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Radiation Oncology/Ovary/Overview

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Ovarian Cancer Overview


Epidemiology

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  • 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

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  • 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

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  • 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

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  • 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):
  • 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

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  • 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

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  • 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™)

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  • 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. (PMID: 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. (PMID: 35040672)

Pathology

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  • 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

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Sex cord-stromal tumors

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  • 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

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  • 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
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