Ovarian cancer is one of the most aggressive tumors of the female genital organs. But assessing diseased tissue and its extent is difficult. A fluorescent dye should help.
Ovarian cancer, ovarian carcinoma, is the third most common malignant disease of the female genital organs. According to the Center for Cancer Registry Data of the Robert Koch Institute, there were about 7,300 new cases in 2018, and more than 5,300 of the patients died from ovarian cancer.
A fluorescent dye shows diseased tissue
In the USA, the American drug authority FDA (Food and Drug Administration) has now approved a novel fluorescent dye. It is intended to help the surgeon identify nests of cancer cells in the abdominal cavity during the operation.
In ovarian cancer, the body produces more of a specific protein in cell membranes called the folate receptor. The dye Cytalux binds to these proteins. These areas light up under a near-infrared fluorescence imaging system.
In the phase 3 study, 134 women aged 33 to 81 years were given intravenous Cytalux before surgery. “The fluorescent substance accumulates in the ovarian cancer cells. A special fluorescent light is then switched on during the operation and small tumor cell nests in the abdominal cavity can be better recognized,” explains Susanne Weg-Remers from the Cancer Information Service of the DKFZ, the German Cancer Research Center in Heidelberg.
Cytalux is used with a near-infrared fluorescence imaging system, effectively illuminating diseased tissue. The patients were examined under both normal and fluorescent light with Cytalux. With the new procedure, the surgeons discovered at least one cancerous lesion in 26.9 percent of the women that could not be seen with the naked eye or by touch.
Ovarian cancer can spread to the abdominal cavity
If the diagnosis is ovarian carcinoma, an operation is usually unavoidable, and thus the removal of the ovaries and fallopian tubes as well as other tissue affected by the tumor. During such an operation, it is often difficult for surgeons to see the extent of the tumor so that they can then decide how much tissue to remove in which areas.
“The ovaries are relatively open in the abdominal cavity,” explains Weg-Remers. “Cancer has an easy time because it is hardly limited by other organs and has enough time to expand. Since there is enough space in the abdominal cavity, the tumor can often spread before the patient develops any symptoms.”
There are no significant symptoms at first
At the beginning of the disease, the patient may suffer from symptoms such as vague digestive problems, and a feeling of fullness or flatulence. Tiredness and exhaustion can also occur, as well as bleeding outside of the menstrual period.
The gynecologist will clarify whether it is ovarian cancer. They feel the ovaries and do an ultrasound scan of the vagina. If ovarian cancer is suspected, a laparoscopy is done to confirm the diagnosis and to take tissue samples for histological examination.
In most cases, such an examination and the corresponding diagnosis take place quite late, when the tumor is already advanced. “Ovarian cancer is often only detected by a doctor when it is no longer limited to the ovaries but has already spread to the abdominal cavity. In a subsequent operation, the new method using fluorescent dyes could help to identify the tumor cell nests,” says Weg-Remers. If the surgeon sees these metastases clearly, he can remove them over a large area.
The abdominal cavity is a complicated area
When the surgeon has opened the abdominal cavity, a rather confusing area is revealed. There are the intestinal loops and the upper abdominal organs, the liver, the spleen, and the stomach. “You have to examine all of this carefully and see whether there are any suspicious areas there. It is therefore understandable that this is made easier by a method that makes the remaining tumor cells visible,” says Weg-Remers.
But the new fluorescence method for detecting tumor cells also has its limits. “The data from the study have shown that while more tumor cells can be detected, apparently not all of them. There were also those that did not stain. In return, the surgeons used the fluorescence method to remove tissue in some cases that was benign and contained no tumor cells but were stained nonetheless. The test, therefore, showed a false-positive result,” Weg-Remers points out.
Ovarian cancer can spread unhindered in the abdominal cavity
The chances of survival from ovarian cancer are not good
The 5-year survival rate is an important criterion for all types of cancer. In the case of breast cancer, it is now very good at 87 percent. “Tumors of the uterine body come second,” explains Weg-Remers. “Here, too, the survival rate is over seventy percent. Then come vulva tumors with a 5-year survival rate of around 70 percent. Cervical cancer is just over 60 percent. Ovarian tumors have the worst prognosis among organ tumors of the female reproductive organs. The 5th -year survival rate is between 40 and 50 percent.”
The fluorescent dye is only approved in the USA
Currently, it is mainly chemotherapy that is used for further treatment after an operation. These adjuvant methods can help improve the chances of recovery. “They fight ovarian cancer cells that have remained in the body despite the operation and prevent them from growing. But experience simply shows that the fewer cancer cells that are left, the more effective it is,” says Weg-Remers.
The approval of the fluorescent dye for the detection of tumor cell nests during ovarian cancer surgery initially only applies to the American market. “So that it also makes it onto the German market, a corresponding approval in Germany is necessary, and until Cytalux arrives in clinical practice, further studies will be needed to prove the benefit,” believes Weg-Remers.
Side effects are not excluded
According to the US study, 30 percent of the patients had side effects from the administration of the fluorescent dye. For example, there were nausea and vomiting or temporary abdominal pain. “These symptoms had subsided in the majority of patients after 24 hours. The dye does not stay in the body permanently, it is transported away and then excreted,” says Weg-Remers.
Another, much more serious long-term consequence could be problems with adhesions. Under the fluorescent dye, the surgeons operate on a much larger area, more tissue is removed. “If you cut into the serous skin that covers the abdominal organs to remove a nest of tumor cells, an open wound develops there. It has to heal. Scar tissue and adhesions can form in the process. This can also be the case, for example when two adjacent wounds stick together,” Weg-Remers points out.
Further studies are required
The US study was based on a relatively small group of cancer patients. Further studies need to follow and additional data need to be collected to demonstrate that patients benefit from the fluorescence method compared to standard treatment methods. So that the survival rates improve when using the method. Furthermore, possible side effects and long-term consequences must be acceptable. “The process could be a step in the right direction, but of course, you have to prove that in studies,” emphasizes Weg-Remers.
Nevertheless, the scientist considers the process with the fluorescent dye to be very promising. “It will probably be some time before the dye is approved in Germany. In principle, however, the dye is not uninteresting, and I expect that the researchers who conducted this study will also follow up the patients,” summarizes Weg-Remers. If the corresponding results are good, the therapy of dangerous ovarian cancer could take a big step forward.