How Should Ovarian Cancer Survivors Be Monitored for Relapse?

Treating an ovarian cancer relapse as soon as it can be detected seems like a good idea. But not so fast, a major study has concluded.

The study involved women with advanced ovarian cancer in complete remission after surgery and platinum-based chemotherapy. The goal was to determine whether these women benefit from new chemotherapy initiated after levels of the blood marker CA-125 increase to a particular threshold—but before physical symptoms appear.

The research found no difference in overall survival for women whose relapse was treated earlier, compared with women whose chemotherapy was delayed until symptoms arose. Also, the women whose treatment began later scored better on quality of life measures.

The findings didn’t surprise Gordon Rustin, MD, director of medical oncology at Mount Vernon Cancer Centre in Middlesex, United Kingdom, who, on behalf of U.K. and other European collaborators, presented the study’s results last spring at a meeting of the American Society of Clinical Oncology. “I tell my patients that if they feel well and have no symptoms suggesting relapse, they are better off not having CA-125 measured during follow-up,” he says. “The major change in my advice is that if I now have a patient who has a rising CA-125 but is very well, I tell them that they can safely delay chemotherapy until they develop symptoms.”

Participants in the study, which enrolled more than 1,440 patients in 10 countries, underwent quarterly tests for CA-125. Among the 37 percent (529 patients) whose CA-125 levels reached twice the upper limit of normal before symptoms appeared, half were randomized to be informed of the increase and started treatment within four weeks; half were not informed, but continued getting CA-125 tests and began treatment after symptoms appeared. Eighty percent of patients with advanced ovarian cancer relapse after first-line chemotherapy, and most benefit from further therapy, says Rustin.

In the U.S., CA-125 holds a primary place in gauging ovarian cancer activity, says Beth Karlan, MD, director of the Women’s Cancer Research Institute and gynecologic oncology at Cedars-Sinai Medical Center in Los Angeles. While no firm guidelines are in place, quarterly monitoring of CA-125 levels, along with imaging (such as CT or PET/CT) once or twice a year, is common in monitoring women with advanced ovarian epithelial cancer in remission.

Karlan notes the study’s findings don’t apply to everybody—for instance, the fraction of patients who have access via clinical trials to new treatments that might work differently than standard chemotherapy regimens. The study also didn’t address variations in the second- or third-line therapies administered, differences in how responsive a patient’s cancer was to chemotherapy with a platinum-containing drug, or the potential impact of secondary surgical debulking (to remove as much of the cancer as possible) in treating some recurrences.

At about $50, CA-125 testing is relatively inexpensive, but it extracts another toll—women’s extreme anxiety about each result, Karlan says. Also, she says, for the women who restart chemotherapy based on rising but relatively low levels of CA-125 alone, quality of life suffers, most likely due to more time spent in treatment and cumulative toxicities such as neuropathy.

Karlan expects it to take awhile before patients and physicians embrace the findings. Ultimately, she hopes the data will empower patients with the knowledge that if they’re not having symptoms, an elevated CA-125 is not an emergency. They can consider exploring a second opinion or clinical trial, do personal things like take planned vacations, and prepare themselves for more treatment. “What Dr. Rustin’s study says is you don’t have to stop everything and enter treatment tomorrow.”