Ovarian cancer

The notion of ovarian cancer combines manifold malignant neoplasms arising from different cells of the genital glands, with a different course, but similar treatment.

Causes of ovarian cancer

Nine out of ten malignant ovarian tumors emerge from the epithelium, the upper layer of the mucous membrane, and this is glandular cancer or adenocarcinoma. Presumably, the majority of cancers occur precisely in the epithelium covering the ovary, but they can also develop from the mucous membrane of the appendages, the fallopian tubes.

It is assumed that regular pregnancies and breastfeeding practiced by our ancestors gave the sex glands physiological rest manifested in cessation of follicle development and ovulation. Modern abandonment of numerous progeny forces the glands to permanent work and, accordingly, during constant fission of epithelial cells the program may malfunction in the direction of malignancy.

Risk factors for ovarian cancer

It has been noted that ovarian cancer is characteristic of women in developed countries, but due to a very small population of affected Japanese women, it was not urbanization that was considered to be the cause, but the diet, the menu orientation towards animal protein foods. Obesity also was included into the pathology initiation causes.

Since the ovaries are hormone-dependent organs, such reason as hormonal imbalance is not excluded, since infertile women develop the condition more often. Studies have shown a threefold increase in the risk of cancer after a long (at least a year) intake of ovulation stimulants applied for ovarian infertility.

The other way round, hormonal contraception and pregnancy, and breastfeeding protect against development of a malignant process in the ovarian tissue.

Early puberty and late menopause favor the pathology, but so far the evidence for this hypothesis is not solid.

The condition is considered to be occupational hazard for women engaged in the production of talc.

How does gynecological surgery affect the development of ovarian cancer?

The incidence of the condition does not increase after gynecological surgery, including hysterectomy or tubal ligation, and of course, ovariectomy, despite the presence of ectopic ovarian tissue that did not originate on the «legitimate» anatomical site. Note that ectopia carries the epithelium of reproductive glands not only into the abdominal cavity, but also into the thyroid and mammary glands, and intestine.

Heredity as the condition cause

This cause has been studied better than all the others, although hardly 1 out of 100 women suffers from hereditary cancer, and their total share among all ovarian cancers does not exceed 10%. Only ovarian cancer can be inherited genetically, or together with mammary cancer. The cause of the disease transmission through the female line lies in the presence of mutated genes BRCA1 or BRCA2.

BRCA1 mutation increases malignant process probability by ¼ to ½, BRCA2 mutation, by less than ¼. Inheritance is highly probable family history includes affected close relatives such as mother or sister, who had cancer of the ovaries and the mammary gland in youth, also with the damage of two ovaries at once. Such families should undergo genetic testing, but a likelihood is not yet the objective reality, especially given the 800 variations of the BRCA1 or BRCA2 gene mutation.

The symptoms of ovarian cancer are associated not so much with the neoplasm type, as with the rate of its growth and spread through the abdominal cavity. Since the abdominal cavity is quite expansive, the signs of the disease do not appear soon, but when the tumor weighs more than a kilogram.

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Ovarian cancer classification

Of the nearly three dozen types of ovarian neoplasms, four types are detected most often: serous, endometrioid, clear-cell and mucinous. Tumors of these cell types can be not only benign and malignant, but also intermediate or borderline. The borderline ones are not yet true cancer, but at the same time they are not benign and capable of forming metastases, therefore their treatment includes chemotherapy.

The most common malignant ovarian tumors are serous cystadenocarcinomas observed in eight out of ten cancer patients, and in nine out of ten when the process is advanced. This cancer variety is practically undetectable at an early stage. Currently, it is believed that serous tumors with low malignancy (well differentiated) and aggressive (poorly differentiated) tumors originate from different parts of the ovaries.
Endometrioid cancer is the second most frequently diagnosed, found in about 10% of patients and most often detected at the initial stage of development. Even more rare clear-cell adenocarcinoma is also detected early, but for Japanese women this cell type is the most frequent.

Symptoms of early ovarian cancer

In the early stage, to which the tumor damage of two ovaries also belongs, the woman feels almost no symptoms. The tumor stretches the profusely innervated peritoneum, but the woman almost does not pay attention to the minor pulling sensations in the lower abdomen, which can hardly be called pain, unexpressed at best.

Compression of the rectum and bladder by ovaries growing in size also goes unnoticed.

Even an increase in the waist circumference which coincides with the growing discomfort in the stomach and a feeling of stomach overflowing does not arouse suspicion, as the woman thinks that she simply put on some weight, and just relocates buttons on her skirt.

In menstruating women, a violation of the cycle is possible. If this causes concern and is not mistaken for a menopausal problem natural for the given age, a visit to a gynecologist will make it possible to discover the problem.

Ovarian cancer stages

Staging of ovarian cancer can be called multifactorial, since each stage from I through III is divided into three variations, and since the beginning of 2014, three divisions within stages IC and IIIA have been added to this, and the previously indivisible stage IV has also been split in two.

The content of each stage is brief:

  1. Stage 1 means that the process has not gone beyond the limits of the organ, while the letter A next to the number indicates that only one ovary is affected, B, both, and C informs about the capsule rupture and cancerous ascites.
  2. Stage 2 with the letters from A to C describes different variations of the tumor spreading to the lesser pelvis tissues.
  3. Stage 3 means that the cancer has spread throughout the abdominal cavity and marked the retroperitoneal lymph nodes.
  4. Stage 4 denotes any type of spreading with metastases to other organs.

Ascites as a symptom of cancer

Symptoms of an advanced process are an increase in the abdomen size due to tumor nodes in the abdominal cavity, and metastases on the peritoneum lining the cavity. Often the tumor causes ascites, a pathological fluid accumulation. The ascitic fluid increases pressure in the cavity, disrupting function of the gastrointestinal organs, and compresses major vessels, which affects the woman’s condition.

The main symptoms of ascites: an inability to eat due to a decrease in the stomach volume, shortness of breath at normal loads, swelling of the legs due to cardiopulmonary insufficiency. Ascites can be combined with effusion in pleural cavities. However, this is not metastatic pleurisy, but fluid transudation from the abdominal cavity.

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Symptoms of advanced ovarian cancer

Cancer nodes can compress the colon and block its lumen, causing intestinal obstruction, a fatal condition that requires urgent medical assistance.

With a large tumor conglomerate, the condition worsens, intoxication increases, and gastrointestinal compression leads to progressive weight loss and weakness, aggravated by regular constipation and respiratory disorders due to restriction in the movements of the diaphragm, which is the respiratory muscle.

Metastases in the inguinal nodes occur infrequently, but tumor conglomerates are localized in the neurovascular bundle area, which causes such a symptom as constant pain.

An expansion of the cancer conglomerate in the lesser pelvis disrupts venous outflow from the lower extremities, which causes their swelling.

Diagnostics of ovarian cancer is by no means easier nowadays, and the main question whether the process is benign or malignant is clarified only by histological examination of a neoplasm fragment removed during an operation or taken at diagnostic laparoscopy.

Why ovarian cancer is rarely detected at an early stage

Screening involves diagnostics of a malignant process which is early and not yet manifested by clinical symptoms. If the condition can be detected not at stage III, but at stage I, then even the minimum treatment will allow the patient to live 3.5 years longer, and with adequate oncological care, the five-year life expectancy will be ensured for 9 patients out of 10, and not just for 2, as is the case with the lately detected tumor process.

Neoplasm diagnostics in the anatomical zone which is inaccessible to observation is difficult, moreover, science cannot specify benign precancerous processes that precede tumor development. Another unknown factor is how long it will take for a small cancer to become advanced. There is an assumption that the condition initially arises from a variety of sites and becomes stage III in an instant. On the other hand, it is believed that ovarian formations grow so slowly that for most people do not have time enough to manifest.

Diagnostics of early ovarian cancer

Two screening examinations are currently recommended: determination of CA-125 marker level and transvaginal ultrasound examination with a special sensor inserted into the vagina.

The marker can also increase in healthy women who smoke and have undergone hysterectomy, and with a small ovarian tumor, only every second woman at most has an increase in its level. An ultrasound scan reveals three out of four small ovarian tissue lesions, overlooking the fourth one.

We still do not have a sufficiently sensitive and inexpensive diagnostic technique that can be used to monitor the state of the reproductive glands with 100% accuracy. But even worse, the widespread introduction of screening did not affect the final result at all, patients did not begin to live longer. There is only one way out, identification of a malignant ovarian tumor requires to regular gynecologist monitoring and examination by the individual program.

Standard diagnostics of ovarian cancer before treatment

The final diagnosis of ovarian cancer is established only by morphology, through microscopic examination of the tumor tissue. Prior to that, there will be only «suspected cancer».

In this situation, an ultrasound scan with a special vaginal sensor will show the spreading of cancer in the lesser pelvis, the true condition of the abdominal cavity will be revealed only during the operation. A CT scan with contrast enhancement has a better sensitivity and is certainly preferable to transvaginal ultrasound, but does not preclude an ultrasound scan for the convenience of further observation.

A colonoscopy is always performed before surgery, because tumor nodes in the abdominal cavity can compress and invade the colon.

For women after 40 years of age, AFP and chorionic gonadotropin markers are tested for the differential diagnostics of cancer and germ cell ovarian neoplasm, and inhibin is determined to exclude sarcomatous growth.

The compulsory menu of primary diagnostics of the process spreading includes ultrasound examination of the lymph nodes, mammography to exclude breast cancer with metastases in the ovaries, and chest radiography.

Cancer diagnostics by marker

The increase in CA-125 depends on the condition stage; if at the beginning of the malignant process development less than half of the patients show an increase in its level, it almost always increases at stage IV, when there are already distant metastases outside the abdominal cavity.

The cellular structure of the tumor also affects the level of CA-125. Thus, with serous cancer, the increase is more common than with other options: endometrioid, clear-cell and mucinous carcinoma. The marker is age-sensitive: the older the woman, the more reliable the result, false negative tests being frequent in young women.

Normally, CA-125 increases during menstruation and in the first half of pregnancy, with smoking and obesity, benign processes of the reproductive organs and inflammatory conditions of gynecological organs.

Therefore, today CA-125 is used not so much for the initial diagnosis, but for monitoring the course of an already established and treated ovarian cancer, helping to assess treatment effectiveness and relapse development.

Surgical treatment of ovarian cancer

The disease is so sensitive to drug treatment that it is impossible to talk about a cure without surgery. In all stages except IV, surgery is necessary even if it is impossible to remove the entire tumor. Ovarian cancer has a unique feature that is completely unacceptable for all other malignant tumors. It is possible to remove part of the tumor leaving what cannot technically be deleted, and it will not cause a process progression.

At the first stage, a cytoreductive operation is performed, in which everything possible is removed. If nodes remain, it is desirable for the remainder to be no greater than a centimeter. The less tumor amount remains for chemotherapy, the second stage, the better the final result.

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What is removed during surgery

The organs removed together with the tumor are the uterus with appendages and the large omentum covering the intestine, where tumor cells accumulate. In some very rare cases of a tiny and non-aggressive process in one reproductive gland, which corresponds to stage IА, if the woman wants to have children, the appendage with the affected ovary is removed, the second healthy ovary is partially resected for a detailed microscopic examination, and the omentum with lymph nodes are removed too.

Endoscopic operations do not allow to assess the abdominal cavity condition, therefore, laparoscopy for ovarian cancer is used to obtain cell analysis and assess the possibility of performing a full-fledged surgical cytoreduction.

If the initial examination reveals a voluminous conglomerate adherent to the pelvic bones and technically non-removable, chemotherapy is performed at the first stage, and surgery is postponed until the situation improves.

Ovarian cancer chemotherapy

After surgery, the issue of chemotherapy is not raised only for cancer stage I without ascites and a well differentiated formation, as well as for non-clear cell carcinoma. All the rest with a completely removed tumor are offered 4 chemotherapy cycles with platinum-based drugs.

Non-operated patients or those having residual nodes after surgery or ascites form of the disease undergo 6 cycles. With the epithelial type, intraperitoneal administration of platinum derivatives practiced by Medicine 24/7 gives a good result with less toxic reactions.

Relapse treatment

A possible relapse of ovarian cancer after treatment is indicated by an increase in CA-125 marker, which can react with growth long before the onset of a detectable tumor, an average of 5 months in advance.

The CA-125 norm is less than 35 U/ml, if the woman had a normal value, then relapse is expected with a double increase, that is, at 70 U/ ml and more. If a woman had CA-125 after treatment higher than normal, then a two-fold increase from the baseline indicates a relapse, for example, the initial value was 55 U/ml, if it raises above 110 U/ml, it would be a reason to start worrying. The second analysis made a week after the first is taken as the true value.

No need to worry if the marker has risen, but no tumor manifestations have been found, and treatment is denied for this reason. Scientific reserach has shown that the result is the same irrespective whether the treatment is started immediately with CA-125 increase, or is postponed until a tumor appears.

Ovarian cancer is not necessarily accompanied by an increase in CA-125, however, this is a relapse and chemotherapy is suggested. The choice of drugs is determined by the duration of the free period, the time from the primary elimination of cancer to the appearance of a new tumor.

This text is based on the materials of NCCN (National Cancer Comprehensive Network).

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