Younger Women with Low Grade Ovarian Cancer Face Worse Outcomes
(July 29, 2015) Research published online in the Journal of Clinical Oncology shows that upon completion of primary therapy, women with low-grade serous carcinoma of the ovary (LGSOC) or peritoneum (LGSPC) who are under the age of 35 and have persistent disease face worse outcomes.
Researchers at the University of Texas MD Anderson Cancer Center in Houston, TX, evaluated 350 patients who were diagnosed with stage 1 to 4 LGSOC or LGSPC before January 2012. LGSOC and LGSPC are rare subtypes of ovarian and peritoneal cancers that are characterized by young age at diagnosis and resistance to chemotherapy.
The researchers found that women over the age of 35 had a 43% reduced likelihood of dying compared to those 35 and younger. Additionally, having disease present upon completion of primary therapy was associated with a 1.78 increased hazard of dying compared to being clinically disease-free.
Women with LGSPC were found to have a 41% decreased likelihood of dying compared to those with LGSOC. “Patients with LGSPC seem to have a better prognosis than those with LGSOC,” the authors concluded.
In 2006, the National Cancer Institute took the rare step of issuing a “clinical announcement,” a special alert it holds in reserve for advances so important that they should change medical practice.
In this case, the subject was ovarian cancer. A major study had just proved that pumping chemotherapy directly into the abdomen, along with the usual intravenous method, could add 16 months or more to women’s lives. Cancer experts agreed that medical practice should change — immediately.
Nearly a decade later, doctors report that fewer than half of ovarian cancerpatients at American hospitals are receiving the abdominal treatment.
“It’s very unfortunate, but it’s the real world,” said Dr. Maurie Markman, the president of medicine and science at Cancer Treatment Centers of America. He added, “The word ‘tragic’ would be fair.”
Dr. Markman said that when a treatment involves a new drug or a new device, manufacturers eagerly offer doctors advice and instructions on its use. But this treatment involves no new drugs or devices, so no one is clamoring to educate doctors about it. They are on their own to learn, and to train their nurses, a commitment that will take time and money.
This year, 21,290 new cases of ovarian cancer are expected in the United States, and 14,180 deaths. Dr. Markman said that for now, a patient’s best option is to ask whether her doctor offers the treatment, and if the answer is no, to find a doctor who does.
Some experts say that the ability to offer abdominal chemotherapy for ovarian cancer should be added to the list of basic “quality measures” — such as making sure all heart attack patients receive certain drugs — that Medicare and other payers use to evaluate hospital performance.
But even at these elite centers, IP treatment did not take off as much as experts thought it should. From 2003 to 2006, as research began showing it had benefits, overall use of the treatment rose from zero to 33 percent of patients. From 2007 to 2008 — after the major, landmark study and the alert from the cancer institute — the use rose to 50 percent of eligible patients.
But then it reached a plateau. Rates varied from one hospital to the next, with 4 percent to 67 percent of patients receiving IP treatment. Researchers say that at smaller, less prestigious hospitals, the rates are even worse.
The hospitals that participated in the study were named in the journal article, but their individual rates were not disclosed.
“We suspected that even at the best centers there would be low integration of IP chemotherapy, but we were surprised to see how low it was across academic centers, and also to see how much variation there was between centers,” said Dr. Alexi A. Wright, the first author of the study and a medical oncologist at the Dana-Farber/Brigham and Women’s Cancer Center in Boston. “It’s the best data we have for improving survival among patients with this cancer.”
Deborah Dennehy, 58, a second-grade teacher from Amesbury, Mass., had IP treatment two years ago at Dana-Farber. She said she gained as much as 10 pounds with each treatment from all the fluid infused, and felt like a “beached whale” for a few days afterward. She lost her hair and temporarily had some numbing in her fingertips from the chemotherapy, but medication prevented nausea. Now, she said, “I feel great.” And given the data on the treatment, she said, “I felt it was totally worth the inconvenience.”
The new study confirmed earlier findings that IP treatment helps women live longer. Among women who had IP treatment, 81 percent were still alive three years later, compared with 71 percent in women who had only intravenous chemotherapy. The findings are based on the records of about 500 women.
Another study, also published in The Journal of Clinical Oncology, in May, found that the benefits of IP therapy are long-lasting: among women followed for 10 years, the risk of death was 23 percent less in those who had IP therapy.
Ovarian cancer is usually not found until it has reached Stage 3, when it has begun to spread inside the abdomen. Studies find that two factors have the greatest impact on survival: removing every visible trace of the tumor with meticulous “debulking” surgery, and finishing the recommended amount of chemotherapy. Studies have found that many women do not have adequate surgery, because they are operated on by doctors who do not specialize in gynecologic cancer.
IP treatment requires that a port be surgically implanted in the abdominal wall so that the drugs can be infused. At many centers, the patients are rolled back and forth on a bed to slosh the chemotherapy around inside them. The treatment is thought to work so well because it essentially soaks any cancer cells that remain after surgery in a highly concentrated bath of cancer-killing drugs.
Dr. Wright said her study was the first to analyze outcomes from IP treatment that was given as part of regular medical practice, and not part of a clinical trial. The results are important because doctors sometimes worry that findings from clinical trials will not hold up in routine medical practice because patients in the trials are carefully selected and may be healthier, more rigorously monitored and given more help with side effects than those in real-world oncology practices.
In this case, Dr. Wright said, the survival benefit proved that women do not have to be in a clinical trial to benefit from IP treatment, and that it can be given successfully in more ordinary settings. Her study also addressed another concern that some oncologists have raised — the toxicity of IP treatment, which had led some women in the clinical trial to stop treatment without finishing it. In Dr. Wright’s study, side effects were less severe and the rates of completing treatment were similar: 89 percent of women who received IP treatment finished the planned course, compared with 91 percent who received only intravenous treatment.
Dr. Deborah K. Armstrong, a professor at Johns Hopkins Kimmel Cancer Center, and the leader of the 2006 study that proved the large survival benefit, attributed the failure of the therapy to catch on to reluctance by oncologists, especially senior ones who might influence colleagues. She said the cumulative data are so strong that oncologists have “no more excuses” for disregarding it.
But to bring about change, patients will have to speak up, she said, adding: “I think it’s going to have to be the advocate community, since they’re the ones who have the most skin in the game, and can put the money where the mouth is, and say, ‘If you can’t give me the best treatment I’ll go someplace else.’ ”