Complex Treatment of Female Genital Tract Neoplasms. Cervical, endometrial and ovarian cancer
Marcin Jędryka Oncogynecologist
Chair of Oncology, Wroclaw Medical University
Dept. of Oncological Gynecology Lower Silesian Cancer Center, Wroclaw Female genital tract neoplasms:
Corpus of the uterus: endometrial cancer; sarcoma Cervix: cervical cancer Adnexa: ovarian cancer and tubal cancer Vagina and vulva: vaginal cancer and vulvar cancer
Colposcopy – ectopic epithelium Colposcopy – ectopy after acetic acid and iodine solution Colposcopy – HSIL pictures Colposcopy – invasive cancer Colposcopy – invasive cancer Risk of metastases to the lymph nodes in ca. colli uteri
FIGO % pelvic nodes % paraortic nodes inolved involved
Ia 1 <1 0
Ia 2 1-4 <1 Ib 10-16 2-4
IIa 25 9-11
IIb 31-40 15-19
III 45-60 30-40
IVa 55-85 40-65
Cervical cancer - treatment
Methods of treatment
100 kobiet jest leczonych:
18 - surgery only
58 - chemoradiotherapy only
24 - both methods
( w I stopniu 43 % chorych jest leczonych tylko chirurgicznie) Optimal surgery of cervical cancer
Radical hysterectomy -the type of radicality should be fit o the patient and her disease – keep to the standards but individual attitude is important ! Always in the aspect of complex traatment – decision making in the team cooperation (radiotherapeutists. oncologists) After preop evaluation (espacially MRI of the pelvis is valuable) Always after discussion of withe the patients and written consent Preferably performed in the oncogyn deptarment by oncogynecologist Radical hysterectomy
1 – cardinal ligaments 2 – sacrouterine ligaments 3 – round ligaments 4 – infundibulopelvic ligaments Radical hysterectomy
1 – paravesical fossa 2 – vesical peritoneal fold 3 – vesicouterine ligament 4 – pararectal fossa 5 – pouch of Douglas 6 – sacrouterine ligament 7 – cardinal ligament Radical hysterectomy
1 – urether 2 – parametrium Radical hysterectomy
1 – urether 2 – divided round ligament Radical hysterectomy
1 – ext. iliac artery 2 – paravesical space 3 – int. iliac artery 4 – pararectal space Radical hysterectomy
1 – ext. iliac artery 2 – ext. iliac vein 3 – interiliac lymph nodes 4 – int. iliac artery Radical hysterectomy
1 – uterine artery 2 – ext. iliac vein 3 – obturator nerve 4 – int. iliac artery 5 – paravesical fossa 6 – pararectal fossa Radical hysterectomy
3 – bladder 4 – divided vesicouterine ligament 5 – urether 6 – divided parametrium 7 – paravesical space Radical hysterectomy
1 – bladder 2 – left urether 3 – right urether 4 – vagina 5 – uterus 6 – vesicouterine ligament – internal part Radical hysterectomy
1 – left urether 2 – sacrouterine ligament 3 - rectum Radical hysterectomy – final specimen Cervical cancer – methods of treatment
Indications for surgery: * early stages (IA ––IIII A) * big fibroids, ovarian tumours, PID in advanced stages (IIB and more) before chemoirradiation Indication for chemoradiotherapy: * advanced stages (IIB – IVA) * early stages after surgery in case of poor prognosis factors * early stages in case of inoperability or lack of consent Radiation of cervical cancer
radical (therapeutic as alone method)
post-op (as adiuvant therapy)
pre-op (to shrink the tumor – IB2)
paliative (haemorrhage, bone metastases) Post-op indication for irradiation
metastases to lymph nodes
parametria infiltration
surgical margins are infiltrated
metastases to adnexa
uterine corpus infiltration Grading G2/G3, LVSI, Currently the standard treatment means chemoirradiation
- FIGO IIB - IVA - Post-op adiuvant treatment
- radiotherapy (tele- and brachyterapy)
- chemotherapy: cisplatin : 40 mg/m2 every week; 6 cycles (combined with teletherapy)
Addition of chemotherapy gives the 10-15% improval of ENDOMETRIAL HYPERPLASIA WITHOUT ATYPIA
Exagerrated proliferation of endometrium due to estrogen stimulation
Hyperplasia of glands and stroma
Divided acc. to histopathological exam: simple, complex
Treatment: progestins ENDOMETRIAL HYPERPLASIA WITH ATYPIA
* Precursor of endometrioid cancer of endometrium * Due to spontaneus single mutations (K- Ras, Ki 67) of endometrial glands * Divided acc. to histopathological exam: simple and complex * Treatment: simple hysterectomy Cancer of endometrium – type I
ENDOMETRIOID CARCINOMA - Adenocarcinoma (typical) - Secretory (variant) - Ciliated cell (variant) - villoglandular (variant) - Adenocarcinoma with squamous differentiated („adenoacanthoma”)
ADENOCARCINOMA MUCINOSUM (<9%) Cancer of endometrium – type II
Nonendometrioid carcinoma:
Serous papillary carcinoma,
Clear cell carcinoma Endometrial cancer. 5-y OS concerning GRADING:
G1 80-85% G2 74-78% G3 50-64% Endometrial cancer. 5-y OS concerning STAGING
FIGO I - 83% FIGO II - 73% FIGO III - 52% FIGO IV - 27% Endometrial cancer. Prognostic factors
Histologic type Grading (G) Staging (FIGO, TNM) Myometrium infiltration Lymph vessels infiltration Cervix infiltration Lymph node metastases Receptors (ER, PR) Molecular biology and gene expression of p53, bcl2, MSI, PTEN Methods of endometrial cancer treatment
Surgery only
Radiotherapy: tele + brachy
Surgery + radiotherapy
Surgery + radiotherapy and adiuvant systemic treatment (chemotherapy, hormonotherapy)
Radiotherapy and subsequent surgery Surgery of endometrial cancer
Qualification: Histologically prooved endometrial cancer
Qualification of internal doctor and anaesthetist: OBESITY, HYPERTENSION, DIABETES, ASTHMA Surgery of endometrial cancer
Stage I: simple hysterectomy with bilateral salpingooophorectomy (abdominal, laparoscopical, robotic) Surgery of endometrial cancer
Stage II and III: radical hysterectomy with bilateral salpingoophorectomy (dependent on technical aspects – obesity, patient's performance status and health ability for longer operation ) Surgery of endometrial cancer
Surgical and histological assessement of disease spread: Hysterectomy alone is not enaugh Full FIGO staging is mandatory
Retroperitoneal lymph nodes assessemnet… (systematic lympadenectomy vs biopsy vs SN) Surgery of endometrial cancer. When systematic lympadenectomy (pelvic and paraortal)?
Stage IC - IIIB Myometrial infiltration > 50% or tu. > 2 cm id diameter IIIC – lymph nodes infiltrated ! Bulky nodes !
Grading G3 Type II cancer (serous or clear cell) ca. adenosquamosous Endometrial cancer Percentage of lymp nodes involvement in stage I in comparison with myometrial invasion and Grading (n=621, metastases in 144 pts. -22%)
Depth of GRADING myometrial G1 G2 G3 infiltration
Inner 1/3 of 3% 5% 9% myometrium
2/3 depth of 0% 9% 4% myometrium
Full thickness of 11% 19% 34% myometrium
Creasman WT, Morrow CP, Bundy BN et al. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987; 60:2035-41 Endometrial carcinoma Probability of lymph nodes metastases depending on FIGO stage and grading in stage I (metaanalysis, Kreienberg 2005)
STAGE Pelvic (%) Paraortal (%)
FIGO Ia, b G1 3 2
FIGO Ib G2,3 9 4-6
FIGO Ic G1-3 18 16
FIGO II 29-41 16-30
FIGO III 66 33
FIGO IV 44 Indications for adiuvant treatment of endometrial cancer (after surgery) Risk factors of relapse in endometrial cancer
Age(> 60y pts.pts . oftenmore advanced, advanced , with G3 and M > 50%)
Carcinoma cells inin lymphatic vessels (LVSI) –– independent risk and predictive factor of metastases to the pelvic lymph nodes, nodes ,
Retroperitoneal lymph nodes metastases Risk factors of relapse in endometrial cancer
myometrial infiltration > ½ depth; grading = G2, G3; cervical infiltration; parametrial infiltration; adnexal metastases; cancer cells in peritoneal cytology; type II cancer: ca clarocellulare , ca serosum; Radiotherapy of endometrial cancer
Low risk group Intermediate risk group (I(I °°°AA--G1,2)G1,2) (I °°°A-G3, I °°°B-G1,2) •• Surgical treatment is * Surgical treatment following sufficeint by brachytherapy only •• No need for irradiation allows to cure 90% of pts. Radiotherapy of endometrial cancer
High Risk Group. Stage IB G3 and II and III Both tele- and brachy therapy is recomended after the surgery Such combined treatment allows to treat more sufficient In high risk factors such as G3, lymph nodes metastases, distant organs metastases chemotherapy should be introduced before irradiation Brachytherapy in oncogynecology
- input of irradiation source in the proximity of cured tissue - different applicators – ovoids, uterine cavity probes, vaginal probes
− after-loading methods; (LDR; cezium ): 2 or 3 applications of probe to the uterine cavity and ovoids to the fornices of vagina; single application time: approx. 6 – 8 hrs, repeated after 5-7 days − (HDR; irydium ): 4 to 6 applications lasting several minutes in ambulatory conditions
Teletherapy in oncogynecology
Accelerators – megavolt energy therapy ensures the proper dose of tumor irradiation preserving the skin and critical organs (such as bl adder or rectum)
Irradiation scheme: total time: 4-5 weeks, each day (5 days in a week) fraction lasts several minutes kilka minut - totally 20 – 25 fractions. Irradiation field: pelvis and sometimes paraortal a rea to the level of L1/L2
Ovarian cancer
Surgical treatment is the primary choice in ovarian cancer patients Real assessment of disease spread often can be done earlier then during the operation
guzki otrzewnej krezki jelita cienkiego (materiał własny)
Ovarian cancer surgery
IA G1G1 the only situation when reproductive possibilities can be preserved (Adnexectomy, staging procedure including lymph nodes sampling) and no adiuvant chemo is demanded In all other cases (almost all of the patients) Optimal, primary cytoreduction = No residual tumor masses after surgery In case of advanced ovarian cancer in case of inoperability
Interval, debulking surgery
Explorative laparotomy/laparoscopy
Secondary cytreduction after neoadiuvant chemotherapy Other types of operations inin ovarian cancer patientspatients:: secondsecond--looklook procedure
cytoreduction of persistent disease
Secondary debulking surgery of relapses
Paliative surgery Chemotherapy of ovarian cancer
* Adiuvant after optimal, primary debulking •Adiuvant after non optimal primary surgery before second cytoreduction •Neoadiuvant therapy – before the ateempt of primary cytoreduction •Secondary - in case of relapse •Paliative – in case of dissemintaed porogression Ovarian cancer Chemo agents
* Cisplatin (DDP) * Ifosfamide (IFX) * Karboplatin (CBDCA) * Etoposide (VP 16) * Ciclophosphamide (CTX) * Gemcytabine (GCB) * Doxorubicine (DOX) * Liposomal DOX * Mitom ycin (MTC) * Melfalan (MPL) * Metotreksat (MTX) * Paclitaxel (PCL) * Mitoxantron (MTZ) * Docetaksel (DCL)
* Topotekan (TPT) Chemo in ovarian cancer – multidrug regime
Response rate (CR/pCR) 70-80% (40-50%/20-30%)
Overall survivall 5 ys ~ 35-40% Overall survival 10 ys ~ 20 -25 %
* Multidrug, first line regime = PCL + DDP = GOLDEN STANDARD * No of cycles – 6 (every 3 week) 2nd line treatment
* Primary response to DDP chemotherapy : PFS > 6 mths - attempt of secondary cytoreduction - CHEMO (DDP/CBDCA + PCL)
* Primary response to DDP chemotherapy : PFS < 6 mths - attempt of secondary cytoreduction - CHEMO: lipo-DOX / TPT / GCB / IFX / VP 16 – choice dependet on patients’ status and costs 2nd line treatment
Time to progression or PFS (progression free survival) ⇓⇓⇓ The most important factor of efficacy of CHEMO II o
Relapse after CTH I o Probability of RR-CTH II o 6 < /12 10 % 12 - /12 29% 18 - /12 63% 18 > /12 94% * Blackledge et al. BJC 1989 Follow-up after ovca treatment - Gynecological examination – every 3 mths - Ca 125 – every 3 mths - Chest X-ray - once a year - Ultrasound or CT assessement of pelvis and abdomen – once a year - PET-CT in suspition of progression when USG, CT ora MRI are not clear Thank you