Genital cancers and pregnancy

Assoc. Prof. Gazi YILDIRIM

Incidence by Age of the More Common Malignancies Seen in

Pregnancy

American Cancer Society, Facts and Figures, 1995

Incidence of Tumor Types in

Pregnant Women

Cancer, fertility and pregnancy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Pentheroudakis G, Orecchia R, Hoekstra HJ, Pavlidis N; ESMO Guidelines Working Group.Ann Oncol. 2010 May;21 Suppl 5:v266-73.

Cancer in pregnancy

• The incidence of cancer in pregnancy is approx 1 in 1000.

• The most common malignancy diagnosed during pregnancy is cervical cancer. (1 in 750)

Cancer in pregnancy

• Cervical cancer (26 %)

• Breast cancer (26 %)

• Leukemias (15 %)

• Lymphomas (10 %)

• Malignant melanomas (8%)

Cervical Cancer in Pregnancy

• Work-up• MRI of pelvis/abdomen• Chest X-ray• Carcinoembryonic Antigen (CEA)• CBC, BUN, Creatine, LFT’s

• Advanced disease• Urine cytology/ cystoscopy• Stool for occult blood/ sigmoidoscopy

Cervical Cancer in

Pregnancy: Treatment by

Stage• Stage IA1 - <3mm invasion; < 7mm wide

• 1.2% positive nodes• Cone biopsy: no further treatment necessary • Vaginal delivery at term• Simple hysterectomy post-partum or Cesarian

hysterectomy at term

Cervical Cancer in

Pregnancy: Treatment by

Stage• Stage IA2 (3-5mm invasion, no vascular inv.):

• 6.3% positive nodes

• Stage IB – Disease confined to cervix

• Stage IIA – vaginal extension• Vaginal delivery: increased risk of hemorrhage and

cervical laceration• Depends on desire for pregnancy

• First trimester: delay of up to 28 weeks – degree of risk unknown

• Radical hyst. and pelvic LND at diagnosis• “Radical” cone biopsy/ trachelectomy/ cerclage and

extraperitoneal pelvic and aortic LND at 16-18 weeks• C-Section and Radical hyst. and pelvic LND when mature

Cervical Cancer in

Pregnancy: Treatment by

Stage• Stage IA2, IB, IIA

• Second trimester: delay of up to 22 weeks• Depends on desire for pregnancy

• Can probably safely wait until maturity

• Third trimester: delay of up to 10 weeks• C-section, Radical hysterectomy and pelvic

Lymph node dissection at maturity

Cervical Cancer in Pregnancy:

Treatment by Stage• Stage IB (bulky) or Stages IIb-IV

• First trimester – delay of up to 28 weeks• Depends on desire for pregnancy

• Unwanted • Whole pelvic radiation therapy/ chemotherapy• If SAB occurs before XRT is finished – proceed with

cesium insertions (about 35 days)• Occasionally will need hysterotomy and pelvic LND

if no SAB and then cesium insertions; or a “small” radical hyst. & pelvic LND if small residual cervical disease

• Wanted• Consider chemotherapy until maturity at 34 weeks

Cervical Cancer in

Pregnancy: Treatment by

Stage• Stage IB (bulky) or Stages IIb-IV

• Second trimester – delay of up to 22 weeks• Unwanted: pregnancy – Radiation therapy as above

• Spontaneous abortion at 35 days

• Wanted: pregnancy – consider chemotherapy until maturity

• Third trimester – delay of up to 10 weeks• C-Section at maturity/ staging lap; transpose ovaries• Start radiation therapy 2 weeks postpartum• Consider chemotherapy until maturity

Ovarian masses

• Incidental finding in pregnancy is common (1-4%)

• Majority are functional or CL cysts and spontaneously resolve by 16 weeks gestation

• Unilateral

• Noncomplex 90% functional

• Less than 5 cm resolve spontaneously

• Noticed in 1st trim

Ovarian masses

• Three main reasons for advising surgery for an adnexal mass in pregnancy are;

• Risk of rupture

• Risk of torsion

• Risk of malignancy

Torsion of adnexa

• The most common time for occurrence is between 6 and 14 weeks and in the immediate puerperium.

• Commonly associated with a cystic neoplasm

• Symptoms are usually sudden onset abdominal pain and tenderness

• Right ovary is involved more frequently than left ovary

• Benign cystic teratomas and cystadenomas are most common..

Ovarian Masses in Pregancy

• Overall incidence• 1:500 pregnancies• Increased incidence secondary to sonography

• Incidence of true neoplasms• 1:1,000 pregancies

• Incidence of ovarian cancer• 1:10,000 – 1:25,000 pregancies

• Unexpected adnexal mass at C-Section• 1:700 pregnancies

Ovarian Masses in

Pregnancy Frequency by

Type• Non-neoplastic – 33%• Corpus luteum cyst• Follicular cyst

• Neoplastic – Benign – 63%• Dermoid (36%)• Serous cystadenoma (17%)• Mucinous cystadenoma (8%)• Others (2%)

• Neoplastic – Malignant – 5%• Low malignant potential (3%)• Adenocarcinoma (1%)• Germ cell / Stromal tumor (1%)

Management of Ovarian

Masses in Pregnancy• Generalizations• Symptoms• Ultrasound/ MRI appearance• Size• Gestational age• Tumor markers

• B-HCG, AFP, CA-125 all increased in pregnancy• CA-125 should be normal after 1st trimester

• Fear of missing cancer or development of complications• Corpus luteum resolves by 14th week• Ovarian cysts “benign” by Ultrasound or MRI, < 6 cm,

that do not change over time, do not require surgery• Cysts greater than 6-8 cm or inc. in size: “usually”

operated on• Cysts which persist after 18th week are “usually”

operated on

• Usually operate at 18 weeks to minimize fetal loss

Complications of Ovarian

Masses in Pregnancy: 10%

Total• Severe pain: 25%

• Obstruction of labor: 15% – C-Section

• Torsion: 10% of cases• Sudden pain, Nausea & Vomiting etc.• Most common at:

• 8-16 week – rapid uterine growth (60%)• Postpartum – involution (40%)

• Hemorrhage: 10% of cases• Ruptured corpus luteum• Germ cell tumor

Complications of Ovarian Masses in

Pregnancy• Rupture/ tumor dissemination (10%)

• Anemia

• Malpresentations

• Necrosis

• Infection

• Ascites

• Masculinization of female fetus• Hilar cell tumor• Luteoma of pregnancy • Sertoli-Leydig cell tumor

Work-up of Ovarian Cancer

• Pelvic ultrasound

• MRI pelvis/ abdomen

• Chest X-ray

• CA-125: elevated in normal pregnancy, should normalize after 12 weeks

• AFP, B-HCG, LDH – predominantly solid mass

• Liver FunctionTests, BUN, Creatinine

• GI studies only if clinically indicated

Management of Ovarian Cancer

• Prognosis not affected by pregnancy

• Tumors of Low Malignant Potential – all stages (20%)

• Adenocarcinoma Stage I, grade 1 or 2 (10%)

• Germ cell tumors (5%) – may require chemotherapy

• Gonadal stromal tumors (15%)

• Surgery at 16-18 weeks if possible

• Frozen section: beware of inaccuracies

• Conservative ovarian surgery• Adnexectomy/ Oophorectomy/ Cystectomy

• Hysterectomy not indicated

• Thorough staging:• Pelvic/ aortic node disection/ Omentectomy/ peritoneal biopsies

Management of Ovarian Cancer

• Epithelial Ovarian Cancer Stage IC – IV• Try to delay chemotherapy until 12-16 weeks of

pregnancy• Try to delay removal of corpus luteum until 14

weeks• First trimester

• TAB followed by appropriate surgery and chemotherapy• Chemotherapy after FNA:

• C-Section and appropriate management at maturity

• Second and Third Trimester• Chemotherapy first

• C-Section and appropriate surgical management at maturity

Malignant Germ Cell Tumors

• Dysgerminoma• 30% of Ovarian malignant neoplasms in

pregnancy• Most stage IA• Average 25cm; solid• Therapy

• Surgery: USO, wedge biopsy of opposite ovary, surgically stage• 25% are bilateral

• Stage IA & IB: No further treatment• Advance stages

• Hysterectomy not required• Chemotherapy

Malignant Germ Cell Tumors

• Endodermal sinus tumor

• Grade 2-3 malignant teratoma

• Choriocarcinoma (non-gestational)

• USO and staging for early disease

• All require chemotherapy regardless of stage

Tumor like Ovarian

Lesions Associated with

Pregnancy• All resolve spontaneously after delivery

• Conservative surgical approach: frozen section +/- oophorectomy• Luteoma of pregnancy - usually an incident. finding at C-

Section• Microscopic. -20cm – multiple nodules• Bilateral: 1/3 of cases• 25% have increased. testosterone• Maternal masculinization. – later ½ of pregnancy• Fetal virilization – 70% of female infants

• Hyperreactio Luteinalis - Bilateral multicystic theca lutein cysts• Large solitary luteinized follicular cyst of pregnancy• Hilar Cell Hyperplasia – masculinized fetus• Intrafollicular Granulosa cell proliferations• Ectopic Decidua

Breast Cancer in

Pregnancy

(2nd most common cancer in

pregnancy)• 20% of cases are in women <40 years old

• 1-2% of cases are pregnant at time of diagnosis

• One case/1500-3000 pregnancies

• Often difficult to diagnose

• Low dose mammogram with appropriate shielding of fetus is “safe”

• MRI – probably best

• Diagnosis often delayed

• Increase incidence of positive nodes (80%)

• Termination of pregnancy & proph. castration is not beneficial

• No adverse effects on prognosis from subsequent pregnancies

Treatment of Breast Cancer

• Treatment same as non-pregnant

• Lumpectomy

• Sentinal node biopsy • 2.5mCi technetium 99 – 4.3 mGy at worst. Usually contraindicated.• +/- radiation• Chemotherapy

• Modified radical mastectomy and nodes

• Adjuvant chemotherapy after 16 weeks• CAF better than CMF in 1st trimester

• Axillary or localized chest wall RXT is probably safe after the first trimester but can be difficult to shield fetus.

• Prognosis:5 Yr Disease Free

Survival

Stage I 85%

Stage II 60%

Stage II 40%

Stage IV 5%

Metastases to Fetus/Placenta

Only 50 cases in literature

• Melanoma (50% of reported cases)

• Leukemia: 1/100 affected pregnancies

• Lymphoma

• Breast

Gestational Age and Effects of

Antineoplastic Therapy

Cancer, fertility and pregnancy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Pentheroudakis G, Orecchia R, Hoekstra HJ, Pavlidis N; ESMO Guidelines Working Group.Ann Oncol. 2010 May;21 Suppl 5:v266-73.