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 Yale-New Haven Hospital, New Haven, Connecticut, USA HealthLINK: Cancer

April 12, 1999

News this month
Improving the Odds for Women with Cervical Cancer

Women with invasive cervical cancer appear to have greatly improved odds of survival when treated with chemotherapy and radiation after surgery, instead of radiation therapy alone. Five major studies released late last month support what is called the first breakthrough in the treatment of invasive cervical cancer in the 40 years since radiation therapy was first used. That's good news for the 12,800 women in the U.S. who will be diagnosed with invasive cervical cancer this year. Each year, about 4,800 women die from the disease.

In the new studies, women who received the cisplatin/radiation combination had the best survival rates.

Survival rates increased
The new studies, sponsored by the National Cancer Institute, involved dozens of institutions and nearly 2,000 women across the country. The studies took place from 1992-97, except for one seven-year study. Among the women studied, survival rates increased 30 to 50 percent when post-surgical treatment included the chemotherapy drug cisplatin along with radiation therapy.

The findings, which will be reported in future issues of the New England Journal of Medicine and Journal of Clinical Oncology and at a spring conference of physicians, are expected to change the type of treatment women receive. In fact, the NCI in February sent letters to thousands of physicians across the country urging them to start using the new treatment modality. Up to now, surgery followed by radiation had been considered standard treatment for invasive cervical cancer. Cancer is considered invasive when it has spread either within the cervix itself, or into nearby areas.

It may be that the chemotherapy made the cancer more susceptible to the radiation…

In the new studies, women who received the cisplatin/radiation combination had the best survival rates. In two of the trials, women in one group received chemotherapy including cisplatin together with radiation while women in the other group received one of the other drugs together with radiation. Radiation therapy remained the same through all the trials, with women receiving external beam radiation therapy directed at the pelvic area.

Exactly why chemoradiation therapy worked better is not clear, but it may be that the chemotherapy made the cancer more susceptible to the radiation. In four of the five trials, patients were enrolled and treated up until 1996 or 1997, and the majority are still alive. In the trial begun earlier (GOG 85) the majority of patients receiving cisplatin-based chemotherapy with radiation were still alive seven and a half years after diagnosis (89.4 months). In contrast, half of the patients on the other arm of this trial--those who received hydroxyurea and radiation--had died by about five years (59.8 months).

STUDY SUMMARIES

Radiation Therapy Oncology Group (RTOG) 9001
Radiation therapy with 5-FU and cisplatin versus radiation therapy alone; 389 patients, stages IIB, III, and IVA, enrolled 1990-1997.

Results: The three-year survival rate for women receiving cisplatin and 5-FU was 75 percent compared to 63 percent for women receiving radiation alone. New England Journal of Medicine

Gynecologic Oncology Group (GOG) 120
Radiation therapy with cisplatin versus radiation therapy with cisplatin, 5-FU, and hydroxyurea versus radiation therapy with hydroxyurea; 526 patients, stages IIB, III, IVA, enrolled 1992-1997.

Results: In both groups receiving radiation and cisplatin, the three-year survival rate was 65 percent compared to 47 percent for women receiving radiation and hydroxyurea. New England Journal of Medicine

Gynecologic Oncology Group (GOG) 123
Radiation therapy with cisplatin versus radiation alone; 368 patients, stage IB bulky, enrolled 1992-1997.

Results: With half of the patients followed for 35.7 months or more, 83 percent of those who received concurrent chemotherapy and radiation therapy are alive, compared to 74 percent of those treated with radiation therapy alone. New England Journal of Medicine

Gynecologic Oncology Group (GOG) 85
Radiation therapy together with the drugs cisplatin and 5 fluorouracil (5-FU) versus radiation therapy with the drug hydroxyurea; 386 patients, stages IIB, III, and IVA, enrolled 1986-1990.

Results: Three years from the time of diagnosis, 67 percent of women receiving radiation with cisplatin and 5FU were alive compared to 57 percent of those receiving radiation therapy and hydroxyurea. Study not yet available online.

Southwest Oncology Group (SWOG) 8797
Radiation therapy with 5-FU and cisplatin versus radiation therapy alone; 243 patients, stages IA2, IB, IIA, with adverse pathology found at time of surgery, enrolled 1992-1996.

Results: The three-year survival rate for women receiving radiation and cisplatin and 5-FU was 87 percent compared to 77 percent for women receiving radiation alone. Study not yet available online.


Physician Referral Online

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Physician Referral Online
Using your own criteria, you can request information from a database of 900 area physicians who have registered to participate.

Request an appointment
We would be happy to assist you in scheduling an appointment with a member of the hospital's medical staff. Use the link above or call:

203-688-2000
or toll free
1-888-700-6543
to talk with a referral coordinator.
Joseph Chambers, MD

Combining Chemotherapy and Radiation in Cervical Cancer

These new studies show the combination of chemotherapy and radiation therapy to treat locally advanced cervical cancer is very promising. The fact that all the studies were released at the same time is significant. Based on these results, radiation therapists and gynecologic oncologists must work closely together to ensure patients with this type of cervical cancer receive both forms of treatment.

Those at greatest risk of invasive cervical cancer are women who do not get regular Pap tests.

Screening for Cervical Cancer
At the same time, we must realize that widespread use of the Pap smear over the last 20 years has been tremendously helpful in detecting precancerous states, thus decreasing the advanced cervical cancers we now see. What concerns me is that up to 40 percent of women in the U.S. are not getting regular Pap tests. Any woman who has become sexually active should have a Pap test at the regular intervals her doctor recommends. That includes women who have had their uterus removed and those past menopause.

Who is at risk
Certain behaviors put women at increased risk of exposure to human papillomavirus (HPV):

  • Unprotected sex
  • Many sexual partners
  • Sex with a man who has had many partners.

Infection with HPV is the most important risk factor for cervical cancer in 95 percent of cases. The HPV DNA test is now available at the department of pathology at Yale University School of Medicine--the first site in Connecticut to offer this FDA-approved diagnostic tool. Used in conjunction with the Pap test, the HPV test may help to determine the best course of treatment for women with slightly abnormal Pap smears.

The Pap test can detect those early precancerous changes in the cells of the cervix, allowing physicians to take action early. Typically, women are diagnosed with cervical cancer between age 35 and 55. Those at greatest risk of invasive cervical cancer, therefore, are women who do not get regular Pap tests.

Treatment Options
Most patients in the U.S. with cervical cancer have what we call stage 1B, which is a relatively early stage. For these women, the treatments of choice will still be radical hysterectomy and sometimes radiation. But in more advanced stages--as demonstrated in these new studies--the use of radiation and chemotherapy seem to be showing excellent results.

The HPV DNA test, currently available in Connecticut only through Yale pathology, helps determine the best course of treatment for women with slightly abnormal Pap smears.

Combining radiation therapy with drug therapy to treat cervical cancer is not new, but past results have been mixed. These new studies, particularly the studies that showed the use of the chemotherapy agent cisplatin, are the most encouraging to date. Over the years we have used a number of chemotherapy protocols at Yale for cervical cancer. An earlier protocol involved radical surgery, chemotherapy and then radiation for women. This new treatment is combining two therapies instead of using them sequentially. Looking at them combined and not sequentially may be the key to improved survivals.

Remember, every type of treatment has a side effect. Patients will need to be followed for a long time to make sure these survival statistics and intervals free of cancer remain as good as reported. We also need to ensure no new toxicities or side effects appear subsequently. However, we're all encouraged by these promising results for treatment of locally advanced cervical cancer.

Dr. Chambers is a gynecologic oncologist on staff at Yale-New Haven Hospital and associate professor of obstetrics and gynecology at Yale University School of Medicine.

The HPV test
Access to this test for infection with the human papillomavirus (HPV) is available to any woman in the Yale-New Haven area whose doctor uses Yale Pathology for cytology lab work. Ask your doctor about the test. A test specimen can be taken during your yearly exam or whenever a Pap test is done and the results returned to your physician.

Yale research
study of HPV test
Yale is conducting a research study of the HPV test to determine its value for women in the Greater New Haven and Shoreline areas who have ASCUS (atypical squamous cells of undetermined significance) Pap smears. Connecticut physicians are eligible to enroll up to 10 ASCUS patients. As part of the study, the HPV Diagnostic Laboratory will perform the HPV test at no cost. Participating physicians must agree to follow HPV-negative patients with a repeat Pap test after six months and to refer all HPV-positive patients on for immediate colposcopy and biopsy. For more information on this study, contact Deborah Blood at (203) 785-6848 or pager (203) 370-4929.

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