I. What every physician needs to know.

Ovarian cancer represents the fifth leading cause of cancer death in women behind lung, breast, colorectal and pancreatic. The American Cancer Society reported that 13,850 women died of ovarian cancer in 2010 with 21,880 new diagnoses. Because of the non-specific signs and symptoms of the cancer, most women present in late stage disease with a very poor prognosis. The 5- year survival for late stage disease is 28% to 45%.

Currently, there are no good screening modalities in normal risk patients including the use of CA-125 and transvaginal ultrasound (TVUS). Ovarian cancer spreads locally to the opposite ovary and uterus followed by intraperitoneally with distant metastasis to the liver and lung. Conventional therapy includes upfront surgical tumor cytoreduction followed by a combination of platinum and taxane-based chemotherapy.

Ovarian cancer involves three tissue types including epithelial cell (85% to 95%), stromal cell (5% to 8%) and germ cell (3% to 5%). Subtypes of the epithelail cell ovarian cancer includes serous (40%), endometriod (20%) and mucinous (25%) tumors all of which have varying risk factors for development. The International Federation of Gynecology and Obstetrics has established the major classification system and mirrors the TNM system:

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Stage I – Tumor limited to ovaries

Stage II – Tumor extension into pelvis

Stage III – Tumor involving the peritoneum, retroperitoneum or inguinal lymph nodes

Stage IV – Distant metastases

II. Diagnostic Confirmation: Are you sure your patient has Ovarian Cancer?

Diagnostic confirmation is made by histological tissue sampling usually at time of surgical cytoreduction.

A. History Part I: Pattern Recognition:

Ovarian cancer presents with vary nonspecific symptoms recognized several months prior to diagnosis. The associated symptoms include:

1) Abdominal fullness, bloating or increased abdominal size

2) Back pain

3) Gastrointestinal like constipation, diarrhea, nausea or vomiting

4) Early satiety

5) Abdominal or pelvic pain

6) Urinary symptoms with increased urgency of frequency

7) Weight loss

8) Fatigue

These symptoms are present in 93% of patients diagnosed. Therefore, any woman, especially postmenopausal, that presents with a constellation of these symptoms for more than a few weeks should be evaluated for possible ovarian malignancy.

B. History Part 2: Prevalence:

Ovarian cancer is the most deadly of all gynecologic malignancies but accounts for only 3% of cancers in women. The incidence is 12.5 per 100,000 women. The incidence and mortality both increase with age. The majority of women present at age greater than 50 with a median age of 60. In postmenopausal women that present with an adnexal mass, 30% are found to be malignant.

Risk factor assessment is an important component in helping risk stratify patients given a very nonspecific history of symptoms upon presentation. Factors that lead to increased ovulatory rupture and release are associated with an increased risk of ovarian cancer. Reversely, factors that limit ovulation are thought to be protective like breastfeeding and multiparity. Therefore, these risk factors include:

1) Delayed childbearing

2) Early menarche

3) Late menopause

4) Nulliparity

5)BRCA1and2 gene mutations

6) Hereditary nonpolyposis colorectal cancer syndrome (HNPCC)

7) Family history in one relative (5%); two relatives (7%)

8) Age over 60

Certain modifiable risk factors like obesity, smoking, sedentary lifestyle and high fat diet have also been associated with an increased risk.

Hereditary disorders includingBRCA1 and 2 gene mutation and HNPCC account for only 10% of all cases of ovarian cancer. However, the lifetime risk for ovarian cancer for BRCA1 is 39% to 46%,BRCA2 mutation 12% to 20% and HNPCC 12%. Because of these increased risks, all patients should be referred to genetic counseling and be considered for prophylactic bilateral salpingo-oophorectomy with possible hysterectomy. If women decline this, then consideration for close follow-up using CA-125 and TVUS should be considered, semianually to annually.

C. History Part 3: Competing diagnoses that can mimic Ovarian Cancer.

The differential based on the nonspecific signs and symptoms are extensive and include gastrointestinal, gynecological and urinary disorders. The differential if an adnexal mass is palpated or found on TVUS include:

1) Benign ovarian cyst or tumor

2) Tubo-ovarian abscess

3) Endometrioma/endometriosis

4) Metastatic disease (Krukenburg tumor, etc.)

5) Ovarian torsion

D. Physical Examination Findings.

There are no specific findings for ovarian cancer. A full physical examination including pelvic and rectal need to be done in all patients. Typical findings can include ascites, pleural effusion, an abdominal mass, inguinal lymphadenopathy, pelvic mass and an umbilical mass called Sister Mary Joseph’s node. If an ovarian mass is palpated, then characteristics concerning for malignancy including being hard, fixed, nontender, size greater than 10 cm or nodular should be noted. Trousseau’s syndrome or superficial migratory thrombophlebitis and the leser-Trélat sign described as sudden appearance of seborrhea has also been seen with this malignancy.

E. What diagnostic tests should be performed?

If ovarian cancer is suspected, then a complete blood count, comprehensive metabolic panel, a serum CA-125, a urine pregnancy test and TVUS should be attained.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

The CA-125 is elevated in more than 80% to 90% of patients with advanced malignancy but less than 50% in early disease. Other conditions that disrupt the lining of the peritoneum can also elevate the CA-125 like pregnancy, endometriosis, pelvic inflammatory disease or other malignancies (pancreatic, breast, lung and colon). If the CA-125 is greater than 35 U/mL in a postmenopausal female with an ovarian mass, then the likelihood of malignancy is greatly increased. The CA-125 is used as a marker in assessing the patient’s response to treatment and for evaluation of reoccurrence if elevated upon presentation. Because of the markers’ poor sensitivity and specificity, it should not be used as a screening tool even if a patient presents with nonspecific signs or symptoms.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Transvaginal ultrasound (US) is the initial test of choice to evaluate for possible ovarian cancer. TVUS has a sensitivity of 86% and specificity of 91% for detecting an adnexal mass and differentiating between a benign or malignant process. Moreover, the US can further delineate if a mass has features consistent with a malignancy like:

1) Solid and cystic components

2) Abdomnal or pelvic fluid (ascites or blood)

3) Wall thickening

4) Internal septae

5) Papillary projections

6) Size greater than 10 cm

A complete computed tomography (CT) scan of the chest, abdomen and pelvis with contrast is also done prior to surgery to help plan the surgery and look for metastatic disease.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

III. Default Management.

The initial management for any patient suspected of having ovarian cancer is surgical evaluation to establish the histological diagnosis, provide staging and attempt at tumor debulking. Evaluation and surgery should be performed by a gynecological oncologist to optimize the patient’s outcome. Surgical resection includes at minimum a total abdominal hysterectomy, bilateral salpino-oophorectomy, pelvic lymph node and omental resection. Surgical staging helps provide information for postoperative management. The goal of resection is to cytoreduce the residual tumor to less than 1 cm, which increases the survival rate. Patients with optimal debulking and Stage I or II disease can have long-term survival of 80% to 95% whereas Stage III or IV has survival rates between 10% to 30%.

Most patients will require postoperative chemotherapy using a platinum and taxane based regimen. Patients with early stage disease and high risk of relapse traditionally receive 3 to 6 cycles of paclitaxel and carboplatin therapy. Patients with advanced disease receive either carboplatin along with paclitaxel for a minimum of 6 cycles.

Patient with optimally cytoreduced cancer should be considered for intraperitoneal platinum and taxane based chemotherapy instead because of increased disease free survival.

Optimal tumor debulking surgery is considered too high risk in certain patients with poor performance status, massive ascite or tumor burden. Neoadjuvant chemotherapy followed by surgery should be considered in these women if their symptoms improve.

Disease recurrence is generally treated with repeat of a platinum based chemotherapy protocol if the patient responded the first time or second line chemotherapy. Patients with relapse after a relatively long remission can also be considered for further tumor debulking surgery. The goal of treatment is palliation with prolonged survival and improvement in quality of life.

Radiation therapy has a very limited role in the treatment.

A. Immediate management.

B. Physical Examination Tips to Guide Management.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

D. Long-term management.

After patients have undergone optimal tumor debulking surgery and chemotherapy, close surveillance is indicated to evaluate for recurrence. Patient should be seen every 2 to 4 months the first 2 years then every 6 months for the next 4 years and then annually. Each visit should include a CA-125 and complete physical examination. Repeat imaging like chest X-ray, chest/abdomen/pelvic CT scan, or PET scan should be attained as clinically indicated.

E. Common Pitfalls and Side-Effects of Management.

IV. Management with Co-Morbidities.

A. Renal Insufficiency.

B. Liver Insufficiency.

C. Systolic and Diastolic Heart Failure.

D. Coronary Artery Disease or Peripheral Vascular Disease.

E. Diabetes or other Endocrine issues.

F. Malignancy.

G. Immunosuppression (HIV, chronic steroids, etc).

H. Primary Lung Disease (COPD, Asthma, ILD).

I. Gastrointestinal or Nutrition Issues.

J. Hematologic or Coagulation Issues.

K. Dementia or Psychiatric Illness/Treatment.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

B. Anticipated Length of Stay.

C. When is the Patient Ready for Discharge.

D. Arranging for Clinic Follow-up.

1. When should clinic follow up be arranged and with whom.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

E. Placement Considerations.

F. Prognosis and Patient Counseling.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

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