Ovarian%20cancer Diagnosis

• The diagnosis of ovarian cancer may be difficult because of nonspecific symptoms
• A thorough medical history should be taken from the woman with specific attention to risk factors or protective factors for ovarian malignancy and a family history of ovarian or breast cancer; refer for genetic risk evaluation
• Most frequent symptoms are abdominal discomfort or vague pain, abdominal fullness, bowel habit changes, urinary urgency or frequency, early satiety, dyspepsia and bloating
  
  • Irregular menses, urinary frequency and/or constipation and occasionally, dyspareunia are common during the early stage of the disease
  • Abdominal distention, bloating, constipation, nausea, anorexia or early satiety are observed when the disease is in the advanced stage
  • Occasionally, patients may present with bowel obstruction due to intraabdominal mass or shortness of breath due to pleural effusion
  • The most common presenting symptom in children and adolescents is abdominal pain, although precocious puberty, irregular menses or hirsutism may also be present

• The presence of 1 of 6 symptoms (ie pelvic pain, abdominal pain, increased abdominal size, bloating, difficulty eating and early satiety) occurring for >12 days per month for <1 year has a 56.7% sensitivity for early-stage ovarian cancer and a 79.5% sensitivity for advanced-stage ovarian cancer

• Pelvic examination is not sensitive for detecting ovarian masses but presence of a pelvic mass at clinical evaluation is an important sign of possible ovarian cancer
• A rectovaginal examination should also be performed to maximize the opportunity to detect a mass
• Space-occupying mass in the lesser pelvis, significantly enlarged (>10 cm) ovary, ovarian irregularity, nodular or fixed pelvic mass, bilateral lesions, nodules in the cul-de-sac, palpable mass in the pleural abdomen, ascites and/or pleural fluid, increase in prolapse of uterus and/or vagina, enlarged supraclavicular lymph node, Sister Mary Joseph Nodule (a deep subcutaneous nodule in umbilical area associated with metastasizing intra-abdominal cancer) should elevate concern

• Recommended in women >40 years of age with persistent unexplained gynecologic or gastrointestinal symptoms
• Complete blood count (CBC)
• Blood chemistry with liver function tests (LFTs)
• Total serum protein and evaluation of nutritional status
• Serum CA-125 levels
  
  • Increased in 85% of women with advanced ovarian cancer and in about 50% of women with stage 1 disease
  • If results showed levels of ≥35 IU/mL, ultrasound exam of the abdomen and pelvis should be performed
  • Unreliable in differentiating benign from malignant masses in premenopausal women because of increased rate of false positives or reduced specificity
    
    • False positive results may be secondary to peritoneal inflammation in endometriosis or adenomyosis, PID, menstruation, uterine fibroids, or benign cysts 

• Human epididymis protein 4 (HE4)
  
  • Studies show that HE4 has a higher positive predictive value as a tumor marker than CA-125
  • Has higher sensitivity during the early stages of ovarian cancer
  • Combination of HE4 and CA-125 in the risk of malignancy algorithms has a good sensitivity and specificity in ovarian cancer triage both in premenopausal and postmenopausal women

• Alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-hCG) and lactate dehydrogenase (LDH)
  
  • Markers for malignant germ cell tumors and may be used to help in intraoperative diagnosis, preoperative planning and post-treatment monitoring for recurrence 
  • Should be measured in all women <40 years of age with a complex ovarian mass because of the possibility of germ cell tumors
  • Primarily used to evaluate adnexal masses found during adolescence or young adulthood
• Carcinoembryonic antigen (CEA) and inhibin
  • If clinically indicated, these are measured to assess for less common ovarian histopathologies 
• Homologous recombination deficiency (HRD) testing
  • Positive results occur in patients with germline BRCA1 and BRCA2 (wild type or unknown) mutations
  • May provide information on the magnitude of benefit of poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitor therapy

• The diagnosis of ovarian carcinoma can only be made on the basis of histological examination
• Invasive growth is a prerequisite for the diagnosis of ovarian carcinoma
• 85-95% of cases are from epithelial cells which are commonly diagnosed in women >50 years old
• 5-8% of cases are from sex cord embryonic gonads which may occur in women of any age
  
  • Certain tumors such as androblastomas may be more common in adolescence

• 3-5% of cases are from germ cells which usually occur in patients 15-19 years of age

• Used to confirm presence of a pelvic mass and to expeditiously distinguish benign adnexal lesions from those requiring further pathological evaluation for malignancy
  
  • No objective imaging criteria is available to predict surgical resectability but may be used to gain preoperative information regarding the extent of the disease at the start of treatment
• Imaging done is with contrast except if contraindicated

• Ultrasound
  
  • Single most effective way of evaluating an ovarian mass
    
    • Transvaginal ultrasonography is preferred due to its increased sensitivity over transabdominal ultrasound but both may be used in assessing larger masses and extra-ovarian disease
  • No single ultrasound finding differentiates benign from malignant ovarian masses
  • Features such as complexity with solid and cystic areas, extramural fluid, echogenicity, wall thickening, septum thickness of >3 mm without sharp boundary line, papillary masses in the cyst cavity, and ascites are suggestive of cancer

• Computed tomography (CT) scan
  
  • CT scan of the pelvis and abdomen should be done to establish the extent of the disease if ultrasound and serum CA-125 results, and clinical status of the patient suggest ovarian cancer
    
    • Also done in case of an abdominal or pelvic mass of unknown origin
  • Useful in diagnosis and planning of management for advanced cancer
  • Helpful to detect presence of pleural fluid and metastases to other parts of the body (ie lungs, mediastinal lymph nodes, omentum, liver, spleen or retroperitoneum)

• Other studies
  
  • Chest X-ray may be used to detect lung metastases
  • Positron emission tomography (PET) scan is helpful to spot small collections of cancer cells but is not recommended for primary cancer detection because of high false positive rates
    
    • Its primary role is to help the selection of patients for secondary debulking surgery by excluding additional sites of disease not seen on CT scan and not amenable to cytoreduction
  • Magnetic resonance imaging (MRI) is not used routinely for assessing women with suspected ovarian cancer
  • Colonoscopy may be done if there is a suspicion of or to rule out bowel involvement

Risk of Malignancy Index (RMI)

• Used in women with suspected ovarian cancer to help guide the management for the patient
• Product of serum CA-125, menopausal status and ultrasound score of the patient
• Simple to use but is negatively affected in the premenopausal age due to high incidence of increased CA-125 levels in this age group which may be secondary to endometriomas, borderline ovarian tumors, or non-epithelial ovarian tumors

• Laparoscopy
  
  • Provides a view of organs that can help plan surgery or other treatments and can help confirm the stage of the cancer
  • Laparoscopic biopsy should be considered if percutaneous image-guided biopsy is not feasible or has not produced an adequate sample 

• Exploratory laparotomy
  
  • Allows adequate exposure and careful examination of the abdominal cavity for surgical staging

• Determines the extent of cancer upon diagnosis
• Important factor in the choice of treatment and may also predict prognosis

FIGO Ovarian Cancer Staging System

• Developed by the International Federation of Gynecology and Obstetrics (FIGO)

Stage I (T1)

• Tumor limited to the ovaries or fallopian tube(s), no regional lymph node (LN) metastasis or distant organ metastasis

Stage IA (T1a)

• Tumor limited to 1 ovary with intact capsule or fallopian tube, no tumor on ovarian or fallopian tube surface, no malignant cells in ascites or peritoneal washings, no regional LN metastasis or distant organ metastasis

Stage IB (T1b)

• Tumor involves both ovaries with intact capsule or fallopian tubes, no tumor on ovarian or fallopian tube surface, no malignant cells in ascites or peritoneal washings, no regional LN metastasis or distant organ metastasis

Stage IC

• Tumor limited to one or both ovaries or fallopian tubes, with any of the following:
  • Stage IC1 (T1c1) Surgical spill
  • Stage IC2 (T1c2) Presence of tumor on ovarian or fallopian tube surface or capsule rupture prior to surgery
  • Stage IC3 (T1c3) Presence of malignant cells in ascites or peritoneal washings

Stage II (T2)

• Tumor in one or both ovaries or fallopian tubes with pelvic extension (below the pelvic brim) or primary peritoneal cancer

Stage IIA (T2a)

• Tumor extension and/or implants on uterus and/or ovaries and/or fallopian tubes

Stage IIB (T2b)

• Tumor extension to other pelvic intraperitoneal tissues

Stage III (T1/T2-N1; T3-N1)

• Tumor in one or both ovaries or fallopian tubes, or primary peritoneal cancer, with histologically or cytologically confirmed peritoneal metastasis outside the pelvis, and/or retroperitoneal lymph node metastasis

Stage IIIA1 (T1/T2-N1)

• Positive retroperitoneal lymph nodes only: IIIA1(i) (N1a) Metastasis ≤10 mm; IIIA1(ii) (N1b) Metastasis >10 mm

Stage IIIA2 (T3a2-N0/N1)

• Microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes

Stage IIIB (T3b-N0/N1)

• Macroscopic peritoneal metastasis outside the pelvis ≤2 cm with or without retroperitoneal lymph node metastasis

Stage IIIC (T3c-N0/N1)

• Macroscopic peritoneal metastasis outside the pelvis >2 cm with or without retroperitoneal lymph node metastasis; includes extension to capsule of liver and spleen

Stage IV (Any T, Any N, M1)

• Distant metastasis, not including peritoneal metastases

Stage IVA (M1a)

• Pleural effusion with positive cytology

Stage IVB (M1b)

• Parenchymal metastases, metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside of the abdominal cavity); transmural involvement of intestine