1. Introduction

According to the data of Tillashayhov et al. (2021) prostate cancer (BC) makes up 10,0% of malignant neoplasms in general population in the territory of the Republic of Uzbekistan [1,2,7,8]. The variability of the clinical picture of BPH, as well as the frequently occurring asymptomatic course of the disease up to generalization of the process make an early diagnosis of the appearance of resistant BPH difficult [3,5]. The first step in determining hormonal resistance is the fact that conventional methods of hormonal therapy for BPH are unsuccessful.

Hormonal resistance of the tumor in some patients with PCa is determined immediately after the start of treatment, in others it develops after several months of successful treatment with hormonal therapy[4,6]. Despite this, to date, there are no characteristic signs and reliable criteria for determining the primary and secondary forms of hormonal resistance, which complicates the choice of adequate therapy for each patient with BPH [9].

2. Materials and Methods

Our study was based on data analysis of 112 patients with hormone-resistant prostate cancer (HRPC) under observation in the oncourological department of the RSNPMCRC from 2008 to 2022.

3. Results

Symptoms and signs of urinary tract obstruction, such as difficult urination, increased frequency of urination and feeling of incomplete emptying, were present in most of our patients. Chronic retention and bilateral hydronephrosis with renal insufficiency were observed in 3 patients. Two patients had urinary incontinence due to sphincter infiltration.

Unfortunately, in most patients the first symptoms were moderate pelvic pain and sometimes lumbar pain, which is the result of tumor progression.

One patient had recurrent thrombophlebitis, disseminated intravascular coagulation and bleeding, due to intense bone marrow involvement. In one patient, subclavian adenopathy was the first manifestation of the disease.

The clinical diagnosis of hormone-resistant PCa was established in case of increasing PSA level and/or objective appearance and/or progression of metastases against the background of castrated blood testosterone level. The criteria for this condition were as follows:

- Castration blood testosterone levels (< 50 ng/mL);

- an increase in PSA demonstrated in three consecutive tests performed at least 2 weeks apart, or

- appearance and progression of bone or soft tissue metastases.

There are many works devoted to diagnosis of probable progression of PCa, including occurrence of hormone-resistant forms, by one or other methods of investigation.

All patients of the main and control groups were assessed for the degree of urinary dysfunction according to IPSS (Table 1).

Table 1. Distribution of patients in the main and control groups according to the degree of urinary dysfunction

In the main group, more than half of the patients had severe urinary disorders, which required urgent measures to diagnose and treat the patients. Only 18.8% of patients had local disturbances that did not alarm either the patients or the doctors.

In the control group, 26.7% of the patients had some dysuric disorders, which were most likely related to complications of radiation therapy, because all 8 patients had previously received a radical course of radiation therapy. Of the 8, 6 patients began to complain of urinary disorders 1 to 6 months after completion of radiation therapy.

In addition to dysuric disorders, patients mainly complained of pelvic and lumbosacral pain. In a certain part of patients (24.1%) the process progressed to a certain level without significant symptoms. In these patients the fact of the process progression was established during the next routine examination. At the same time, local progression was registered in 9 patients, and in 18 patients new metastases appeared in lymph nodes (7 patients) and pelvic bone metastases appeared (11 patients). In one case with metastases in the pelvic bone, lung metastases not characteristic of prostate cancer were diagnosed. In the course of the examination, if necessary, we performed restaging of the process (Table 2).

Table 2. Distribution of patients with hormone-resistant PCa according to the stage of the pathological process after detection of hormonal resistance

In patients with progressing symptoms of BPH the repeated examinations at different terms after the "completion" of treatment revealed the progression of pathological process in many patients. Out of 7 patients with 1 stage only one had tumor progression from 1 a to 1 b, the rest had progression, in 4 local and in 2 two - distant metastases without a considerable increase of primary volume.

If before the treatment only 58 (51,8%) patients were diagnosed with the highly differentiated tumor forms corresponding to G1-2, then at the moment of resistance 72 (64,3%) patients had already had these degrees of differentiation. In the control group histological analysis was not performed due to complete control of the cancer. The reason for this is the elimination of low differentiated tumor clones under the influence of treatment and accumulation of resistant cell clones.

There are many studies proving the dependence of tumor hormone resistance directly on the type of cells that form it. In all patients with developed hormone resistance we reviewed the primary and histological material obtained during repeated examinations. The preparations for the study were prepared by standard methods of biopsy sample preparation for morphological study. Histological analysis was performed by an experienced, highly qualified physician pathomorphologist, because, most histological forms of BPH resemble acinar adenocarcinoma and have slightly distinguishable morphological features from it. To avoid bias in drawing conclusions, the primary histopreparations were examined separately from the repeat ones. Primary hormone-resistant prostate cancer usually occurs in tumors such as basal cell carcinoma, urothelial prostate cancer, neuroendocrine cancer, and stromal prostate cancer, which occur in the general population of prostate cancer patients at most 5-7%. Secondary resistance occurs in patients with acinar adenocarcinoma and with tubular cancer. The reason for this fact has not yet been fully elucidated.

The conclusions of the comparative analyses (revision of drugs) of the study are shown in Table 3.

Table 3. Results of histological examination of biopsy material in patients with GERD

4. Conclusions

To date, there is no specific time frame for concluding tumor resistance to hormone therapy after unsuccessful hormone therapy. All possible, routine imaging and histological examinations of the tumor should be used to determine if hormonal resistance has developed.