Therapeutic pathomorphose and structural-functional state of ovarian cancer after neoaduvant chemotherapy and hormone therapy
Authors: Mikhanovsky O.A. , Lukashova O.P. , Kharchenko Yu.V. , Sukhina O.M. , Dolhaia O.V. 
Published: January 2025

Background. Ovarian cancer is the most deadly oncological disease among gynecological cancers with a 5-year survival rate of 26–42%, which is associated with asymptomatic course in the early stages, late diagnosis, frequent recurrence, chemoresistance, which increases with adjuvant therapy of each subsequent recurrence. Treatment of patients with OC is intricated and occupies a special place in practical medicine. The combined method of surgical intervention and neoadjuvant and adjuvant polychemotherapy using platinum and taxane drugs is generally recognized.
Purpose – study of the therapeutic pathomorphosis, structural and functional state of ovarian cancer after neoadjuvant chemotherapy and hormone therapy.
Materials and methods. Two groups of patients with serous papillary cystocarcinoma (SPCC) of stage III-II were studied. Patients of the first group (27 people) underwent cytoreductive neoadjuvant polychemotherapy (NPCT) with the use of cisplatin and paclitaxel with subsequent surgery. Patients of the second group (13 people) were prescribed hormonal treatment with tamoxifen simultaneously with NPCT. In the postoperative period, all patients underwent 6 cycles of adjuvant chemotherapy. 12 patients with primary SPCC were serve as a control. Morphological indicators of residual neoplastic tissue from the surgical material were studied ву standard histological and electron microscopic methods,. The obtained results were processed using descriptive statistics and nonparametric criteria with the Biostat PC software package and the nonparametric method of maximum likelihood estimation for small samples.
Results. It was found that primary SPCC is characterized by significant tumor and cellular heterogeneity. The study of residual tissue after NPHT showed that the use of NPHT leads to the mass death of tumor cells (TC) sensitive to the drugs used, which allows surgical intervention. However, part of the TCs avoids damage, and in each case the response of tumors to therapy is characterized by its own peculiarity. Thus, part of the tumors (20%) consists of fairly large fields of big TCs, and in the tumors of 25 percent of patients there is a pronounced growth of papillary structures, with the presence of giant, 2-nuclear and pleomorphonuclear TCs. The frequency of such cases may be an indicator of the progression of such tumors with the emergence of new tumor clones resistant to the used chemotherapeutic agents due to the mutational action of NPCT, and is observedin 45% of patients. In other cases, the phenomena of fibrosis prevail in the surgical material. However, sometimes small nests of TCs in the thickness of the connective tissue (CT) are found, and sometimes the surface of the CT is covered by a layer of small epithelial cells. Such phenomena are manifestations of post-therapeutic tumor regression. Therefore, the combination of such signs can be considered criteria for such regression. In NPCT, it occurs in 55% of cases. However, in total, viable TCs are found in the surgical material in 80% of patients, which may indicate significant chemoresistance of this ovarian cancer form. With the combined use of NPCT and hormonal therapy, the frequency of patients with detected tumors is somewhat lower and is 53.8%, the progression rate significantly decreases, and post-therapeutic fibrosis processes are observed more often than with NAHT (46.2% versus 20). That is, the combined use of chemo- and hormonal therapy increases the effectiveness of treatment. The mechanisms of the combined action of the drugs used may lie in the different targets at which these drugs are directed (damage to the genetic apparatus for chemotherapy, and estrogen receptor inhibitors for hormonal therapy). These mechanisms require further careful study, taking into account such factors as the level of estrogens, their receptors, etc.
Conclusions. It has been shown that both in primary tumors of patients with serous papillary carcinoma and in NPCT, pronounced tumor and cellular heterogeneity is noted. SPCC is characterized by marked chemoresistance, as evidenced by the presence of viable tumor cells in 80% of cases after chemotherapy. NPCT is characterized by both regression and tumor progression processes, which are 55 and 45%, respectively. The use of combined treatment leads to a significant increase in the tumor regression rate (84.6% versus 55). With the combined use of chemo- and hormonal treatment, there is also a tendency to reduce the frequency of patients with the presence of tumor cells from 80 to 53.8%. Signs of chemoresistance to the drugs used force us to pay attention to the feasibility of adjuvant treatment with their use. Further studies will allow us to establish the mechanisms of the combined action of chemotherapeutic and hormonal drugs to increase the effectiveness of treatment.