2010 Ovarian Cancer Study

Following is a cancer site analysis by Stacy South, MD, on ovarian cancer including statistical comparisons for patients diagnosed at MMH. Unless stated otherwise, the statistical graphs and tables found in this study include only analytic cases.

Introduction

Ovarian cancer is the second most common gynecologic cancer in the United States, but the leading cause of gynecologic cancer death. The American Cancer Society estimates there will be 21,990 new cases diagnosed in 2011 with 15,460 cancer-related deaths. Moreover, ovarian cancer is the ninth most common cancer among women, but ranks fifth in cancer deaths. This data reflects the relatively poor long-term survival, averaging 40% for all stages combined.

The cause of the overall poor outcomes is multi-factorial. Ovarian cancer is commonly diagnosed at an advance stage due to the relatively non-specific signs and symptoms which develop. Once the cancer has spread, it is harder to cure. Moreover, ovarian cancer has a high rate of recurrence. Even stage I tumors which are confined to the ovary have as high as a 40% chance of recurrence. Our chemotherapy regimens currently available seem able to kill the disease and render remissions, but the cancer often recurs. Patients tend to be living longer with the cancer, but ultimately they succumb to the disease. 

Risk Factors and Preventative Measures

The lifetime risk of ovarian cancer in the general United States population is 1.4%, or about 1 woman out of 70. The highest rate of diagnosis is in women in their 50’s. There are known risk factors and several protective measures for ovarian cancer.

98-02 Ovarian Cancer Cases Distribution by Age

The risk of ovarian cancer seems to be increased in women with a history of:

  • Ovarian cancer in the family (Genetics)
    • One relative with ovarian cancer carries about a 5% risk
    • Two relatives with ovarian cancer carries up to a 7% risk
    • Two first degree relatives with ovarian cancer could carry a risk between 25-50%
    • **only about 10-15% of ovarian cancer patients have a family history of the disease.
  • Increased estrogen exposure/reproductive issues
    • Infertility and nulligravid (never had a pregnancy)
    • Perimenopausal/postmenopausal hormone exposure
    • Early menarche (age menstrual cycles started) and/or late menopause
    • Endometrioisis
    • Polycystic ovarian syndrome

The risk of ovarian cancer seems to be decreased in women with a history of:

  • Birth control pill use (decrease risk by about 20% with each five years of use, with maximum of 50% at 15 years)
  • Multiparity (multiple pregnancies)
  • Tubal ligation (35% reduction in risk; up to 70% when combined with a history of birth control pill use)
  • Breast feeding

Many of the risk factors listed above cannot be modified and thus we cannot impact those factors. However, the protective factors are measures which we can actively pursue and thus decrease the risk of ovarian cancer for patients. 

Screening and Early Detection

Survival from ovarian cancer is related to stage at diagnosis. Thus the goal of a screening test would be to identify asymptomatic woman with early stage disease, improving the overall survival. Unfortunately much research has been devoted to creating effective screening tests for ovarian cancer without success. Various blood tests measuring tumor markers in combination with ultrasound have been studied. The data shows limited success when used in the general population as: much of the abnormalities found were benign (>90%), many of the cancers found were already advanced stage, and there were adverse effects resulting from ‘unnecessary’ surgery. Therefore, screening of the asymptomatic general population is not recommended.

However, women identified to be at increased risk (i.e., family history) should be counseled. It is important to note that only about 10-15% of patients diagnosed with ovarian cancer have a family history of the disease.  Relatively low risk individuals without a strong (multiple close relatives) family history should discuss their individual risk factors with their physician and understand the limited data showing the effectiveness of screening and potential adverse effects. 

Women with a strong family history suggestive of a genetic syndrome should undergo genetic counseling and possible gene testing for known mutations placing families at risk for ovarian cancer and other malignancies. Screening in this population still has not been proven to be cost-effective, but at least does yield a slightly higher success rate. Often these women are counseled concerning risk-reducing surgeries, such as removal of the ovaries and tubes once child bearing is complete.

Given the lack of good screening measures, early detection needs to be a focus. Many women diagnosed with ovarian cancer report vague symptoms for at least three months, with more than half having symptoms for six or more months. They often ignore the symptoms, allowing the disease to grow and spread. One of the mainstays of treatment for ovarian cancer is surgery to remove as much of the cancer as possible. If all of the cancer is removed, then overall survival is significantly increased. Earlier recognition and surgery may increase the likelihood of complete surgical removal. 

The symptoms commonly associated with ovarian cancer include:

  • Bloating
  • Pelvic or abdominal pain
  • Difficulty eating or feeling full quickly
  • Urinary symptoms (urgency or frequency)

The key to diagnosing ovarian cancer using these symptoms is the frequency of occurrence. Women will usually have these symptoms almost daily for more than a few weeks. This should prompt the patient to seek care, preferably with their gynecologist, and undergo appropriate evaluation.

Histology

Ovaries consist of essentially three cell/tissue types: epithelial cells, germ cells, and stromal tissue. The most common cells to undergo malignant transformation are the epithelial cells present on the surface of the ovary. However, germ cell malignancies are the predominant histology type in adolescent and young adults. It is important to determine the histologic type as it influences the recommended treatments and overall prognosis.

The specific types of ovarian cancers are as follows:

  • Epithelial accounting for about 90% of ovarian cancers. This category is subdivided into serous, mucinous, endometrioid, clear cell, transitional cell, mixed, or undifferentiated. 
  • Germ cell malignancies arise from the primordial germ cell, essentially representing the future “egg”. This type only accounts for about 5% of ovarian cancers. However, in young women ages 10-30, it accounts for as much as 70% of the cases. This category is also subdivided into six main types not discussed here.
  • Sex cord-stromal malignancies arise from either the cells supporting the egg development or the connective tissues of the ovary. These tumors tend to be less aggressive. This category is again subdivided into six types which will not be discussed.

The epithelial histology types are generally classified as low grade or high grade cancers. The low grade tumors tend to be diagnosed earlier and thus have better outcomes. There is increasing evidence that the pathogenesis of low grade tumors may be different than high grade tumors, indicating that low grade tumors may warrant a different therapy. However, based on currently available information, low and high grade invasive cancers are treated similarly.

Another variant of low grade epithelial tumors are the borderline tumors, also called low malignant potential tumors. These tumors show atypical cells with no invasion and thus are a separate entity from an invasive cancer. These tumors have similar characteristics and pathogenesis as low grade invasive cancers, but currently are not considered a pre-cancerous lesion.

Histology

Staging

Ovarian cancers are staged using the International Federation of Gynecology and Obstetrics (FIGO) and the Tumor Node Metastasis (TNM) staging systems. The 7th edition released in 2010 is the most recent version. In general, 25% of cases are diagnosed in stage I (confined to the ovary) or stage II (confined to the pelvis). Thus, 75% are advance stage, either involving the abdominal cavity or abdominal/pelvic lymph nodes (stage III) or metastatic to distant sites (stage IV). 

From 1998 to 2002, there were 27 cases of ovarian cancer diagnosed at MMH. Most of these were stage IV. This is relatively skewed data. MMH did not have a gynecologic oncologist during this time frame. Thus, most cases diagnosed would reflect cases either found incidentally during surgery for a probable benign pelvic mass by a gynecologist or patients presenting to the hospital the advance symptoms. Most cases diagnosed in the community would have been referred to other institutions for management.
 
Staging

Treatment

The cornerstone of treatment for ovarian cancer is surgery followed by chemotherapy. Surgery is used to determine the stage of the cancer. The tumor is removed and other tissues are also removed to determine if the cancer has spread. Staging consists of:

  • Collection of pelvic/abdominal fluid present or washings
  • Exploration of the entire abdomen and pelvis with biopsies of any suspicious lesions/adhesions and or random biopsies
  • Removal of the omentum
  • Removal/sampling of pelvic and para-aortic lymph nodes
  • Removal of uterus, cervix, tubes, ovaries

The goal of surgery in advance stage patients is complete removal of all tumors/cancer, termed an optimal debulking. Women who have an optimal debulking surgery followed by chemotherapy have a higher overall survival rate and decreased risk of recurrence. If large amounts of disease are left behind after surgery, then repeat surgery after chemotherapy may provide survival benefit over chemotherapy alone. 

Chemotherapy is recommended for most patients diagnosed with ovarian cancer. Patients with low grade stage I disease may not benefit from chemotherapy. However, all other patients are counseled about chemotherapy. The standard of care for chemotherapy in ovarian cancer is use of a combination of a taxane and a platinum given intravenously. Most oncologist specifically use taxol and carboplatin due to tolerability and ease of administration. There is recent data showing a possible survival advantage using a combination of intravenous and intraperitoneal (directly into the abdomen) administration of these drugs for patients with optimally debulked advance stage disease. However, this regimen carries more risks and side effects. The combination of surgery and chemotherapy will result in about 70% of patient being disease free at completion. However, about 70% will recur in two years.

Once ovarian cancer recurs, it is often difficult to obtain another remission (eliminate the disease). The primary goal of treatment at this time is quality of life. However, the general approach is similar. If optimal debulking is possible, then surgery is recommended followed by chemotherapy. Otherwise, chemotherapy alone is used. However, there are no standard recommendations as to which chemotherapy drugs to use in the recurrent setting. Research shows that many drugs are effective. Thus, the decision to use one drug over another is guided by the patient’s other medical issues, acceptance of known side effects, convenience of scheduling, etc. Again, the focus is to provide a high quality of life with the best ability to kill the cancer.

Radiation is effective at treating ovarian cancer. However, radiation is seldom used. This is due to the sporadic nature of the disease. Radiation is generally used as a local therapy to one part of the body. Ovarian cancer tends to create multiple areas of nodules throughout the abdomen and pelvis. Radiation to the entire abdomen and pelvis has significant side effects and is often not tolerated. If there is a local area of recurrence, then radiation is an option, especially in someone who is not a good surgical candidate.

Treatment

Survival

Survival is most dependent on the stage of ovarian cancer at diagnosis. With appropriate treatment, ovarian cancer detected before it has spread to other organs (stage I) shows a greater than 80% chance of surviving five years or more. However, only 20% or less of patients with stage IV disease at diagnosis are alive at five years. Nearly all patients who develop recurrent ovarian cancer will die of their disease. However, some patients can achieve another remission or at least several more good quality years of life.

Survival

Conclusion

Ovarian cancer continues to be the leading cause of gynecologic cancer death. We must continue to focus our efforts on the diagnosis, treatment and prevention of this deadly disease. In addition, the awareness of risk factors and early symptom recognition must continue to be emphasized.

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