Unanswered Questions and Controversies

New cancer treatments are continually being developed and tested against standard therapies. In order for a new drug to become part of standard recommendations it must be proven to be superior to current standards through rigorous clinical trials.

In addition to new therapies there are many unanswered controversies in the way Gynecologic Oncologists use known treatments. These controversies result in treatment decisions that differ from one institution to another based on differences in physician training, philosophy, and beliefs but not on definitive evidence. Until these questions are definitively answered by large-scale clinical trials, women with gynecologic cancers will not be treated uniformly with best clinical practices and therapies.

Up the Volume works to make these large-scale clinical trials possible.

Frequently Asked Questions and Controversies about:

Ovarian cancer
Uterine cancer
Cervical cancer

Other questions about treatment:

How can newer radiological imaging techniques, such as PET-CT scans, improve the care for gynecologic cancer patients?

How do targeted biologic agents fit into the treatment of patients with gynecologic cancers?

These and many other questions and controversies continue to result in a large variation of treatment recommendations among experts in the field of gynecologic oncology. If definitive answers to these and other important questions are not reached, there will continue to be disparities in the effectiveness of treatment for gynecological cancers dependent on where a patient is treated.

In order to maximize the quality and length of life for all women with gynecologic cancers we must answer these and many other questions.

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Frequently Asked Questions and Controversies about Ovarian Cancer

Is there a screening test to identify ovarian cancer in its earliest stages?

70-80% of women diagnosed with ovarian cancer have advanced disease. If ovarian cancer could be detected early, the long-term survival rate would be greater than 85%. With advanced ovarian cancer only 30-40% of women are expected to live for more than 5 years despite recommended treatments. These facts raise two questions:

How can we identify ovarian cancer in its earliest stages and better treat women with advanced ovarian cancer?

To date, there is no accurate and reproducible screening test for ovarian cancer. Ultrasounds and blood levels of CA-125 have been used for decades without improving the detection rate of early ovarian cancer. Media hype and overzealous investigators periodically send premature and misleading information into the public forum; however, there is no dependable tool available to detect early ovarian cancer.

Many laboratories across the country and around the world continue to search for the test that will identify early ovarian cancer in asymptomatic women. When this test is discovered it will revolutionize the care of women with respect to ovarian cancer.

In order to find this test we need to continue to store tissue and body fluids from women with early and advanced ovarian cancer as well as unaffected women. With continued biologic and genetic testing of these samples there is reasonable hope that a test will be discovered. Any clinical trial designed to evaluate ovarian cancer should include blood, urine, and tissue samples from each participant.

In cases of advanced ovarian cancer, should surgery be followed by chemotherapy or should chemotherapy be followed by surgery?

Despite rigorous clinical trials over the past several decades, many controversies still remain on the timing and order of surgery and chemotherapy as well as the aggressiveness of surgical resection and the proper recipe for chemotherapy administration. Due to these inconsistencies, ovarian cancer patients are treated differently in different parts of the world as well as in different regions of the United States.

The first and most critical controversy to sort out is the determination of timing and order of treatments. Should patients be treated with primary debulking (cytoreductive) surgery followed by chemotherapy or should chemotherapy be administered first followed by cytoreductive surgery?

Data are conflicting. In order to answer this important controversy a large randomized trial must be accomplished by cooperative groups of board certified Gynecologic Oncologists trained to be comfortable with both aggressive surgical and chemotherapeutic applications. Results from a trial of this sort may result in longer lives for ovarian cancer patients by years, not weeks or months, and or improve the quality of life for those afflicted women. Up the Volume exists to support this sort of trial.

How aggressive should surgery be?

Another controversy revolves around the degree of aggressiveness of surgical resection. While data suggest that the removal of all visible disease is the most important part of treatment in women with advanced ovarian cancer there is controversy about whether or not the benefits outweigh the side effects of extensive surgery.

Since the 1990s there has been an increased emphasis on more completeresection of metastatic ovarian cancer in the upper abdomen, not just the pelvis. Because this is not practiced by all Gynecologic Oncologists, and due to the concern of more side effects resulting from more advanced surgery, this controversy will not be put to rest until it is critically evaluated by large randomized trials. Again, results from a trial of this sort have the potential for lengthening the lives of ovarian cancer patients by years.

Should chemotherapy be administered intravenously or intraperitoneally?

This has been debated for many years. For decades the standard way chemotherapy was administered for the treatment of advanced ovarian cancer was via an intravenous drip through the patients' veins. Over the years it has been demonstrated that patients who are treated with chemotherapy administered directly into the peritoneal cavity (intraperitoneal chemotherapy) have a significant increase in the length of their lives by 12-16 months. However, the increased level of treatment-related side effects has been called into question. Until large-scale trials using less toxic intraperitoneal chemotherapies are performed there will be an ongoing debate about whether the survival benefit of this treatment outweighs the toxicity.

Do targeted biologic agents, (treatments made to target specific biologic or genetic differences in cancer cells) improve cancer outcomes when added to chemotherapy?

Chemotherapy can generically be thought of as systemic medications to treat cancers, meaning they affect all parts of the body. Its use has always been a balance between the effect on killing cancer cells and the side effects on the patient. The two categories of chemotherapy that are most useful in the primary treatment of ovarian cancer aretaxanes and platinum compounds. While the combination of these two classes of chemotherapy medications has proven superior to others, we have yet to find the magic bullet that will offer women with advanced ovarian cancer a high rate of cure. While pharmaceutical companies will continue to identify newer chemotherapies that will be tested against ovarian cancer, there is an increased interest in adding biologically or genetically targeted therapies to the treatment regimen for advanced ovarian cancer. This will again require multiple large randomized trials to identify the correct combination of chemotherapeutic and targeted therapies.

Until agreement can be arrived at for each of these controversies there will be regional disparities in the treatment of women with advanced ovarian cancer. These disparities will continue to result in inequities in the treatment outcomes, with some living longer lives or lives with a higher quality. We can resolve this by critically evaluating the issues and outlining the best recommendations for treating ovarian cancer patients universally.

By ending these controversies we can maximize the lives of women with ovarian cancer.

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Frequently Asked Questions and Controversies about Uterine Cancer

Does the number of lymph nodes removed and evaluated matter?

Fortunately, most women with endometrial cancer are detected with early disease, require little postoperative therapy, and have an excellent chance for long-term survival. For the 20% of women with advanced endometrial cancer there are many unanswered questions.

Standard recommendations for women diagnosed with endometrial cancer include a surgical procedure that removes the uterus, cervix, fallopian tubes, ovaries, and lymph nodes. The number of lymph nodes removed has never been standardized and is a controversial topic among experts. Not only is it thought that the number of lymph nodes evaluated relates to survival but it also relates to the type of postoperative treatment that is recommended to endometrial cancer patients. A large-scale randomized trial is needed to determine the true value of this surgical procedure.

How do we best treat metastatic endometrial cancer? Should radiation follow chemotherapy, should chemotherapy follow radiation, or should chemotherapy and radiation be delivered concomitantly? Should targeted therapies be added to treatments?

Postoperative treatment recommendations vary and have important implications for the survival of women with endometrial cancer. By answering these questions with large-scale randomized trials we will be able to better treat women with endometrial cancer and maximize their quality and length of life.

Frequently Asked Questions and Controversies about Cervical Cancer

Who should receive the HPV vaccination and how can it be made available?

In developed countries, such as the United States, cervical cancer has become more a matter of prevention than treatment. This is because of widely available cervical screening programs that utilize PAP smears and related tests. Additionally, HPV vaccines have been developed against the most common cancer-causing strains of human papilloma virus, HPV-16 and HPV-18. It is conceivable that with improvements in the vaccines and with wide usage in children and young women, cervical cancer could be eradicated in the future.

However, currently women in under-developed countries suffer from high rates of late stage cervical cancer resulting in more deaths than most other cancers in women. Better screening and vaccination programs in these countries would revolutionize cervical cancer survival worldwide. We must extend ourselves to these women around the world in an attempt to eradicate this disease globally. There are many underserved areas in our own country that could be used to study these issues. The results could then be applied to other places around the world.

How do we best treat distantly metastatic cervical cancer? Do we use chemotherapy or chemotherapy combined with radiation therapy?

Like endometrial cancer, when cervical cancer spreads to other distant locations in the body, best treatment options only offer a modest improvement in the length of life. Large-scale trials must be accomplished to test various therapies such as radiation, chemotherapy, and biologic therapies against advanced cervical cancer in order to determine the most effective treatment options.