A non-invasive 25-Gene PLNM-Score urine test for detection of prostate cancer pelvic lymph node metastasis.

BACKGROUND: Prostate cancer patients with pelvic lymph node metastasis (PLNM) have poor prognosis. Based on EAU guidelines, patients with >5% risk of PLNM by nomograms often receive pelvic lymph node dissection (PLND) during prostatectomy. However, nomograms have limited accuracy, so large numbers of false positive patients receive unnecessary surgery with potentially serious side effects. It is important to accurately identify PLNM, yet current tests, including imaging tools are inaccurate. Therefore, we intended to develop a gene expression-based algorithm for detecting PLNM. METHODS: An advanced random forest machine learning algorithm screening was conducted to develop a classifier for identifying PLNM using urine samples collected from a multi-center retrospective cohort (n = 413) as training set and validated in an independent multi-center prospective cohort (n = 243). Univariate and multivariate discriminant analyses were performed to measure the ability of the algorithm classifier to detect PLNM and compare it with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram score. RESULTS: An algorithm named 25 G PLNM-Score was developed and found to accurately distinguish PLNM and non-PLNM with AUC of 0.93 (95% CI: 0.85-1.01) and 0.93 (95% CI: 0.87-0.99) in the retrospective and prospective urine cohorts respectively. Kaplan-Meier plots showed large and significant difference in biochemical recurrence-free survival and distant metastasis-free survival in the patients stratified by the 25 G PLNM-Score (log rank P < 0.001 and P < 0.0001, respectively). It spared 96% and 80% of unnecessary PLND with only 0.51% and 1% of PLNM missing in the retrospective and prospective cohorts respectively. In contrast, the MSKCC score only spared 15% of PLND with 0% of PLNM missing. CONCLUSIONS: The novel 25 G PLNM-Score is the first highly accurate and non-invasive machine learning algorithm-based urine test to identify PLNM before PLND, with potential clinical benefits of avoiding unnecessary PLND and improving treatment decision-making.

Non-invasive Urine Test for Molecular Classification of Clinical Significance in Newly Diagnosed Prostate Cancer Patients.

Objective: To avoid over-treatment of low-risk prostate cancer patients, it is important to identify clinically significant and insignificant cancer for treatment decision-making. However, no accurate test is currently available. Methods: To address this unmet medical need, we developed a novel gene classifier to distinguish clinically significant and insignificant cancer, which were classified based on the National Comprehensive Cancer Network risk stratification guidelines. A non-invasive urine test was developed using quantitative mRNA expression data of 24 genes in the classifier with an algorithm to stratify the clinical significance of the cancer. Two independent, multicenter, retrospective and prospective studies were conducted to assess the diagnostic performance of the 24-Gene Classifier and the current clinicopathological measures by univariate and multivariate logistic regression and discriminant analysis. In addition, assessments were performed in various Gleason grades/ISUP Grade Groups. Results: The results showed high diagnostic accuracy of the 24-Gene Classifier with an AUC of 0.917 (95% CI 0.892-0.942) in the retrospective cohort (n = 520), AUC of 0.959 (95% CI 0.935-0.983) in the prospective cohort (n = 207), and AUC of 0.930 (95% 0.912-CI 0.947) in the combination cohort (n = 727). Univariate and multivariate analysis showed that the 24-Gene Classifier was more accurate than cancer stage, Gleason score, and PSA, especially in the low/intermediate-grade/ISUP Grade Group 1-3 cancer subgroups. Conclusions: The 24-Gene Classifier urine test is an accurate and non-invasive liquid biopsy method for identifying clinically significant prostate cancer in newly diagnosed cancer patients. It has the potential to improve prostate cancer treatment decisions and active surveillance.

Androgen deprivation therapy and side effects: are GnRH antagonists safer?

Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and antagonists is the mainstay of advanced prostate cancer treatment. Both drug classes decrease levels of luteinizing hormone and follicle-stimulating hormones (FSH), thereby lowering testosterone to castrate levels. This is associated with adverse events (AEs), including cardiovascular (CV) disorders, bone fractures, metabolic dysfunction, and impaired cognitive function. This literature review discusses these AEs, with a focus on CV and bone-related events. A hypothesis-generating meta-analysis of six clinical trials showed a potentially increased risk for CV disorders with GnRH agonists versus the GnRH antagonist degarelix. While no study has directly compared GnRH agonists versus antagonists with a primary CV outcome, one hypothesis for this observation is that GnRH agonists lead to initial surges in FSH that may negatively impact CV health, whereas antagonists do not. GnRH agonists are associated with metabolic and cognitive AEs and while data are lacking for GnRH antagonists, no differences in risk are predicted. Other common AEs with ADT include injection site reactions, which are much more common with degarelix than with GnRH agonists, which may reflect differing administration and injection techniques. Future studies are needed to further evaluate and compare the safety profiles of GnRH agonists and antagonists, especially in patients with pre-existing CV disease and other co-morbidities. Physicians should carefully evaluate benefits and risks when prescribing ADT and ensure that side effects are well managed.

Development and validation of a 25-Gene Panel urine test for prostate cancer diagnosis and potential treatment follow-up.

BACKGROUND: Heterogeneity of prostate cancer (PCa) contributes to inaccurate cancer screening and diagnosis, unnecessary biopsies, and overtreatment. We intended to develop non-invasive urine tests for accurate PCa diagnosis to avoid unnecessary biopsies. METHODS: Using a machine learning program, we identified a 25-Gene Panel classifier for distinguishing PCa and benign prostate. A non-invasive test using pre-biopsy urine samples collected without digital rectal examination (DRE) was used to measure gene expression of the panel using cDNA preamplification followed by real-time qRT-PCR. The 25-Gene Panel urine test was validated in independent multi-center retrospective and prospective studies. The diagnostic performance of the test was assessed against the pathological diagnosis from biopsy by discriminant analysis. Uni- and multivariate logistic regression analysis was performed to assess its diagnostic improvement over PSA and risk factors. In addition, the 25-Gene Panel urine test was used to identify clinically significant PCa. Furthermore, the 25-Gene Panel urine test was assessed in a subset of patients to examine if cancer was detected after prostatectomy. RESULTS: The 25-Gene Panel urine test accurately detected cancer and benign prostate with AUC of 0.946 (95% CI 0.963-0.929) in the retrospective cohort (n = 614), AUC of 0.901 (0.929-0.873) in the prospective cohort (n = 396), and AUC of 0.936 (0.956-0.916) in the large combination cohort (n = 1010). It greatly improved diagnostic accuracy over PSA and risk factors (p < 0.0001). When it was combined with PSA, the AUC increased to 0.961 (0.980-0.942). Importantly, the 25-Gene Panel urine test was able to accurately identify clinically significant and insignificant PCa with AUC of 0.928 (95% CI 0.947-0.909) in the combination cohort (n = 727). In addition, it was able to show the absence of cancer after prostatectomy with high accuracy. CONCLUSIONS: The 25-Gene Panel urine test is the first highly accurate and non-invasive liquid biopsy method without DRE for PCa diagnosis. In clinical practice, it may be used for identifying patients in need of biopsy for cancer diagnosis and patients with clinically significant cancer for immediate treatment, and potentially assisting cancer treatment follow-up.

Considerations for the use of gonadotropin-releasing hormone agonists and antagonists in patients with prostate cancer.

Prostate cancer is the second most common cause of cancer-related deaths in men, representing a major source of morbidity and mortality. Androgen deprivation therapy is the primary treatment for patients with advanced prostate cancer at disease presentation, which can be achieved either with surgical or chemical castration. The development of gonadotropin-releasing hormone agonists revolutionized the treatment of advanced prostate cancer, replacing the need for surgical castration. Agonists downregulate gonadotropin-releasing hormone agonist receptors in the pituitary gland, and thus decrease the release of luteinizing hormone and testosterone. Although agonists are a common therapeutic option to date, their use is associated with testosterone surges, metabolic dysfunction and an increase in the risk of cardiovascular disease; they might contribute to tumor flares and potentially an increase in non-cancer mortality. More recently, gonadotropin-releasing hormone antagonists have entered the prostate cancer treatment landscape. Unlike agonists, antagonists directly inhibit the androgen receptor in the pituitary gland, and thus do not cause initial testosterone surges. In this article, we provide a concise review of the mechanism of actions, safety and efficacy of the approved agonists and antagonists for prostate cancer treatment.

The effects of Cernitin® on inflammatory parameters and benign prostatic hyperplasia: An in vitro study.

The pollen extract Cernitin® is widely used for treatment of benign prostatic hyperplasia (BPH) and non-bacterial chronin prostatitis. However, little is known about the underlying molecular mechanisms to explain the clinical effects of Cernitin®. In this study, we sought to investigate the cellular mechanisms by which Cernitin® induces its effects on human prostatic cell lines BPH-1 and WPMY-1 and primary human peripheral blood mononuclear cells (hPBMCs) in vitro. We examined the effects of Cernitin® formulas T60 and GBX on the protein expression, proliferation, and cytokines production. Results revealed that Cernitin® upregulated antiinflammatory cytokine interleukin (IL)-10 and its receptors IL-10RA and IL-10B in addition to the upregulation of tumour necrosis factor-related apoptosis-inducing ligand in hPBMC. Interestingly, the levels of proinflammatory cytokines IL-6 and IL-8 were also increased. Furthermore, Cernitin® had significantly increased the level of IL-10 in BPH-1 and WPMY-1 cells. The level of IL-6 was also significantly increased in these cells although both T60 and GBX inhibited STAT-3 phosphorylation. Moreover, Cernitin® formulas had significantly reduced androgen receptor and prostate-specific antigen protein expression in stromal cells (p < .05). Treatment with GBX and T60 had significantly inhibited proliferation of BPH (p < .001) and stromal cells (p < .05), in a dose-dependent manner. Taken together, treatment with Cernitin® showed to regulate cytokines level in both prostatic cell lines and hPBMCs and it was associated with decreased androgen receptor and prostate-specific antigen levels WPMY-1 cells.

Structured Population-based Prostate-specific Antigen Screening for Prostate Cancer: The European Association of Urology Position in 2019.

Prostate cancer (PCa) is one of the first three causes of cancer mortality in Europe. Screening in asymptomatic men (aged 55-69yr) using prostate-specific antigen (PSA) is associated with a migration toward lower staged disease and a reduction in cancer-specific mortality. By 20yr after testing, around 100 men need to be screened to prevent one PCa death. While this ratio is smaller than for breast and colon cancer, the long natural history of PCa means many men die from other causes. As such, the nonselective use of PSA testing and radical treatments can lead to overdiagnosis and overtreatment. The European Association of Urology (EAU) supports measures to encourage appropriate PCa detection through PSA testing, while reducing overdiagnosis and overtreatment. These goals may be achieved using personalized risk-stratified approaches. For diagnosis, the greatest benefit from early detection is likely to come in men assessed using baseline PSA levels at the age of 45yr to individualize screening intervals. Multiparametric magnetic resonance imaging as well as risk calculators based on family history, ethnicity, digital rectal examination, and prostate volume should be considered to triage the need for biopsy, thus reducing the risk of overdiagnosis. For treatment, the EAU advocates balancing patient's life expectancy and cancer's mortality risk when deciding an approach. Active surveillance is encouraged in well-informed patients with low-risk and some intermediate-risk cancers, as it decreases the risks of overtreatment without compromising oncological outcomes. Conversely, the EAU advocates radical treatment in suitable men with more aggressive PCa. Multimodal treatment should be considered in locally advanced or high-grade cancers. PATIENT SUMMARY: Implementation of prostate-specific antigen (PSA)-based screening should be considered at a population level. Men at risk of prostate cancer should have a baseline PSA blood test (eg, at 45yr). The level of this test, combined with family history, ethnicity, and other factors, can be used to determine subsequent follow-up. Magnetic resonance imaging scans and novel biomarkers should be used to determine which men need biopsy and how any cancers should be treated.

Correction: Interaction between c-jun and Androgen Receptor Determines the Outcome of Taxane Therapy in Castration Resistant Prostate Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0079573.].

Factors Predicting the Off-treatment Duration in Patients with Prostate Cancer Receiving Degarelix as Intermittent Androgen Deprivation Therapy.

BACKGROUND: Intermittent androgen deprivation therapy (IAD) is commonly used in prostate cancer because of the benefits of the off-treatment period (OTP). The off-treatment time for patients depends on cancer progression, often measured as a rise in prostate-specific antigen (PSA). OBJECTIVE: To evaluate if certain factors can predict OTP duration following 7-mo degarelix therapy. DESIGN, SETTING, AND PARTICIPANTS: This multivariable analysis included 191 prostate cancer patients with baseline PSA 4-50 ng/ml or PSA doubling time <24 mo entering the first OTP with PSA ≤4 ng/ml and testosterone <0.5 ng/ml. OTP continued until disease progression, measured as PSA >4 ng/ml. Despite a study-defined OTP maximum of 24 mo, a 50% failure rate was not observed within certain strata. A Weibull distribution was used to estimate median time to PSA >4 ng/ml adjusted for the following variables: age; baseline (or end of induction period [EOI]) PSA; baseline testosterone; cancer stage/previous curative treatment; and Gleason score. According to the results and the utility of these factors in clinical practice, the model was reduced in a stepwise manner. Time to testosterone recovery (testosterone >0.5 and >2.2 ng/ml) was estimated in a similar manner. RESULTS: The full five-factor model showed that baseline PSA (p<0.0001), age (p=0.004), prostate cancer stage/previous therapy (p=0.023), and baseline testosterone (p=0.039) influenced OTP. A reduced two-factor model (baseline PSA, age) showed that only baseline PSA influenced OTP (p<0.0001), and patients with baseline PSA ≤4 ng/ml had the longest OTP. In addition, EOI PSA (p<0.0001) and age (p=0.050) significantly influenced OTP. The times to testosterone >0.5 and >2.2 ng/ml were longer for older patients and those with lower baseline testosterone levels. CONCLUSION: Patients with lower baseline and EOI PSA, and older patients can stay off therapy longer and therefore may benefit more from degarelix IAD. These factors may help in proposing an algorithm to predict the OTP and optimise visit frequency. PATIENT SUMMARY: We describe extended analysis results for a trial in which patients with prostate cancer received intermittent androgen deprivation treatment. Prostate-specific antigen levels at baseline and at the end of the induction period, as well as older age, predicted the duration of the off-treatment period. Testosterone recovery was slower in older patients and in patients who had lower pretreatment testosterone levels. These factors may help in deciding whether to choose continuous or intermittent treatment as a strategy. TRIAL REGISTRATION: Clinicaltrials.gov NCT00801242.

Intermittent androgen deprivation therapy in patients with prostate cancer: Connecting the dots.

Intermittent androgen deprivation therapy (IADT) is now being increasingly opted by the treating physicians and patients with prostate cancer. The most common reason driving this is the availability of an off-treatment period to the patients that provides some relief from treatment-related side-effects, and reduced treatment costs. IADT may also delay the progression to castration-resistant prostate cancer. However, the use of IADT in the setting of prostate cancer has not been strongly substantiated by data from clinical trials. Multiple factors seem to contribute towards this inadequacy of supportive data for the use of IADT in patients with prostate cancer, e.g., population characteristics (both demographic and clinical), study design, treatment regimen, on- and off-treatment criteria, duration of active treatment, endpoints, and analysis. The present review article focuses on seven clinical trials that evaluated the efficacy of IADT vs. continuous androgen deprivation therapy for the treatment of prostate cancer. The results from these clinical trials have been discussed in light of the factors that may impact the treatment outcomes, especially the disease (tumor) burden. Based on evidence, potential candidate population for IADT has been suggested along with recommendations for the use of IADT in patients with prostate cancer.

Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes enzalutamide resistance in prostate cancer cells.

One mechanism of resistance of prostate cancer (PCa) to enzalutamide (MDV3100) treatment is the increased expression of AR variants lacking the ligand binding-domain, the best characterized of which is AR-V7. We have previously reported that Phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), is a lipid kinase that links to CDK1 and AR pathways. The discovery of PIP5Kα inhibitor highlight the potential of PIP5K1α as a drug target in PCa. In this study, we show that AR-V7 expression positively correlates with PIP5K1α in tumor specimens from PCa patients. Overexpression of AR-V7 increases PIP5K1α, promotes rapid growth of PCa in xenograft mice, whereas inhibition of PIP5K1α by its inhibitor ISA-2011B suppresses the growth and invasiveness of xenograft tumors overexpressing AR-V7. PIP5K1α is a key co-factor for both AR-V7 and AR, which are present as protein-protein complexes predominantly in the nucleus of PCa cells. In addition, PIP5K1α and CDK1 influence AR-V7 expression also through AKT-associated mechanism dependent on PTEN-status. ISA-2011B disrupts protein stabilization of AR-V7 which is dependent on PIP5K1α, leading to suppression of invasive growth of AR-V7-high tumors in xenograft mice. Our study suggests that combination of enzalutamide and PIP5K1α may have a significant impact on refining therapeutic strategies to circumvent resistance to antiandrogen therapies.

Influence of Melatonin on the Proliferative and Apoptotic Responses of the Prostate under Normal and Hyperglycemic Conditions.

The antitumor properties of melatonin (MLT) are known for prostate cancer cells. This study investigated whether MLT affects prostate maturation and interferes with tissue injuries induced by diabetes. MLT was administered to Wistar rats from 5 weeks of age in the drinking water (10 µg/kg b.w.), and diabetes was induced at the 13th week by streptozotocin (4.5 mg/100g b.w., i.p.). The animals were euthanized in the 14th and 21st weeks. MLT reduced the immunostained cells for androgen receptor (AR) by 10% in younger rats. Diabetes decreased cell proliferation and increased apoptosis. MLT treatment impeded apoptosis (p = 0.02) and augmented proliferation (p = 0.0008) and PCNA content in prostate following long-term diabetes due to restoration of testosterone levels and expression of melatonin receptor type 1B. The effect of MLT (500 µM, 5 mM, and 10 mM) on androgen-dependent (22Rv1) and androgen-independent (PC3) cancer cells and human prostate epithelial cells (PNTA1) under normal and hyperglycemic conditions (HG, 450 mg/dL) was analyzed. Contrary to PNTA1 and 22Rv1 cells, MLT improved the proliferation of PC3 cells in hyperglycemic medium. The combined data indicated that MLT had proliferative and antiapoptotic effects in prostate cells subjected to HG levels and it seems to involve specific MLT pathways rather than AR.

Anthropometric Measures at Multiple Times Throughout Life and Prostate Cancer Diagnosis, Metastasis, and Death.

BACKGROUND: Previous studies of prostate cancer (PCa) risk and anthropometrics (ie, body measurements) were based on single measurements or obtained over limited time spans. OBJECTIVE: To study the association between anthropometrics measured at multiple time points in life and their relation to later diagnosis, metastasis, or death from PCa. DESIGN, SETTING, AND PARTICIPANTS: This case-control study includes 27 167 Swedish men enrolled in two population-based projects from 1974 to 1996. PCa diagnosis up to December 31, 2006, disease information, gestation time, and anthropometrics at birth, military conscript testing, and adulthood were collected. A total of 1355 PCa cases were matched with 5271 controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariate conditional logistic regression was used to determine whether clinical diagnosis, metastasis, or PCa death was associated with low birth weight (weight <2500 g); with small size for gestational age; or with weight, length, or body mass index (BMI) at birth, adolescence (aged 16-22 yr), or early middle age (aged 44-50 yr). RESULTS AND LIMITATIONS: Apart from weight at adolescence, which was associated with an increased risk of PCa diagnosis (odds ratio [OR] per 5 kg: 1.05; 95% confidence interval [CI], 1.01-1.09; p=0.026), preadulthood measurements were not associated with any PCa end point. Adulthood parameters were not associated with diagnosis. In contrast, weight and BMI at early middle age were significantly associated with metastasis (OR per 5 kg: 1.13; 95% CI, 1.06-1.20; p<0.0001, and OR: 1.09; 95% CI, 1.05-1.14; p<0.0001) and death (OR per 5 kg: 1.11 (95% CI, 1.03-1.19; p=0.005, and OR: 1.08; 95% CI, 1.03-1.13; p=0.003), respectively. It remains unclear whether these results apply to men of nonwhite origin, to populations with active PCa screening programs, or to countries without socialized health care. CONCLUSIONS: The analyses of these large data sets demonstrate that significant effects of body characteristics (with links to metabolic syndrome) measured at early middle age are associated with PCa disease severity, metastatic progression, and outcome. Conversely, measurements at birth and adolescence are not associated with PCa prevalence or outcome. PATIENT SUMMARY: Increased weight and body mass index in adults is associated with a higher risk of prostate cancer metastasis and death.

Achievements and perspectives in prostate cancer phase 3 trials from genitourinary research groups in Europe: introducing the Prostate Cancer Consortium in Europe.

CONTEXT: Phase 3 trials have made major contributions to advances in prostate cancer (PCa). However, funding limitations and excess bureaucracy are now making it difficult to conduct trials. OBJECTIVE: To describe the collaborative groups in Europe and their academic phase 3 PCa trials. EVIDENCE ACQUISITION: Leaders of collaborative groups from Scandinavia, the European Organisation for Research and Treatment of Cancer (EORTC), France, Spain, the United Kingdom, Germany, Switzerland, The Netherlands, and Ireland were asked to provide information. EVIDENCE SYNTHESIS: Approximately 40 academic European phase 3 trials focussing on PCa have been completed, and about 10 are accruing patients. Cross-border trials have been successfully conducted led by EORTC (11), Scandinavian Prostate Cancer Group (9), European Association of Urology (1), Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficiency (STAMPEDE) (1), and the French Genito-Urinary Tumor Group (1). Among these studies were practise-changing trials showing the superiority of prostatectomy over watchful waiting in patients <65 yr of age, the benefits of combining androgen-deprivation therapy (ADT) with radiation therapy (RXT) in high-risk localised disease, the superiority of long-term versus short-term ADT, the benefit of RXT in men treated with ADT, and the role of adjuvant RXT. To bridge the numbers gap for phase 3 studies, the Prostate Cancer Consortium in Europe (PEACE) is a recently established initiative that aims to favour cross-border networks of investigators. PEACE 1 is testing the addition of abiraterone and that of RXT directed at the primary cancer in patients with de novo metastatic PCa treated with ADT. PEACE 2 is testing the addition of cabazitaxel and that of pelvic irradiation in patients with at least two criteria for high-risk localised PCa. CONCLUSIONS: European academic phase 3 trials have contributed to establishing the current standard treatment of PCa. The PEACE consortium was recently tasked with the goal of addressing unanswered questions and specific biology-related issues more efficiently. PATIENT SUMMARY: The Prostate Cancer Consortium in Europe was established to conduct comparative trials aiming at assessing new treatments for prostate cancer patients.

EAU policy on live surgery events.

CONTEXT: Live surgery is an important part of surgical education, with an increase in the number of live surgery events (LSEs) at meetings despite controversy about their real educational value, risks to patient safety, and conflicts of interest. OBJECTIVE: To provide a European Association of Urology (EAU) policy on LSEs to regulate their organisation during urologic meetings. EVIDENCE ACQUISITION: The project was carried out in phases: a systematic literature review generating key questions, surveys sent to Live Surgery Panel members, and Internet- and panel-based consensus finding using the Delphi process to agree on and formulate a policy. EVIDENCE SYNTHESIS: The EAU will endorse LSEs, provided that the EAU Code of Conduct for live surgery and all organisational requirements are followed. Outcome data must be submitted to an EAU Web-based registry and complications reported using the revised Martin criteria. Regular audits will take place to evaluate compliance as well as the educational role of live surgery. CONCLUSIONS: This policy represents the consensus view of an expert panel established to advise the EAU. The EAU recognises the educational role of live surgery and endorses live case demonstration at urologic meetings that are conducted within a clearly defined regulatory framework. The overriding principle is that patient safety must take priority over all other considerations in the conduct of live surgery. PATIENT SUMMARY: Controversy exists regarding the true educational value of live surgical demonstrations on patients at surgical meetings. An EAU committee of experts developed a policy on how best to conduct live surgery at urologic meetings. The key principle is to ensure safety for every patient, including a code of conduct and checklist for live surgery, specific rules for how the surgery is organised and performed, and how each patient's results are reported to the EAU. For detailed information, please visit www.uroweb.org.

Is intermittent androgen-deprivation therapy beneficial for patients with advanced prostate cancer?

Use of intermittent androgen-deprivation therapy (IADT) in patients with prostate cancer has been evaluated in several studies, in an attempt to delay the development of castration resistance and reduce side-effects associated with ADT. However it is still not clear whether survival is adversely affected in patients treated with IADT. In this review, we explore the available data in an attempt to identify the most suitable candidate patients for IADT, and discuss factors that may inform appropriate patient stratification. ADT is first-line treatment for advanced/metastatic prostate cancer and is also recommended for use with definitive radiotherapy for high-risk localised prostate cancer. The changes in hormone levels induced by ADT can lead to short- and long-term side-effects which, although treatable in most cases, can significantly reduce the tolerability of ADT treatment. IADT has been investigated in several phase II and phase III studies in patients with locally advanced or metastatic prostate cancer, in an attempt to delay time to tumour progression and reduce the side-effect burden of ADT. In selected patient groups IADT is no less effective than continuous ADT, ameliorating the impact of ADT-related side-effects, and, to a degree, their impact on patient health-related quality of life (HRQL). Further comparative study is required, particularly in relation to HRQL and long-term complications associated with ADT.