Radiation Oncology/Ovary/Overview

Ovarian Cancer Overview

Epidemiology

• Median age 60's, peak incidence 80's
• 22K cases per year in US; 4th most common cancer in women
• 14K deaths per year in US; 5th most common cause of cancer death in women

Risk factors

• Genetics
  • One first-degree relative: 4-5% lifetime risk
  • Two first-degree relatives: 25-50% lifetime risk
  • BRCA1/BRCA2
  • HNPCC
• Hormone exposure: nulliparity, early menarche, late menopause, hormone replacement
• Ovarian trauma, including multiple cycles of ovulation
• Environmental: endometriosis, obesity, smoking, diet

Screening

• Prostate, Lung, Colorectal, and Ovarian Screening Trial (1993-2001)
  • Randomized. 34,261 women in the screening arm. General population, age 55-74. Transvaginal ultrasound and CA-125. Screening compliance 83% to 78%
  • 2009 PMID 19305319 -- "Results from four rounds of ovarian cancer screening in a randomized trial." (Partridge E, Obstet Gynecol. 2009 Apr;113(4):775-82.)
    • Outcome: Data from first 4 annual screens. Positive screen ~5% (about 2/3 TVU and 1/3 CA-125). Ratio of surgery to cancer detection 20:1. Overall yield ~5/10,000 screened. Majority (72%) late stage.
    • Conclusion: Ratio of surgeries to screen-detected cancers high, and most were late stage

Presentation

• Generally present with ill-defined symptoms and diagnosis may be delayed
  • Abdominal pain, nausea, anorexia, early satiety or constipation.
  • Irregular vaginal bleeding
  • Dyspareunia
  • Urinary symptoms
• Palpable adnexal mass
  • Pre-menopausal: 5% risk of malignancy
  • Post-menopausal: 30-60% risk of malignancy
• Paraneoplastic presentation (rare):
  • Leser-Trelat Sign – Sudden multiple seborrheic keratoses
  • Trousseau’s Syn – Migratory thrombophlebitis
• Hormonal effects – Germ Cell Tumors
  • Precocious puberty, amenorrhea, virilization
• Meigs' syndrome - Ascites, an ovarian tumor, and right-sided pleural effusion
• 80% have spread beyond the ovary at presentation.

Anatomy

• Located in lateral pelvis, beneath external illiac artery and in front of internal illiac artery
• Attached to the uterus by ovarian ligament and the body wall by suspensory ligament; within the broad ligament
• There are 3 major tissue types in the ovary, which give rise to different types of tumors:
  • Surface: covered by ovarian epithelium
  • Stroma:
    • Soft tissue consisting of spindle-shaped cells (regarded by some anatomists as unstiped muscle cells and others as connective-tissue cells)
    • On the surface of the ovary, this tissue is much condensed, and forms a layer (tunica albuginea) composed of short connective-tissue fibers, with fusiform cells between them
  • Follicle:
    • Single oocyte
    • Granulosa cells surround the oocyte and respond to FSH and LH
    • Theca is the surrounding protective layer

Work Up

• Transvaginal ultrasonography (TVU) is more sensitive compared to CT
  • Classic TVU finding is a “complex” cyst, defined as containing both solid and cystic components
  • "Simple" cyst, defined as having thin walls, fluid-filled, without a mass component, septations, or internal echogenicity is frequently benign but workup must be individualized
• Percutaneous biopsy should be avoided due to risk of cyst rupture and seeding into peritoneal cavity
• Surgery
  • Exploratory laparotomy perfomed to 1) confirm pathology, 2) stage patient, and 3) perform maximum cyto-reduction (residual disease <1cm)
  • Should be performed by a GYN Oncologist
  • Ascites or peritoneal washings
  • Inspection of serosal surfaces with biopsy of any suspicious lesions
  • Inspect stomach, small bowel, large bowel, peritoneum, mesentery, and solid organs
  • TAH/BSO
  • Infracolic omentectomy
  • Pelvic and paraortic LN sampling
  • Peritoneal biopsies
  • Pelvic cul-de-sac biopsy
  • Bladder
  • Bil Sidewalls
  • Bil Paracolic gutters
  • Diaphragm

Pathology

• Epithelial tumors - most common, 65%
  • Serous tumors: 25% of ovarian tumors, 40% of epithelial tumors
    • Benign (60%): Serous cystadenoma, cystadenofibroma
    • Borderline (15%): Serous borderline tumors, microinvasive serous carcinoma
    • Malignant (25%): Serous cystadenocarcinoma, serous carcinoma, serous micropapillary carcinoma, serous psammomacarcinoma
  • Mucinous tumors: 15% of ovarian tumors, 25% of epithelial tumors
    • Benign (80%): Mucinous cystadenoma, mucinous adenofibroma
    • Borderline (10%): Mucinous borderline tumors, microinvasive mucinous carcinoma
    • Malignant (10%): Mucinous cystadenocarcinoma, mucinous carcinoma
  • Endometrioid tumors: 20% of ovarian tumors, 35% of epithelial tumors
    • Benign: Endometrioid cystadenoma, endometrioid adenofibroma
    • Borderline: Endometrioid borderline tumors
    • Malignant (Majority): Endometrioid carcinoma
  • Brenner tumors (benign, borderline, or malignant) - composed of urothelial-like cells
  • Other: Clear cell adenocarcinoma, urothelial carcinoma (transitional cell), mixed epithelial-papillary cystadenoma of borderline malignancy of mullerian type
• Sex cord - stromal tumors - 8%
  • Stromal cells: fibroblasts, theca cells, Leydig cells
  • Primitive sex cords: granulosa cells, Sertoli cells
  • Are hormonally active. Affect all age groups. 70% are Stage I at diagnosis (unlike epithelial tumors which are usually Stage III-IV).
• Germ cell tumors - 15%
  • Benign: mature teratoma
  • Malignant: 90% of malignant tumors are epithelial: dysgerminoma, immature teratoma, yolk sac tumor (endodermal sinus tumor), embryonal carcinoma

• Note: Borderline tumors (tumors of Low Malignant Potential; LMP) have absence of stromal invasion

Epithelial Ovarian Cancer

• Please see the epithelial ovarian cancer page

Sex cord-stromal tumors

• Granulosa cell tumors
  • About 5% of malignant ovarian tumors. The most common malignant sex cord-stromal tumor
  • More common in post-menopausal women
  • Present with vaginal bleeding (due to hormone)
  • May be associated with endometrial hyperplasia, endometrial polyps, or endometrial carcinoma
  • Most patients have an excellent prognosis, 90% 10-year survival
  • May have late recurrence, 10-20 years after treatment
• Fibroma, Fibrothecoma, and Thecoma
  • 4% of ovarian tumors
  • These 3 tumors form a spectrum of benign tumors
  • Occur in pre- and post-menopausal women
  • Fibroma is most common sex cord tumor
  • Thecomas are active (as compared to fibromas) and can have estrogenic activity
• Sertoli-Leydig cell tumor
  • Very rare (<0.5% of ovarian tumors)
  • Young women
  • Symptoms are related to virilizing hormones
  • Most behave in a benign fashion but can act malignant
  • Recur relatively soon after treatment
• Treatment approach includes surgery, and adjuvant platinum-based chemotherapy for high risk Stage I and Stage II-IV

Germ cell tumors

• 30% of ovarian tumors, but only 1-3% of malignant ovarian tumors
• More common in younger women and also more likely to be malignant (up to 1/3)
• Symptoms
  • Due to rapid growth of tumor, resulting in stretching of the ovarian capsule; leads to early diagnosis
  • Abdominal pain, distension, pelvic fullness, and urinary symptoms
• Histology:
  • Dysgerminoma (counterpart to seminoma)
  • Nondysgerminoma
• Serum levels
  • Endodermal sinus tumor (yolk sac tumor): AFP elevated
  • Embryonal carcinoma: AFP and bHCG elevated
  • Choriocarcinoma: bHCG elevated
  • Pure immature teratoma: normal AFP and bHCG; though AFP may be elevated in 30%
  • Mature cystic teratoma (dermoid cyst): normal AFP and bHCG
• Most common malignant germ cell tumor is dysgerminoma which occur most commonly in adolescence
• Stage I 60-70%
• Surgery: Principles of management similar to epithelial ovarian CA, except fertility can be preserved with ipsilateral salpingo-oopherectomy
• Adjuvant chemotherapy:
  • Adjuvant BEP for 3-4 cycles
  • Stage I disgerminoma can be observed (DeVita, 8th ed.) if fertility preservation is important, with 15-20% recurrence rate. Salvage with chemotherapy is high
• Role for RT limited, due to excellent chemo responsiveness and impact on fertility