CES2019-01: Cáncer ginecológico III - Visión del oncólogo

CES2019.01 – Cáncer ginecológico III – Visión del
oncólogo
Mauricio Lema Medina MD
@Onconerd

Topics
• Cervical cancer
• Ovarian cancer
• Endometrial cancer

Objetivo
• Obtener un conocimiento GENERAL del manejo USUAL de pacientes
con las patologías a discutir desde la sospecha diagnóstica, hasta el las
pautas de seguimiento post-tratamiento, pasando por los aspectos
más relevantes de tratamientos con intención curativa.

Cancer New cases (World) Deaths (World) New cases (Colombia) Deaths (Colombia)
Breast 2’088.849 (2) 626.679 (5) 13.380 (1) 3.702 (4)
Prostate 1’276.106 (4) 358.989 (8) 12.712 (2) 3.166 (5)
Lung 2’093.876 (1) 1’761.007 (1) 5.856 (5) 5.236 (2)
Stomach 1’033.701 (5) 782.685 (3) 7.419 (4) 5.505 (1)
Colon & rectum 1’849.518 (3) 880.792 (2) 9.140 (3) 4.489 (3)
Lymphoma (NH) 509.990 (10) 248.724 (11) 4.170 (6) 1.676 (10)
Uterine cérvix 569.847 (8) 311.365 (9) 3.853 (7) 1.775 (9)
Leukemia 437.003 (12) 309.006 (10) 3.126 (8) 2.192 (7)
Ovarian 295.414 (17) 184.799 (14) 2.414 (9) 1.252 (11)
Pancreas 458.918 (11) 402.232 (7) 2.311 (10) 2.142 (8)
Liver 841.080 (6) 781.636 (4) 2.279 (11) 2.216 (6)
Multiple mieloma 159.885 (21) 106.105 1323 (14) 806 (14)
Esophagus 572.034 (7) 508.585 (6) 922 (15) 710 (15)
Hodgkin 79.999 (25) 26.167 743 (16) 216
Brain 296.851 (16) 241.037 (12) 1884 (12) 1.176 (12)
Gallbladder 219.420 (19) 165.087 (17) 1657 (13) 1.104 (13)
All 18’078.957 9’555.027 101.893 46.057
http://gco.iarc.fr/today/

FIGO CANCER REPORT 2018 (Bhatla N. Int J Gynecol Obstetrics 2018; 143 (Suppl. 2): 22-36

Clinical suspicion
Colposcopy and
biopsy
Suspicious cytology
TNM/Stage

Workup Comment 1 Comment 2
H&P
Colposcopy and biopsy
Chest imaging In stage I: plain CXR, followed by CT if abnormal
Consider pelvic MRI Preferred for FIGO stage IB2, and higher
FDG PET-CT For FIGO stage IB2, II, III, and IVa.
Also consider after incidental cervical cancer after total
hysterectomy
In stage IB1 if fertility sparing desired
Chest/abdomen/pelvic CT
(if PET-CT not available)
For FIGO stage IB2, II, III, and IVa.
Also consider after incidental cervical cancer after total
hysterectomy
In stage IB1 if fertility sparing desired.
Cervical cancer
https://www.nccn.org

Clinical suspicion
Colposcopy and
biopsy
Suspicious cytology
TNM/Stage
Early Locally-advanced Metastatic

Cervical cancer

Stage IB:
Confined to the cervix
Depth more than 5 mm
Width more than 7 mm

Bulky Stage IB:
Confined to the cervix
More than 4 cm

Cervical cancer
Concurrent platinum-based radiotherapy

Cervical cancer
Concurrent platinum-based radiotherapy
High-risk features: LVSI or invasion
of the outer one-third of the
cervical storm

Locally-advanced cervical
cancer

Improved Treatment for Cervical Cancer —
Concurrent Chemotherapy and Radiotherapy
Thomas, G. M. (1999). Improved Treatment for Cervical Cancer ? Concurrent Chemotherapy and Radiotherapy. New England
Journal of Medicine, 340(15), 1198–1200. https://doi.org/10.1056/NEJM199904153401509

Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a
systematic review and meta-analysis of individual patient data from 18 randomized
trials.
Meta-Analysis Collaboration. (2008). Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials. Journal of Clinical Oncology, 26(35), 5802–5812. ht

Cisplatino: 40 mg/m2/cada semana por 6 (Junto con teleterapia)
Teleterapia (EBR) – Lunes a viernes, por 6-7 semanas - 4000-5000 cGY
Braquiterapia (4000 -5000 cGy)
1 7 14 21 28 35 (Días)

Cervical cancerConcurrent platinum-based radiotherapy

Stage Absolute 5-yr survival
benefit
Ib-IIa 10%
IIb 7%
III-IVa 3%
Reducing uncertainties about the effects of chemoradiotherapy for
cervical cancer: a systematic review and meta-analysis of individual
patient data from 18 randomized trials.
Meta-Analysis Collaboration. (2008). Reducing Uncertainties About the Effects of Chemoradiotherapy for Cervical Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data From 18 Randomized Trials. Journal of Clinical Oncology, 26(35), 5802–5812. ht

Post-operative radiation
therapy (PORT)

High risk (any) Intermediate-risk (any
two of three)
Low-risk
(no high-risk factors,
and only one of three)
Positive margins Tumor size >4 cm Tumor size >4 cm
LN metastases (N1) LVSI LVSI
Parametrial spread Deep stromal invasion Deep stromal invasion

Cervical cancer surveillance
interval history and physical examination every 3-6 mo for 2y, every 6-12 mo for 3-5 y, then annually based on
patient’s risk of disease recurrence
Cervical/vaginal cytology annually as indicated for the detection of lower genital tract neoplasia
Imaging as indicate based on symptoms or examination findings suspicious for recurrence
Laboratory assessment as indicated based on symptoms or examination findings suspicious for recurrence
Patient education regarding symptoms of potential recurrence, periodic self-examinations, lifestyle, obesity,
exercise, sexual health (including vaginal dilator use, lubricants/moisturizers, hormone replacement therapy),
smoking cessation, nutrition counseling, and potential long-term and late effects of treatment

Ovarian Cancer Histologies
Epithelial - 85%
Older than 40
Serous
75%
Mucinous
20%
Bulky
Differential
diagnosis with
Pseudomixoma
Endometrioid
2%
Others
Clear cells
Brenner
Indifferentiated
tumors
Mixed histologies
DeVita. Cancer: Principles and Practice of Oncology, 9th Edition
Diapositiva diseñada por Ana Milena Roldán, MD

HISTOLOGÍA CÁNCER DE
OVARIO
5% GERMINALES
75% DE NEOPLASIAS OVÁRICAS MALIGNAS EN MUJERES <30 AÑOS
TERATOMA QUÍSTICO
Con frecuencia
contienen cabellos,
dientes y hueso
calcificado.
1% malignos
Struma ovárico
DISGERMINOMA
Equivalente al
Seminoma del varón
10-15% bilaterales
B- HCG y AFP
OTROS:
Tumor del Seno
Endodérmico
Carcinoma
Embrionario
Coriocarcinoma
Gonadoblastoma

HISTOLOGÍA
10% ESTROMA OVÁRICO
DE LA GRANULOSA
Productor de
estrógenos
Ocasionan
trastornos
menstruales y
pubertad precoz
T. C. DE LEYDIG Y
SERTOLI
Productor de
andrógenos
Ocasionan
virilización e
hirsutismo
TECOMAS
Productor de
estrógenos y
andrógenos
ANDROBLASTOMA
Productor de
andrógenos
Primera causa de
virilización de origen
ovárico
El patólogo también debe informar el grado de diferenciación:
Grado I para los bien diferenciados y Grado III para los pobremente diferenciados.

Abdominal distention
Abdominal / Pelvic
imaging
Suspicious abdominal or
pelvic mass
Workup
Ascites
Non-specific
Bloating
Pelvic/abdominal pain
Difficulty eating
Feeling full quickly
Urinary symptoms (urgency, frequency)

Workup
H&P
Abdominal / pelvic exam
Ultrasound and CT/MRI as clinically indicated
Chest CT or Chest X ray as clinically indicated
Ca 125 or other tumor markers as clinically indicated
Evaluate nutritional status
GI evaluation as clinically indicated
Obtain a family history
Refer to gynecologic oncologist for clinically suspicious lesions
Ovarian cancer

Abdominal distention
Abdominal / Pelvic
imaging
Suspicious abdominal or
pelvic mass
Ovarian cancer
suspected
Ascites
Non-specific
Bloating
Pelvic/abdominal pain
Difficulty eating
Feeling full quickly
Urinary symptoms (urgency, frequency)
Surgical candidate
Not a surgical
candidate

Surgical candidate
Stage IA or IB
Grade 1
-Endometroid
Surveillance
Stage IA or IB Grade 3 or Clear Cell
(some grade 2)
Stages IC-IV
Platinum-based
chemotherapy
Surveillance
GOG 218: Carboplatin +
Paclitaxel +/- Bevacizumab
(Stages III or IV)

Vergote (EORTC): Preoperative
Carboplatin + Paclitaxel x2-3 months
Not a surgical
candidate Bulky stage III or IV disease. or poor
surgical candidate
Intervaldebunking
surgery

Epithelial ovarian cancer surveillance
Interval history and physical examination (including pelvic exam) every 2-
4 mo for 2 y, then 3–6 mo for 3 y, then annually after 5 y
Chest/abdominal/pelvic CT, MRI, PET/CT, or PET as clinically indicated
Chest x-ray as indicated
CBC and chemistry profile as indicated
Ca-125 or other tumor markers if initially elevated
Refer for genetic risk evaluation
Long-term wellness care

Criterios para investigación genética para cáncer hereditario
Caso índice
Ca ovario
Ca páncreas
Ca próstata metastásico
Azkenazi + Ca mama
Azkenazi + Ca próstata (Gleason ≥7)
Ca mama ≤50 años
Ca mama triple negativo ≤60 años
Ca de mama x2 (primarios)
NCCN, 2018

Ca de mama, con ≥1 familiar cercano con:
Caso índice
Cáncer de mama ≤50 años
Cáncer de ovario
NCCN, 2018
Cáncer de mama en varón
Cáncer de próstata de alto grado (Gleason ≥7)
Cáncer de próstata metastásico
≥2 familiares con cáncer de mama

Sin cáncer
Caso índice
Gen de susceptibilidad mutado en la familia
Gen de susceptibilidad mutado en el individuo
Individuo con familiar y 1er y 2ndo grado con:
NCCN, 2018
Cáncer de mama ≤45 años
Cáncer de ovario
Cáncer de mama en varón
Cáncer de próstata de alto grado (Gleason ≥7)
Cáncer de próstata metastásico
≥2 familiares con Ca de mama, con uno ≤50 años
≥2 primarios de Ca mama en el mismo individuo

Caso índice
Individuo con familiares del mismo lado con ≥3:
NCCN, 2018
Ca de mama, sarcoma, Ca adrenocortical, tumores
cerebrales, leucemia
Ca colon, Ca endometrio, Ca tiroides, Ca renal,
cambios dermatológicos, macrocefalia, hamartomas
gastrointestinales
Ca lobulillar de mama, Ca gástrico difuso
Ca mama, Ca gastrointestinal o pólipos
hamartomatosos, Ca ovarianos (sex chords), Ca
páncreas, Ca Sertoli, Childhood skin pigmantation
Li-Fraumeni (p53)
Cowden (PTEN)
CIDH (E-Cadherin)
STK

Criterios para investigación genética para cáncer de mama hereditario
Cáncer de mama con cualquiera de los siguientes:
Ca ovario
Ca páncreas
BRCA1/2 mutado en cualquier tumor
Judía Azkenazi
≥2 Ca mama adicionales en pt/familia cercana
Ca mama ≤50 años*
Ca mama triple negativo ≤60 años
Ca de mama x2 (primarios)
NCCN, 2018
En la paciente con (cualquiera):
*Otro cáncer de mama primario, historia familiar de cáncer de mama, historia familiar desconocida o limitada, o menor de 45 años
Ca de mama ≤50 años
Ca de ovario
Ca de mama en varón
Ca de próstata de alto grado (Gleason ≥7)
Ca de próstata metastásico
≥2 familiares con cáncer de mama
≥1 familiar cercano con:

Pure endometrial cancer
Endometrioid

Total hysterectomy and bilateral
salpingo-oophorectomy, and surgical
staging
No cervical involvement
Total hysterectomy and bilateral
salpingo-oophorectomy, and surgical
staging
Cervical involvement
Preoperative
External-beam RT

High-risk endometrial cancer
Serous
Clear cell
Undifferentiated
Dedifferentiated
Carcinosarcoma

Total hysterectomy and bilateral salpingo-oophorectomy,
and surgical staging
High-risk histology
Adjuvant systemic chemotherapy
Adjuvant RT (stages IB-IV) + brachytherapy (All)

Drug MOA Included in Main toxicities
Cisplatin Similar to
alkylating
agents (anti
DNA agent)
Chemo-RT
Single-agent metastatic
And, other protocols
Renal dysfunction
Nausea/vomiting
Hypokalemia
Hypomagnesemia
Otic toxicity
Peripheral neuropathy
Carboplatin Similar to
alkylating
agents (anti
DNA agent)
Adjuvant and first-line agent in ovarian
and endometrial cancer
Nausea/Vomiting
Myelosuppression
Thrombocytopenia
Paclitaxel Microtubule
poison
GOG 240: Cisplatin + Paclitaxel +
Bevacizumab
GOG 218: Ovarian cancer
Joint pain
Myelosuppression
Peripheral neuropathy
Bevacizumab Anti VEGF
monoclonal
antibody
Metastatic cervical cancer - in first-line
Post surgery in high-risk stage III/IV
ovarian cancer
Hypertension
Bleeding
Delayed wound healing
Proteiunria

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