CÁNCER DE OVARIO Diagnóstico y Tratamiento Dr. HERNÁNDEZ 2019

CÁNCER DE OVARIO
DIAGNÓSTICO Y TRATAMIENTO
Dr. PEDRO HERNÁNDEZ MORÓN
CIRUJANO ONCÓLOGO
GINECÓLOGO ONCÓLOGO
Instituto Regional de enfermedades Neoplásicas
IREN NORTE
2019
DR. PEDRO HERNÁNDEZ MORÓN 1

CA OVARIO
• 6% todos cánceres • 1/70 mujeres

ginecológicos. • 90% carcinoma
• 4-5º en frecuencia epitelial
• Edad: 45-70 • Diagnóstico: 75% 2/3
• Post menopáusicas. pacientes en estadios
avanzados
• Nulíparas
• Mortalidad: 3.3
• Incidencia: 5.5
GYNECOLOGIC ONCOLOGY CLINICAL DISAIA 8th Edition 2014

FACTORES
 Raza blanca
 Dieta rica en grasas
Teoría de la ovulación
 Exposición a radiación incesante
3
TIPOS DE CÁNCER DE OVARIO
TIPOS DE NEOPLASIAS
DR. PEDRO HERNÁNDEZ MORÓN
4
SINTOMATOLOGÍA
5
Genes de susceptibilidad al Cáncer
de Ovario
Cáncer de ovario
BRCA1 (~ 70%)
Hereditario
(5%-10%)
Otros genes HNPCC BRCA2 (~20%)

(~8%) (~2%)
Dr. PEDRO HERNÁNDEZ MORÓN 6
GENES Y CÁNCER DE OVARIO

CARCINOGÉNESIS
Pathogenesis of Epithelial Ovarian

STIC a Ovario es EC IIA Cancer, Robert J. Kurman, 2010.

CARCINOGÉNESIS
Pathogenesis of Epithelial
Ovarian Cancer, Robert J.
Kurman, 2010.

CARCINOGÉNESIS
New insights into ovarian cancer pathology J. Prat* 2012.

Pathogenesis of Epithelial Ovarian Cancer, Robert J. Kurman 2010.

CARCINOGÉNESIS
Patogénesis Carcinoma de Ovario, Sánchez Juvenal, 2014

11
Type I: 10%
• Low-grade serous, low-grade endometrioid,
clear cell, mucinous and transitional (Brenner) carcinomas.
• is low aggressive, presents in early stage. 20%.
• shared lineage with benign cystic neoplasm, often through
an intermediate step (borderline tumor).
Type II: 90%
• is highly aggressive, evolves rapidly
• always presents in advanced stage III-IV. 80%
• include high-grade serous carcinoma, undifferentiated
carcinoma, and malignant mixed mesodermal tumors
(carcinosarcoma). Frequent TP53 mutations > 80%
Pathogenesis of Epithelial Ovarian Cancer, Robert J. Kurman, 2010.

WHO Classification of Tumours of Female
Reproductive Organs, 2014
The Utility of Inmunohistochemistry, Serous – high grade
Carcinoma of Ovary
70%
< 5%
10.4%
10%
3%
c-ERB2
The Utility of Imnmunohistochemistry in Differencial Diagnosis of Gynecologic

Disorders, Robert Kurman, 2014

Carcinoma of Ovary
 Carcinoma seroso de ovario

 Carcinoma indiferenciado
Ki-67
 Carcinosarcoma
Tipo I: 10%; Tipo II: 90%


Inmunohistochemical of Low grade and high
grade serous carcinoma de Ovario
Serous high grade


Carcinoma of Ovary
 TP 53: Sobreexpresión, indica mutación del gen supresor
tumoral. Mayor potencial de metástasis y resistencia al
tratamiento químico.
 Favorable (Negativo)
 Desfavorable (positivo)
 Ki-67 (MIB1): Proliferación celular. Indicador de
agresividad tumoral
 Favorable < = 10% (Negativo)
 Desfavorable > 20% (positivo)
 P16: Patrón de expresión.
 Negativo
 Positivo
The Utility of Imnmunohistochemistry in Differencial Diagnosis of Gynecologic Disorders, Robert
Kurman, 2014
Pathology Ca Ovario Clasificación Prat OMS 2013
IHQ The Utility of Inmunohistochemistry, Serous – high grade
Carcinoma of Ovary
 c-ERB2:
 Receptor de factor de crecimiento.
 Se sobreexpresa en 25-30% del cáncer de mama.
 Se asocia con enfermedad agresiva
 RE y RP :
 < 10% negativo - Desfavorable
 >= 20% positivo – Favorable.

Pathology Ca Ovario Clasificación Prat OMS 2013

DIAGNÓSTICO
• Cuadro Clínico.
• Ultrasonografia doppler
• RMI INDICE DE JACOBS
• MT:
 HE4
 ROMA Score: CA 125 + HE4, Status menopaúsico
 COPENHAGEN Score (CPH-I): CA 125+HE4 + Edad
 CA 125
 CEA
 CA 19-9
 Ratio CA 125 /CEA > 25 Primario ovary;
< 25 Excluir Ca GI, Mama (Chorus)
 Ratio CA 125 / CA 19-9 < 25 = Carcinomatosis
Si CA 19-9 elevado(Chorus)
Kehoe et al, CHORUS; Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian
Cancer: SGO and ASCO Practice Guideline, Wright 2016

DIAGNÓSTICO
 OVA1 Test Score
 CA 72-4
 CA 15-3
 OTROS: ESTRADIOL, INHIBINA A Y B
 Marcadores Tumores Germinales: AFP, B-HCG,
DHL, CEA, PLAP
• TAC AP
• RMN AP: DIFUSIÓN Y DINAMICA
• PET SCAN.
• Anatomía Patológica
• Inmunohistoquímica
• Marcadores moleculares
Kehoe et al, CHORUS; Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian
Cancer: SGO and ASCO Practice Guideline, Wright 2016

CA DE OVARIO
MT CA MUCINOSO: Otros MT:
CA 19-9  Mesotelina
CEA  Ac. Lifosfatidico
CA 72-4  Calicreinas
CA 15.3
Los estudios diagnósticos secundarios: Quistes de ovario son TAC,
RMN y determinación de CA125, β-hCG; asociada a
coriocarcinoma, AFP, asociada a tumor del seno endodérmico,
LDH; asociada a disgerminoma y proteína 4 del epidídimo humano
HE4; asociada a cáncer de ovario).

ALGORITMO ROMA: CA 125 + HE4
HE4 < 150 picomoles/L.
Guidelines, ACOG 2014

Sospechar
Cuadro clínico: malignidad:
Clinical implications
 The challenge is to detect a microscopic lesion during the occult
period.
 We know also the preclinical natural history of HGSC which lasts on
average 4 years as in situ, stage 1 and 2 cancers and approximately 1
year as stage 3 /4 cancers before they become clinically apparent.
Precoz:
 No causan síntomas.
 Los síntomas inespecíficos; incluyen hinchazón del abdomen
(debido a una masa o acumulación de líquido; ASCITIS)
 Presión en la pelvis o dolor abdominal y/o síntomas urinarios
From the Ovary to the Fallopian Tube: A History of Ovarian Carcinogenesis, G. Chene 2015.

Cuadro clínico:
Sospechar
Precoz: malignidad:
 No causan síntomas.
 Los síntomas inespecíficos; incluyen hinchazón del abdomen
(debido a una masa o acumulación de líquido, ASCITIS)
 Presión en la pelvis o dolor abdominal bajo y/o síntomas
urinarios
FORMA TARDÍA :
 Distensión – Tumor abdominal 75%
 Dolor abdominal 20%
 Trastorno urinario 16%
 Pérdida de peso
 Sangrado vaginal
Gynecologic Oncology, Berek and Hacker 6th Edition 2015

DIAGNÓSTICO
El nivel máximo de normalidad más usado
para el CA 125:
• Post menopausia: es de 35 UI/ml en
• Pre menopausia: es 65 UI/ml en la
• Ca 125 Normal
• 60% EC Precoz
• 25% EC Avanzados
Although CA125 is elevated in 83% of women with epithelial ovarian

cancer, it is elevated in only 50% of those with stage I disease.
Ovarian Cancer Diagnosis and Tretament: Andrew E Green, MSKC: Aug 2016
Ecografía Transvaginal Doppler:
 Más efectiva en Diagnóstico precoz.
 Sensibilidad: cerca al 95-100%
 Especificidad: 83%

Sospechar
 No permite estudio de grandes quistes
malignidad:
Ascitis Mixtas/complejas
Aspecto sólido. Multilocular
Excrecencias >= 5mm. Shunt arteriovenosos
Tabiques >= 3mm. Tamaño:
Cápsula gruesa >= 3mm.  > 10cm
Bordes irregulares mujer fértil.
Bilateral  > 5cm
Neoformación vascular postmenopáusica.
o IR Índice de resistencia doppler : < 0,4 25

o IP Índice de pulsatilidad : < 1
Sospechar
malignidad:
o IR Índice de resistencia doppler : < 0,4*

o IP Índice de pulsatilidad : < 1
o PS Índice de velocidad sistólica : >= 10 cm/s.
Patologías IR BAJO:
Quiste Hemorrágico
Quiste Cuerpo lúteo
Endometriosis
* Kerkel
** Sassone
26

 Ascitis
 Aspecto sólido.
 Excrecencias >= 5mm.**
 Tabiques >= 3mm.
 Cápsula gruesa >= 3mm.
 Bordes irregulares
 Bilateral
Sospechar
malignidad:
* Kerkel
Update on Imaging of Ovarian Cancer Rosemarie Forstner 2016 ** Sassone
27

ALGORITMO RMI: JACOBS
Guidelines, ACOG 2014

INDICE DE JACOBS: RMI
Score Ecográfico:
1. Quiste multifolicular
2. Areas sólidas
3. Metástasis
4. Ascitis
5. Lesiones bilaterales
< 250 Manejo por Ginecólogo
≥ 250 Manejo por Ginecólogo Oncólogo

Tumour Analysis (IOTA) protocolo (Timmerman et al; 2000)
Attending the following features:
 Bilaterality
 Type of mass(
CRITERIOS DE All masses were classified into one of five
categories:
oIOTA
Unilocular cyst, Unilocular-solid cyst, Multilocular cyst,
TIMMERMAN
Multilocular-solid cyst and
o Solid mass
 Internal Wall (smooth or with papillae < 3mm or ≥ 3 mm length
 Septae (Not present, incomplete, complete; thin < 3mm or thick ≥
3mm)
 Echogenicity (Anechoic, low-level echogenic, ground glass
appearance, haemorrhagic or mixed echogenic)
 Presence of internal shadows
 Presence of free fluid in Douglas pouch
La combinación de HE4 y CA125 en suero aumenta la precisión

predictora de de una masa de los anexos.
MARCADOR TUMORES GERMINALES
LDH (+)
PLAP (+)
GYNECOLOGIC
ONCOLOGY BEREK
AND HACKER'S 6th
Edition 2015

Marcadores Tumorales
 The serum levels of CA125

Epithelial ovarian cancer CA-125
generallyEPITELIAL
reflect
the volume of the disease.CEA
Mucinous cystadenocarcinoma EPITELIAL
 Elevated
Endodermal sinus tumor CA125 prior to surgery
AFP is useful
GERMINALfor
following the progress of the
Embryonal cell carcinoma hCG, AFP
patient during
GERMINAL
and after treatment.
Choriocarcinoma hCG GERMINAL
 CA15-3, CA19-9 and lipophosphatidic acid
Dysgerminoma LDH-1, LDH-2, PLAP GERMINAL
have been shown to have independent
Granulosa cell tumor Inhibina B y A GERMINAL
expression to CA125.
Polyembrioma AFP, hCG GERMINAL
GERMINAL
Cancer Principles and Practice of Oncology; DEVITA, HELLMAN Y ROSENBERG, 10th Edition 2017

32
NIVEL BIOMARCADOR
Marcador Ca 125:
 Mayor de 400 es compatible con carcinomatosis.
 Menores de 400, probable citorreducción óptima.
 Mayores de 500, probabilidad de citorreducción
subóptima.
 Mayor de 1000, irresecable/Inoperable
 Los criterios de citorreducción subóptima se
encuentran establecidos en los estudios de
Scorpion, Curaco, Fagotti, Makar, PCI Sugarbaker
y Suidan.
Gynecologic Oncology, Berek and Hacker 6th Edition 2015.

TAC
Ca Ovario:
 CT convencionales: para la detección de
implantes peritoneales.
 Sensibilidad 63-79%,
 Especificidad. 82%
 La TC helicoidal:
 La sensibilidad de 85-93%.
 Computed tomography (CT) scanning can not
identify peritoneal metastases down to the
size of approximately 5 mm.
Dr. PEDRO HERNÁNDEZ

MORÓN 34
Magnetic resonance imaging scanning
(MRI)
 This modality seems to be a more accurate
way of detecting peritoneal metastases utside
the true pelvis.
 Sensibilidad 87%
 Especificidad 99%
 Recurrencia :
 Sensitivity of 96%
 Specificity of 100%

MORÓN 35
CA OVARIO EC III-IV
RMN UNRESECTABILITY
Criteria for non-resectability:
Optimal cytoredcution is not possible when:
• Tumour in the porta hepatitis,
• Disease in the inter segmental fissure of the liver,
• Disease the diaphragm,
• Disease in the lesser sac,
• Disease gastrosplenic ligament;
• Presacral extra-peritoneal disease and
• Lymph node enlargement at the level of the coeliac axis
or above.
The accuracy of MRI in predicting irresectability can be as
high as 93-96%.
MR imaging in ovarian cancer S.A.A. Reznekb 2007

PET
 Recent studies have demonstrated high sensitivity

and a positive predictive value in identifying
potentially resectable recurrent ovarian cancer with
negative CT findings.
 Sensibilidad 83-86%
 Especificidad 54-86%

MORÓN 37
AJCC Cancer Staging Manual 8th Edition, 2017.
Ovary
AJCC CANCER STAGING MANUAL Amin 8th

Edition 2017

AJCC Cancer Staging Manual 8th Edition, 2017
Ovary
AJCC CANCER STAGING MANUAL Amin 8th

Edition 2017

Ovary
AJCC CANCER STAGING MANUAL Amin 8th Edition 2017

Ovary
AJCC CANCER STAGING MANUAL Amin 8th Edition 2017

OVARIAN CANCER STAGING
I
PRECOZ
II
Localmente
avanzado
C79.6 Tumor maligno III

Secundario de ovario
Tumor Krukenberg
IV
AVANZADO
AJCC Cancer
FIGO Cancer Staging ManualStaging Manual, Sixth Edition
2014.
OvaryUteri
Cervix
Avanzado Stage IV
• Involvement of retroperitoneal lymph nodes must be proven cytologically or histologically.

• Extension of tumor from omentum to spleen or liver (stage IIIC) should be differentiated from
isolated parenchymal metastases (stage IVB).
Jaime Prat Staging classification for cancer of the ovary, fallopian tube,
and peritoneum. FIGO Committee on Gynecologic Oncology, 2014

SURGERY STAGING IN OVARIAN CANCER
TREATMENT
Ovarian cancer of cytoreductive surgery; Sugarbaker April 2013

OVARIAN CANCER STAGING
CANCER PRECOZ: I
 ESTADIAJE DE OVARIO
CÁNCER AVANZADO: II-IV
 CITOREDUCCIÓN DE OVARIO.
 PRIMARIA
 SECUNDARIA
 TERCIARIA
 CUATERNARIA
NCCN, Guidelines Clinical Oncology, 2019

Berek and Hacker's Gynecologic Oncology, 6th Edition 2015 Lippincott Williams & Wilkins.

STAGING LAPARATOMY OR LAPAROSCOPIC:
CONGELACIÓN / IMPRONTA
CANCER PRECOZ: I
 Anexectomia/resección tumor + congelación
 Citologia peritoneal
 Histerectomia ampliada a vagina
 Linfadenectomia pelvica bilateral
 Linfadenectomia paraaortica
 Biopsias multiples peritoneales: PCD, PCI, mesenterio,
mesos
 Frotis PCD, PCI, SD
 Omentectomia infracólica
 Biopsia douglas, vesical, pelvis
 Apendicectomia
 Biopsias de adherencias.
Berek and Hacker's Gynecologic Oncology, 6th Edition 2015 Lippincott Williams &
Wilkins

SURGERY
STAGING
TREATMENT
* Consider fertility preservation

in selected young patients.
** With exceptions for
retro peritoneal staging (see
specific recommendations on
surgery of early-stage ovarian
cancer)
ESGO Ovarian Cancer Surgery

Algorithms Querleu_v.2 2017

SURGERY
STAGING
TREATMENT
*With exceptions for IIIB (e.g.,

poor patient condition or very
extensive military disease on
the bowel for whom NACT
may be preferable)
DR. PEDRO HERNÁNDEZ

MORÓN
48
SURGERY
STAGING
TREATMENT


49
STAGING OVARIAN CANCER
LYMPHADENECTOMY MUCINOUS
• Serous ovarian carcinoma (SOC) is clinically and

pathologically, high agressive and surgery with
lymphadenectomy is procedure standard.
• Overall survival (OS) in patients who did not undergo
lymphadenectomy was not significant differences.
• The routine lymphadenectomy may be excluded in
women with clinically apparent primary mucinous
ovarian cancer.
Is lymphadenectomy necessary in mucinous ovarian cancer? Ivan Salgado-Ceballos May 2017




STAGING MUCINOUS OVARIAN CANCER
Mucinous Ovarian Carcinoma Philippe Morice, Mar 2019

Mucinous Ovarian Carcinoma Philippe Morice, Mar 2019

CA OVARIO MUCINOSO
CLASIFICACIÓN
 Incidence is less common much closer to 3%
 mEOC generally occur in young women and are diagnosed
an early stage I, with 83% and 17% at stage II or higher
 Mucinous ovarian tumors can be classified:
• as benign,
• borderline or
• malignant and
 Can be further classified into invasive and noninvasive.
 Borderline the infiltrative pattern is associated with a worse
prognosis
 Mucinous ovarian carcinomas (mEOC) display stromal
invasion of >5 mm or 10mm2 [10,11].
Early stage mucinous ovarian cancer: A review Crane and Brown Jun 2018
Recent Insights into Mucinous Ovarian Carcinoma Ricci, May 2018

CA OVARIO MUCINOSO
CLASIFICACIÓN
 The intestinal type is the most common of mEOC

 Suggest a primary mOC: unilateral involvement, larger size
(typically >10 cm), and coexisting borderline, Brenner, or
dermoid tumors
 Suggest Metastatic disease: Bilateral tumors, surface
involvement, signet ring cells, lymphvascular invasion,
desmoplastic reaction, hilar involvement, and a nodular
growth pattern.

CA OVARIO MUCINOSO
MANAGEMENT
• Stage IA MOC can be observed after surgery.

• Survival stage IA over 90%, and surgery alone is sufficient.
• Stage IB and more advanced MOCs are treated with:
 oxaliplatin and Capecitabine / carboplatin
 +/− Bevacizumab.
• Patients with stage IB-II disease should receive adjuvant
treatment (oxaliplatin).
• Platinum-based, carboplatin & Paclitaxel chemotherapy as
single agents is chemoresistance. LOW RATE
• All sensitive to oxaliplatin & FU with additive or synergistic
effect

CA OVARIO MUCINOSO
Management of Apparent Early Stage Mucinous Ovarian Cancer
CA OVARIO MUCINOSO
SURVIVAL
• The median OS for each histological subtype was:
o 47.7 months for HG-SOC,
o 15.4 months for mucinous, and
o 36.6 months for clear-cell carcinomas.
• Mucinous ovarian tumors had a shorter overall median
survival of 14.8 for mEOC
• Survival to serous carcinomas, 45.1 months HGSOC.
• The median PFS in bevacizumab was 17.4 months vs 8.8
months in arms without bevacizumab

CIRUGÍA MINÍMAMENTE INVASIVA
LAPAROSCOPIA EN CÁNCER GINECOLÓGICO:

Ca de Cérvix
Ca de Ovario
Ca de Endometrio y
Ca de Trompa de falopio
ELECTROCIRUGÍA:
• BISTURÍ ARMONICO: SONOSURG
• LIGASURE (PINZAS PARA
SELLADO DE VASOS).
• ERBE: Sistema Electroquirúrgico (SEQ)
combinado con Gas Argón

CÁNCER PRECOZ - LAP
SISTEMA
RUMI KOH
ESTADIAJE DE OVARIO LAP

Hernández Morón P. IREN NORTE.
CIRUGÍA LAP
Servicio de Ginecología Oncológica, IREN NORTE.
CIRUGÍA LAPAROSCÓPICA Y CÁNCER

CIRUGÍA LAPAROSCÓPICA

CIRUGÍA LAP
Cx. OVARIO LAP

LINFADENECTOMIA PÉLVICA Y PARAAÓRTICA
LAP
CÁNCER PRECOZ
 Ca Ovario
LAP PHM Remix 15-11-10.Rmx

SONOSURG: EQUIPO ULTRASÓNICO Y
LIGASURE
BISTURÍ ARMÓNICO
Tissue Fusion System

LIGASURE Y ARMÓNICO
AVANCES EN ELECTROCIRUGÍA

LAPAROSCOPIA DIAGNÓSTICA
ÍNDICE FAGOTTI
Indications
Cáncer precoz: EC I
• Evaluación y manejo de masa anexial
• Estadificación Cáncer bordeline y cáncer invasivo
• Reestadiaje para cáncer precoz de ovario y
trompa de falopio
Estadios avanzados: II, III y IV:
• Evaluación Laparoscópica para determinar
operabilidad / Irresecabilidad
• Second look
• Debulking limitado/ mano asistida
Laparoscopy for diagnosing resectability of disease in patients with advanced

ovarian cancer, Fagotti Clin Oncol. 2008

Índice FAGOTTI: Scorpion Study
operabilidad / resecabilidad.
• Siete (7) Parámetros: 0 ausente y 2 presente.
Criterios: Parameters:
• Enfermedad omental supracólica (1) omental cake supracolic
• Carcinomatosis peritoneal irresecable (2) peritoneal carcinosis
• Carcinomatosis diafragmática extensa. (3) diaphragmatic carcinosis
• Enfermedad mesentérica infiltrante. (4) meseneteric retraction
• Carcinomatosis intestinal. (5) bowel infiltration
• Infiltración gástrica. (6) stomach infiltration
• Metástasis hepática. (7) liver metastases
Algorithm for Treating Advanced Ovarian Cancer Increases Complete

Resection Rate By Sarah Bronson. Clin Oncol. May 2015;12:239–245.

Indications:
Estadios avanzados: III y IV: Índice FAGOTTI
operabilidad / resecabilidad.
• Citorreducción optima: < de 1 cm.
• < 8 Resecable: Cx. Citorreductora óptima (< 8/14)
• > = 8 Irresecable: 3 cursos QT Neoadyuvante (8/14)
Algorithm for Treating Advanced Ovarian Cancer Increases Complete Resection

Rate By Sarah Bronson. Clin Oncol. May 2015

CITORREDUCCIÓN EN CÁNCER DE OVARIO
Lo ideal
Resección completa sin evidencia de tumor residual.
“La sobrevida es mayor a menor tumor residual
(R0)”
 Optima: El implante residual ≤ 1cm.
 Subóptima: El implante > 1cm.
Gynecologic oncology, Berek and Hacker, 5th Edition 2015.

CA OVARIO AVANZADO III-IV
Treament Advanced Ovarian By Wright. Clin Oncol. ASCO May 2015

CÁNCER DE OVARIO
LOCALMENTE AVANZADO
Citorreducción Primaria Óptima Ovario; Hernández Morón P.; IREN NORTE

DEBULKING EC III-IV: CRITERIA
• Midline laparotomy is required to manage stage III to IV ovarian
cancers (expert agreement).
• Complete resection of all visible diseases is the goal of surgical
management.
• Voluntary use of incomplete surgery (upfront or interval) is
discouraged (grade A).
• Primary surgery is recommended in patients who can be
debulked upfront to no residual tumor with a reasonable
complication rate (grade A).
 Metastatic (stage IVB) disease may be resectable.
 Central or multisegmental parenchymal liver metastases,
multiple parenchymal lung metastases (preferably histologically
proven), nonresectable lymph node metastases, and multiple
Brain metastases are not resectable (expert agreement).
Guidelines for Ovarian Cancer Surgery Algorithms Querleu_ ESGO v.2 2017

76
DEBULKING EC III-IV: NON CRITERIA
Criteria against DEBULKING patients are not candidates for
primary surgery (according to ESGO 2017).
• Diffuse deep infiltration of the root of small bowel mesentery
• Diffuse carcinomatosis of the small bowel involving such large
parts that resection would lead to a short bowel syndrome
(remaining bowel < 1.5m)
• Diffuse involvement/deep infiltration of:
o stomach/duodenum
o head or middle part of pancreas
• Involvement of coeliac trunk, hepatic arteries, left gastric artery
• Central or multisegmental parenchymal liver metastases
• Multiple parenchymal lung metastases (preferably histologically
proven)
• Non-resectable LNs
• Brain metastases Guidelines for Ovarian Cancer Surgery Algorithms Querleu_ ESGO v.2 2017

77
CA OVARIO EC IIIC-IV
SCORE DE FAGOTTI
Translational Advances in Gynecologic Cancers by Michael J. Birrer-Ceppi 2017

CA OVARIO EC IIIC-IV: CRITERIA SUBOPTIMAL
Predictors of suboptimal cytoreduction (residual disease >1

cm). Three multicenter studies and one meta-analysis
evaluated the use of CT AP and CA-125:
• Clinical factors that were associated with suboptimal
cytoreduction were:
• Age ≥ 60,
• CA-125 ≥ 500 U/ml, and
• ASA classification of 3 or 4
• Radiologic predictors of suboptimal cytoreduction were:
Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic
Oncology and American Society of Clinical Oncology Clinical Practice Guideline, Alexi A.Wright, SGO;
ASCO May 2016.

CA OVARIO EC IIIC-IV: CRITERIA SUBOPTIMAL
• Radiologic predictors of suboptimal cytoreduction were:

 Retroperitoneal lymph nodes above the renal Hilum
(including supradiaphgragmatic) > 1 cm,
 Diffuse small bowel adhesions or thickening,
 Small bowel mesentery lesions >1 cm,
 Root of the superior mesenteric artery lesions >1 cm,
 Perisplenic lesions >1 cm, and
 Lesser sac lesions >1 cm.
Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: Society of Gynecologic
Oncology and American Society of Clinical Oncology Clinical Practice Guideline, Alexi A.Wright,
SGO; ASCO May 2016.

CITOREDUCCIÓN DE OVARIO
CITOREDUCCIÓN PRIMARIA, SECUNDARIA y TERCIARIA

HERNÁNDEZ MORÓN P. IREN NORTE
HERNÁNDEZ MORON P. IREN NORTE.

CA OVARIO EC III-IV
SCORE DE FAGOTTI MODIFICADO
Appropriate approach for four clinical subgroups
1) Patients with unfavorable preoperative factors
Such factors include:
The percentage of 21.8% and 30%,
Primary Debulking Surgery vs Neoadjuvant Chemotherapy for Newly

Diagnosed Advanced Ovarian Cancer Anna Fagotti, MD, Giovanni
Scambia, MD Jun 15, 2017
CA OVARIO EC III-IV
SCORE DE FAGOTTI
2) Patients with residual tumor > 10 mm at PDS
• These women been suitable for surgery, but for some
reason (eg, intraoperative complications or technical
unresectability) debulking is then aborted.
• The survival curves [PFS], 10 months to 13.6 months),
demonstrate that PDS has no benefit in this population,
except for palliative purposes in a few instances.
• Therefore, cost-benefit ratio, women in this category
should be triaged directly to NACT after disease histology.
• The percentage of women is from 8.5% to 19%.
Primary Debulking Surgery vs Neoadjuvant Chemotherapy for Newly Diagnosed

Advanced Ovarian Cancer Anna Fagotti, MD, Giovanni Scambia, MD Jun 15,
2017

CA OVARIO EC III-IV
SCORE DE FAGOTTI
2) Patients with residual tumor > 10 mm at PDS
• It is very difficult to predict preoperatively into this class.
• However, greater openness to considering:
o Neoadjuvant chemotherapy,
o Use of advanced radiologic images (eg, diffusion-
weighted MRI), and
o Minimally invasive approaches for assessment of disease
diffusion — instead of automatically attempting debulking
— might reduce the number of patients in this category.
• In these first two groups, account for 30% to 40%.
• The effect of NACT on survival is equal to that of PDS, but
NACT appears to be superior in terms of quality of life and
cost-effectiveness.
2017

CA OVARIO EC III-IV
SCORE DE FAGOTTI
3) Patients with residual tumor = 0 at PDS
• Including data from RCTs, women in this
category, population (35.8% to 51.7%).
• Derive the greatest survival benefit from PDS,
with a median PFS of 24 months to 26
months.[11,12]
• Absence of unresectability criteria as previously
defined[14] or a laparoscopic score < 10 [15]
ensure that residual tumor = 0 in nearly 100% of
cases.

2017

CA OVARIO EC III-IV
SCORE DE CHESNAIS
A pre-operative predictive score to evaluate the feasibility of complete cytoreductive

surgery in patients with epithelial ovarian cáncer Marion Chesnais, Nov 2017

PCI SCORE: CA OVARIO EC III-IV
1-39
Fig. 1. Schematic drawing of the Peritoneal Cancer Index as described by Jacquet and
Sugarbaker [7]. (Courtesy of E.M.L.E. Jansen).
MRI with diffusion-weighted imaging to predict feasibility of complete cytoreduction
with the peritoneal cancer index (PCI) in advanced stage ovarian cancer patients
EJR Mar 2019
CA OVARIO EC III-IV
This score alow assess the probability of a
complete cytoreduction: Elias et all reported
were:
• Ca Colorectal PCI: < 16 Probability
• : ≥ 16 Suboptimal
• For Ca gastric PCI: < 15 .
For Sugarbaker: Ca Colorectal
• PCI < 20
• PCI > 20 treated only palliatively
• Peudomyxoma peritonei PCI > 20
Completeness of cytoreduction (CCR), Score:
CCR-0 no residual tumor
CCR-1 nodules ≤ 2.5 mm.
CCR-2 nodules 2.5mm - 2.5 cm.
CCR-3 residual tumor > 2.5 cm.
PCI: 1-39
Selection of patients and staging of peritoneal surface
Malignancies Cotte-Gilly 2010
This score alow assess the probability of a
complete cytoreduction: all reported were:
• Ca Ovario PCI: ≥ 16 suboptimal surgical
cytoreduction.
• PCI score >13, suboptimal surgical
cytoreduction, Ovarian cancer FIGO
stage and tumor grading p=0.005), and
• PCI score >13 p=0.012 were the factors
that had significant impact on OS and
shorter PFS
• PSC ≥ 3 have shorter PFS (Predictive
score of cytoreduction)
Peritoneal cancer index as a predictor of survival in advanced stage

PCI: 1-39 serous epithelial ovarian cancer: a prospective study, Elzarkaa-Shaalan
JGO 2018

PCI Score Ovarian Cancer:
PCI score of 13 as a cut-off level
 The median disease-free interval with:
• PCI ≤13 was 16.3 months (95% CI),
• PCI >13 this was 5.6 months (95%
CI); p≤0.001.
 The median OS with:
• PCI ≤13 was 22.2 months (95% CI)
• PCI >13 was 17.9 months (95% CI;
p=0.004).
Peritoneal cancer index as a predictor of survival in advanced stage

PCI: 1-39 serous epithelial ovarian cancer: a prospective study, Elzarkaa-Shaalan
JGO 2018

CA OVARIO
LINFADENECTOMIA EC IIIC-IV
The LION study; led by Philipp Harter:
• The median OS in patients underwent
lymphadenectomy was similar who did not 65.5 vs
69.2 months.
• The median PFS was the same in both groups (25.5
months).
• Who underwent lymphadenectomy had:
 more complications,
 including infections and need for transfusions.
No Need for Lymphadenectomy in Advanced Ovarian Cancer Roxanne Nelson,

ASCO June 13, 2017

CA OVARIO EC III-IV
LINFADENECTOMIA
Cytoreductive surgery for ovarian cancer Philipp Harter 2010

CA OVARIO
The lymphadenectomy Stage IIIC-IV Ovarian Cancer:
The conclusion from a large randomized trial, the
Lymphadenectomy In Ovarian Neoplasms (LION) study:
• Patients with advanced ovarian cancer who undergo
a complete resection.
• Need not also undergo systematic lymphadenectomy
because it has no effect on progression-free survival
(PFS) or overall survival (OS).
• No Survival Effect.
• Increased Complications

ASCO June 13, 2017

CA OVARIO
The LION study; led by Philipp Harter:

ASCO June 13, 2017

GOALS OF CYTOREDUCTIVE SURGERY
OPTIMAL STATUS.
 Goal of cytoreductive surgery is the removal of all of the primary cancer and, if
possible, all metastatic disease.
 Hacker and Berek showed that patients whose largest residual lesions were
≤5 mm had a superior survival by Hoskins et al.(GOG)
 The median survival was 40 months, compared with 18 months for patients
whose lesions were ≤1.5 cm and 6 months for patients with nodules >1.5 cm.
 Optimal cytoreduction is difficult for irresecability:
• extensive disease on the diaphragm,
• in the parenchyma of the liver,
• along the base of the small-bowel mesentery,
• in the lesser omentum,
• or in the porta hepatis.
Berek and Hacker's Gynecologic Oncology, 5th Edition 2010 . Lippincott Williams & Wilkins.
Manual de Oncología, Granados 4th edition, 2010.

SURVIVAL - CYTOREDUCTION
Survival versus diameter of largest residual disease. (From Hacker NF, Berek JS, Lagasse LD, Nieberg RK, Elashoff RM. Primary
cytoreductive surgery for epithelial ovarian cancer. Obstet Gynecol 1983;61:413-420, with permission from the American College of
Obstetricians and Gynecologists.)
Berek and Hacker's Gynecologic Oncology, 5th Edition 2010 .Lippincott Williams &
Wilkins.

CA OVARIO AVANZADO:
DIAGNÓSTICO PREVIO DEBULKING PRIMARIO
MODALIDADES:
• LAPAROSCOPIA DIAGNÓSTICA
• BIOPSIA GUIADA POR ULTRASONOGRAFIA/TAC.
• CITOLOGÍA PERITONEAL
Criterios de Fagotti, permiten determinar los criterios de
Inoperabilidad e Irresecabilidad
Criterios de Fagotti >= 8 Reciben 3-6 Cursos de QT
Criterios de Fagotti < 8 Probable Citorreducción óptima.
CYTOREDUCTION OVARIAN CANCER AVANZADO, Fagotti,

Gynecologic Oncology, 2004 y 2008. Lippincott Williams & Wilkins.

CYTOREDUCTION: ¿OPERABILITY –
UNRESECTABILITY?
Citorreducción Primaria de Ovario, Hernández Morón P.

Algoritm stage IIIC or IV Ovarian cancer
Neoadjuvant chemotherapy for newly

diagnosed, advanced ovarian
cancer: Society of Gynecologic
Oncology and American Society of
Clinical Oncology Clinical Practice
Guideline, Alexi A.Wright, SGO; ASCO
May 2016.
Servicio de Ginecología Oncológica

CITORREDUCCIÓN OPTIMA
Estadios avanzados: III y IV:
 Evaluación Laparoscópica para determinar
operabilidad o resecabilidad.
 Citorreducción optima: < de 1 cm. NO
ENFERMEDAD MACROSCOPICA
El CA 125 según algunos autores con valores de:
• < 500 U/ml tienen un probabilidad de cirugía
óptima de hasta 73%
• > 500 U/ml cirugía óptima solo es de 22%

CITORREDUCCIÓN OPTIMA
Estadios avanzados: III y IV:
 Evaluación Laparoscópica para determinar operabilidad o
resecabilidad.
 Citorreducción optima: < de 1 cm. NO ENFERMEDAD MACRO
La probabilidad de lograr una citorreducción óptima o
subóptima. Indicadores definitorios:
 Presencia ascitis masiva con o sin compromiso respiratorio
 Tumor palpable
 Implantes tumorales fondo douglas
 Ca 125 > 1000
 Nivel Karnofsky < 70
Resultados: Cito óptima: >= 2 parámetros : 32%
1 parámetro : 62%
Ninguno : 88%

CIRUGÍA CITORREDUCTORA
AVANCES EN ELECTROCIRUGÍA
Bisturí armónico
Ligasure: Sellador de vasos
Hernández Morón P. CITORREDUCCIÓN PRIMARIA ÓPTIMA.

CITORREDUCCIÓN
AVANCES ELECTROCIRUGÍA
Ligasure:
Atlas
Impact
Advance
OMENTECTOMÍA INFRACÓLICA
CÁNCER DE OVARIO AVANZADO
LE: Ca Localmente Avanzado LAP Diagnóstica: Ca Localmente

Avanzado EC IIIC: PIV: 10
Laparoscopia diagnóstica
QT adyuvante
ERBE JET2 – ARGÓN PLASMA
Generador de AF y RF
Sistema de sellado de vasos.
Extensas zonas cruentas.
Citoreducciones

ERBE JET2 – ARGÓN PLASMA
EPIPLON EN
CAKE
Citorreducción Primaria de Ovario; Hernández Morón P. IREN NORTE.

INTERVAL DEBULKING CRITERIA
 Interval debulking:
 If a patient did not have the opportunity of surgery primary,
then a delayed debulking after more than 3 cycles of
neoadjuvant chemotherapy(expert agreement).
 After suboptimal cytoreduction, core or fine needle biopsy,
or positive ascitic fluid cytology for carcinoma
 Surgery should be proposed to patients fit for surgery with
response or stable disease compatible with complete
resection (grade A).
 A patient with inoperable tumor who progresses during
neoadjuvant chemotherapy should not be operated on unless for
palliative reasons.
 Careful review of pathology in serous adenocarcinoma (possible
low grade) and additional workup in mucinous adenocarcinoma
(possible GI tract secondary) are recommended when
applicable(Expert). Guidelines for Ovarian Cancer Surgery Algorithms Querleu_ ESGO
v.2 2017
108
CITORREDUCCIÓN SECUNDARIA
Criteria:
• Indicated in patients with recurrent of ovarian cancer, after
Optimal primary cytoreduction, with complete response to
chemotherapy, platinum-sensitive.
• Can be considered in who recur more than 6-12 months
since completion of initial chemotherapy.
• Have an isolated focus (or limited foci) of disease
amenable to complete resection, and
• Do not have ascitis
• Patients are encouraged to participate in ongoing trial
evaluating the true benefit of secondary cytoreduction.
Ovarian cancer management, Fleming GF, Seidman J; Principles and Practice of

Gynecologic Oncology Dennis Chi 7th Edition 2017

Desktop II Study – Score AGO +
Surgery in Recurrent Ovarian Cancer:

The Arbeitsgemeinschaft
Gynaekologische Onkologie (AGO)
DESKTOP OVAR Trial, Philipp Harter &
Du Bois 2006
FIG. 2. Design of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian

Committee Descriptive Evaluation of preoperative Selection KriTeria for
OPerability in recurrent OVARian cancer (AGO OVAR DESKTOP II). DR. PEDRO HERNÁNDEZ MORÓN 110
AGO CRITERIA
Surgery for Relapsed Ovarian Cancer: When Should it Be Offered? Philipp Harter &
Andreas Du Bois 2012

Secondary cytoreduction:
• These data imply that the goal of secondary cytoreduction should be to
achieve residual disease of < 0.5 cm, and in some instances, radical
surgical techniques may be required to obtain this goal.
• Patients are encouraged to participate in ongoing trial evaluating the true
benefit of secondary cytoreduction.
Secondary Cytoreduction as a “Second Chance” for Patients with Ovarian Cancer, Sonoda 2012
Guidelines Cytoreduction secondary criteria, Dennis Chi 2006

Considered inclusion criteria for secondary cytoreductive
surgery: DESKTOP III – CRITERIA AGO
• The good performance by ECOG score 0–1.
• The single site of recurrence regardless of platinum-free
interval (DFI) or
• Multiple sites of recurrence but Not carcinomatosis and
Platinum-free interval DFI >12 months, and
• Not carcinomatosis.
• Women with carcinomatosis but DFI > 30 months
• Not ascites or small-volume ascites (<500 ml).
• Women not meeting these criteria were treated by
chemotherapy alone.
Secondary cytoreductive surgery - viable treatment option in the management of platinum sensitive
recurrent ovarian cancer Michal Felsinger Jun 2018

SURVIVAL
No residual OS
45.2 mos.
> 10mm
OS 19.7 mos.
1-10mm
OS 19.6 mos.
Fig 1. Overall survival of patients with secondary cytoreductive surgery with no

residual tumour, residual tumour 1-10 mm and residual tumour >10 mm.
When should Surgery be used for Recurrent Ovarian Carcinoma, M. Bommert, P. -

Harter April 2018

CYTOREDUCTION OVARIAN CLASSIFICATION
Tertiary cytoreduction in
patients with recurrent
epithelial ovarian, fallopian
tube, or primary peritoneal
cancer: An updated. Shih -
R. Barakat GO, Feb 2010

CT – ANTICUERPOS MONOCLONALES
RECURRENT OVARIAN, PRIMARY PERITONEAL

INHIBIDORS DE LA PARP
A recent randomized phase II trial compared:

• Olaparib (200 mg bid and 400 mg bid) to
• Pegylated liposomal doxorubicin (50 mg/m2) in
BRCA
patients progressing within 12 months of
platinum.
• Iniparib,
• Veliparib
Poly-ADP-ribose polymerase (PARP) is a nuclear enzyme that contributes to the

repair of single-stranded breaks in DNA along the base excision repair pathway

INHIBIDORS DE LA PARP
MULTIPATHWAY TARGETED AGENTS

• Sorafenib
• Vandetanib
• Imatinib
• Dasatinib
• Cabozantinib
Poly-ADP-ribose polymerase (PARP) is a nuclear enzyme that contributes to the

repair of single-stranded breaks in DNA along the base excision repair pathway

Survival
Figure 1. Ten-year relative survival for epithelial ovarian cancer by stage of disease.
Information from the Surveillance, Epidemiology and End Results (SEER) database
(N ¼ 40,692) (Reproduced with permission) [1].
Surgery for advanced epithelial ovarian cancer Neville F. Hacker, May 2017

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CÁNCER DE OVARIO

DR. PEDRO HERNÁNDEZ MORÓN 1

• 6% todos cánceres • 1/70 mujeres

GYNECOLOGIC ONCOLOGY CLINICAL DISAIA 8th Edition 2014

DR. PEDRO HERNÁNDEZ MORÓN 2

GYNECOLOGIC ONCOLOGY CLINICAL DISAIA 9th Edition 2018

DR. PEDRO HERNÁNDEZ MORÓN

GYNECOLOGIC ONCOLOGY CLINICAL DISAIA 9th Edition 2018

DR. PEDRO HERNÁNDEZ MORÓN

Otros genes HNPCC BRCA2 (~20%)

DR. PEDRO HERNÁNDEZ MORÓN 7

Pathogenesis of Epithelial Ovarian

DR. PEDRO HERNÁNDEZ MORÓN 8

DR. PEDRO HERNÁNDEZ MORÓN 9

New insights into ovarian cancer pathology J. Prat* 2012.

DR. PEDRO HERNÁNDEZ MORÓN 10

Patogénesis Carcinoma de Ovario, Sánchez Juvenal, 2014

Pathogenesis of Epithelial Ovarian Cancer, Robert J. Kurman, 2010.

DR. PEDRO HERNÁNDEZ MORÓN 12

The Utility of Imnmunohistochemistry in Differencial Diagnosis of Gynecologic

DR. PEDRO HERNÁNDEZ MORÓN 13

 Carcinoma seroso de ovario

The Utility of Imnmunohistochemistry in Differencial Diagnosis of Gynecologic

DR. PEDRO HERNÁNDEZ MORÓN 14

Serous high grade

The Utility of Imnmunohistochemistry in Differencial Diagnosis of Gynecologic

DR. PEDRO HERNÁNDEZ MORÓN 15

The Utility of Imnmunohistochemistry in Differencial Diagnosis of Gynecologic

DR. PEDRO HERNÁNDEZ MORÓN 17

DR. PEDRO HERNÁNDEZ MORÓN 18

DR. PEDRO HERNÁNDEZ MORÓN 19

DR. PEDRO HERNÁNDEZ MORÓN 20

HE4 < 150 picomoles/L.

Guidelines, ACOG 2014

DR. PEDRO HERNÁNDEZ MORÓN 21

DR. PEDRO HERNÁNDEZ MORÓN 22

Gynecologic Oncology, Berek and Hacker 6th Edition 2015

DR. PEDRO HERNÁNDEZ MORÓN 23

Although CA125 is elevated in 83% of women with epithelial ovarian

Dr. PEDRO HERNÁNDEZ MORÓN

o IR Índice de resistencia doppler : < 0,4 25

o IR Índice de resistencia doppler : < 0,4*

Dr. PEDRO HERNÁNDEZ MORÓN

Dr. PEDRO HERNÁNDEZ MORÓN

Guidelines, ACOG 2014

DR. PEDRO HERNÁNDEZ MORÓN 28

DR. PEDRO HERNÁNDEZ MORÓN 29

La combinación de HE4 y CA125 en suero aumenta la precisión

DR. PEDRO HERNÁNDEZ MORÓN 31

 The serum levels of CA125

Dr. PEDRO HERNÁNDEZ MORÓN

DR. PEDRO HERNÁNDEZ MORÓN 33

Dr. PEDRO HERNÁNDEZ

Dr. PEDRO HERNÁNDEZ

MR imaging in ovarian cancer S.A.A. Reznekb 2007

DR. PEDRO HERNÁNDEZ MORÓN 36

 Recent studies have demonstrated high sensitivity

Dr. PEDRO HERNÁNDEZ

AJCC CANCER STAGING MANUAL Amin 8th

DR. PEDRO HERNÁNDEZ MORÓN 38

AJCC CANCER STAGING MANUAL Amin 8th

DR. PEDRO HERNÁNDEZ MORÓN 39

AJCC CANCER STAGING MANUAL Amin 8th Edition 2017