New drug makes ovarian cancer lesions visible

Ovarian cancer is the third-most-common gynecological cancer in Germany and the seventh-most-common in people with ovaries across the world. In Germany, there were roughly 7,300 new cases in 2018, and more than 5,300 ovarian cancer patients died in the same year, according to the Robert Koch Institute, Germany's public health institute.

A a new drug reveals diseased tissue

The US Food and Drug Administration (FDA) has now approved a novel drug that makes use of fluorescence to help surgeons detect cancer cell lesions in the abdominal cavity during surgery.

In ovarian cancer, the body produces more of a certain protein in cell membranes, called the folate receptor. The new drug Cytaluxbinds to these proteins. And under a near-infrared fluorescence imaging system, Cytalux makes these areas light up.

In the phase III study, Cytalux was administered intravenously before surgery to 134 women aged 33 to 81 in the US. 

"The fluorescent agent accumulates in the ovarian cancer cells. A special fluorescent light is then switched on during surgery, and it is easier to detect small tumor cell lesions in the abdominal cavity," Susanne Weg-Remers, of the German Cancer Research Center (DKFZ) in Heidelberg, told DW.

Cytalux is used with a near-infrared fluorescence imaging system to make diseased tissue "glow." Patients were examined under both normal and fluorescent light with Cytalux. Using the new technique, the surgeons detected at least one cancerous lesion in 26.9 percent of the women that was not visible to the naked eye or by palpation.

Ovarian cancer can spread to the abdominal cavity

If the diagnosis is ovarian cancer, surgery is usually unavoidable, and with it the removal of the ovaries and fallopian tubes as well as other tissue affected by the tumor. During surgery, it is often a problem for surgeons to identify the extent of the tumor and then decide how much tissue to remove and in which areas.

"The ovaries are relatively open in the abdomen," Weg-Remers said. "The cancer has an easy time of it, because it is hardly limited by other organs. ... Because there is enough space in the abdominal cavity, the tumor can often spread before the patient experiences any symptoms."

No significant symptoms at first

At the beginning of the disease, the patient may suffer from symptoms such as vague digestive discomfort, bloating or flatulence. Fatigue and exhaustion can occur, as well as bleeding outside of menstrual periods.

The gynecologist will determine whether ovarian cancer is present. To do this, they palpate the ovaries and do an ultrasound examination through the vagina. If ovarian cancer is suspected, a laparoscopy is done to confirm the diagnosis and to take tissue samples for fine tissue examination. 

In most cases, such an examination and the corresponding diagnosis occur quite late, when the tumor has already progressed. 

"Ovarian cancer is often not detected by a physician until it is no longer confined to the ovaries, but has already spread to the abdominal cavity," Weg-Remers said. "In subsequent surgery, the new method using fluorescence could help detect the tumor cells." 

If the surgeon sees these metastases clearly, he can remove them and the tissue surrounding them.

The abdominal cavity is a complicated area

Once the surgeon has opened the abdominal cavity, they're faced with a complicated picture: The intestines are side by side with the upper abdominal organs, the liver, the spleen and the stomach. A tumor hiding somewhere in this area might not be easy to catch.

"The FDA's approval of Cytalux can help enhance the ability of surgeons to identify deadly ovarian tumors that may otherwise go undetected," said Alex Gorovets, deputy director of the Office of Specialty Medicine in the FDA’s Center for Drug Evaluation and Research. "By supplementing current methods of detecting ovarian cancer during surgery, Cytalux offers health care professionals an additional imaging approach for patients with ovarian cancer."

But the new fluorescence method for detecting tumor cells also has its limitations.

"The data from the study showed that it can detect more cancer lesions, but apparently not all," Weg-Remers said. "There were also those that did not stain. Conversely, in some cases, the operators used the fluorescence method to remove tissue that was benign and did not contain tumor cells, but still showed up as stained. So the examination showed a false-positive result." 

Ovarian cancer survival rates aren't good

The five-year survival rate is tracked for all types of cancer. For breast cancer, it is now very good at 87%.

"In second place are tumors of the uterine body," Weg-Remers said. "There, too, the survival rate is higher than 70%. Then come tumors of the vulva, with a five-year survival rate of about 70%. Cervical cancer is just over 60%. Ovarian tumors have the worst prognosis among tumors of the female reproductive organs. The five-year survival rate is between 40 and 50%."

So far the drug is only approved in the US

Right now, further treatment after surgery often involves chemotherapy.

"They fight ovarian cancer cells that have remained in the body despite surgery and prevent their growth," Weg-Remers said. "But experience simply shows that the fewer cancer cells that are still present, the more effective this is."

The drug for fluorescent detection of cancerous tissue during surgery has initially only been approved for the US market.

Weg-Remers said she believed that "until Cytalux reaches clinical practice, more studies will be needed to prove its benefits."

Side effects cannot be ruled out

According to the US study, 30% of the patients experienced side effects, including nausea and vomiting, as well as transient abdominal pain.

"Adverse reactions consisting of nausea, vomiting, abdominal pain, flushing, indigestion, chest discomfort and itching were reported during the administration of CYTALUX," the company reports on its website.

"These complaints had subsided after 24 hours in the majority of patients," Weg-Remers said. "The drug does not remain permanently in the body; it is removed and then excreted."

Another, much more alarming potential long-term consequence, could be adhesion concerns. With the new method, surgeons operate on a much larger area, and more tissue is removed.

"When you cut into the serous skin that covers the abdominal organs to remove tumor cells, an open wound develops there," Weg-Remers said. "That has to heal. In the process, scar tissue and adhesion structures may form. This could also be the case, for example, if two adjacent wounds stick together."

Further studies are needed

The US study was based on a relatively small group of female cancer patients. Further studies must follow, and additional data must be collected to prove that patients benefit from the fluorescence method compared to standard treatment methods ― in other words, that survival rates improve when the method is used.

Any side effects and long-term consequences have to be balanced out by the benefits. "The method could be a step in the right direction, but of course that has to be proven accordingly in studies," Weg-Remers emphasized.

Nevertheless, the researcher considers the fluorescence procedure to be promising.

"It will probably be some time before it's approved in Germany. In principle, however, the drug is not uninteresting, and I expect that the researchers who conducted this study will follow up on the patients," Weg-Remers said.

If the results are good, the new treatment method could mean a big step forward in the fight against ovarian cancer.

This article was translated from German.