Search Results (39)

Background: Androgen deprivation therapy (ADT) is a primary treatment for prostate cancer (PCa) that effectively reduces androgen levels to suppress tumor progression. However, growing evidence suggests potential cognitive side effects, raising concerns about the long-term neurological consequences of this treatment. Objective: This scoping review aims to synthesize the existing evidence linking ADT to cognitive changes in men with PCa, identifying the key cognitive domains affected and outlining gaps in the existing literature. Methods: A systematic literature search was conducted according to the PRISMA-ScR guidelines in CINAHL, PubMed, Scopus, and Web of Science. Studies investigating cognitive function in ADT-treated PCa patients were included, covering randomized controlled trials (RCTs) and cohort, case–control, and cross-sectional studies. The extracted data included the study design, evaluated cognitive characteristics, measurement tools, and overall findings. Results: A total of 22 studies met the inclusion and exclusion criteria. Cognitive assessments varied across studies. While some studies reported cognitive impairments in ADT-treated patients—particularly in working, verbal, and visual memory and executive function—others found no significant effects. The variability in prostate cancer staging, epidemiological study designs, and treatment regimens; the exclusion of comorbid conditions; and the differences in assessment tools, sample sizes, and study durations hinder definitive conclusions about the cognitive effects of ADT. Conclusions: This scoping review highlights the heterogeneous and often contradictory evidence regarding ADT-associated cognitive dysfunction. While certain cognitive domains may be affected, methodological inconsistencies limit robust conclusions. Standardized cognitive assessments and longer longitudinal studies are required to clarify ADT’s role in cognitive decline. As the PCa survival rate increases with extended ADT use, integrating routine cognitive monitoring into clinical practice should be considered for PCa patients. Full article

(1) The primary prostate cancer treatment involves androgen deprivation therapy, with or without chemotherapy. Immunotherapy has emerged as a promising strategy against cancer due to its ability to modulate the immune system, overcome immune evasion, and stimulate the attack on tumor cells. Thus, this review urges an exploration of the underlying mechanisms to validate the efficacy and safety of dendritic cell immunotherapy for prostate cancer treatment. (2) An extensive literature search identified 45 eligible studies in PubMed, Web of Science, SCOPUS, and Embase databases. Phase I and II clinical trials and in vitro studies (PROSPERO registration number CRD42024538296) were analyzed to extract information on patient selection, vaccine preparation, treatment details, and disease progression. (3) Despite significant variability in vaccine development and treatment protocols, vaccines were shown to induce satisfactory immune responses, including T-cell activation, increased CD4 and CD8 cell populations, upregulated expression of HLA-A2 and HLA-DR, enhanced migratory capacity of dendritic cells, and elevated interferon levels. Cytokine responses, particularly involving Interleukin 10 (IL-10) and Interleukin 12 (IL-12), varied across studies. Immunotherapy demonstrated potential by eliciting positive immune responses, reducing PSA levels, and showing an acceptable safety profile. However, side effects such as erythema and fever were observed. (4) The analyzed treatments were well-tolerated, but variability in clinical responses and side effects underscores the need for further research to optimize the efficacy and safety of this therapeutic approach. Full article

Background: The ideal timing of androgen deprivation therapy (ADT) for patients with biochemical recurrence (BCR) of prostate cancer (PCa) remains controversial due to its side effects and uncertain impact on survival outcomes. Methods: We performed a review of the current literature by comprehensively searching the PubMed, Embase, and Cochrane databases to determine the optimal timing of ADT initiation after biochemical recurrence. We selected 26 studies including systematic reviews, randomized controlled trials (RCTs), and retrospective studies, while also reviewing practice guidelines. Results: Not all patients with BCR cancer experience clinical or radiological progression. While early ADT may delay progression, evidence of its effect on PCa-specific mortality remains inconclusive. The PSA thresholds for initiating ADT vary, complicating decision-making. Key predictors of progression include a short PSA doubling time (PSADT), a high Gleason score (GS), and a brief interval to BCR of PCa post-radiotherapy (RT). Combining ADT with androgen receptor pathway inhibitors (ARPIs) has been shown to improve metastasis-free survival in high-risk patients. Conclusion: The ideal timing of ADT initiation in BCR PCa remains uncertain. Early ADT can help control the progression, but its effect on PCa-specific mortality is unclear. Stratifying patients by their risk factors, such as their PSADT, GS, and time to BCR can guide individualized treatment. In high-risk patients, delaying ADT should be avoided, while combining ADT with an androgen receptor pathway inhibitor (ARPI) may further improve outcomes. Full article

Background: Prostate cancer (PC) and its treatment are often associated with side effects such as fatigue, muscle loss, and diminished quality of life (QoL). Physical exercise, particularly resistance training (RT) and aerobic training (AT), has been suggested as a strategy to mitigate these effects. However, the comparative efficacy of RT, AT, and combined RT/AT on QoL, body composition, physical fitness, and laboratory markers in PC patients is still insufficiently understood. Methods: Randomized controlled trials (RCTs) investigating structured RT, AT, or combined RT/AT programs in PC patients undergoing various treatments were included. The primary outcome was QoL, assessed using EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires. Secondary outcomes included body composition, fitness, and laboratory parameters. The studies were sourced from PubMed, Embase, and CENTRAL through May 2024. The effect sizes were pooled using random-effects models, and the risk of bias was systematically assessed following the GRADE approach. Results: A total of 30 RCTs, encompassing 2216 PC patients, were analyzed. Combined RT/AT significantly improved QoL subdomains, including global health, and cognitive and sexual function, while reducing fatigue and urinary symptoms. RT alone improved body composition by increasing lean body mass and reducing body fat percentage. Both RT and combined RT/AT enhanced strength (chest and leg press) and VO₂peak. No significant changes were observed in laboratory markers, such as PSA or lipid levels. The effects of isolated AT remain unclear due to limited data. Conclusions: RT and combined RT/AT significantly improve QoL, fitness, and body composition in PC patients, with no detectable effect on PSA or lipid levels. Further research is needed to elucidate the specific effects of AT and to investigate long-term outcomes. Full article

Although Androgen Deprivation Therapy (ADT) is effective in controlling prostate cancer (PCa) and increasing survival, it is associated with a myriad of side effects that cause significant morbidity. Previous research has shown that PCa patients starting on ADT are neither fully informed nor well-equipped to manage the breadth of ADT’s side effects. The ADT Educational Program (a 1.5 h interactive class plus a book) was developed as an evidence-based resource for patients dealing with ADT. Our aim here was to compare the efficacy of an online version of the class with a previously assessed in-person version of the class. Using mixed MANOVAs within a non-randomized comparison design, we assessed: (1) changes in patients’ experiences of self-efficacy to manage and bother associated with side effects approximately 10 weeks after attending a class, and (2) potential differences in these variables between online and in-person class formats. Side effect bother decreased from pre- to post-class but did not differ between in-person (n = 94) and online (n = 137) class cohorts. While self-efficacy to manage side effects was slightly higher post-class in both cohorts, the increase was not statistically significant. Average self-efficacy ratings were significantly higher among in-person versus online class participants (p < 0.05; η_p² = 0.128). Both online and in-person classes are associated with a significant reduction in the severity of side effect bother reported by PCa patients, suggesting non-inferiority of online versus in-person formats. Online classes offer greater accessibility to the program for patients outside the reach of in-person classes, increasing the availability of the program to more PCa patients and family members across Canada. Full article

This review delves into the intricate roles of interleukin-8 (IL-8) and its receptors, CXCR1 and CXCR2, in prostate cancer (PCa), particularly in castration-resistant (CRPC) and metastatic CRPC (mCRPC). This review emphasizes the crucial role of the tumour microenvironment (TME) and inflammatory cytokines in promoting tumour progression and response to tumour cell targeting agents. IL-8, acting through C-X-C chemokine receptor type 1 (CXCR1) and type 2 (CXCR2), modulates multiple signalling pathways, enhancing the angiogenesis, proliferation, and migration of cancer cells. This review highlights the shift in PCa research focus from solely tumour cells to the non-cancer-cell components, including vascular endothelial cells, the extracellular matrix, immune cells, and the dynamic interactions within the TME. The immunosuppressive nature of the PCa TME significantly influences tumour progression and resistance to emerging therapies. Current treatment modalities, including androgen deprivation therapy and chemotherapeutics, encounter persistent resistance and are complicated by prostate cancer’s notably “immune-cold” nature, which limits immune system response to the tumour. These challenges underscore the critical need for novel approaches that both overcome resistance and enhance immune engagement within the TME. The therapeutic potential of inhibiting IL-8 signalling is explored, with studies showing enhanced sensitivity of PCa cells to treatments, including radiation and androgen receptor inhibitors. Clinical trials, such as the ACE trial, demonstrate the efficacy of combining CXCR2 inhibitors with existing treatments, offering significant benefits, especially for patients with resistant PCa. This review also addresses the challenges in targeting cytokines and chemokines, noting the complexity of the TME and the need for precision in therapeutic targeting to avoid side effects and optimize outcomes. Full article

Castration-resistant prostate cancer (CRPC) remains a significant therapeutic challenge due to its resistance to standard androgen deprivation therapy (ADT). The emergence of androgen receptor splice variant 7 (AR-V7) has been implicated in CRPC progression, contributing to treatment resistance. Current treatments, including first-generation chemotherapy, androgen receptor blockers, radiation therapy, immune therapy, and PARP inhibitors, often come with substantial side effects and limited efficacy. Natural compounds, particularly those derived from herbal medicine, have garnered increasing interest as adjunctive therapeutic agents against CRPC. This review explores the role of AR-V7 in CRPC and highlights the promising benefits of natural compounds as complementary treatments to conventional drugs in reducing CRPC and overcoming therapeutic resistance. We delve into the mechanisms of action underlying the anti-CRPC effects of natural compounds, showcasing their potential to enhance therapeutic outcomes while mitigating the side effects associated with conventional therapies. The exploration of natural compounds offers promising avenues for developing novel treatment strategies that enhance therapeutic outcomes and reduce the adverse effects of conventional CRPC therapies. These compounds provide a safer, more effective approach to managing CRPC, representing a significant advancement in improving patient care. Full article

The management of high-risk prostate cancer (PCa) presents a significant clinical challenge, often necessitating treatment intensification due to the potential presence of micrometastases. While radical prostatectomy (RP) constitutes one of the primary treatment modalities, the integration of neoadjuvant and adjuvant therapies suggests a paradigm shift towards more aggressive treatment strategies, also guided by new imaging modalities like positron emission tomography using prostate-specific membrane antigen (PSMA-PET). Despite the benefits, treatment intensification raises concerns regarding increased side effects. This review synthesizes the latest evidence on perioperative treatment intensification and de-escalation for high-risk localized and locally advanced PCa patients eligible for surgery. Through a non-systematic literature review conducted via PubMed, Scopus, Web of Science, and ClinicalTrials.gov, we explored various dimensions of perioperative treatments, including neoadjuvant systemic therapies, adjuvant therapies, and the role of novel diagnostic technologies. Emerging evidence provides more support for neoadjuvant systemic therapies. Preliminary results from studies suggest the potential for treatments traditionally reserved for metastatic PCa to show apparent benefit in a non-metastatic setting. The role of adjuvant treatments remains debated, particularly the use of androgen deprivation therapy (ADT) and adjuvant radiotherapy in patients at higher risk of biochemical recurrence. The potential role of radio-guided PSMA lymph node dissection emerges as a cutting-edge approach, offering a targeted method for eradicating disease with greater precision. Innovations such as artificial intelligence and machine learning are potential game-changers, offering new avenues for personalized treatment and improved prognostication. The intensification of surgical treatment in high-risk PCa patients is a dynamic and evolving field, underscored by the integration of traditional and novel therapeutic approaches. As evidence continues to emerge, these strategies will refine patient selection, enhance treatment efficacy, and mitigate the risk of progression, although with an attentive consideration of the associated side effects. Full article

Prostate cancer (PC) stands as the most frequently diagnosed non-skin cancer and ranks as the second highest cause of cancer-related deaths among men in the United States. For those facing non-metastatic PC necessitating intervention, solely local treatments may not suffice, leading to a possible transition toward systemic therapies, including androgen deprivation therapy (ADT), chemotherapy, and therapies targeting androgen. Yet, these systemic treatments often bring about considerable adverse effects. Additionally, it is observed that overweight men are at a higher risk of developing aggressive forms of PC, advancing to metastatic stages, and succumbing to the disease. Consequently, there is a pressing demand for new treatment options that carry fewer side effects and enhance the current standard treatments, particularly for the majority of American men who are overweight or obese. In this article, we will review the metabolic response to ADT and how lifestyle modulation can mitigate these ADT-associated metabolic responses with a particular focus on the two clinical trials, Carbohydrate and Prostate Study 1 (CAPS1) and Carbohydrate and Prostate Study 2 (CAPS2), which tested the effects of low-carbohydrate diets on the metabolic side effects of ADT and PC progression, respectively. Furthermore, we will summarize the findings of serum metabolomic studies to elucidate the potential mechanisms by which ADT and low-carbohydrate diets can affect the metabolic response to mitigate the metabolic side effects while maximizing therapeutic efficacy. Full article

Prostate cancer is a multi-focal disease that can be treated using surgery, radiation, androgen deprivation, and chemotherapy, depending on its presentation. Standard dose-escalated radiation therapy (RT) in the range of 70–80 Gray (GY) is a standard treatment option for prostate cancer. It could be used at different phases of the disease (e.g., as the only primary treatment when the cancer is confined to the prostate gland, combined with other therapies, or as an adjuvant treatment after surgery). Unfortunately, RT for prostate cancer is associated with gastro-intestinal and genitourinary toxicity. We have previously reported that the metabolic modulator lonidamine (LND) produces cancer sensitization through tumor acidification and de-energization in diverse neoplasms. We hypothesized that LND could allow lower RT doses by producing the same effect in prostate cancer, thus reducing the detrimental side effects associated with RT. Using the Seahorse XFe96 and YSI 2300 Stat Plus analyzers, we corroborated the expected LND-induced intracellular acidification and de-energization of isolated human prostate cancer cells using the PC3 cell line. These results were substantiated by non-invasive ³¹P magnetic resonance spectroscopy (MRS), studying PC3 prostate cancer xenografts treated with LND (100 mg/kg, i.p.). In addition, we found that LND significantly increased tumor lactate levels in the xenografts using ¹H MRS non-invasively. Subsequently, LND was combined with radiation therapy in a growth delay experiment, where we found that 150 µM LND followed by 4 GY RT produced a significant growth delay in PC3 prostate cancer xenografts, compared to either control, LND, or RT alone. We conclude that the metabolic modulator LND radio-sensitizes experimental prostate cancer models, allowing the use of lower radiation doses and diminishing the potential side effects of RT. These results suggest the possible clinical translation of LND as a radio-sensitizer in patients with prostate cancer. Full article

Background and Objectives: 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. Materials and Methods: 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 (n = 33) was selected, and matched for prostate cancer treatment and age. The rate of change in trabecular bone score (TBS) was also calculated. Results: 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 (p < 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. Conclusions: 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. Full article

(1) Background: Paraphilic disorders, marked by intense sexual fantasies and behaviors, present formidable challenges. This review addresses concerns fueled by scandals and child abuse. Emphasizing paraphilias’ complexity, it systematically reviews the pharmacotherapy literature, aiming to enhance understanding and guide future research. (2) Methods: A comprehensive search from 1990 to 2023 across major databases identified 28 relevant English-language studies. Inclusion criteria focused on adult pharmacotherapy for paraphilias, and results were evaluated using the Newcastle–Ottawa Scale. (3) Results: Synthesizing data from selected studies, diverse treatments such as SSRIs and antiandrogens were analyzed, revealing variable effectiveness and side effect profiles. Poor quality of the current literature has been reported. (4) Conclusions: Highlighting the pivotal role of the serotonergic system, this review underscores the efficacy of SSRIs and androgen deprivation therapy. GnRH analog-associated side effects and the importance of a combined assessment approach are discussed. Critical insights contribute to understanding and ethical considerations in paraphilic disorders. Full article

Castration resistance poses a significant challenge in the management of advanced prostate cancer (PCa), with androgen deprivation therapy (ADT) or chemotherapy being the primary treatment options. However, these approaches often lead to significant side effects and the development of therapeutic resistance. Therefore, it is crucial to explore novel treatment options that can efficiently target PCa, improve patient survival, and enhance their quality of life. Neferine (Nef), a bioactive compound derived from plants, has emerged as a promising candidate for cancer treatment due to its ability to induce apoptosis, autophagy, and cell cycle arrest. In this study, we investigated the potential anticancer effects of Nef in androgen receptor (AR)-positive LNCaP and VCaP cells, representative models of androgen-dependent PCa. Our findings demonstrate that Nef effectively inhibits cell growth, proliferation, and the tumorigenic potential of androgen-dependent PCa cells. Furthermore, Nef treatment resulted in the excessive production of reactive oxygen species (ROS), leading to the activation of key markers of autophagy and apoptosis. These results suggest that Nef has the potential to target the oncogenic characteristics of androgen-dependent PCa cells by exploiting the potency of ROS and inducing autophagy and apoptosis in AR-positive PCa cells. These findings shed light on the therapeutic potential of Nef as a novel treatment option with reduced side effects for androgen-dependent prostate cancer. Further investigations are warranted to assess its efficacy and safety in preclinical and clinical settings. Full article

Patients with localized recurrent prostate cancer (PCa) are eligible for androgen-deprivation therapy, salvage radical prostatectomy (RP) or radiation therapy. These treatments are associated with serious side-effects, illustrating the need for alternative local treatment options with lower morbidity rates. All patients who underwent magnetic resonance imaging (MRI)-guided salvage focal cryoablation (SFC) with localized recurrent PCa between 2011–2021 (n = 114) were included. Two subgroups were formed: patients without (n = 99) and with prior RP (n = 15). We assessed the recurrence- (RFS) and treatment-free survival (TFS), measured from date of treatment to date of recurrence or initiation of additional salvage treatment, using Kaplan–Meier plots. Complications were reported using the Clavien–Dindo (CD) scale. Overall 1-year and 5-year RFS were 76.0% and 25.1%, and overall 1-year and 5-year TFS were 91.5% and 58.2%, respectively. Patients without prior RP showed a significantly higher 1-year (78.5% vs. 52.5%) and 5-year RFS (28.1% vs. 0.0%; p = 0.03), and a trend towards a higher 1-year (92.6% vs. 79.0%) and 5-year TFS (60.2% vs. 23.0%; p = 0.10) compared to those with prior RP. A total of 46 complications occurred in 37 patients, and the overall complication rate was 32.4% (37/114 patients). The majority (41/46; 89.1%) of complications were minor (CD 1–2). Overall (31.3 vs. 40.0%) and major (3.0 vs. 13.3%) complication rates were lower in patients without compared to those with prior RP, respectively. MRI-guided SFC is an effective and safe therapy for patients with recurrent PCa, and has proved to delay and potentially prevent the initiation of salvage treatments. Patients with locally recurrent PCa after prior RP had an increased risk of recurrence, a shortened time to additional treatment, and more complications compared to those without prior RP, which should be considered when selecting patients for SFC. Full article

This study focuses on men undergoing androgen deprivation therapy (ADT) treatment for prostate cancer who also participated in an exercise programme as part of their rehabilitation. Our aim was twofold. First, we aimed to describe and analyse how the participants talk about their treatment and its side-effects in relation to the body and masculinity. Second, we aimed to describe the participants’ understanding of and motivation to participate in a physical activity programme designed by healthcare professionals to deal with anticipated and unwanted bodily changes following treatment. Focus group interviews and individual interviews were conducted. Theoretically, the study leans on phenomenological theories of embodiment combined with a sociologically informed framework found in critical studies on men and masculinity. The results showed that the medical suspension of testosterone impacted not only the men’s understanding of themselves as men but also how they approached their own bodies. Testosterone was discussed as a source of masculinity and masculine traits. Consequently, the absence of testosterone following treatment led to ongoing reflections on how to understand the (ageing) body and its relationship to masculinity. The ageing ADT body, with growing breasts and a lack of libido, became a site of emasculation and bodily detachment. The men addressed this by displaying stoic masculinity; instead of addressing the problem emotionally they turned their attention and aspirations to having a capable body and being able to carry out physical work. However, participation in the exercise programme depended on recruitment by their physicians and was motivated by the opportunity to socialise with other men in the same situation. Full article