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 unspited 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 performed 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

Ovarian-Adnexal Reporting & Data System (O-RADS™)

 * O-RADS™ is an acronym for an Ovarian-Adnexal Imaging-Reporting-Data System which will function as a quality assurance tool and clinical support system for the standardized description of ovarian/adnexal pathology and its management.
 * A uniform vocabulary using the most predictive internationally agreed upon lexicon descriptors for describing the imaging characteristics of ovarian/adnexal masses has been applied to a data-based risk stratification classification for consistent interpretations leading to appropriate management in clinical practice.
 * The system’s goal is to optimize ovarian cancer outcomes while minimizing unnecessary surgery in patients at low risk of malignancy.
 * Rochelle F Andreotti et al. O-RADS US Risk Stratification and Management System: A Consensus Guideline from the ACR Ovarian-Adnexal Reporting and Data System Committee. Radiology. 2020 Jan;294(1):168-185. ( 31687921)
 * Elizabeth A Sadowski et al. O-RADS MRI Risk Stratification System: Guide for Assessing Adnexal Lesions from the ACR O-RADS Committee. Radiology. 2022 Apr;303(1):35-47. ( 35040672)

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