comprehensive surgical staging except low risk group •In advanced EC:Cytoreductive surgery •MIS](https://reader034.vdocuments.mx/reader034/viewer/2022042408/5f2490e0f315265d1630bc01/html5/thumbnails/29.jpg)
Low risk Group
LND and Survival
Kim HS, Jpn J Clin Oncol 2012
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İntermediate,High Risk Group; LAND and Survival
Kim HS, Jpn J Clin Oncol 2012
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SEPAL Study (Survival Effect of Para-Aortic
Lymphadenectomy in endometrial cancer)
•Todo Y, Lancet, 2010
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LN Metastasis; Prognostic Significance
Recurrence;LN (+) > LN (-) : 6X
Morrow CP, Gynecol Oncol 1991
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LND -Survival
LND, no effect on survival in low risk group
LND,positive effect on survival in intermediate
and high risk group
Kim HS, Jpn J Clin Oncol 2012 (Metaanalysis)
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Lymphadenectomy-Summary
Correct question
• Whom
• When
Wrong question
• Yes
• No
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Surgical Treatment in Stage II
Clinical
Occult ECC (+)
•Cervical adenocarcinoma should be excluded
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Clinical Stage II EC
•Extrafascial hysterectomy + Staging + Rtx
•Radical Hysterectomy + Staging +Adj. Rtx (if indicated)
•T R E A T M E N T
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Stage II; Radical Hys. vs Simple Hys.
Simple Hys. Radical Hys.
No of patients 315 127
LA (%) 233 (74) 126 (99.2)
Adj RT (%) 220/258 (85) 43/119 (36)
Rec(%) 57 (18) 10 (7.8)
Local rec.(%) 27 (8.5) 3 (2.4)
Distant rec.(%) 34 (11) 7 (5.5)
Death (%) 16/136 (12) 2/59 (3.4)
•Eltabbakh GH, Gynecol Oncol 1999; Calvin DP, Am J Clin Oncol 1999; Feltmate CM, Gynecol Oncol 1999;
•Mariani A, Gynecol Oncol 2001; Sartori E, Int J Gynecol Cancer 2001; Ayhan A, Gynecol Oncol 2004
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Advanced Stage EC
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Advanced stage& Treatment
Cytoreductive Surgery
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Advanced Stage S U R G E R Y
•Exp.
•TAH +
BSO •Oment.
•Lmp.
•Debulk. •Eradication of ALL
Macroscopic tumors
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r
Microscopic 40,6 mo
1 cm or less 34 mo
More than 1 cm 11 mo
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Advanced Stage EC
MORBIDITY %16 -24
Lambrou, Oncol, 2004 Gynecol Ayhan, Int J Gynecol Cancer, 2002
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Topics of debate in surgical treatment of early stage EC
• LND to all patients?
• Type of LND ; sampling vs systematic?
• Only pelvic vs PABPLND?
• LND;therapeutic or diagnostic ?
•MIS vs Laparotomy ? • Sentinel Lymph Node Concept?
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Role of MIS in Endometrial Carcinoma
Application
Complications
QOL
Oncogic out-come and safety
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Laparoscopy
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Early stage endometrial cancer
MIS
Evaluation of peritoneal cavity
Peritoneal cytology
•MI > %50
•G3
•Cervical involvement
•Adnexal involvement
•Laparoscopic lymphadenectomy
•LAVH or LH
•Prognostic factors
•IP disease
•L/T
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•Laparoscopy is associated with similar or lower complication rates compared to laparotomy
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Laparotomy vs Laparoscopy
Author Recurrence (%) DFS(%)
LPT LS LPT LS
Eltabbakh GH 10.5 7 92 90
Holub Z 6.8 6.2 93.2 93.7
Langebrekke A 4.1 0 95.9 100
Kuoppala T 2 2.5 95 100
Magrina JF, Curr Opin Obstet Gynecol, 2005
•Recurrence and DFS are similar between laparoscopy and laparotomy group
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Quality of Life
0
20
40
60
80
bas
eline
1 M
3 M
6 M
Laparotomy
Control
Laparotomy
Laparoscopy
Control
Zullo F, Am J Obstet Gynecol 2005
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Robotic Surgery
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• 415 EC
– 183 robotic (97% pelvic, 73% paraaortic LND)
– 232 laparoskopic (%94% pelvic, %63 paraaortic LND)
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•Recurrence and over-all survival are similar in both group
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MIS in EC SUMMARY
• If performed experienced
surgeon – Similar oncologic outcome with
laparotomy
– Short hospital stay
– Better QOL
– Early adjuvant treatment
– Preferable in morbid obese patients
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Topics of debate in surgical treatment of early stage EC
• LND to all patients?
• Type of LND ; sampling vs systematic?
• Only pelvic vs PABPLND?
• LND;therapeutic or diagnostic ?
• MIS vs Laparotomy ?
•Sentinel Lymph Node Concept?
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Why SLN mapping?
• Avoid excessive lymphadenectomy and reduce operative time and morbidity
• Proper tailoring of the extent of lymphadenectomy
• Increase the detection rate of positive node(IHC,ultrasectioning)
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•Current Practice
•“LESS IS MORE”
•Sentinel Node Mapping •Lymphadenectomy
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Uterine SLN Complex Lymphatic Drainage
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Debate Cervical vs. Fundal
Injections vs. Hysteroscopic
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Blue Dye Cervical Injection Under Anesthesia Isosulfan Blue 1% (50mg/5ml)
2cc at 3 O’clock & 2cc at 9 O’clock
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Improving SLN detection rates How many cases are needed?
• After the first 30 cases – Rate of successful mapping increased from 77% to 94%
(P=0.03)
•Khoury-Collado F, et al. Gynecol Oncol 2009
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MSKCC Results
Number of cases: 266
SLN Detection rate: 84%
•Khoury-Collado F, et al. Gynecol Oncol 2011
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SLN Mapping for EC
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Sentinel node mapping(Algorithm)
• After applying the algoritm,the false negative rate for detecting nodal metastasis dropped from 15% to 2%
Barlin et al .Gynecol Oncol 2012;125:531-5
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Recurrence
Stage (%)
Stage I 15
Stage II-IV 25-45
Overall 15
Site (%)
Distant 65
Vagina 6
Pelvic 15
Aalders, Gynecol Oncol, 1983
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Recurrent EC-Treatment
• Patient’s performance
• Primary treatment
• Site of recurrence
Surgery XRT
HORMONAL THERAPY
CHEMOTHERAPY AND TARGETED THERAPY
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Local Recurrence
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Isolated Lymphatic Recurrence
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Isolated intestinal recurrence
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Pelvic Exenteration (Pelvic reccurence)
Endometrial cancer ?
Total exenteration is better than standart debulking surgery plus XRT has not shown
5Y OS; %30-56
Major surgical complication;60-80% Fistula, abcess , septisemia
Barakat RR, Gynecol Oncol,1996; 1999; Morris M, Gynecol Oncol, 1996;
Kuten A, Int J Radiat Oncol Biol Phys, 1989
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Peritoneal Carcinomatosis
• Peritoneal Carcinomatosis
Cytoreductive surgery?????
Chemo.or Hormanal Therapy(G1)
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Surgical Treatment of EC Summary
• In early stage EC,comprehensive surgical staging except low risk group
• In advanced EC:Cytoreductive surgery
• MIS has similar oncologic outcome,less complications,better QOL vs open surgery
• MIS or vaginal Hys. is preferable in obese patients with EC because of morbidity
• Sentinel LN mapping is applicable but not standart yet.
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Thanks!
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Pelvic Lymphadenectomy
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Paraaortic Lymphadenectomy
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Stage
Stage %
I 73
II 11
III 13
IV 3
Levine DA. Cancer J 2002; 8:31-40
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Cytoreduction in Stage IV EC
Residual tumor is prognostic for outcome Neoadj Ctx ? Postoperative standard Treatment?
Relatively small number of patients
All studies are retrospective
•C O N C L U S I O N
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MIS vs LPT Primary Results
Recurrence-free Survival
(RFS) Overall Survival (OS)
•MIS: Minimal invaziv cerrahi, LPT: Konvansiyonel cerrahi
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NCCN Guideline
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Follow-up and Recurrence
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Recurrence
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LND; Sampling vs Systematic
• # 11.443
• Stage I 78.7%, Stage II 10.3%, stage III 11.0% • Grade 1 31.5%, grade 2 40.6%, grade 3 24.3% • Detection of one positive LN involvement %45
• Low risk group (Stage IA, all G; stage IB G1,2) 5Y DFS ; no advantage
• Intermediate and high risk group; 5 Y DFS – LN #1:75.3% – LN #6-10: 84.1% – LN #>20: 86.8% (p<0.001)
•Chan JK, Cancer, 2007
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Local Recurrence
local recurrence, usually at vaginal cuff
Confirmation by radiologic exam(PET-CT,MRI)
• lokal recur.in RT-naive site: < 3cm – EBPRT /+,- Brachitherapy
> 3 cm:Debulking /+,- IORT
Neoadjuvan KT +Debulking or RT
• Local recur. in previously RT: Exenteration ,Debulking +IORT