Modern aspects of diagnosis and treatment of ovarian cancer

At the beginning of the third millennium, ovarian cancer (OC) remains one of the most serious cancer diseases. Occupying the third place in the oncogynecological pathology, ovarian cancer is the leading cause of death in cancer patients. In the structure of cancer incidence, ovarian tumors take 5-7 place, accounting for 4-6% of malignant tumors in women.

The purpose of the literature review was to study modern aspects of diagnosis and treatment of ovarian cancer.

According to the gynecology department of the Russian Cancer Research Center. NN Blokhin RAMS, 5-year survival of patients with stage I disease was 75.2%, with stage II - 41.1%, with III - 35.0%, with IV - 17%. According to the International Federation of Obstetricians and Gynecologists (1998), based on 10,912 observations of ovarian cancer from 100 cancer centers in the world, at the beginning of primary treatment 64% of patients already have late stages of the disease, with a five-year survival rate of patients of all stages does not exceed 69% III - IV stages varies in different countries from 5 to 24%.

In Ukraine, the incidence of ovarian cancer is 16.4 per 100,000 population, and the death rate is 9.8 per 100,000 population.

The age range of those affected with ovarian cancer varies between 40-60 years and more. The peak incidence in Ukraine falls to the age of 60-64 years. The largest in composition and nature of the lesion group are epithelial tumors. These include serous, mucinous, endometrioid, light cell, mixed epithelial, unclassifiable epithelial tumors, Brenner's tumor and undifferentiated carcinoma.

[1], [2], [3], [4]

What causes ovarian cancer?

At present, there is no doubt that malignant neoplasms (including ovarian cancer) are based on damage to the genetic apparatus in the terminal (sexual) and somatic cells, making these cells sensitive to the effects of external, carcinogenic factors capable of triggering the malignancy process. Depending on the cell in which the original mutation - sexual or somatic - occurred, the cancer may be hereditary or sporadic.

Fundamental works devoted to the detection of hereditary forms of ovarian cancer and genetic heterogeneity were the works of N. Lynch, in which he stated that approximately 18% of oncological patients in a family history have relatives affected by cancer of different localization, especially the organs of the female reproductive system.

One of the significant achievements of molecular genetic studies of hereditary forms of ovarian and breast cancer was the discovery of the BRCA1 (Brest cancer associated gene) and BRCA2 genes, the terminal mutations of which, apparently, predispose the hereditary predisposition to these tumors. It was assumed that the syndrome of heritable ovarian cancer is at least partly the result of a dominant autosomal inheritance of a recessive gene with high penetrance. In 1990, on the long arm of the 17th chromosome, the first gene, pretending to be the suppressor gene in breast and ovarian cancer, BRCA1, was mapped. The BRCA1 gene is located at the 17q21 locus. There are versions that BRCA1 is involved in the regulation of transcription of cell division, induction of apoptosis, DNA repair and recombination, maintenance of genome stability. Examination of BRCA1 expression also confirms the assumption that this gene participates in the regulation of cell growth and / or differentiation.

The association of BRCA1 expression with both cell proliferation and their differentiation suggests that BRCA1 is involved in the regulation of the genetic program that provides for the terminal differentiation of cells and the possibility of preserving their phenotype. The area associated with the inheritance of the BRCA2 gene on the physical map corresponds to the region 13ql2-13. In this area of the 13th chromosome, a frequent loss of heterozygous alleles was noted in sporadic cases of breast and ovarian cancer.

In sporadic ovarian tumors, a high percentage of mutations in p53 genes (from 29 to 79%), increased expression of the epidermal growth factor receptor (9-17%), expression of the Her2 / neu genes (16-32%), and activation of the Kiras gene were detected.

How is ovarian cancer diagnosed?

Early diagnosis of ovarian cancer is difficult, because at the initial stages the disease has no pathognomonic clinical symptoms. This leads to the fact that in 70% of patients the disease is diagnosed in later stages. Progression of ovarian cancer is mainly due to dissemination through the peritoneum. This explains the low-symptom course of the disease in the early stages.

A survey of primary patients with ovarian cancer is conducted in accordance with the recommendations of the International Cancer Union (UICC) for refining diagnosis and monitoring of patients with ovarian cancer.

Currently, in the clinic for the purpose of early and differential diagnosis, the definition of tumor-associated marker CA-125 (Cancer Antigen-12.5) is widely used in patients with ovarian tumors. For the first time, monoclonal antibodies to this antigen were obtained and described in 1981. R.S. Bast et al. A discriminating level is considered to be 35 U / ml. In the process of embryogenesis, CA-125 is expressed by the cells of the epithelium of the fetal serous membranes and their derivatives, and is also found in the epithelium of the coeloma, the placenta extract. In adults, slight protein expression is retained in tissues, derivatives of fetal serous membranes - in peritoneal and pleural cavity mesothelium, pericardium, endometrium, tubal epithelium and endocervix. In this case, the serum values of this marker are close to zero.

The increase in serum levels of CA-125 is characteristic not only for tumor involvement of the ovaries. Cases of positive reactions to this marker in patients with acute hepatitis, pancreatitis, peritonitis, tuberculosis, with effusions of various etiologies, endometriosis, during menstruation are described.

In the study of blood serum of patients with stage I disease, the parameters of CA-125 did not differ from the norm and averaged 28.8 U / ml, which indicates the doubtful application of the test in these patients for the purpose of early diagnosis. Starting with the II stage of the disease, the marker level increased significantly and averaged 183.2 U / ml. With advanced stages of the disease, the level of the marker grows even more, sometimes reaching several thousand units. The higher the stage of the disease and the more metastatic lesion of the peritoneum, the higher the average parameters of CA-125.

Using the CA-125 marker it is possible to monitor the effectiveness of the treatment. For this, it is necessary to determine its level after each course of chemotherapy.

The use of CA-125 is possible for early detection of recurrence of the disease. If the patient's level of remission in the remission of CA-125 was "positive," it was almost 100% likely to have a hidden recurrence.

At present, studies are being conducted on the use of cancer embryonic antigen (CEA) and CA-19-9 for the diagnosis of ovarian cancer.

Malignant epithelial tumors of the ovaries are characterized mainly by implantation metastasis, which is carried out both by extension and by exfoliation of tumor cells from the surface of the affected ovarian tissue with the current of the intraperitoneal fluid.

How is ovarian cancer treated?

In the treatment of patients with ovarian cancer apply 3 basic methods: surgical, medicinal and radiation.

Operative intervention is now given primary importance as an independent method and the most important stage in a complex of therapeutic measures. Practically for all ovarian tumors, a median laparotomy should be performed. It allows for a thorough revision of the abdominal cavity and retroperitoneal space.

Radical surgery is assessed by the size of the residual tumor: optimal cytoreductive surgery - no residual tumor, but CA-125 remains elevated, sometimes ascites or pleurisy; subtotal - residual tumor up to 2 cm in the largest measurement or small dissemination along the peritoneum; not optimal - residual tumor more than 2 cm.

Organ-preserving operations can not be performed with moderate or low degree of tumor differentiation or presence of intraoperative findings that change the stage of the disease. In this case, the extirpation of the uterus with appendages is performed.

The data from the literature indicate that even in patients with stage I-II ovarian cancer, which the clinicians regard as "early," metastases in the retroperitoneal lymph nodes of various localizations are diagnosed with a purposeful study. According to a large cooperative study, laparotomy was the most accurate method of determining the stage of ovarian cancer. Of the 100 patients with stage I-II ovarian cancer, 28% of the estimated I and 43% of the prospective stage II disease had later stages of the process. There is the complexity of palpation and visual diagnostics of metastases in retroperitoneal lymph nodes, which is explained by the fact that even tumor-affected lymph nodes are not enlarged, densely elastic consistency, free or relatively shiftable. In addition, only in the para-aortic zone, 80 to 120 lymph nodes are retroperitoneal, and almost all of them can be affected by metastases.

In metastatic lesions of retroperitoneal lymph nodes and the absence of residual tumor in the abdominal cavity, after standard surgery, extended operations (standard volume and lymphadenectomy) are performed. In this case, remove the iliac, para-aortic, and if necessary, inguinal lymph nodes.

In the presence of a tumor that affects neighboring organs, a combined operation is performed. When performing combined operations in patients with ovarian cancer, mainly resect the part of the intestine, urinary tract, liver, removal of the spleen.

It should be noted that the expansion of the standard volume of surgical intervention, i.e., the performance of combined operations, is considered expedient by many authors in the case of an optimal operation. In cases, if the combined operation has a residual tumor more than 2 cm, the long-term results of treatment do not improve.

Depending on the size of the residual tumor, operations are divided into the following types:

1. Primary cytoreductive surgery: removal of the largest possible tumor volume and metastases before the start of subsequent therapy. Its goal should be full or the maximum possible removal of the tumor.
2. Intermediate cytoreductive surgery: performed in patients after a short course of induction chemotherapy (usually a 2-3-year course).
3. The "Second look" operation is a diagnostic laparotomy that is performed to evaluate the residual tumor in the absence of clinical manifestations of the disease after the course of chemotherapy.
4. Secondary cytoreductive surgery: most secondary cytoreductive operations are performed with localized relapses that occur after combined treatment.
5. Palliative surgery: mainly performed to alleviate the condition of the patient, for example, with intestinal obstruction in the background of the adhesion process or the progression of the disease.

The surgery can quickly lead to an effective tumor reduction, but can not completely eliminate all viable tumor cells. Thus, the biological significance of surgical intervention should not be overestimated. Surgical reduction of a kilogram tumor to a residual weight of 1 g will reduce the number of cells from just 1012 to 109. This effort is clearly useless without additional treatment methods, but it is very essential for successful chemotherapy.

Chemotherapy, along with the surgical method, is considered an important component in the treatment of patients with ovarian cancer. Most clinicians recognize the need for chemotherapy for all stages of the disease.

Conducting preoperative chemotherapy is recommended for a massive tumor lesion of the peritoneum and a large omentum with signs of ingrowth into the anterior abdominal wall; infiltrative growth of the ovarian tumor (as evidenced by the drainage dissemination along the peritoneum of the small pelvis, there is a significant displacement of the intestinal loops, changes in the topography of the pelvic organs, retroperitoneal location of the tumor with signs of ingrowth into the main vessels); pronounced exudation - pleurisy / ascites.

After evaluating the effect of chemotherapy, a cytoreductive operation is performed.

Radiation therapy for ovarian cancer, applied since the beginning of the 20th century, has undergone an extremely complicated history of development. Over the years, malignant ovarian tumors have attempted to use all available types and methods of radiotherapy: from deep roentgenotherapy, manual cobalt and radium applicators, intravenous and intracavitary radiotherapy to remote gamma therapy. Remote radiation therapy varied from local irradiation of individual tumor foci to irradiation of the pelvic organs and abdominal cavity; in static and rotational modes; open fields and with shielding of vital organs. In this case, radiation exposure was used in various combinations and sequences with surgical intervention and chemotherapy as in patients with localized and widespread tumoral process.

Radiation therapy for ovarian cancer has traditionally been used as an additional method of treating patients with tumors that did not respond to chemotherapy and helping patients with relapses after initial treatment, including chemotherapy and surgery. Radiation therapy may also be useful for palliative treatment of incurable patients with symptomatic pelvic tumors or distant metastases.

Prof. AA Mikhanovsky, Cand. Honey. OV Slobodyanyuk. Modern aspects of diagnosis and treatment of ovarian cancer.