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![Cumulative Incidence Plot Depicting the Rates of AKI After Stratifying Patients According to the Type of ADT Used (no ADT vs LHRH Agonists vs Bilateral Orchiectomy)—ADT = androgen deprivation therapy; AKI = acute kidney injury; CI = confidence interval; LHRH = luteinizing hormone–releasing hormone. Reprinted with permission from Gandaglia et al. Eur Oncol. 2014.[33]](profile/Judd-Moul/publication/270907611/figure/fig1/AS:392168524009487@1470511670862/Cumulative-Incidence-Plot-Depicting-the-Rates-of-AKI-After-Stratifying-Patients-According.png)
Cumulative Incidence Plot Depicting the Rates of AKI After Stratifying Patients According to the Type of ADT Used (no ADT vs LHRH Agonists vs Bilateral Orchiectomy)—ADT = androgen deprivation therapy; AKI = acute kidney injury; CI = confidence interval; LHRH = luteinizing hormone–releasing hormone. Reprinted with permission from Gandaglia et al. Eur Oncol. 2014.[33]
Source publication
Androgen deprivation therapy (ADT) is key to the treatment of men with advanced prostate cancer. ADT can consist of surgical (bilateral orchiectomy) or medical strategies (eg, luteinizing hormone-releasing hormone agonists or gonadotropin-releasing hormone [GnRH] antagonists). The substantial reduction of testosterone levels achieved with ADT is as...
Context in source publication
Context 1
... Propensity-score matching was used to reduce the inher- ent bias due to differences between pa- tients who were treated with ADT and those who were not. For patients receiv- ing ADT, the estimated 10-year AKI rate was significantly higher (30.7%, compared with 24.9% for ADT-naive patients), and the incidence rates over 5 years and 10 years were also higher in men treated with LHRH agonists than in those who underwent bilateral orchi- ectomy ( Figure 1). Multivariate analysis of the type of ADT received confirmed a significantly higher risk of AKI in men treated with LHRH agonists (HR = 1.24; 95% CI, 1.18-1.31) ...
Citations
... Hormone therapy (androgen deprivation therapy, ADT) is preferred in conjunction with radiation therapy to make treatment more promising. However, long-term ADT treatment is uncertain and has negative consequences (Crawford and Moul 2015). Bicalutamide, the first-generation anti-androgen, is used in androgen deprivation therapy in combination with other chemotherapeutic drugs (Nozawa et al. 2016). ...
Prostate cancer is the second most frequent and the fifth greatest cause of death in men. Although diet has been connected to the prevalence of cancer in addition to other factors, the relation between cancer and prevention is weak. Treatment options are at risk due to cell resistance. To identify new combinations, we tried plant-derived quercetin with bicalutamide on cell lines. To determine the cytotoxicity and apoptotic potential of plant-derived quercetin and its combination, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide] and dual stain assays were performed. In silico protein–ligand interaction was performed to support the in vitro findings. A thin layer, column, and high-performance chromatography were used to purify quercetin along with an authentic sample. In the cytotoxic study, quercetin was minimized by 80% similar to bicalutamide and a combination of quercetin and bicalutamide by 50% when compared to controls by 2%. Quercetin and bicalutamide showed a similar binding affinity for androgen receptors (9.7 and 9.8), hub genes (10.8 and 10.0), and a few other PCa-related genes (9.4 and 9.1). We propose to conclude that the combination of quercetin plus bicalutamide can be used for chemotherapy if additional in vivo studies are conducted. The intake of foods high in polyphenolic compounds can help to prevent prostate cancer. Examination of quercetin on several cell lines will provide a definite conclusion to combat cancers.
... While the role of ADT is well established for metastatic disease, there are limited data supporting its use in biochemical or local recurrence [34,35]. ADT itself is associated with side effects, including thromboembolic events, fatigue, sexual and urinary dysfunction, and skeletal fractures, as well as the development of higher grade castrationresistant prostate cancer after years of treatment [28,[36][37][38][39]. To that end, oligometastaticdirected therapy was studied as a method to delay the need for ADT [13]. ...
Image-guided focal therapy has increased in popularity as a treatment option for patients with primary and locally recurrent prostate cancer. This review will cover the basic indications, evaluation, treatment algorithm, and follow-up for patients undergoing image-guided ablation of the prostate. Additionally, this paper will serve as an overview of some technical approaches to cases so that physicians can familiarize themselves with working in this space. While the focus of this paper is prostate cryoablation, readers will obtain a basic literature overview of some of the additional available image-guided treatment modalities for focal prostate therapy.
... Apart from these findings, it should also be taken into consideration that there are multiple adverse effects associated with ADT [64][65][66][67]. This raises the question in whom to appropriately start ADT treatment. ...
Simple Summary
Prostate cancer (PCa) is the second most frequent malignancy in the male population worldwide. Men with a nodal invasion established after radical prostatectomy with lymph node dissection are a heterogeneous group of patients who require more thorough stratification and therapy individualization, which remain uncovered by current guidelines. Considering a multitude of prognostic factors and novel diagnostic techniques, classifying patients into narrower and more specified risk groups should be a vital part of lymph node positive PCa management in the future.
Abstract
Lymph node invasion in prostate cancer is a significant prognostic factor indicating worse prognosis. While it significantly affects both survival rates and recurrence, proper management remains a controversial and unsolved issue. The thorough evaluation of risk factors associated with nodal involvement, such as lymph node density or extracapsular extension, is crucial to establish the potential expansion of the disease and to substratify patients clinically. There are multiple strategies that may be employed for patients with positive lymph nodes. Nowadays, therapeutic methods are generally based on observation, radiotherapy, and androgen deprivation therapy. However, the current guidelines are incoherent in terms of the most effective management approach. Future management strategies are expected to make use of novel diagnostic tools and therapies, such as photodynamic therapy or diagnostic imaging with prostate-specific membrane antigen. Nevertheless, this heterogeneous group of men remains a great therapeutic concern, and both the clarification of the guidelines and the optimal substratification of patients are required.
... Apart from those findings it should also be taken into consideration, that there are multiple adverse effects associated with ADT [47][48][49][50]. This raises the question in whom to appropriately start ADT treatment. ...
Simple Summary: Prostate cancer (PCa) is the second most frequent malignancy in male population worldwide. Men with nodal invasion established after radical prostatectomy with lymph node dissection are heterogeneous group of patients, requiring more thorough stratification and therapy individualization, which remains uncovered by current guidelines. Considering a multitude of prognostic factors and novel diagnostic techniques, classifying patients into narrower and more specified risk groups should be a vital part of lymph node positive PCa management in the future. Abstract: Lymph node invasion in prostate cancer is a significant prognostic factor indicating worse prognosis. While it affects significantly both survival rates and recurrence, proper management remains a heated issue. Thorough evaluation of risk factors associated with nodal involvement, such as lymph node density or extracapsular extension, is crucial to establish potential expansion of the disease and to substratify patients clinically. There are multiple strategies that may be taken into consideration for patients with positive lymph nodes. Nowadays therapeutic methods are generally based on observation, radiotherapy, and androgen deprivation therapy. However current guidelines are incoherent in terms of indication of the most effective management approach. Future management strategies will be expected to reach for novel diagnostic tools and therapies, such as photodynamic therapy or diagnostic imaging with prostate specific membrane antigen. Nevertheless, this heterogeneous group of men remains a vast therapeutic concern, and both clarification of the guidelines and optimal substratification of patients is required.
... The low number of patients within the normal weight range may be a factor impacting this specific study outcome. These numbers are likely reflective of this population [31,32], in addition to the prevalence of central adiposity as a common side effect of ADT [33]. A significant association was noted between high BMI and WCC count. ...
Background
Circulating tumour cells (CTCs) represent a morphologically distinct subset of cancer cells, which aid the metastatic spread. The ExPeCT trial aimed to examine the effectiveness of a structured exercise programme in modulating levels of CTCs and platelet cloaking in patients with metastatic prostate cancer.
Methods
Participants (n = 61) were randomised into either standard care (control) or exercise arms. Whole blood was collected for all participants at baseline (T0), three months (T3) and six months (T6), and analysed for the presence of CTCs, CTC clusters and platelet cloaking. CTC data was correlated with clinico-pathological information.
Results
Changes in CTC number were observed within group over time, however no significant difference in CTC number was observed between groups over time. Platelet cloaking was identified in 29.5% of participants. A positive correlation between CTC number and white cell count (WCC) was observed (p = 0.0001), in addition to a positive relationship between CTC clusters and PSA levels (p = 0.0393).
Conclusion
The presence of platelet cloaking has been observed in this patient population for the first time, in addition to a significant correlation between CTC number and WCC.
... 13 Androgen receptors are expressed on several immunologic cells and play an important role in immune system regulation, 14 and previous studies have demonstrated that ADT is associated with an increased risk of pneumonia, cardiovascular disease, and acute kidney injury in patients with prostate cancer. [15][16][17] Among pneumonia-causing pathogens, Streptococcus pneumoniae is prevalent in approximately 60% of infections and remains a major cause of morbidity and mortality worldwide. 18,19 The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is effective for preventing pneumococcal infections in 65% to 84% of patients with diabetes mellitus (DM), chronic pulmonary diseases, or congestive heart failure (CHF). ...
... The analyses were also adjusted for cancer treatment modalities, including ADT, radiotherapy, surgery, chemotherapy, and targeted therapy. [10][11][12][15][16][17] The details of cancer treatment modalities, such as ADT regimens and types of prostate surgery, are listed in Table 2. Influenza vaccination status was considered a potential confounder and was adjusted for in the analysis because most patients received both PPSV23 and influenza vaccines. The interaction of influenza vaccination with PPSV23 vaccination was also considered in the regression model, and subgroup analyses were performed (Table 3). ...
... ADT is an important treatment modality for patients with prostate cancer, and several studies have demonstrated an increased risk of pneumonia in patients with prostate cancer who receive gonadotropin-releasing hormone. [15][16][17] A population-based cohort study using data from the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository assessed 20,310 men newly diagnosed with nonmetastatic prostate cancer and demonstrated that current ADT treatment was associated with a higher risk of hospitalization for community-acquired pneumonia. 17 Several mechanisms have been proposed by previous studies to explain the correlation of ADT with pneumonia, including castration-induced morphologic/biochemical changes to respiratory cell membranes and changes in the synthesis, secretion, and clearance of phospholipids in pulmonary surfactants because of androgen deficiency. ...
Background
The 23‐valent pneumococcal polysaccharide vaccine (PPSV23) is indicated for adults who have a high risk of pneumonia; however, its effectiveness in patients with prostate cancer who are at a risk of pneumonia because of age and cancer treatments, including androgen‐deprivation therapy, is unknown.
Methods
Between 2000 and 2010, 38,735 patients with prostate cancer were diagnosed in Taiwan. After exclusions and exact matching for age, previous pneumonia, and influenza vaccination, 2188 vaccinated patients and 2188 unvaccinated patients were recruited. The incidence density of all‐cause bacterial pneumonia hospitalizations was analyzed.
Results
Over 7 years of follow‐up, patients who received the PPSV23 had a significantly lower incidence density, with 142.8 per 1000 person‐years versus 162.0 per 1000 person‐years for unvaccinated patients. More patients in the vaccinated cohort were never hospitalized for pneumonia compared with those in the unvaccinated cohort (64.2% vs 62.2%, respectively). After adjusting for the Charlson comorbidity index, cancer treatment modalities, and socioeconomic levels, the risk of pneumonia‐related hospitalization in the PPSV23 vaccination cohort was 0.48 times lower than that in the unvaccinated cohort (adjusted incidence rate ratio, 0.48; P = .046). For patients who received the influenza vaccination, subgroup analysis demonstrated that PPSV23 vaccination significantly decreased the risk (adjusted incidence rate ratio, 0.45; P < .001). Compared with unvaccinated controls, PPSV23‐vaccinated patients had a lower cumulative incidence for the first occurrence of pneumonia‐related hospitalization (34.49% vs 36.36%; P = .178) and higher overall survival (47.5% and 42.3%, respectively; P < .001).
Conclusions
Vaccination of elderly patients who have prostate cancer with the relatively common and inexpensive PPSV23 can decrease the risk of pneumonia and prolong survival.
... One of these treatments is inhibiting the production of androgen hormones via surgery or inhibiting its binding to androgen receptors (5). This approach is a well-known treatment strategy for advanced and metastatic prostate cancer (6). ...
Side effects and chemotherapy resistance, demand new therapeutics with minimal side effects. Here, we investigated the combined effect of curcumin and metformin on the LNCaP prostate cancer cell line. LNCaP cells were treated with curcumin, metformin, and their combination at different concentrations. Cell viability was assessed by MTT assay and expression of Bax, Bcl-2, mTOR, hTERT, PUMA, p53 and p21 genes was analyzed by real-time PCR. Apoptosis and cell cycle were assessed by flow cytometry. Our results revealed that the viability of cells treated with curcumin, metformin, and their combination was significantly (P < 0.05) reduced with increasing the concentration and prolonging the treatment time. Meanwhile, the combination showed a synergistic effect within 48 h. In the curcumin treated group, the expression of Bcl-2 and hTERT genes diminished. In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined. Although all treatments induced apoptosis, the combination of curcumin and metformin showed the maximum level of apoptosis, cytotoxicity, and expression of Bax gene. The combination of curcumin and metformin showed synergistic effects within 48 h. This combination could be a potential therapeutic candidate for prostate cancer to be further investigated.
... Currently, the most common treatment for metastatic PCa is androgen deprivation therapy (ADT), such as the anti-androgen flutamide (FLUT) and surgery, which might accompany radiation. Unfortunately, the benefit of these treatments is temporary, as many patients experience disturbing side effects from androgen deficiency [5,6]. Moreover, current ADT is the main suspect of increasing PCa patient risk of depression [7,8] and suicide rates [2]. ...
Prostate cancer (PCa) patients commonly experience clinical depression. Recent reports indicated that monoamine oxidase-A (MAO-A) levels elevate in PCa, and antidepressant MAO-Is show anti-PCa properties. In this work, we aimed to find potential drugs for PCa patients suffering from depression by establishing novel anti-PCa reversible monoamine oxidase-A inhibitors (MAO-AIs/RIMA); with an endeavor to understand their mechanism of action. In this investigation, twenty synthesized flavonoid derivatives, defined as KKR compounds were screened for their inhibitory potentials against human MAO-A and MAO-B isozymes. Meanwhile, the cytotoxic and antiproliferative effects were determined in three human PCa cell lines. MAO-A-kinetics, molecular docking, SAR, cell morphology, and cell migration were investigated for the most potent compounds. The screened KKRs inhibited MAO-A more potently than MAO-B, and non-toxically inhibited LNCaP cell proliferation more than the DU145 and PC3 cell lines, respectively. The results showed that the three top MAO-AI KKRs compounds (KKR11, KKR20, and KKR7 (IC50s 0.02–16 μM) overlapped with the top six antiproliferative KKRs against LNCaP (IC50s ~9.4 μM). While KKR21 (MAO-AI) and KKR2A (MAO-I) were ineffective against the PCa cells. Furthermore, KKR21 and KKR11 inhibited MAO-A competitively (Kis ≤ 7.4 nM). Molecular docking of the two compounds predicted shared hydrophobic and distinctive hydrophilic interactions—between the KKR molecule and MAO-A amino acid residues—to be responsible for their reversibility. The combined results and SAR observations indicated that the presence of specific active groups—such as chlorine and hydroxyl groups—are essential in certain MAO-AIs with anti-PCa effects. Additionally, MAO-A inhibition was found to be associated more with anti-PCa property than MAO-B. Distinctively, KKR11 [(E)-3-(3,4-dichlorophenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)prop-2-en-1-one] exhibited anti-metastatic effects on the DU145 cell line. The chlorine substitution groups might play vital roles in the KKR11 multiple actions. The obtained results indicated that the flavonoid derivative KKR11 could present a novel candidate for PCa patients with depression, through safe non-selective potent inhibition of MAOs.
... Results of studying ADT-induced major cardiovascular diseases in men with PC are so far conclusive [28,[40][41][42][43]. However, a previous study reported that neoadjuvant ADT was associated with an increased risk of all-cause mortality among men with CHF or myocardial infraction in high-risk localized PC [28]. ...
Few studies have assessed the benefits of androgen deprivation therapy (ADT) in men with metastatic prostate cancer (PC; mPC) at an old age or with major cardiovascular conditions. A retrospective cohort consisted of 3835 men with newly diagnosed mPC from the Taiwan Cancer Registry of 2008–2014. Among them, 2692 patients received only ADT in the first year after the cancer diagnosis, and 1143 patients were on watchful waiting. The inverse probability of treatment-weighted Cox model was used to estimate the effects of ADT on all-cause mortality and PC-specific mortality according to age, and the status of congestive heart failure (CHF), coronary arterial diseases (CADs), and stroke at the baseline. After a median follow-up of 2.65 years, 1650 men had died. ADT was associated with a 17–22% risk reduction in all-cause and PC-specific mortality in men without stroke, CAD, or CHF in the 65–79-year group. The survival benefit diminished in men with any of these preexisting conditions. In contrast, ADT was not found to be associated with any survival benefit in the ≥80-year group, even though they did not present with any major cardiovascular disease at the baseline. Patients who had CHF, CAD, or stroke at the baseline did not show a survival benefit following ADT in any of the age groups. Men who have preexisting major cardiovascular diseases or are ≥80 years do not demonstrate a survival benefit from ADT for mPC. The risk–benefit ratio should be considered when using ADT for mPC in older men especially those with major cardiovascular comorbidities.
... Perhaps, the most notable contributor to the subjective well-being of a man with metastatic HSPC is the delaying or deferring of ADT, the side effects of which can significantly hamper a patient's lifestyle and systemic health [11]. With ADT, in addition to decrease in subjective feelings of wellness associated with androgen loss, there has been reported increased risk of osteoporosis, cardiovascular-related mortality, and diabetes [26]. Consistent with prior retrospective reports [12,27] and the recently reported randomized phase II STOMP trial [9], our study also suggests that SABR can substantially delay initiation of ADT in men with oligometastatic HSPC for up to a year. ...
Purpose
Local ablative treatment to oligometastatic patients can result in long-term disease-free survival in some cancer patients. The importance of this treatment paradigm in prostate cancer is a rapidly evolving field. Herein, we report on the safety and preliminary clinical outcomes of a modern cohort of oligometastatic prostate cancer (OPC) patients treated with consolidative stereotactic ablative radiation (SABR).
Methods
Records of men with OPC who underwent consolidative SABR at our institution were reviewed. SABR was delivered in 1–5 fractions of 5–18 Gray. Kaplan–Meier estimates of local progression-free survival (LPFS), biochemical progression-free survival (bPFS; PSA nadir + 2), distant progression-free survival (DPFS), and time-to-next intervention (TTNI) were calculated.
Results
In total, 66 OPC patients were identified with consolidative SABR delivered to 134 metastases: 89 bone, 40 nodal, and 5 viscera. The majority of men (49/66) had hormone-sensitive prostate cancer (HSPC). Crude grade 1 and 2 acute toxicities were 36% and 11%, respectively, with no ≥ grade 3 toxicity. At 1 year, LPFS was 92% and bPFS and DPFS were 69%. Of the 18 men with HSPC who had deferred hormone therapy , 11 (56%) remain disease free following SABR (1-year ADT-FS was 78%). In 17 castration-resistant men, 11 had > 50% prostate-specific antigen (PSA) declines with 1-year TTNI of 30%.
Conclusions
Consolidative SABR in OPC is feasible and well tolerated. The heterogeneity and small size of our series limit extrapolation of clinically meaningful outcomes following consolidative SABR in OPC, but our preliminary data suggest that this approach warrants continued prospective study.
