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Australian Journal of General Practice May 2024Prostate cancer (PCa) is the most common malignancy after skin cancer in men in Australia. Its management varies according to tumour stage. Due to the significant... (Review)
Review
BACKGROUND
Prostate cancer (PCa) is the most common malignancy after skin cancer in men in Australia. Its management varies according to tumour stage. Due to the significant dependence on androgen receptor signalling, agents that interfere with this pathway (most commonly medical castration in the form of androgen deprivation therapy [ADT]) are the mainstay treatment of advanced disease.
OBJECTIVE
This review provides a contemporary update on ADT, with further discussion of emerging novel therapies for primary care.
DISCUSSION
ADT is currently indicated for the treatment of metastatic prostate cancer, disease recurrence following attempted local curative therapy, as well as combined use with radiotherapy for intermediate/high-risk disease. There has been rapid development of new pharmaceuticals targeting the androgen receptor. These are reviewed historically with an emphasis placed on emerging therapies, their common side effects, and how to manage them in the general practice setting.
Topics: Humans; Male; Prostatic Neoplasms; Androgen Antagonists; Antineoplastic Agents, Hormonal; Australia
PubMed: 38697060
DOI: 10.31128/AJGP-11-23-7028 -
European Journal of Cancer (Oxford,... Jun 2024Prostate cancer (PC) is the most prevalent cancer in men in Switzerland. However, evidence on the real-world health care use of PC patients is scarce. The aim of this...
BACKGROUND
Prostate cancer (PC) is the most prevalent cancer in men in Switzerland. However, evidence on the real-world health care use of PC patients is scarce. The aim of this study is to describe health care utilization, treatment patterns, and medical costs in PC patients over a period of five years (2014-2018).
METHOD
We used routinely collected longitudinal individual-level claims data from a major provider of mandatory health insurance in Switzerland. Due to the lack of diagnostic coding in the claims data, we identified treated PC patients based on the treatments received. We described health care utilization and treatment pathways for patients with localized and metastatic PC. Costs were calculated from a health care system perspective.
RESULTS
A total of 5591 PC patients met the inclusion criteria. Between 2014 and 2018, 1741 patients had outpatient radiotherapy for localized or metastatic PC and 1579 patients underwent radical prostatectomy. 3502 patients had an androgen deprivation therapy (ADT). 9.5% of these patients had a combination therapy with docetaxel, and 11.0% had a combination with abiraterone acetate. Docetaxel was the most commonly used chemotherapy (first-line; n = 413, 78.4% of all patients in chemotherapy). Total medical costs of PC in Switzerland were estimated at CHF 347 m (95% CI 323-372) in 2018.
CONCLUSION
Most PC patients in this study were identified based on the use of ADT. Medical costs of PC in Switzerland amounted to 0.45% of total health care spending in 2018. Treatment of metastatic PC accounted for about two thirds of spending.
Topics: Humans; Male; Prostatic Neoplasms; Switzerland; Aged; Health Care Costs; Middle Aged; Prostatectomy; Aged, 80 and over; Patient Acceptance of Health Care; Insurance Claim Review; Androgen Antagonists
PubMed: 38678761
DOI: 10.1016/j.ejca.2024.114072 -
Medicina (Kaunas, Lithuania) Mar 2024: Androgen deprivation therapy (ADT) for prostate cancer has greatly improved treatment outcomes. As patient survival rates have increased, reports of decreased bone...
: Androgen deprivation therapy (ADT) for prostate cancer has greatly improved treatment outcomes. As patient survival rates have increased, reports of decreased bone density and increased bone fractures as side effects of ADT have emerged. The prevalence of osteoporosis in Japanese men was 4.6%. The purpose of this study was to evaluate the effect of osteoporosis treatment in prostate cancer patients who underwent ADT in Japan. : The subjects were 33 male patients who had undergone ADT for prostate cancer, who were noted to have decreased bone density. Mean age was 76.2 ± 7.7 years (64-87). Medications included vitamin D in one case, bisphosphonates (BP) in 27 cases, and denosumab in five cases. The evaluation method examined the rate of change in bone mineral density (BMD) before osteoporosis treatment and 1 year after. For comparison, a group without osteoporosis treatment intervention ( = 33) was selected, and matched for prostate cancer treatment and age. The rate of change in trabecular bone score (TBS) was also calculated. : The percentage changes in BMD before and 1 year after treatment were as follows: lumbar spine, 7.1 ± 5.8% in the treatment group versus -3.9 ± 4.1% in the no treatment group; femoral neck, 5.5 ± 6.2% in the treatment group versus -0.9 ± 3.9% in the no treatment group; total femur, 6.6 ± 6.4% in the treatment group versus the no treatment group which was -1.7 ± 3.2%. In all cases, there was a clear significant difference ( < 0.01). The percent change in TBS was further calculated in the same manner. There was no significant difference between the two groups: +1.7 ± 3.8% in the treated group versus +0.3 ± 4.1% in the untreated group. : Osteoporosis treatment in Japanese patients with prostate cancer on ADT therapy was found to significantly increase BMD compared to the untreated group. BP and denosumab were found to be very effective in increasing BMD.
Topics: Humans; Male; Osteoporosis; Aged; Japan; Androgen Antagonists; Prostatic Neoplasms; Bone Density; Aged, 80 and over; Middle Aged; Denosumab; Bone Density Conservation Agents; Diphosphonates; Vitamin D
PubMed: 38674197
DOI: 10.3390/medicina60040551 -
Biosensors Apr 2024Prostate cancer (PCa) displays diverse intra-tumoral traits, impacting its progression and treatment outcomes. This study aimed to refine PCa cell culture conditions for...
Prostate cancer (PCa) displays diverse intra-tumoral traits, impacting its progression and treatment outcomes. This study aimed to refine PCa cell culture conditions for dynamic monitoring of androgen receptor (AR) activity at the single-cell level. We introduced an extracellular matrix-Matrigel (ECM-M) culture model, enhancing cellular tracking during bioluminescence single-cell imaging while improving cell viability. ECM-M notably tripled the traceability of poorly adherent PCa cells, facilitating robust single-cell tracking, without impeding substrate permeability or AR response. This model effectively monitored AR modulation by antiandrogens across various PCa cell lines. Single-cell imaging unveiled heterogeneous antiandrogen responses within populations, correlating non-responsive cell proportions with drug IC50 values. Integrating ECM-M culture with the PSEBC-TSTA biosensor enabled precise characterization of ARi responsiveness within diverse cell populations. Our ECM-M model stands as a promising tool to assess heterogeneous single-cell treatment responses in cancer, offering insights to link drug responses to intracellular signaling dynamics. This approach enhances our comprehension of the nuanced and dynamic nature of PCa treatment responses.
Topics: Humans; Prostatic Neoplasms; Extracellular Matrix; Male; Cell Line, Tumor; Androgen Antagonists; Receptors, Androgen; Single-Cell Analysis; Microscopy; Biosensing Techniques; Luminescent Measurements
PubMed: 38667168
DOI: 10.3390/bios14040175 -
Journal For Immunotherapy of Cancer Apr 2024Androgen deprivation therapy (ADT) is pivotal in treating recurrent prostate cancer and is often combined with external beam radiation therapy (EBRT) for localized...
Myeloid-derived suppressor cells attenuate the antitumor efficacy of radiopharmaceutical therapy using Y-NM600 in combination with androgen deprivation therapy in murine prostate tumors.
RATIONALE
Androgen deprivation therapy (ADT) is pivotal in treating recurrent prostate cancer and is often combined with external beam radiation therapy (EBRT) for localized disease. However, for metastatic castration-resistant prostate cancer, EBRT is typically only used in the palliative setting, because of the inability to radiate all sites of disease. Systemic radiation treatments that preferentially irradiate cancer cells, known as radiopharmaceutical therapy or targeted radionuclide therapy (TRT), have demonstrable benefits for treating metastatic prostate cancer. Here, we explored the use of a novel TRT, Y-NM600, specifically in combination with ADT, in murine prostate tumor models.
METHODS
6-week-old male FVB mice were implanted subcutaneously with Myc-CaP tumor cells and given a single intravenous injection of Y-NM600, in combination with ADT (degarelix). The combination and sequence of administration were evaluated for effect on tumor growth and infiltrating immune populations were analyzed by flow cytometry. Sera were assessed to determine treatment effects on cytokine profiles.
RESULTS
ADT delivered prior to TRT (ADT→TRT) resulted in significantly greater antitumor response and overall survival than if delivered after TRT (TRT→ADT). Studies conducted in immunodeficient NRG mice failed to show a difference in treatment sequence, suggesting an immunological mechanism. Myeloid-derived suppressor cells (MDSCs) significantly accumulated in tumors following TRT→ADT treatment and retained immune suppressive function. However, CD4+ and CD8+ T cells with an activated and memory phenotype were more prevalent in the ADT→TRT group. Depletion of Gr1+MDSCs led to greater antitumor response following either treatment sequence. Chemotaxis assays suggested that tumor cells secreted chemokines that recruited MDSCs, notably CXCL1 and CXCL2. The use of a selective CXCR2 antagonist, reparixin, further improved antitumor responses and overall survival when used in tumor-bearing mice treated with TRT→ADT.
CONCLUSION
The combination of ADT and TRT improved antitumor responses in murine models of prostate cancer, however, this was dependent on the order of administration. This was found to be associated with one treatment sequence leading to an increase in infiltrating MDSCs. Combining treatment with a CXCR2 antagonist improved the antitumor effect of this combination, suggesting a possible approach for treating advanced human prostate cancer.
Topics: Animals; Male; Myeloid-Derived Suppressor Cells; Mice; Prostatic Neoplasms; Radiopharmaceuticals; Humans; Cell Line, Tumor; Yttrium Radioisotopes; Disease Models, Animal; Androgen Antagonists; Combined Modality Therapy
PubMed: 38663936
DOI: 10.1136/jitc-2023-008760 -
ELife Apr 2024Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a...
Relationship between circulating FSH levels and body composition and bone health in patients with prostate cancer who undergo androgen deprivation therapy: The BLADE study.
BACKGROUND
Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM), and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD), and bone turnover markers at baseline conditions and after 12 months of ADT.
METHODS
Twenty-nine consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the luteinizing hormone-releasing hormone antagonist degarelix. FBM, LBM, and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase, and C-terminal telopeptide of type I collagen were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis, -test or sign test and Pearson or Spearman tests for continuous variables were used when indicated.
RESULTS
At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms ( = 0.36) and legs ( = 0.33). Conversely, a stronger correlation was observed between FSH and total FBM ( = 0.52, p = 0.006), fat mass at arms ( = 0.54, p = 0.004), and fat mass at trunk ( = 0.45, p = 0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index/FBM ratio was observed ( = -0.64, p = 0.001). This is an ancillary study of a prospective trial and this is the main limitation.
CONCLUSIONS
FSH serum levels after ADT could have an impact on body composition, in particular on FBM. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and to guide the clinicians in the tailored evaluation of body composition in PC patients undergoing ADT.
FUNDING
This research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript.
CLINICAL TRIAL NUMBER
clinicalTrials.gov NCT03202381, EudraCT Number 2016-004210-10.
Topics: Aged; Aged, 80 and over; Humans; Male; Middle Aged; Absorptiometry, Photon; Androgen Antagonists; Body Composition; Bone Density; Follicle Stimulating Hormone; Oligopeptides; Prostatic Neoplasms
PubMed: 38656229
DOI: 10.7554/eLife.92655 -
Lakartidningen Apr 2024The treatment of metastatic prostate cancer has seen drastic changes in the recent years with more intense treatment at initial diagnose. The new standard is... (Review)
Review
The treatment of metastatic prostate cancer has seen drastic changes in the recent years with more intense treatment at initial diagnose. The new standard is combination therapy with castration as the backbone and the addition of new hormonal therapies with or without chemotherapy. For patients with minimal metastatic spread it is also recommended to give radiotherapy to the primary tumour. Since many patients now can look forward to longer survival it is paramount to take care of the side-effects of the treatments, where focus is on cardiovascular disease and bone health management. Precision medicine has started also in prostate cancer; testing of BRCA1/2 mutation is mandatory for treatment with PARP inhibitors.
Topics: Humans; Male; Prostatic Neoplasms; Androgen Antagonists; Neoplasm Metastasis; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Orchiectomy
PubMed: 38651316
DOI: No ID Found -
Lakartidningen Apr 2024There is a long history of curative treatment of prostate cancer. However, as prostate cancer often grows very slowly, and symptoms do not have time to develop during a... (Review)
Review
There is a long history of curative treatment of prostate cancer. However, as prostate cancer often grows very slowly, and symptoms do not have time to develop during a person's lifetime, a more tentative approach has become more and more common in many cases. This may be through either watchful waiting or active surveillance. In the first case palliative hormonal treatment is given in the case of progression, in the latter curative treatment would be the choice. When treatment is deemed necessary for localized disease, surgery and radiotherapy are considered equivalent in terms of efficacy and overall risk of side effects. For locally advanced disease, radiotherapy is the recommended first-hand choice outside the SPCG 15 study. Focal treatment, which may lead to less side effects than surgery or radiotherapy, is not recommended outside trial settings due to lack of long-term follow-up data.
Topics: Humans; Male; Prostatic Neoplasms; Watchful Waiting; Prostatectomy; Androgen Antagonists; Palliative Care
PubMed: 38650398
DOI: No ID Found -
Aging Apr 2024Prostate cancer (PCa) is the second disease threatening men's health, and anti-androgen therapy (AAT) is a primary approach for treating this condition. Increasing...
OBJECTIVE
Prostate cancer (PCa) is the second disease threatening men's health, and anti-androgen therapy (AAT) is a primary approach for treating this condition. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in the development of PCa and the process of AAT resistance. The objective of this study is to utilize bioinformatics methods to excavate lncRNAs association with AAT resistance and investigate their biological functions.
METHODS
AAT resistance-related risk score model (ARR-RSM) was established by multivariate Cox analysis. Paired clinical tissue samples of 36 PCa patients and 42 blood samples from patients with PSA over 4 ng/ml were collected to verify the ARR-RSM. , RT-qPCR, CCK-8 and clone formation assays were displayed to verify the expression and function of AL354989.1 and AC007405.2.
RESULTS
Pearson correlation analysis identified 996 lncRNAs were associated with AAT resistance (ARR-LncRs). ARR-RSM was established using multivariate Cox regression analysis, and PCa patients were divided into high-risk and low-risk groups. High-risk patients showed increased expression of AL354989.1 and AC007405.2 had poorer prognoses. The high-risk score correlated with advanced T-stage and -stage. The AUC of ARR-RSM outperformed tPSA in diagnosing PCa. Silencing of AC007405.2 and AL354989.1 inhibited PCa cells proliferation and AAT resistance.
CONCLUSIONS
In this study, we have discovered the clinical significance of AC007405.2 and AL354989.1 in predicting the prognosis and diagnosing PCa patients. Furthermore, we have confirmed their correlation with various clinical features. These findings provide potential targets for PCa treatment and a novel diagnostic and predictive indicator for precise PCa diagnosis.
Topics: Aged; Humans; Male; Androgen Antagonists; Biomarkers, Tumor; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Prognosis; Prostatic Neoplasms; RNA, Long Noncoding
PubMed: 38643469
DOI: 10.18632/aging.205754