Analysis of the Role of Comprehensive Treatment Model in the Treatment of Prostate Cancer

The incidence of prostate cancer is gradually increasing. There are many methods for clinical treatment of prostate cancer, such as surgical treatment and endocrine treatment. In the case of advanced prostate cancer, we must not only extend patients’ survival times but also enhance their quality of life. Endocrine medications are the most effective therapy for advanced prostate cancer. This research will investigate the therapeutic impact of a complete treatment model in prostate cancer in order to discover a trustworthy clinical treatment model. This research discovered that, as compared to endocrine treatment, radical resection of prostate cancer may diminish and reach lower serum PSA levels in a short amount of time, as well as sustain low PSA levels and delay progression to castration resistance. Moreover, the comprehensive treatment mode can effectively reduce the possibility of complications. The research results show that the comprehensive treatment model can play an important role in the treatment of prostate cancer.

A Model-Based Framework to Identify Optimal Administration Protocols for Immunotherapies in Castration-Resistance Prostate Cancer

Prostate cancer (PCa) is one of the most frequent cancer in male population. Androgen deprivation therapy is the first-line strategy for the metastatic stage of the disease, but, inevitably, PCa develops resistance to castration (CRPC), becoming incurable. In recent years, clinical trials are testing the efficacy of anti-CTLA4 on CRPC. However, this tumor seems to be resistant to immunotherapies that are very effective in other types of cancers, and, so far, only the dendritic cell vaccine sipuleucel-T has been approved. In this work, we employ a mathematical model of CRPC to determine the optimal administration protocol of ipilimumab, a particular anti-CTLA4, as single treatment or in combination with the sipuleucel-T, by considering both the effect on tumor population and the drug toxicity. To this end, we first introduce a dose-depending function of toxicity, estimated from experimental data, then we define two different optimization problems. We show the results obtained by imposing different constraints, and how these change by varying drug efficacy. Our results suggest administration of high-doses for a brief period, which is predicted to be more efficient than solutions with prolonged low-doses. The model also highlights a synergy between ipilimumab and sipuleucel-T, which leads to a better tumor control with lower doses of ipilimumab. Finally, tumor eradication is also conceivable, but it depends on patient-specific parameters.

Cabazitaxel in the treatment of metastatic castration-resistant prostate cancer

The incidence of prostate cancer in the structure of malignant neoplasms occupies the fourth place, it is 7.3%. 1 414 259 new cases and 375 304 deaths were estimated worldwide in 2020. In recent decades, there was a significant increase in the number of cases of metastatic castration-resistant prostate cancer (mCRPC). There is no consensus on the optimal treatment choice, nowadays. The various therapeutic options are offered for these aims. But, the regimes and the consistence of their application are problematical and far from being resolved. The aim of this review is to analyze the studies on the use of cabazitaxel in the treatment of mCRPC. The history of the taxanes application in advanced and metastatic prostate cancer dates back to 2004, when the United States Food and Drug Administration registered docetaxel as first-line therapy for patients with metastatic prostate cancer. Cabazitaxel the new second generation taxane appeared in 2010, and showed the activity in the development of castration resistance. The drug demonstrated high antitumor activity and significant efficacy at the time of progression against the background of treatment with docetaxel and androgen receptor inhibitors. The results of the number of the randomized clinical trials associated with the various aspects of treatment tactics in mCRPC are available for the analysis, nowadays. However, these data and especially the clinical benefit are ambiguous, and sometimes contradictory. The review presents the results of the scientific researches, international clinical studies concerning the various aspects of mCRPC, in particular the choice of modern optimal treatment tactics.

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 2: Clinic–Pathologic Correlations

Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA guidelines) to critically evaluate human tissue-based studies (immunohistochemistry, molecular analysis, etc.), experimental research (cell lines, mouse models), and clinical trials. Despite some controversial results and study limitations, PD-L1 expression by tumor cells may be related to clinic–pathologic features of adverse outcome, including advanced tumor stage (high pT, presence of lymph node, and distant metastases), positivity of surgical margins, high Grade Group, and castration resistance. Different PD-L1 positivity rates may be observed in matched primary PCs and various metastatic sites of the same patients. Over-fixation, type/duration of decalcification, and PD-L1 antibody clone may influence the immunohistochemical analysis of PD-L1 on bone metastases. PD-L1 seemed expressed more frequently by castration-resistant PCs (49%) as compared to hormone-sensitive PCs (17%). Some series found that PD-L1 positivity was associated with decreased time to castration resistance. Treatment with ipilimumab, cyclophosphamide/GVAX/degarelix, or degarelix alone may increase PD-L1 expression. Correlation of PD-L1 positivity with overall survival and outcomes related to tumor recurrence were rarely investigated; the few analyzed series produced conflicting results and sometimes showed limitations. Further studies are required. The testing and scoring of PD-L1 should be standardized.

Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance

Although castration-resistant prostate cancer (CRPC) as a whole, by its name, refers to the tumors that relapse and/or regrow independently of androgen after androgen deprivation therapy (ADT), untreated tumor, even in early-stage primary prostate cancer (PCa), contains androgen-independent (AI) PCa cells. The transformation of androgen-dependent (AD) PCa to AI PCa under ADT is a forced evolutionary process, in which the small group of AI PCa cells that exist in primary tumors has the unique opportunity to proliferate and expand selectively and dominantly, while some AD PCa cells that have escaped from ADT-induced death acquire the capability to survive in an androgen-depleted environment. The adaptation and reprogramming of both PCa cells and the tumor microenvironment (TME) under ADT make PCa much stronger than primary tumors so that, currently, there are no effective therapeutic methods available for the treatment of CRPC. Many mechanisms have been found to be related to the emergence and maintenance of PCa castration resistance; in this review, we focus on the role of inflammatory signaling in both PCa cells and the TME for the emergence and maintenance of CRPC and summarize the recent advances of therapeutic strategies that target inflammatory signaling for the treatment of CRPC.

Glutamine and Cholesterol Plasma Levels and Clinical Outcomes of Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Taxanes

Altered metabolism is a hallmark of cancer. Malignant cells metabolise glutamine to fulfil their metabolic needs. In prostate cancer, androgen receptor signalling promotes glutamine metabolism, which is also involved in cholesterol homeostasis. We aimed to determine whether the plasma glutamine levels correlate with the blood lipid profile, clinical characteristics and outcomes in patients with metastatic castration resistance prostate cancer (mCRPC) undergoing taxanes. We retrospectively assessed the glutamine and glutamate levels in plasma samples by a bioluminescent assay. Pre-treatment glutamine, glutamate, cholesterol and triglycerides levels were correlated with patients’ clinical characteristics, taxanes response and clinical outcomes. Seventy-five patients with mCRPC treated with taxanes were included. The plasma glutamine levels were significantly higher in patients that received abiraterone or enzalutamide prior to taxanes (p = 0.003). Besides, patients with low glutamine levels were more likely to present a PSA response to taxanes (p = 0.048). Higher glutamine levels were significantly correlated with shorter biochemical/clinical progression-free survival (PSA/RX-PFS) (median 2.5 vs. 4.2 months; p = 0.048) and overall survival (OS) (median 12.6 vs. 20.3; p = 0.008). High cholesterol levels independently predicted early PSA/RX-PFS (p = 0.034). High glutamine and cholesterol in the plasma from patients with mCRPC were associated with adverse clinical outcomes, supporting the relevance of further research on metabolism in prostate cancer progression.

Abiraterone acetate – 10 clinically relevant facts

Prostate cancer is one of the most frequently diagnosed cancers in men. Number of newly diagnosed cases is increasing due to several factors and the most important ones seem to be: population ageing and more sensitive diagnostic procedures. Secondary – the higher efficacy of treatment with its influence on improving patients’ overall survival and the specific mechanism of action of drugs used in systemic therapy lead to growing population of men suffering from prostate cancer in general and, specifically – patients with castration resistance. It is hormone therapy to play the key role in systemic treatment of prostate cancer with increasing significance of novel drugs focused on inhibition of molecular signal transduction mediated by androgen receptor. Abiraterone acetate is the representative of this therapeutic class. The paper describes the most clinically relevant data regarding the drug.