Evolution of Androgenic Deprivation in Treatment of Prostate Cancer in Kinshasa

Context and Objective: Prostate cancer (PCa) is hormone-dependent cancer. In our area, most patients often arrive at the locally advanced stage or the metastatic stage. This justifies the choice of androgen deprivation as the mode of treatment. The objective of this study was to describe the socio-demographic characteristics of patients with PCa. Identifying the period during which the disease remains susceptible to androgen deprivation. Assessing the patient’s prognosis in terms of survival. Methods: This is a retrospective observational study of the course of patients managed for PCa. It involved 51 cases and was conducted at the Pointe à Pitre clinic (CPAP) in Matete Township during a period of 4 years (from March 2014 to June 2018). Results: The mean age of patients was 69.4 ± 9.7 years (40 - 92 years); 39.2% of patients with PCa were aged between 70 - 79 years; 45.1% had consulted for dysuria and 25.5% were hypertensive. All had performed the prostate biopsy, 47.1% were diagnosed at the metastatic stage, with PSA ≥ 100 ng/ml, Gleason scores 8 - 10, and clini-cal-stage TNM 3 - 4. About 51% were subjected to androcure, 23.5% had been surgically cased and 3.9% had undergone radical prostatectomy. 41.1% had resisted castration within a median of 1.4 years of response to treatment. The median survival was 30 months, with a mean survival of 26.6 months. Conclusion: Prostate cancer involved most of the patients in the age bracket of 70 to 79 years. The diagnosis was performed lately with a high resistance rate of castration and median survival of 30 months.


Introduction
Prostate cancer (PCa) is the most common cancer in men in America (Afro-Americans and Afro-Caribbean) and Europe [1] [2] [3]. Patients with localized or sometimes locally advanced forms benefit from radical prostatectomy or radiotherapy. On the other hand, in patients with aggressive or metastasized forms; the treatment options may be radiotherapy but more commonly androgen deprivation [4]. To reduce the plasma level of testosterone and its derivative, dihydrotestosterone (DHT), androgen deprivation; apart from surgical castration still used by Anglo-Saxons, other practitioners prefer hormone therapy [5]. This hormone therapy has evolved with the emergence of LH-RH analogs, then treatment with non-steroidal anti-androgens, and finally, more recently, LH-RH antagonists, and Gn-RH agonists [6]. Depending on the patient's response, this hormone therapy goes from the first to the third line [7] [8]. Over 90% of patients treated respond to androgen deprivation. Unfortunately, transiently, its duration varies from a few months to a few years. The median being 12 to 18 months, then relapse is observed in 100% of cases. After the escape from this first line of hormone therapy, responses to alternative hormonal manipulations are rare, the tumor is resistant to castration [7] [8]. Once the hormone-independence stage has been reached, the tumor is resistant to castration. Median overall survival is 34 months [6]. Castration-resistant PC (CRPC) is an advanced form characterized by disease progression after surgical or pharmaceutical castration (androgen deprivation). The process by which prostate cancer cells become resistant to castration is not clear, but androgenic privations have been shown to offer a selective advantage to androgen-independent cells, which eventually grow and repopulate the tumor [9]. Compared with castration sensitive PCa, the prognosis of patients with CRPC is poor and survival is reduced. Until very recently, treatment options were mainly limited to symptomatic relief of bone metastases, which are more common in CRPC than in the castration-sensitive form [9] [10] [11] [12]. To provide a clear picture of the burden of CRPC, one must consider the prevalence of the disease, the relative time of onset versus diagnosis, patient characteristics including demographics, comorbidity, the onset of disease, metastatic form, and probable survival. There is, however, insufficiency of epidemiological evidence specifically characterizing CRPC outside of the settings of controlled trials in which patients may not represent the general population and normal disease progression. This can lead to its sub-optimal management; for example, the identification of patients with CRPC who are at risk of developing metastases is currently hampered by a poor understanding of its real epidemiology. Identifying people with CRPC may seem straightforward after androgen deprivation (drug or surgical). The characterization of the disease in epidemiological terms, eg incidence, prevalence, and survival, is however less clear. This can be attributed at least in part to the difficulty of defining, and therefore of studying, the patient population. The varying terminology-CRPC, HRPC (Hormone-refractory PCa), AIPC (Androgen-independent PCa), ERPC (Endocrine-resistant PCa)-reflects subtle differences in dentition that may hamper research comparison. Practitioners can also use a variety of diagnostic methods: prostate-specific antigen (PSA) assays, the development of metastases, or other factors to determine if a patient is defined as CRPC. The recently published European Association of Urology (EAU) guidelines aim to standardize the diagnosis of CRPC and include a list of five defining factors of CRPC [4].
These are as follows: • Serum testosterone level.
• Three consecutive increases in Prostate Specific Antigen (PSA) 2 weeks apart resulting in two increases of 50% over the nadir. • Anti-androgen stops for at least 4 weeks.
• Progression of PSA despite secondary hormonal manipulations. • Progression of bone or soft tissue damage.
CRPC is a heterogeneous disease, and despite the availability of such guides for diagnosing CRPC, in practice, this can vary. Also, besides, the routes of treatment and clinical practice, particularly the stage of the disease at the onset of androgen deprivation therapy, vary widely between geographic locations and even the individual's clinic. Therefore, establishing common epidemiological estimates for the CRPC population becomes very complex and may become less relevant for individual scenarios [13].
In our environment, most affected patients consult at the advanced stage of the disease; thus, justifying androgen deprivation as a mode of treatment.
This study aimed to improve the clarity of the epidemiological evidence around CRPC, by identifying, assessing, and describing the most relevant elements that characterize the affected patient population using observational data.
Our objective was to assess the responses to hormonal deprivation, patient survival and to identify the different predictors of mortality.

Inclusion Criteria
We considered patients' files with a PCa which was treated and operated during the period of our study.

Non Inclusion Criteria
Incomplete or absent files on during data collecting have not been taken into account.

Collection of Data
We collected data by completing an ad hoc form related to the documentary review focused on the medical records and registers of patients.

Statistical Analyses
The data were computerized using Excel 2010 software and were analyzed using SPSS version 17 software. Tables or graphs were used, as appropriate, for the presentation of the results. The continuous quantitative variables with Gaussian distribution were presented as mean ± standard deviation; those with non-normal distribution in the form of the median (extremes). Qualitative variables were described as relative frequency (%). Comparison of proportions, medians, and means was performed using Chi-square, Mann Whitney Wilcoxon, and Student's t-tests, respectively. Independent determinants of resistance to surgical castration and PSA ≥ 100 ng/ml were identified using logistic regression. Kaplan Meier's method estimated the probability curve of resistance to surgical castration. It also described survival between the date of diagnosis of CaP and death (complete data) and the end of the study (censored data). The Log-rank test was used to compare survival curves. Cox's regression looked for independent predictors of mortality. A p-value < 0.05 was considered the threshold of statistical significance.

Ethical Considerations
During the collection and analysis of our data, confidentiality was strictly enforced.

General Characteristics of the Study Population
About 51 patients, the average age was 69.4 ± 9.7 years, with extremes of 40 to 92
From an evolutionary point of view; the rate of castration resistance was 43.1% within a median of 1.4 (1 -3) years of response to treatment ( Table 2).

Evaluation of Castration Resistance
Castration resistance was observed from the 5th month of treatment, especially for carrier patients with metastases.

Resistance to Castration According to Gleason Score
Patients with a Gleason score between 8 and 10 had a higher frequency of resistance compared to those with a Gleason score between 6 and 7; log-rank test (p = 0.018) (Figure 1).

Risk of Resistance According to the D'AMICO Classification
According to D'AMICO's classification, the risk of castration resistance was variable: -

Assessment of Patients' Survival versus Castration Resistance
Patients resistant to castration had significantly reduced survival compared to those who did not (p = 0.029) (Figure 2).

Assessment of Survival about Prostate Specific Antigen Level
The survival of patients with a PSA level ≥ of 100 ng/ml (p = 0.006) was significantly lower compared to the others (Figure 3).

Assessment of Survival about Gleason Score
The survival of patients with a Gleason score of 8 -10 (p 0.004) was significantly lower than those with a score of 6 -7 ( Figure 4).    (Table 6).

Discussion
The current study is one of the few to have explored the course of androgen deprivation in 51 patients treated for PCa Apart from the response to this hormonal deprivation, the objective was to evaluate the survival of the patients and to look for the different predictors of mortality. In Table 1 [20] Daniel et al. [21] Mohamed Ait Chtouk [22] Rozet et al. [ [48]. Other studies [49] report that 10% to 20% of PCa evolve into CRPC approximately 5 years after the start of treatment (Table 8).

Conclusion
Prostate cancer is a public health challenge in our area.

Limitations of the Study
This publication is considered as a pilot study which will be validated by others. The