Valor de la biopsia del ganglio centinela en cáncer endometrial

Presentación del tema: "Valor de la biopsia del ganglio centinela en cáncer endometrial"— Transcripción de la presentación:

1 Valor de la biopsia del ganglio centinela en cáncer endometrial
Am J Clin Oncol 2016; The Role of Lymphadenectomy Versus Sentinel Lymph Node Biopsy in Early-stage Endometrial Cancer A Review of the Literature. Roi Tschernichovsky, BGC tasa detección alta pocos falsos negativos Aumento detección de metástasis por ultrestadificación Pocos datos sobre resultados oncológicos a largo plazo sobre BGC A corto plazo supervivencia general o supervivencia libre de enfermedad como LND Conclusiones: ganglio centinela es una opción alternativa a la LND para determinar la afectación ganglionar en cáncer de endometrio inicial con menos morbilidad y más preciso Jueves, 3 de noviembre 2016 33 Reunión Nacional de la Sección de Ginecología Oncológica y Patología Mamaria

2 1º estudio: BGC en cáncer endometrio
1996 15 pacientes Laparotomía Trazador azul isosulfan Inyección subserosa Tasa detección 67% Tasa falsos negativos 50% (2/4) Implicados ganglios pélvicos y aórticos GYNECOLOGIC ONCOLOGY 62, 169–173 (1996) Intraabdominal Lymphatic Mapping to Direct Selective Pelvic and Paraaortic Lymphadenectomy in Women with High- Risk Endometrial Cancer: Results of a Pilot Study W. BURKE, M.D., CHARLES LEVENBACK, M.D., CARMEN TORNOS, M.D.,* MITCHELL MORRIS, M.D., J. TAYLOR WHARTON, M.D., AND DAVID M. GERSHENSON, M.D. Department of Gynecologic Oncology and *Division of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 Artículo corto. 3 paginas, 1 de fotos y 9 referencias bibliográficas Mapeo 10/15 pacientes 31 ganglios: 15 aórticos , todos por encima de AMI, 6 iliaco común y 12 pélvicos Large-caliber lymphatic channels coursing above the ies was not attempted. limits of the dissection were routinely observed. 4 casos positivos: 2 en SN, 1 caso sin mapeo 1 aórtico mapeo neg y obturador pos. It is obvius that the lymphatic drainage patterns of the uterus are much more complex than those observed in mapping studies of cutaneous malignancies In our uterine cases, bilateral lymphatic channels in the infundibulopelvic and broad ligaments were seen in every patient. As a result, multiple nodes at widely separated anatomic sites were identified. Observaciones interesantes: No blue paraaortic nodes were identified below the level of the origin of the inferior mesenteric artery large-caliber lymphatic channels were often seen traversing both the pelvic and paraaortic areas without leading into an identifiable node. there is such wide variation in the location of pelvic nodes with dye uptake that attempts to limit the extent of nodal sampling to a small, defined anatomic area are not likely to be feasible the patient with extensive gross lymphadenopathy demonstrated no uptake of dye into nodes. Lymphatic mapping may not be applicable in such situations Burke TW, et al. Gynecologic Oncology Volume 62, Issue 2, August 1996, Pages

3 ESMO–ESGO–ESTRO consensus conference on endometrial cancer
Recommendation 5.3. Level of evidence: IV Retrospective cohort studies or case–control studies Strength of recommendation: D Moderate evidence against efficacy or for adverse outcome, generally not recommended Consensus: 100% yes (37 voters) SLND is still experimental, but large series suggest that it is feasible. SLND increases the detection of lymph nodes with small metastases and isolated tumour cells; however, the importance of these findings is unclear Annals of Oncology 27: 16–41, 2016 International Journal of Gynecological Cancer & Volume 26, Number 1, January 2016 Radiotherapy and Oncology 117 (2015) 559–581

4 La linfadenectomía ha sido la base en el diagnóstico de la enfermedad metastásica, pero se asocia a morbilidad. The concept of a sentinel lymph node (SLN), the node(s) most likely to harbor the first metastasis from the primary tumor, was first introduced in 1960 following observations of parotid gland carcinoma. It was later described in 1977 with the addition of lymphangiography in patients with penile carcinoma, and has since been incorporated into the routine management of breast cancer, cutaneous melanoma, and vulvar carcinoma, allowing for lowered morbidity without compromising therapy. Histerectomía total con salpingo-ooforectomía bilateral y la estadificación quirúrgica completa mediante disección de los ganglios linfáticos ha sido el estándar de atención recomendado para el cáncer de endometrio desde 1985 Linfadenectomia se propuso con 2 objetivos: to identify patients with nodal spread who might benefit from adjuvant therapy; to eliminate occult metastatic disease, which would have been overlooked with hysterectomy alone 2 recent randomized controlled trials failed to demonstrate a survival benefit ASTEC (A Study in the Treatment of Endometrial Cancer) 1408 pacientes High-risk and advanced-stage patients benefit from chemotherapy, which has been shown to prolong survival in randomized controlled trials

5 2016 Gran Variabilidad en la Práctica Quirúrgica
No estadificación Según histología y grado prequirúrgico Según biopsia intra-operatoria del útero Según biopsia inta-operatoria de la linfadenectomía pélvica Según RM, +/- TC Estadificación de todos los CE mediante BGC Estadificación de todos los CE

6 ESMO–ESGO–ESTRO consensus conference on endometrial cancer
… the role of lymphadenectomy in early endometrial cancer is unclear and controversy remains regarding the indications for, the anatomic extent of, and the therapeutic value of lymphadenectomy in the management of the disease. The definition of an adequate lymphadenectomy has not been standardised… …it has been shown that para-aortic nodes may be positive in the absence of positive pelvic nodes, suggesting that para-aortic lymph nodes should be removed in cases where a lymphadenectomy is indicated Annals of Oncology 27: 16–41, 2016 International Journal of Gynecological Cancer & Volume 26, Number 1, January 2016 Radiotherapy and Oncology 117 (2015) 559–581

7 ESMO–ESGO–ESTRO consensus conference on endometrial cancer
Recommendation 5.2: If a lymphadenectomy is performed, systematic removal of pelvic and para-aortic nodes up to the level of the renal veins should be considered Level of evidence: IV Strength of recommendation: B Consensus: 91.9% (34) yes, 2.7% (1) abstain, 5.4% (2)no (37 voters). Annals of Oncology 27: 16–41, 2016 International Journal of Gynecological Cancer & Volume 26, Number 1, January 2016 Radiotherapy and Oncology 117 (2015) 559–581

8 ESMO–ESGO–ESTRO consensus conference on endometrial cancer
5.4: Lymphadenectomy is a staging procedure and allows tailoring of adjuvant therapy Level of evidence: III Strength of recommendation: B Consensus: 100% yes

9 ESMO–ESGO–ESTRO consensus conference on endometrial cancer
5.4: Lymphadenectomy is a staging procedure and allows tailoring of adjuvant therapy Level of evidence: III Strength of recommendation: B Consensus: 100% yes 5.5: Patients with low-risk endometrioid carcinoma (grade 1 or 2 and superficial myometrial invasion <50%) have a low risk of lymph node involvement, and two RCTs did not show a survival benefit. Therefore, lymphadenectomy is not recommended for these patients Level of evidence: II Strength of recommendation: A Consensus: 100% yes

10 ESMO–ESGO–ESTRO consensus conference on endometrial cancer
5.4: Lymphadenectomy is a staging procedure and allows tailoring of adjuvant therapy Level of evidence: III Strength of recommendation: B Consensus: 100% yes 5.5: Patients with low-risk endometrioid carcinoma (grade 1 or 2 and superficial myometrial invasion <50%) have a low risk of lymph node involvement, and two RCTs did not show a survival benefit. Therefore, lymphadenectomy is not recommended for these patients Level of evidence: II Strength of recommendation: A Consensus: 100% yes 5.7: For patients with high risk (grade 3 with deep myometrial invasion >50%), lymphadenectomy should be recommended Level of evidence: IV Strength of recommendation: B Consensus: 73.0% (27) yes, 8.1% (3) abstain, 18.9% (7) no (37 voters)

11 ESMO–ESGO–ESTRO consensus conference on endometrial cancer
5.4: Lymphadenectomy is a staging procedure and allows tailoring of adjuvant therapy Level of evidence: III Strength of recommendation: B Consensus: 100% yes 5.5: Patients with low-risk endometrioid carcinoma (grade 1 or 2 and superficial myometrial invasion <50%) have a low risk of lymph node involvement, and two RCTs did not show a survival benefit. Therefore, lymphadenectomy is not recommended for these patients Level of evidence: II Strength of recommendation: A Consensus: 100% yes 5.6: For patients with intermediate risk (deep myometrial invasion >50% or grade 3 superficial myometrial invasion <50%), data have not shown a survival benefit. Lymphadenectomy can be considered for staging purposes in these patients Level of evidence: II Strength of recommendation: C Consensus: 100% yes 5.7: For patients with high risk (grade 3 with deep myometrial invasion >50%), lymphadenectomy should be recommended Level of evidence: IV Strength of recommendation: B Consensus: 73.0% (27) yes, 8.1% (3) abstain, 18.9% (7) no (37 voters)

12 ¿Cuál es la estrategia ideal para estadificar el cáncer endometrial?
Charles Levenback Rules: 2012 IGCS Vancouver Acceso quirúrgico mínimamente invasivo No precise estudio patológico intraoperatorio Factible en la mayoría de los casos Técnicamente sencillo Baja morbilidad Ratio coste beneficio aceptable Esté validado

13 ¿Cuál es la estrategia ideal para estadificar el cáncer endometrial?
Charles Levenback Rules: 2012 IGCS Vancouver Acceso quirúrgico mínimamente invasivo No precise estudio patológico intraoperatorio Factible en la mayoría de los casos Técnicamente sencillo Baja morbilidad Ratio coste beneficio aceptable Esté validado Quizás la BGC sea el procedimiento que más se acerca a cumplir la lista actualmente

14 Problemas con la BGC en CE
No está estandarizado Trazador Lugar de inyección Dosis Volumen Tiempo

15 ¿Qué trazador utilizar?
Azul Tecnecio ICG Barato Fácil disponibilidad Uso intra-operatorio Obesidad  Alergias Caro Manipulación especial Inyección pre-cirugía No se ve SPECT-CT Colaboración medicina nuclear Caro por equipamiento inicial Uso intra-operatorio Buena visión canales linfáticos Tasa detección alta Spect ct correlación baja Combinaciones

16 ¿Qué trazador utilizar?
Ideal Tasa detección alta Sin falsos negativos Nº limitado de GC Fácil de manejar Precio ajustado Procedimiento sencillo Con tecnecio No se ven los canales linfáticos Cada ganglio solo se visualiza indirectamente Algunas zonas son difíciles de escanear con la sonda, que es muy direccional Se necesita la linfoescintografía (SPECT-CT) El procedimiento es menos cómodo para la paciente A veces la logística con medicina nuclear es complicada How J et al. Gyn Oncol 2015

17 ¿Que trazador utilizar?
En cáncer de mama. 134 pacientes 06/ /2013 246 GC Ventajas del ICG Inyección en quirófano Sin participación previa de medicina nuclear Sin linfoescintografía Más barato Visión directa “The present study has validated the ICG method by demonstrating that it is statistically non-inferior to the goldstandard method that used Tc-labeled albumin, allowing us to conclude that the ICG method can be used as a reliable and safe alternative to the radiotracer method. Conclusions The ICG method has previously been shown to be surgically simple procedure that identifies axillary SNs in breast cancer patients, without the use or radiopharmaceutical. The present study has validated the ICG method by demonstrating that it is statistically non-inferior to the goldstandard method that used Tc-labeled albumin, allowing us to conclude that the ICG method can be used as a reliable and safe alternative to the radiotracer method. This finding is potentially of major importance in clinical practice since the ICG method has advantages over the current gold standard radiotracer method including (a) direct implementation in the operating room and (b) no prior preparation by, or involvement of, nuclear medicine physicians. The lack of need for a nuclear medicine department will appeal to centers without such a department. We did not investigate costs in the present study. However it is likely that the ICG method will cost less than the radiotracer method since nuclear medicine personnel are not required and pre-operative radiotracer injection and lymphoscintigraphic SN identification are eliminated. The disadvantages of the technique are that a separate incision is preferred to identify and isolate the SN, and that the sentinel node is not always visualized transcutaneously before the incision so sentinel node location is not always available before the incision. Furthermore, extra-axillary sentinel nodes (e.g. those in the intramammary chain) are not visualized as readily as with lymphoscintigraphy. The indocyanine green method is equivalent to the 99mTc-labeled radiotracer method for identifying the sentinel node in breast cancer: A concordance and validation study B. Ballardini a, *, L. Santoro b , C. Sangalli a , O. Gentilini a , G. Renne d , G. Lissidini a , G.M. Pagani a , A. Toesca a , C. Blundo a , A. del Castillo a , N. Peradze a , P. Caldarella a P. Veronesi a,c a Division of Breast Surgery, European Institute of Oncology, Via Ripamonti 435, Milan, Italy b Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy c University of Milan, School of Medicine, Milan, Italy d Division of Pathology, European Institute of Oncology, Milan, Italy Ballardini B, et al. EJSO 39 (2013)

18 ¿Donde inyectar el trazador?
En fondo Peritumoral Cervical Acceso fácil Tasa de detección bilaterales altas en pelvis Detección aórtica baja ( 2% superficial, 17 % profunda) Cormier B, Rozenholc AT, Gotlieb W, et al. Sentinel lymph node procedure in endometrial cancer: a systematic review and proposal for standardization of future research. Gynecol Oncol. 2015;138:478–485 Cervical, superficial o profundo

19 Cérvix Submucosa Subserosa 20 estudios TD 84% TD aórtica 7% 8 estudios
Cérvix es el lugar de inyección más utilizado, más reproducible y fácil. Poca TD área aórtica 20 estudios TD 84% TD aórtica 7% 8 estudios TD 78% TD aórtica 59% 5 estudios TD 72% TD aórtica 28,9%

20 Nº medio ganglios centinelas
Doble punción Cérvix Fondo uterino A través del cérvix Aguja protegida Profundidad controlada TASA DETECCIÓN GLOBAL 103/111 93% PELVICA 99/111 89% P. BILATERAL 68/111 61% AÓRTICA 66/111 59,5% AÓRTICA SOLO 4/111 4% Nº medio ganglios centinelas PELVICOS 2,8 AÓRTICOS 2,3 TOTALES 4,1

21 Metástasis aórtica aislada
Authors Year N P(−)/PA(+) when considering pelvic LNs (−) patients Chen 1983 74 3/66 (4.5%) Creasman 1987 GOG 33 621 12/563 (2.1%) Morrow 1991 895 18/802 (2.2%) Lanson 1993 50 0/48(0.0%) Ayhan 1995 209 6/179(3.4%) Fanning 1996 60 Not shown Yokoyama 1997 63 4/49 (8.2%) Onda 173 2/145 (1.4%) Hirahatake 200 2/160 (1.3%) McMeekin 2001 607 8/568 (1.4%) Mariani 2004 566 5/229 (2.2%) Nomura 2006 155 4/105 (3.8%) 2008 281 9/233 (3.4%) Hoekstra 2009 1487 7/1409 (0.5%) Lee 349 7/264 (2.7%) Fujimoto 355 7/313 (2.2%) Abu-Rustum 847 12/734 (1.6%) Chiang 2011 171 2/156 (1.3%) Total 7163 103/6024 (1.7%) Chiang AJ. Gynecol Oncol 2011

22 Metástasis aórtica aislada
Authors Year N P(−)/PA(+) when considering pelvic LNs (−) patients Chen 1983 74 3/66 (4.5%) Creasman 1987 GOG 33 621 12/563 (2.1%) Morrow 1991 895 18/802 (2.2%) Lanson 1993 50 0/48(0.0%) Ayhan 1995 209 6/179(3.4%) Fanning 1996 60 Not shown Yokoyama 1997 63 4/49 (8.2%) Onda 173 2/145 (1.4%) Hirahatake 200 2/160 (1.3%) McMeekin 2001 607 8/568 (1.4%) Mariani 2004 566 5/229 (2.2%) Nomura 2006 155 4/105 (3.8%) 2008 281 9/233 (3.4%) Hoekstra 2009 1487 7/1409 (0.5%) Lee 349 7/264 (2.7%) Fujimoto 355 7/313 (2.2%) Abu-Rustum 847 12/734 (1.6%) Chiang 2011 171 2/156 (1.3%) Total 7163 103/6024 (1.7%) 103/6024 (1,7%) Linfadenectomia aórtica es un desafío No hay consenso Límites / templates Grado indicaciones complicaciones mayores No es factible en muchos LRP de rescate (basado en plantillas GU) es estandarizada Chiang AJ. Gynecol Oncol 2011

23 Metástasis aórtica aislada
Autor Hoekstra MSKCC Mariani Creasman McMeekin Lap 2 Pacientes 1487 1942/847 566/337/92 621 607 2616/971 Años N(+) 85 (6,9%) 125 (14,7%) 54 70 (11%) 47 (8%) 65 (6,69%) N(+) aort aislada 7 (8,23%) 0,5 12 (9,6%) 1,6 5 (9,25%) 2,2 12 (17%) 2,1 8 (17%) 1,4 12 (18,5%) 2,3 N(+)pelvis 113 49 36 20 31 N(+) p+a 24 14 22 19 Media g. pelvis 9 (0-30) 16 (1-80) 16 (1-55) 16(2-35) 18(12-24) Media g. aorta 2 (0-12) 5 (1-32) 6 (1-43) 7 (0-18) 7(4-11) Nodal Metastasis Risk in Endometrioid Endometrial Cancer. Michael R. Milam OBSTETRICS & GYNECOLOGY VOL. 119, NO. 2, PART 1, FEBRUARY 2012 Pelvic and Periaortic Nodal Metastasis Risk in High-Risk Patients Periaortic Lymph Nodes No(n=551) Yes (n=31) Positive P< .001 No (n532) (520) (12) Yes (n50) (31) (19)

24 Metástasis aórtica aislada
321 endometrioides N (+) 27 (8,4%) Solo pelvis 3 Pelvis+Aorta 15 Solo aorta 9 (2,8%) N(-) 294 9/27 Osi Donostialdea

25 Ultraestadificación No guías clínicas claramente establecidas aún para la ultraestadificación Kim Ballester Desai Niikura Donostia Pacientes 508 125 120 100 111 Microm. 4 7 5 3 CTA 19 1 LVMD 4,5% 6,4% 4% 8% 9 % LVMD N(+) 36% 40% 50% 44% 47% The clinical significance of low-volume metastases in EC is unclear. La proporción de enfermedad ganglionar metastásica diagnosticada por ultraestadificación es alta

26 5% Ultraestadificación
No guías clínicas claramente establecidas aún para la ultraestadificación Kim Ballester Desai Niikura Donostia Pacientes 508 125 120 100 111 Microm. 4 7 5 3 CTA 19 1 LVMD 4,5% 6,4% 4% 8% 9 % LVMD N(+) 36% 40% 50% 44% 47% The clinical significance of low-volume metastases in EC is unclear. La proporción de enfermedad ganglionar metastásica diagnosticada por ultraestadificación es alta 5%

27 Bajo riesgo Linfadenectomía BGC
Recommendation 5.5: …Therefore, lymphadenectomy is not recommended for these patients ¿Puede ser una alternativa a la NO linfadenectomía en estas pacientes? Mediante BGC y ultra-estadificación, ¿ podríamos aumentar la detección de metástasis? ¿Nos podría explicar algunos casos de CE inicial que recidivan? ¿Y proponer tratamientos complementarios? SEER 19329 pacientes 4095 bajo riesgo 1,4% N(+) Most patients with endometrial cancer present at an early clinical stage with low risk for nodal metastases, estimated at 3% to 5% for well-differentiated tumors with only superficial invasion of the myometrium Kosary CL. Cancer of the corpus uteri. In: Ries LAG, Young JL, Keel GE, et al, eds. SEER Survival Monograph: Cancer Survival Among Adults: US SEER Program, , Patient and Tumor Characteristics. Bethesda, MD: National Cancer Institute, SEER Program; 2007 Creasman WT, Morrow CP, Bundy BN, et al. Surgical pathologic spread patterns of endometrial cancer. Cancer. 1987;60: 2035–2041. Algoritmo Clínica Mayo The algorithm was retrospectively validated in a 2011 study of 602 women, and identified those patients who would not benefit from LND with a 98.2% negative predictive value (NPV). Convery PA, Cantrell LA, Santo ND, et al. Retrospective review of an intraoperative algorithm to predict lymph node metastasis in low-grade endometrial adenocarcinoma. Gynecol Oncol. 2011;123:65–70. low concordance rate of pathology results among preoperative, intraoperative (frozen section), and posthysterectomy specimens. LND-associated Morbidity Lymphedema following LND for endometrial cancer staging was 23% when compared with hysterectomy alone. 1.9% rate of intraoperative complications including ureteral, bowel, and vascular injuries and a 3.6% rate of early postoperative events including hemoperitoneum, pelvic abscess, and sepsis. TABLE 2. Proposed Criteria for Omitting LND in Endometrial Cancer Source Criteria MayoClinic Criteria for omission of pelvic LND Endometrioid histology Grade 1-2 <50% myometrial invasion (pathology)* Tumor diameter r2 cm (pathology) No intraoperative evidence of metastatic disease No cervical involvement Criteria for omission of para-aortic LND <50% myometrial invasion (pathology) No positive pelvic lymph nodes Todo Criteria for possible omission of pelvic LND Nonserous histology Tumor volume index <25 (MRI) Preoperative serum CA-125 < 70 U/mL (age < 50) Preoperative serum CA-125 < 28 U/mL (ageZ50) Tumor volume index <40 (MRI) Preoperative serum CA-125 < 90 U/mL (age < 50) Preoperative serum CA-125 < 30 U/mL (ageZ50) Kang <50% myometrial invasion (MRI) Absence of extension beyond uterine corpus (MRI) Absence of enlarged lymph nodes (MRI) Preoperative serum CA-125r35 IU/mL Urzal <50 myometrial Invasion (pathology) Absence of cervical involvement (pathology) Absence of lymphovascular space involvement (pathology) Vargas et al, Gyn Oncol 2014

28 Osi Donostialdea CASOS 111 BAJO RIESGO 42 2 (4,76%) MM GC neg 40
ALTO RIESGO 69 11 N (+) 16% 10% solo pelvis 1 pelvis + aorta 5 solo aorta 58 N (-)

29 Alto riesgo 1º BGC 2º linfadenectomía Seleccionar adenopatías
Recommendation 5.7: For patients with high risk (grade 3 with deep myometrial invasion >50%), lymphadenectomy should be recommended Level of evidence: IV Strength of recommendation: B Consensus: 73.0% (27) yes, 8.1% (3) abstain, 18.9% (7) no (37 voters) 1º BGC Seleccionar adenopatías Ultraestadificación Mejorar estadificación quirúrgica 2º linfadenectomía Si GC neg y tasa falsos negativos fuera mínima, solo BGC??? Si GC pos, completamos linfadenectomía???. ¿Es terapéutica la linfadenectomía?

30 Principal limitación del algoritmo es el área aórtica. Objetivos
Riesgo intermedio Recommendation 5.6: For patients with intermediate risk (deep myometrial invasion >50% or grade 3 superficial myometrial invasion <50%), data have not shown a survival benefit. Lymphadenectomy can be considered for staging purposes in these patients Level of evidence: II Strength of recommendation: C Consensus: 100% yes (37 voters) 1385 pacientes BGC 190 N(+) 13,7% 37 Falsos negativos (19%) 9 FN (algoritmo)(5%) Principal limitación del algoritmo es el área aórtica. Objetivos Disminuir la morbilidad Evitar el sobretratamiento Identificar todos los casos N(+). Algoritmo MSKCC Reducing overtreatment and medical waste are considered one of the greatest challenges to contemporary medical practice and an actionable opportunity to decrease both health care costs and harm to patients M. Smith, R. Saunders, L. Stuckhardt, J.M. McGinnis (Eds.), Best Care at Lower Cost: The Path to Continuously Learning Health Care in America, The National Academies Press, Washington (DC), 2013. Cormier, B et al, Gynec Onc 2015

31 Algoritmo para estadificación CE
Examen cavidad abdominal y lavado peritoneal Biopsia GC Evaluación retroperitoneal Cualquier ganglio sospechoso se extirpa Si no GC en hemipelvis, linfedenectomía ipsilateral Disección aórtica discrecional Barlin JN, et al. (MSKCC) Gynecol Oncol 2012

32 111 pacientes CE Clásico BGC Solo LPB MSKCC Nº linfadenectomías 69 8 111+6 (LAC) 12+31(uni) N(+) 11/21 20/21 6/21 17/21

33 Osi Donostialdea CASOS 111 BAJO RIESGO 42 2 (4,76%) MM GC neg 40
ALTO RIESGO 69 11 N (+) 16% 10% solo pelvis 1 pelvis + aorta 5 solo aorta 58 N (-)

34 Seroso, >50%, ielv, cito +
111 CASOS BGC 8 NO GC 1 N(+) Seroso, >50%, ielv, cito + P 0/18 A 6/16 103 GC 84 NEG End, G1, >50% P 0/13 (3GC-) A 2/18 (1GC-) 19 POS 18,4% 9 MACROS MICROS 2 MICRO Sin linfa

35 Solo GC pos GC+GnoC GC solo micro Solo GC micro End, G1, >50%
A 1/22 Claras,<50% P 0/9 A 1/23 End, G2, >50%, ielv P 2/20 A 0/10 GC+GnoC Seroso, >50% P 1/18 A 1/17 End, G1, >50%, ielv 2/18 4/16 End G1, >50% P 1/9 A 2/7 Claras, <50%, ielv P 4/14 A 13/23 Mixto: end G3/claras >50% P 2/16 (GC) A 3/7 (No GC) GC solo micro P 0/22 (3 neg, 1 micro) A 1/22 (4GCneg) Solo GC micro 8 Solo microenfermedad Linfa negativa 2 Micrometástasis Sin linfadenctomía

36 Importancia clínica de enfermedad ganglionar mínima
63 pacientes CE Estadio I-II Con factores de riesgo 9/63 LVMD (14,8%) Factor de riesgo independiente para recurrencia extrapélvica Supervivencia 20% menor a los 8 años respecto a N(-) LVMD valor pronóstico en otros cánceres MSKCC 844 pacientes 44 (5,2%) LVMD Tratamiento como N(+) Supervivencia a 3 años mejor que N(+) The study by Todo et al.looked at 63 patients with FIGO stage I–II endometrialcarcinoma with at least one adverse risk factor: grade 3 tumor, serous/clear cell histology, deep myoinvasion, cervical involvement, LVSI, or positive peritoneal washings.22 Within the cohort, ITCs and MM were identified in nine (14.8 %) patients. They found that the presence of ITC/ MM was an independent risk factor for recurrence (hazard ratio 17.9; 95 % CI 1.4–232.2). The 8-year OS and RFS rates were lower in the ITC/MM group than in the nodenegative group (OS 71.4 % vs %; RFS 55.6 % vs %); however, given the small number of patients, statistical significance was not reached. Furthermore, with only nine patients with low-volume metastases, the authors did not distinguish between those with ITCs versus MM Todo Y, Kato H, Okamoto K, et al. Isolated tumor cells and micrometastases in regional lymph nodes in stage I to II endometrial cancer. J Gynecol Oncol. 2016;27:e1. Todo et al described a series of 63 patients with FIGO stage I-II endometrial cancer who had undergone SLNB with ultrastaging. All patients were classified as intermediate risk based on the presence of at least one of the following risk factors: (1) FIGO grade 3; (2) deep myometrial invasion; (3) clear cell or serous histology; (4) cervical involvement; (5) lymphovascular space invasion; and (6) positive peritoneal cytology. LVMD was detected in 14.8% of patients and was found to be an independent risk factor for extrapelvic recurrence (HR, 17.9; 95% CI, ). In addition, the 8-year overall survival and RFS were >20% lower in the LVMD group compared with those in the node-negative group. This did not reach statistical significance, possibly due to sample size limitations. Touhami et al found that the size of a detected SLN metastasis is predictive of the risk of having non-SLN involvement. In this study, 34.8% of patients with a positive SLN had non-SLN metastasis. However, although the rate of non-SLN involvement in patients with SLN macrometastases was 60.8%, only 5% of patients with SLN harboring LVMD had metastatic non-SLNs (P < ). Notably, no other predictive factors for non-SLN involvement were identified. Prospective studies are required before an optimal postsurgical management strategy for patients with LVMD can be formulated. Touhami O, Trinh XB, Gregoire J, et al. Predictors of non-sentinel lymph node (non-SLN) metastasis in patients with sentinel lymph node (SLN) metastasis in endometrial cancer. Gynecol Oncol. 2015;138:41–45. Todo Y et al. J Gynecol Oncol (2016) 27 St. Clair CM, et al Ann Surg Oncol (2016) 23

37 Conclusiones La BGC es un procedimiento aún sin estandarizar
La BGC y la ultraestadificación patológica aumentan la tasa de detección de enfermedad ganglionar Permite una cirugía más selectiva y probablemente con menos morbilidad Precisa dedicación y esfuerzo Posiblemente sustituirá a la linfadenectomía sistemática en CE Son precisos más estudios para conocer la importancia pronóstica y el tratamiento adecuado de la micro- enfermedad ganglionar

38 Osi Donostialdea 2006 linfadenectomía laparoscópica 2007 LACR
2008 WM laparoscopia 2009 Traquelectomía radical 2010 BGC azul cérvix 2014 BGC ICG endometrio Muchas gracias

39

40 Kurmar S et al. Gynecol Oncol 2013

41 SENTIENDO DONOSTIA Pacientes 125 111 Fechas 07/ /2009 06/ /2016 Trazador Azul+Tecnecio ICG Hospitales 9 1 Lugar Cérvix Doble punción Tasa detección 88,8% 92,8% TD aórtica 5% 59,5% N + 20 21 Falso neg 3 LVND 10 LAC 14% 62% Nº GC 3(1-9) 4,2 Nº GC pel 1(0-6) 1(1-5) 1,5(0-3) 1,5(0-7) Nº Gc aorta 2(2-3) 2,3(0-7) Nº no GC 14(1-50) 21 (13-56)

42 GC positivos GC 278 PELVIS ALTO RIESGO 167 POS 22 13,17% BAJO RIESGO
111 2 1,8% TOTAL 429 265 34 12,83 % 164 1,21 % 151 AORTA 98 12 12,24 % 53 0 %

43 Afectación ganglionar
Prevalencia metástasis ganglionar (1) Bajo riesgo: 10% Alto riesgo: 20% Localización metástasis ganglionar (2,3,4) Pelvis N+ 60-70% también aórticas Metástasis Aórtica exclusiva General 1-4% 68,2% 57,3% (1)Creasman WT1987, (2) BoronovRC 1984, (3) Turan T 2011,(4 ) Mariani A 2008, (5) Cooke EW 2011

44 ¿Es un buen modelo teórico para la BGC?
Tumor frecuente Buen pronóstico Afectación ganglionar limitada (10%) Valor pronóstico Importante para determinar los tratamientos adyuvantes Linfadenectomía sistemática es compleja y genera morbilidad

45 Ultraestadificación Pendiente establecer protocolo de ultra-estadificación en patología ginecológica Macrometástasis >2 mm Micrometastasis 0,2-2 mm Células tumorales aisladas <0,2 mm El significado clínico de las metástasis ganglionares de bajo volumen no está bien definido Cormier, B et al, Gynec Onc 2015 39% (10-60%) metástasis solo por ultraestadificación 56 microenfermedad 27 MM 28 CTA 5,6%  estadio Si GC +; 35% enfermedad GnoC

46 Biopsia Ganglio Centinela alternativa a la linfadenectomía
Limita la morbilidad de la linfadenectomía completa. Selecciona los ganglios con mayores probabilidades de ser metastásicos Permite la ultraestadificación e incrementa la tasa de detección de ganglios positivos Señala ganglios en localizaciones poco habituales Enseña la anatomía del sistema linfático Solo por la ultraestadificación es una buena razón para realizar BGC

47 Clásico BGC 111 103 GC 19 (17%) N(+) CE 69 (62%) Linfa 11 (9,9%)

48 Nuestro problema Osi Donostialdea CE 111 Linfa 69 N (-) 58 N(+)
N(+) pelvis 5 Bilaterales 4 GC pos 1 GC neg Unilateral Otro lado neg CE 111 Linfa 69 N (-) 58 N(+) 11(9,9%) Solo pelvis 1 Pelv+aorta 5 Solo aorta 5 (4,5%) No linfa 42 Osi Donostialdea