Investigating the role of the IGF axis as a predictor of biochemical recurrence in prostate cancer patients post-surgery.

BACKGROUND: Between 20% and 35% of prostate cancer (PCa) patients who undergo treatment with curative intent (ie, surgery or radiation therapy) for localized disease will experience biochemical recurrence (BCR). Alterations in the insulin-like growth factor (IGF) axis and PTEN expression have been implicated in the development and progression of several human tumors including PCa. We examined the expression of the insulin receptor (INSR), IGF-1 receptor (IGF-1R), PTEN, and AKT in radical prostatectomy tissue of patients who developed BCR post-surgery. METHODS: Tissue microarrays (TMA) of 130 patients post-radical prostatectomy (65 = BCR, 65 = non-BCR) were stained by immunohistochemistry for INSR, IGF-1R, PTEN, and AKT using optimized antibody protocols. INSR, IGF1-R, PTEN, and AKT expression between benign and cancerous tissue, and different Gleason grades was assessed. Kaplan-Meier survival curves were used to examine the relationship between proteins expression and BCR. RESULTS: INSR (P < 0.001), IGF-1R (P < 0.001), and AKT (P < 0.05) expression was significantly increased and PTEN (P < 0.001) was significantly decreased in cancerous versus benign tissue. There was no significant difference in INSR, IGF-1R, or AKT expression in the cancerous tissue of non-BCR versus BCR patients (P = 0.149, P = 0.990, P = 0.399, respectively). There was a significant decrease in PTEN expression in the malignant tissue of BCR versus non-BCR patients (P = 0.011). Combinational analysis of the tissue proteins identified a combination of decreased PTEN and increased AKT or increased INSR was associated with worst outcome. We found that in each case, our hypothesized worst group was most likely to experience BCR and this was significant for combinations of PTEN+INSR and PTEN+AKT but not PTEN+IGF-1R (P = 0.023, P = 0.028, P = 0.078, respectively). CONCLUSIONS: Low PTEN is associated with BCR and this association is strongly modified by high INSR and high AKT expression. Measurement of these proteins could help inform appropriate patient selection for postoperative adjuvant therapy and prevent BCR.

Enzalutamide: targeting the androgen signalling pathway in metastatic castration-resistant prostate cancer.

Significant progress has been made in the understanding of the underlying cancer biology of castration-resistant prostate cancer (CRPC) with the androgen receptor (AR) signalling pathway remaining implicated throughout the prostate cancer disease continuum. Reactivation of the AR signalling pathway is considered to be a key driver of CRPC progression and, as such, the AR is a logical target for therapy in CRPC. The objective of this review was to understand the importance of AR signalling in the treatment of patients with metastatic CRPC (mCRPC) and to discuss the clinical benefits associated with inhibition of the AR signalling pathway. A search was conducted to identify articles relating to the role of AR signalling in CRPC and therapies that inhibit the AR signalling pathway. Current understanding of prostate cancer has identified the AR signalling pathway as a logical target for the treatment of CRPC. Available therapies that inhibit the AR signalling pathway include AR blockers, androgen biosynthesis inhibitors, and AR signalling inhibitors. Enzalutamide, the first approved AR signalling inhibitor, has a novel mode of action targeting AR signalling at three key stages. The direct mode of action of enzalutamide has been shown to translate into clinical responses in patients with mCRPC. In conclusion, the targeting of the AR signalling pathway in patients with mCRPC results in numerous clinical benefits. As the number of treatment options increase, more trials evaluating the sequencing and combination of treatments are required. This review highlights the continued importance of targeting a key driver in the progression of CRPC, AR signalling, and the clinical benefits associated with inhibition of the AR signalling pathway in the treatment of patients with CRPC.

Management of prostate cancer in older patients: updated recommendations of a working group of the International Society of Geriatric Oncology.

In 2010, the International Society of Geriatric Oncology (SIOG) developed treatment guidelines for men with prostate cancer who are older than 70 years old. In 2013, a new multidisciplinary SIOG working group was formed to update these recommendations. The consensus of the task force is that older men with prostate cancer should be managed according to their individual health status, not according to age. On the basis of a validated rapid health status screening instrument and simple assessment, the task force recommends that patients are classed into three groups for treatment: healthy or fit patients who should have the same treatment options as younger patients; vulnerable patients with reversible impairment who should receive standard treatment after medical intervention; and frail patients with non-reversible impairment who should receive adapted treatment.

Perspectives on treatment of metastatic castration-resistant prostate cancer.

The arrival of several new agents--cabazitaxel, abiraterone acetate, enzalutamide, and radium-223--is changing the treatment options and management of patients with metastatic castration-resistant prostate cancer (mCRPC). Many other novel agents are also being investigated. As new drugs become approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. This review article is a summary of a European Treatment Practices Meeting, which was convened to discuss these latest data on novel agents and current treatment strategies in the mCRPC setting.

The identification and internal validation of a preoperative serum biomarker panel to determine extracapsular extension in patients with prostate cancer.

BACKGROUND: Accurate preoperative staging of prostate cancer (PCa) is important but current diagnostic methods cannot accurately determine extracapsular extension (ECE), resulting in the possible triage of patients towards a less appropriate arm of therapy. This has consequences to patient care and better methods of preoperatively determining ECE are required. METHODS: We followed a biomarker development pathway and compared the preoperative serum expressions of VEGF-D, PEDF, IGF-I, IGFBP3, and CD14 in patients from the Irish Prostate Cancer Research Consortium (PCRC) with radical prostatectomy determined ECE against patients with nonECE. RESULTS: The expression measurements of five proteins were fitted into a logistic regression model and backwards variable elimination methods were applied which resulted in a model with IGFBP3 and CD14 as the best combination biomarker panel. This panel was tested in an independent cohort of patients using an optimized multiplex electrochemiluminescence assay. Receiver operating characteristic curves were generated and the areas under the curve (AUC) were calculated as an estimation of prediction accuracy. The biomarker panel was validated with an AUC of 76.6%, and a sensitivity and specificity of 80% and 75% was obtained. CONCLUSIONS: This is the first internally validated, preoperative serum biomarker panel that identifies ECE in patients with Gleason score 7 PCa with AUC 76.6%. The panel surpasses the routinely used diagnostic standards in accuracy and may help to improve preoperative cancer staging, better inform treatment options, and improve the referral patterns of patients with urgently treatable cancers towards more appropriate arms of therapy.

A comment on the International Society of Geriatric Oncology guidelines: evidence-based advice for the clinical setting.

Largely a disease of older men, prostate cancer is likely to become a growing burden in the developed world as the population ages and overall life expectancy increases. Furthermore, prostate cancer management in older men is not optimal, reflecting the lack of training dedicated to senior adults in fellowship programs and the lack of specific guidelines to manage senior adults. The International Society of Geriatric Oncology (SIOG) convened a multidisciplinary Prostate Cancer Working Group to review the evidence base and provide advice on the management of the disease in senior age groups. The Working Group reported that advancing age, by itself, is not a reliable guide to treatment decision making for men with either localized or advanced prostate cancer. Instead, the SIOG guidelines advise health care teams to assess the patient's underlying health status, which is largely dictated by associated comorbid conditions, but also by dependency in activities of daily living and nutritional status, and to use the findings to categorize the individual into one of four groups: healthy, vulnerable, frail, or terminally ill. The guidelines recommend that a patient categorized as healthy or vulnerable (i.e., with reversible problems following geriatric intervention) should receive the same approach to treatment as a younger patient. Frail patients should be managed using adapted treatment strategies, and the terminally ill should receive symptomatic/palliative care only. The guidelines may have ongoing relevance as the treatment options for prostate cancer expand.

Chairman's foreword. Recent advances in prostate cancer management.

Recent advances in prostate cancer management were discussed at the third annual Interactive Genitourinary Cancer Conference (IGUCC3) held from 30 April to 1 May 2011. The objectives of IGUCC3 included exploring available therapeutic options and current controversies in prostate cancer care, promoting closer multidisciplinary collaboration and a patient-centred approach, and considering challenges in the management of metastatic castration-resistant prostate cancer and the opportunities presented by new treatment options.

Optimising repeat prostate biopsy decisions and procedures.

What's known on the subject? and What does the study add? Due to the fear of missing clinically significant cancer, it is often uncertain whether a repeat biopsy should be performed in men with ≥ 1 prior negative prostate biopsies but persistent suspicion of prostate cancer. However, the repeat biopsy may again be negative and a biopsy may be associated with anxiety, discomfort and complications (resulting in hospitalisation in 4.1% of men). This review discusses strategies to optimise repeat biopsy procedures in order to better predict the biopsy outcome. Optimising repeat biopsy procedures include adjusting the location and number of cores and the use of MRI to detect suspicious areas. The use of diagnostic markers, e.g. (Prostate CAncer) gene 3, which is predictive of biopsy outcome, can aid in guiding repeat biopsy decisions and reduce the number of unnecessary and uncomfortable biopsies. To review strategies to optimise repeat biopsy procedures and to better predict the biopsy outcome. As it is often uncertain whether a repeat biopsy should be performed in men with ≥ 1 previous negative prostate biopsies but persistent suspicion of prostate cancer. The repeat biopsy may also be negative and a biopsy may be associated with anxiety, discomfort and occasionally (severe) complications. A search in PubMed was performed to find English language original and review articles related to repeat prostate biopsies. Strategies to optimise repeat biopsy procedures include applying the appropriate indications and adjusting the location and number of biopsy cores. The PROGENSA™ Prostate CAncer gene 3 (PCA3) Assay is a highly prostate cancer-specific test. A higher PCA3 Score corresponds with an increased probability of a positive repeat biopsy and including the PCA3 Score in multivariate models significantly increased their predictive accuracy for predicting repeat biopsy outcome. The PCA3 Score seems also to be predictive of future biopsy outcome. In clinical practice it is often uncertain whether a prostate biopsy should be repeated or not. Optimising repeat biopsy procedures and the use of diagnostic markers, such as PCA3, can increase the probability of a positive repeat biopsy and reduce the number of unnecessary and uncomfortable biopsies.

Urologists and oncologists: adapting to a new treatment paradigm in castration-resistant prostate cancer (CRPC).

The treatment landscape for men with castration-resistant prostate cancer (CRPC) is undergoing significant changes; a redefinition of the respective roles of oncologists and urologists will probably occur. In addition, the advent of the multidisciplinary team or coordinated-care approach, which has been gathering momentum over the last decade, will become not simply a preference but a clear necessity. In the present review, we explore the current wave of new treatments and describe the possibility of more complex approaches to combined therapy. New treatment options include abiraterone acetate, cabazitaxel, MDV3100 (in development), radium-223 (in development) and sipuleucel-T. We also present the traditional roles of the urologist and oncologist in caring for patients with CRPC and discuss how these may change. Compounding the new potential for treatment success, as well as the complexity of therapeutic strategies, is the emergence of novel biomarkers to evaluate treatment efficacy and to assist in patient prognosis. The prospects for successful treatment of patients with CRPC have developed considerably so that these patients may soon have a reasonable expectation of therapeutic efficacy and meaningful extension of their lives.

PCA: prostate cancer, patient-centred approach or both?

What's known on the subject? and What does the study add? Several studies have explored patient-specific expectations of prostate cancer management, while others have investigated physicians' perceptions. However, the opinions of both groups have seldom been compared in one study. Therefore, the present study compares the results of two surveys, one among physicians and one among patients, on patient-physician communication and patients' expectations of prostate cancer management. The present review aims to highlight the differences and similarities in opinion on prostate cancer management between physicians and patients. It reflects the most important results of two surveys on patient-specific expectations in prostate cancer management, done among European prostate cancer specialists and patients with prostate cancer. These results are compared with published data. In addition, the authors' opinion on the survey results and on optimal prostate cancer management is included. To evaluate differences and similarities in opinions on and expectations of prostate cancer management between physicians and patients. Two surveys on patient-specific opinions and expectations in prostate cancer management were done in 2011 among European prostate cancer specialists and patients with prostate cancer. Survey results were complemented with existing published data and with the authors' opinion. Most specialists spent 15-29 min on delivering the diagnosis, and about the same amount of time on explaining treatment options. This time was considered insufficient by 35% and 48% of patients, respectively. There was a large discrepancy between physicians' and patients' opinions about the type of provided prognostic and therapeutic information, indicating that patients may not have completely understood this information. Shared decision-making was preferred by both patients and specialists. Treatment efficacy was the most important factor determining treatment choice for both groups, while the physician's opinion or experience also had a great impact on patients' treatment choice. Patient-support groups have an important role in providing relevant information and in exchanging experiences between patients. The supportive role of partners/relatives was more appreciated when discussing treatment options than during diagnosis. Although patients' expectations are generally matched by their caring physician(s), physicians can still improve quality of care by taking adequate time for their patients, by using terminology that is easily understood by patients and by encouraging shared decision-making. A multidisciplinary team may be an important part of the treatment paradigm, with the individual patient's needs and preferences as the centre of care.

Management of acute urinary retention: a worldwide survey of 6074 men with benign prostatic hyperplasia.

OBJECTIVES: To evaluate the management of acute urinary retention (AUR) associated with benign prostatic hyperplasia (BPH) in real-life practice. To identify predictors of successful trial without catheter (TWOC). MATERIALS AND METHODS: In all, 6074 men catheterized for painful AUR were enrolled in a prospective, cross-sectional survey conducted in public and private urology practices in France, Asia, Latin America, Algeria and the Middle East. Patient clinical characteristics, type of AUR and its management (type of catheterization, hospitalization, TWOC, use of α(1)-blockers, immediate or elective surgery) and adverse events observed during the catheterization period were recorded. Predictors of TWOC success were also analysed by multivariate regression analysis with stepwise procedure. RESULTS: Of the 6074 men, 4289 (71%) had a spontaneous AUR and 1785 (29%) had a precipitated AUR, mainly as the result of loco-regional/general anaesthesia (28.5%) and excessive alcohol intake (18.2%). Presence of BPH was revealed by AUR in 44% of men. Hospitalization for AUR varied between countries, ranging from 1.7% in Algeria to 100% in France. A urethral catheter was inserted in most cases (89.8%) usually followed by a TWOC (78.0%) after a median of 5 days. Overall TWOC success rate was 61%. Most men (86%) received an α(1)-blocker (mainly alfuzosin) before catheter removal with consistently higher TWOC success rates, regardless of age and type of AUR. Multivariate regression analysis confirmed that α(1)-blocker before TWOC doubled the chances of success (odds ratio 1.92, 95% CI 1.52-2.42, P < 0.001). Age ≥70 years, prostate size ≥50 g, severe lower urinary tract symptoms, drained volume at catheterization ≥1000 mL and spontaneous AUR favoured TWOC failure. Catheterization >3 days did not influence TWOC success but was associated with increased morbidity and prolonged hospitalization for adverse events. In the case of TWOC failure, 49% of men were recatheterized and had BPH surgery and 43.5% tried another TWOC with a success rate of 29.5%. Elective surgery was preferred to immediate surgery. CONCLUSIONS: TWOC has become a standard practice worldwide for men with BPH and AUR. In most cases, an α(1)-blocker is prescribed before TWOC and significantly increases the chance of success. Prolonged catheterization is associated with an increased morbidity.

Applying random forests to identify biomarker panels in serum 2D-DIGE data for the detection and staging of prostate cancer.

In recent years, Prostate Specific Antigen (PSA) testing is widespread and has been associated with deceased mortality rates; however, this testing has raised concerns of overdiagnosis and overtreatment. It is clear that additional biomarkers are required. To identify these biomarkers, we have undertaken proteomics and metabolomics expression profiles of serum samples from BPH, Gleason score 5 and 7 using two-dimensional difference in gel electrophoresis (2D-DIGE) and nuclear magnetic resonance spectroscopy (NMR). Panels of serum protein biomarkers were identified by applying Random Forests to the 2D-DIGE data. The evaluation of selected biomarker panels has shown that they can provide higher prediction accuracy than the current diagnostic standard. With careful validation of these serum biomarker panels, these panels may potentially help to reduce unnecessary invasive diagnostic procedures and more accurately direct the urologist to curative surgery.

Core fucosylation and alpha2-3 sialylation in serum N-glycome is significantly increased in prostate cancer comparing to benign prostate hyperplasia.

One of the most urgent requirements in prostate cancer diagnosis is the development of a blood-based test which would be able to distinguish prostate cancer from benign prostate hyperplasia (BPH). Previously published results found a significant difference between specific glycan levels in patients with advanced prostate cancer and healthy controls. N-Glycans from the whole serum glycoproteins were measured using our fully quantitative high-throughput N-glycan analysis in combination with exoglycosidase digestions in sera from 13 BPH and 34 prostate cancer samples (17 Gleason score 5 and 17 Gleason score 7). The levels of core-fucosylated biantennary glycans and α2-3-linked sialic acids were significantly increased in prostate cancer patients compared with patients with BPH. Triantennary trigalactosylated glycans and tetraantennary tetrasialylated glycans with outer arm fucose were significantly decreased, and tetraantennary tetrasialylated glycans increased in Gleason 7 compared with Gleason 5. All these glycans can distinguish prostate cancer patients from BPH or Gleason 7 from Gleason 5 prostate cancer patients better than the current clinical test, prostate-specific antigen; therefore, their measurement may provide a new noninvasive approach to diagnose prostate cancer. However, additional validation studies would need to be carried out to further support this finding. Decreases in triantennary trigalactosylated glycans and/or bisected core-fucosylated biantennary monosialylated glycans and increases in tetraantennary tetrasialylated glycans correlate with perineural invasion, which could further help to diagnose tumor spread and predict patients' survival.

Characterisation and manipulation of docetaxel resistant prostate cancer cell lines.

BACKGROUND: There is no effective treatment strategy for advanced castration-resistant prostate cancer. Although Docetaxel (Taxotere®) represents the most active chemotherapeutic agent it only gives a modest survival advantage with most patients eventually progressing because of inherent or acquired drug resistance. The aims of this study were to further investigate the mechanisms of resistance to Docetaxel. Three Docetaxel resistant sub-lines were generated and confirmed to be resistant to the apoptotic and anti-proliferative effects of increasing concentrations of Docetaxel. RESULTS: The resistant DU-145 R and 22RV1 R had expression of P-glycoprotein and its inhibition with Elacridar partially and totally reversed the resistant phenotype in the two cell lines respectively, which was not seen in the PC-3 resistant sublines. Resistance was also not mediated in the PC-3 cells by cellular senescence or autophagy but multiple changes in pro- and anti-apoptotic genes and proteins were demonstrated. Even though there were lower basal levels of NF-κB activity in the PC-3 D12 cells compared to the Parental PC-3, docetaxel induced higher NF-κB activity and IκB phosphorylation at 3 and 6 hours with only minor changes in the DU-145 cells. Inhibition of NF-κB with the BAY 11-7082 inhibitor reversed the resistance to Docetaxel. CONCLUSION: This study confirms that multiple mechanisms contribute to Docetaxel resistance and the central transcription factor NF-κB plays an immensely important role in determining docetaxel-resistance which may represent an appropriate therapeutic target.

Effects of titanocene dichloride derivatives on prostate cancer cells, specifically DNA damage-induced apoptosis.

BACKGROUND: While locally advanced prostate cancer is initially treatable with androgen ablation, eventually cells develop a castrate-resistant phenotype. Currently, there are no effective treatments for this form of the disease with Docetaxel only providing a small survival advantage. In this study, the effects of novel derivatives of titanocene dichloride on prostate cancer cell lines has been investigated. METHODS: Cellular effects were assessed using the crystal violet assay and the clonogenic survival assay. Cell cycle and apoptosis were assessed by propidium iodide staining. DNA damage was analyzed by comet assay and Western analysis. DNA damage response inhibition was achieved by pre-incubation with an ATM/ATR inhibitor; CGK733 and DNA-PK inhibitor; DMNB. RESULTS: These analogs caused a reduction in cell number. In particular titanocene Y and C had significant effects in all cell lines. A reduction in clonogenic survival was found in response to titanocene Y in three cell lines while the PC-3 cells exhibited increased resistance.Further analysis showed no effect on cell cycle however, the analogs were found to induce apoptosis in a dose-dependent manner in all cell lines. These analogs associate with DNA, induce DNA damage and a differential damage response. Inhibition of key regulators of this DNA damage response sensitized the PC-3 cell line to titanocene-induced apoptosis and significantly reduced the clonogenic capacity of the cells. CONCLUSION: These results demonstrate the mechanism of action of these novel titanocene dichloride analogs and their potential use in castrate-independent advanced prostate cancer.

The role of secreted frizzled-related protein 2 expression in prostate cancer.

AIMS: Improved prostate cancer (PCa)-specific biomarkers are urgently required to distinguish between indolent and aggressive disease, in order to avoid overtreatment. In this study, we investigated the prostatic tissue expression of secreted frizzled-related protein (SFRP)-2. METHODS AND RESULTS: Following immunohistochemical analysis on PCa tissue microarrays with samples from 216 patients, strong/moderate SFRP-2 expression was observed in epithelial cells of benign prostatic hyperplasia, and negative/weak SFRP-2 expression was observed in the majority of tumour epithelia. However, among Gleason grade 5 carcinomas, 40% showed strong/moderate SFRP-2 expression and 60% showed negative SFRP-2 expression in epithelial cells. Further microscopic evaluation of Gleason grade 5 tumours revealed different morphological patterns, corresponding with differential SFRP-2 expression. The first subgroup (referred to as Type A) appeared to have a morphologically solid growth pattern, whereas the second subgroup (referred to as Type B) appeared to have a more diffuse pattern. Furthermore, 100% (4/4) of Type A patients experienced biochemical recurrence, as compared with 0% (0/6) of Type B patients. CONCLUSIONS: These results imply: (i) that there is a loss of SFRP-2 expression from benign to malignant prostate glands; and (ii) differential SFRP-2 expression among two possible subgroups of Gleason grade 5 tumours.

Risk stratification for benign prostatic hyperplasia (BPH) treatment.

• Benign prostatic hyperplasia (BPH) is a common cause of bothersome lower urinary tract symptoms. In the past, the aim of drug treatment was to relieve symptoms until surgery became necessary, predominantly using an α-blocker or a 5α-reductase inhibitor (5ARI) as monotherapy. • Together with improving knowledge about the pathogenesis of BPH, there is now strong evidence from large randomized trials that risk stratification and appropriate treatment with combined α-blocker/5ARI therapy can significantly reduce the risk of disease progression and avoid long-term complications such as acute urinary retention and surgery. • BPH will increasingly be managed in primary care in the future and, if new management strategies based on this evidence are to be implemented cost effectively, there is a need to introduce shared care between the primary and secondary care sectors to optimise use of resources and expertise.

Epstein criteria for insignificant prostate cancer.

UNLABELLED: Study Type - Prognosis (systematic review). LEVEL OF EVIDENCE: 2b. What's known on the subject? and What does the study add? Overtreatment of prostate cancer is a major problem in contemporary urological practice. The Epstein Criteria reduces overtreatment by identifying insignificant prostate cancers that may be amenable to surveillance therapy. This systematic review of the Epstein Criteria validation studies provides a collective insight into the application and accuracy of the Epstein Criteria to predict for insignificant prostate cancer across different institutions and geographies. OBJECTIVE: • To review the accuracy of the Epstein Criteria for insignificant prostate cancer and to explore the effect of the modified Gleason classification system on this system. METHODS: • We searched PubMed, EMBASE and the Cochrane Database using search terms 'Epstein Criteria', 'Prostate Cancer', 'Validation' and 'Insignificant Cancer' between 1994 to 2010 for validation articles. • These were divided into pre-2005 and post-2005 and concordances for organ-confined status, Gleason score ≤ 6 and insignificant cancer were analysed. RESULTS: • A pre-2005 study showed concordance for insignificant prostate cancer, Gleason score ≤ 6 and organ-confined status at 84%, 90.3% and 91.6%, respectively. • Five post-2005 validation studies were concordant for insignificant cancer, Gleason score ≤ 6 and organ-confined status at 37-76%, 54.3-75.9% and 80.0-96.9%, respectively. CONCLUSIONS: • The Epstein Criteria has a suboptimal accuracy for predicting for insignificant prostate cancer. • The modification to Gleason scoring may be responsible for a reduced accuracy over time. • However, significant heterogeneity in the validation studies means better quality validation studies are required.

Maximizing outcomes in genitourinary cancers across the treatment continuum.

Key controversies concerning the management of genitourinary cancers across the treatment continua were discussed at the second annual Interactive Genitourinary Cancer Conference (IGUCC) held in February 2010 in Athens, Greece. Prostate cancer is the most common form of cancer among western men and prevention strategies are needed. Trials evaluating 5α-reductase inhibitors have reported beneficial and clinically meaningful results, but uptake remains low for primary prostate cancer prevention. Prostate cancer detection programmes are also important as curative treatments for advanced disease are unavailable. Two large landmark randomized controlled trials reported conflicting results concerning screening efficacy and uncovered high levels of over-diagnosis and potential over-treatment. Tailored management strategies after diagnosis are important and predictive markers that distinguish between aggressive and indolent tumours are needed. The majority of newly diagnosed cases of prostate cancer are clinically localized. Active surveillance of favourable risk patients may be beneficial in the intermediate term, while an integrated approach of multi-modality therapy in patients with adverse features is recommended. The benefits of new technologies such as high-intensity focused ultrasound (HIFU) and robotic prostatectomy have not been established in prospective randomized trials vs current standards of care. A multidisciplinary approach is essential to evolving the management of advanced prostate cancer into a chronic disease paradigm. Docetaxel plus prednisone is the standard first-line chemotherapy for patients with metastatic castration-resistant prostate cancer (mCRPC), but the optimal timing of chemotherapy initiation has not been addressed in randomized clinical trials. Retrospective analyses suggest that asymptomatic patients with adverse prognostic factors for survival may also benefit from receiving chemotherapy. Bladder cancer is a common malignancy and the most expensive cancer per patient. Non-muscle-invasive bladder cancer is a heterogenous disease that requires dynamic multidisciplinary management. Aggressive early intervention may be beneficial in some cases. Platinum-based therapies represent the first-line standard of care for advanced bladder cancer, but the maximum benefit may have been reached for conventional chemotherapies and new strategies are needed. Several ongoing clinical trials are assessing combination chemotherapy and targeted therapy.