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To reach a consensus on recommendations for the management of high-risk and post-operative non-metastatic prostate cancer by a group of Radiation Oncologists in Catalonia dedicated to prostate cancer.A modified Delphi approach was employed to reach consensus on controversial topics in Radiation Oncology on high-risk non-metastatic (eight questions) and post-operative (eight questions) prostate cancer. An agreement of at least 75% was considered as consensus. The survey was electronically sent 6 weeks before an expert meeting where topics were reviewed and discussed. A second-round survey for the controversial questions only was sent and answered by participants after the meeting.After the first round of the survey, 19 experienced Radiation Oncologists attended the meeting and 74% fulfilled the second-round online questionnaire. An agreement of 9 of the 16 questions was accounted for the first round. After the meeting, an additional agreement was reached in 3 questions leading to a final consensus on 12 of the 16 questions. There are still controversial topics like the use of PET for staging of high-risk and post-operative non-metastatic prostate cancer and the optimal dose to the prostate bed in the salvage setting.This consensus contributes to establish recommendations and a framework to help in prostate cancer radiation therapy and pharmacological management in daily clinical practice of high-risk and post-operative non-metastatic prostate cancer.

Background: The relative benefits of radiotherapy (RT) dose escalation and the addition of short-term or long-term androgen deprivation therapy (STADT or LTADT) in the treatment of prostate cancer are unknown. Objective: To perform a network meta-analysis (NMA) of relevant randomized trials to compare the relative benefits of RT dose escalation ± STADT or LTADT. Design, setting, and participants: An NMA of individual patient data from 13 multicenter randomized trials was carried out for a total of 11 862 patients. Patients received one of the six permutations of low-dose RT (64 to

The optimal duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains controversial. The DART 01/05 trial was designed to determine whether long-term androgen deprivation is superior to short-term androgen deprivation when combined with high-dose radiotherapy. The 5-year results showed that 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy significantly improved biochemical control, metastasis, and overall survival, especially in patients with high-risk disease. In this report, we present the 10-year final results of the trial.This open-label, phase 3, randomised, controlled trial was done in ten hospitals in Spain. The eligibility criteria included patients aged 18 years or older with histologically confirmed T1c to T3, N0, and M0 adenocarcinoma of the prostate, according to the 2002 classification of the American Joint Committee on Cancer, with intermediate-risk and high-risk factors, prostate-specific antigen (PSA) less than 100 ng/mL, and a Karnofsky performance score of at least 70%. Patients were randomly assigned (1:1) to receive 4 months of neoadjuvant and concomitant short-term androgen deprivation (STAD) plus high-dose radiotherapy (minimum dose 76 Gy; median dose 78 Gy) or to receive the same treatment followed by 24 months of adjuvant long-term androgen deprivation (LTAD), via a randomisation scheduled generated by Statistical Analysis Software programme (version 9.1) and an interactive web response system. Patients assigned to the STAD group received 4 months of neoadjuvant and concomitant androgen deprivation (oral flutamide 750 mg per day or oral bicalutamide 50 mg per day) with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy was added during the first 2 months of treatment. Patients assigned to LTAD continued with goserelin every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival at 5 years. For this 10-year study we analysed overall survival, metastasis-free survival, biochemical disease-free survival, and cause-specific survival. Analysis was by intention to treat. This trial is closed and is registered at ClinicalTrials.gov (NCT02175212) and in the EU Clinical Trials Register (EudraCT 2005-000417-36).Between Nov 7, 2005, and Dec 20, 2010, 355 patients were enrolled. One patient in the STAD group withdrew from the trial, hence 354 participants were randomly assigned to STAD (n=177) or LTAD (n=177). The median follow-up was 119·4 months (IQR 100·6-124·3). The 10-year biochemical disease-free survival for LTAD was 70·2% (95% CI 63·1-77·3) and for STAD was 62·3% (54·9-69·7; hazard ratio [HR] 0·84; 95% CI 0·50-1·43; p=0·52). At 10 years, overall survival was 78·4% (72·1-84·8) for LTAD and 73·3% (66·6-80·0) for STAD (HR 0·84; 95% CI 0·55-1·27; p=0·40), and metastasis-free survival was 76·0% (69·4-82·7) for LTAD and 70·9% (64·0-77·8) for STAD (HR 0·90; 95% CI, 0·37-2·19; p=0·81). For the subgroup of high-risk patients, the 10-year biochemical disease-free survival was 67·2% (57·2-77·2) for LTAD and 53·7% (43·3-64·1) for STAD (HR 0·90; 95% CI 0·49-1·64; p=0·73), the 10-year overall survival was 78·5% (69·6-87·3) for LTAD and 67·0% (57·3-76·7) for STAD (HR 0·58; 95% CI 0·33-1·01; p=0·054), and the 10-year metastasis-free survival was 76·6% (95% CI 67·6-85·6) for LTAD and 65·0% (55·1-74·8) for STAD (HR 0·89; 95% CI 0·33-2·43; p=0·82). Only 11 (3%) of 354 patients died from prostate cancer, all of them in the high-risk subgroup (five in the LTAD group and six in the STAD group). 76 (21%) patients died from other causes (mainly second malignancies in 31 [9%] and cardiovascular disease in 21 [6%]). No treatment-related deaths were observed.After an extended 10-year follow-up, we were unable to support the significant benefit of LTAD reported at 5 years. However, the magnitude of the benefit was clinically relevant in high-risk patients. Intermediate-risk patients treated with high-dose radiotherapy do not benefit from LTAD. A biological characterisation with the inclusion of genomic testing is needed in the decision-making process.Grupo de Investigación en Oncología Radioterápica and Sociedad Española de Oncología Radioterápica, the National Health Investigation Fund, and AstraZeneca.

Background: Randomised trials have investigated various androgen deprivation therapy (ADT) intensification strategies in men receiving radiotherapy for the treatment of prostate cancer. This individual patient data meta-analysis of relevant randomised trials aimed to quantify the benefit of these interventions in aggregate and in clinically relevant subgroups. Methods: For this meta-analysis, we performed a systematic literature search in MEDLINE, Embase, trial registries, the Web of Science, Scopus, and conference proceedings to identify trials with results published in English between Jan 1, 1962, and Dec 30, 2020. Multicentre randomised trials were eligible if they evaluated the use or prolongation of ADT (or both) in men with localised prostate cancer receiving definitive radiotherapy, reported or collected distant metastasis and survival data, and used ADT for a protocol-defined finite duration. The Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium was accessed to obtain individual patient data from randomised trials. The primary outcome was metastasis-free survival. Hazard ratios (HRs) were obtained through stratified Cox models for ADT use (radiotherapy alone vs radiotherapy plus ADT), neoadjuvant ADT extension (ie, extension of total ADT duration in the neoadjuvant setting from 3–4 months to 6–9 months), and adjuvant ADT prolongation (ie, prolongation of total ADT duration in the adjuvant setting from 4–6 months to 18–36 months). Formal interaction tests between interventions and metastasis-free survival were done for prespecified subgroups defined by age, National Comprehensive Cancer Network (NCCN) risk group, and radiotherapy dose. This meta-analysis is registered with PROSPERO, CRD42021236855. Findings: Our search returned 12 eligible trials that provided individual patient data (10 853 patients) with a median follow-up of 11·4 years (IQR 9·0–15·0). The addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0·83 [95% CI 0·77–0·89], p

Background Health-related quality of life (HRQoL) is greatly affected by prostate cancer (PCa) and associated treatments. This study aimed to measure the impact of radiotherapy on HRQoL and to further validate the Spanish version of the 16-item Expanded Prostate Cancer Index Composite (EPIC-16) in routine clinical practice. Methods An observational, non-interventional, multicenter study was conducted in Spain with localized PCa patients initiating treatment with external beam radiotherapy (EBRT) or brachytherapy (BQT). Changes from baseline in EPIC-16, University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), and patient-perceived health status were longitudinally assessed at end of radiotherapy (V2) and 90 days thereafter (V3). Psychometric evaluations of the Spanish EPIC-16 were conducted. Results Of 516 patients enrolled, 495 were included in the analysis (EBRT, n = 361; BQT, n = 134). At baseline, mean (standard deviation [SD]) EPIC-16 global scores were 11.9 (7.5) and 10.3 (7.7) for EBRT and BQT patients, respectively; scores increased, i.e., HRQoL worsened, from baseline, by mean (SD) of 6.8 (7.6) at V2 and 2.4 (7.4) at V3 for EBRT and 4.2 (7.6) and 3.9 (8.2) for BQT patients. Changes in Spanish EPIC-16 domains correlated well with urinary, bowel, and sexual UCLA-PCI domains. EPIC-16 showed good internal consistency (Cronbach’s alpha = .84), reliability, and construct validity. Conclusion The Spanish EPIC-16 questionnaire demonstrated sensitivity, strong discriminative properties and reliability, and validity for use in clinical practice. EPIC-16 scores worsened after radiotherapy in different HRQoL domains; however, a strong tendency towards recovery was seen at the 3-month follow-up visit.

Càncer de pròstata; Teràpia de privació d'andrògens Cáncer de próstata; Terapia de privación de andrógenos Prostate cancer; Androgen-deprivation therapy PURPOSE The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer–specific mortality. RESULTS Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer–specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT. Funding support for this study comes from the Prostate Cancer Foundation and ASTRO to AUK. AUK also thanks generous donations from the DeSilva, McCarrick, and Bershad families. A.T. acknowledges support from Cancer Research UK (C33589/A28284 and C7224/A28724) the National Institute for Health Research (NIHR) Cancer Research Network. This project represents independent research supported by the National Institute for Health research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. N.G.Z. is supported by the American Cancer Society – Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG‐20‐013‐01‐CCE (2020).

Poly (ADP-ribose) polymerase (PARP) inhibitors have antitumor activity in advanced prostate cancer associated with loss of homologous recombination repair (HRR) function. About 20% of all patients with advanced prostate cancer present germline or tumor mutations in HRR-related genes, the most common being BRCA2, mutated in approximately 10% of all advanced prostate cancers. Challenges related to sample availability, tumor heterogeneity and access to NGS technology need to be addressed for a successful implementation of genomic stratification in routine clinical practice. The recent regulatory approvals of PARP inhibitors olaparib and rucaparib represent the first molecular biomarker-guided drugs for men with prostate cancer. While these findings represent a significant advance in the field of precision medicine and prostate cancer, there are still many unsolved questions on the optimal use of PARP inhibitors in this disease. Several clinical trials have shown that different mutations in various genes are associated with distinct magnitudes of sensitivity to PARP inhibitors, with BRCA2 mutations associating with more frequent and durable responses, questioning the benefit for subset of patients with mutations in other HRR-associated genes. In this review, we scrutinize the clinical development of different PARP inhibitors for the treatment of advanced prostate cancer, and we discuss how the study of additional biomarkers and the design of rational drug combinations can maximize patient benefit from this drug class.

The optimal prognostic value of testosterone following androgen deprivation therapy (ADT) is controversial. We studied the effect of serum testosterone levels on clinical outcome in localized prostate cancer (PCa) treated with ADT and high-dose radiotherapy (HRT).The DART01/05 trial randomized 355 men with intermediate and high-risk PCa to 4 months of ADT plus HRT (STADT, N = 178) or the same treatment followed by 24 months of ADT (LTADT, N = 177). This study included patients treated with LTADT who had at least 3 determinations of testosterone during ADT (N = 154). Patients were stratified into 3 subgroups by testosterone level: minimum20 ng/dL; median 20-49 ng/dL; and maximum ≥50 ng/dL. Kaplan-Meyer and Cox regression analysis were used for overall survival (OS) and FineGray regression model for metastasis free survival (MFS), biochemical disease-free survival (bDFS) and time to TT recovery.There were no statistically significant differences in 10-year bDFS, MFS, or OS between the20 ng/mL and 20-49 ng/dL subgroups. Multivariate analysis showed that a median testosterone ≥50 ng/dL was significantly associated with a decrease in bDFS (HR: 6.58, 95%CI 1.28-33.76, p = 0.03). Time to testosterone recovery after ADT did not correlate with bDFS, MFS, or OS and was not significantly associated with any of the testosterone subgroups.Our results do not support the concept that additional serum testosterone suppression below 20 ng/dL is associated with better outcomes than 20-49 ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.

Approximately 30% of patients who undergo radical prostatectomy for prostate cancer develop disease progression. The only potentially curative treatment in these patients is postoperative radiotherapy with or without hormonotherapy. One of the standards of care in nonsurgical patients is hypofractionated radiotherapy. However, the current evidence based is insufficient to define the optimal dose and fractionation schedule for postoperative radiotherapy. In this context, the aim of this editorial is to assess the main efficacy and toxicity data for postoperative hypofractionated radiotherapy and discuss the potential to implement this fractionation in routine clinical practice.

Key Points Question What is the optimal minimum duration of androgen deprivation therapy (ADT) when treating high-risk prostate cancer with high-dose radiotherapy? Findings This patient-level cohort study of 3 cohorts found a significant interaction between the type of high-dose radiotherapy (external beam radiotherapy with or without a brachytherapy boost) and optimal duration. Prolonging ADT for 18 to 28 months was associated with a 63% reduction in death or metastasis with external beam radiotherapy; when a brachytherapy boost was added, the nonlinear association between ADT and distant metastasis-free survival was broad and spanned 12 months. Meaning The findings of this cohort study suggest that patients receiving external beam radiotherapy alone may benefit from ADT durations of 18 months or more; if a brachytherapy boost is added, a duration of 18 months or possibly less may be optimal., Importance Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain. Objective To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). Design, Settings, and Participants This was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivación Androgénica y Radio Terapía (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021. Exposures High-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs). Main Outcomes and Measures The primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months). Results This cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to, This cohort study explores associations between the duration of androgen deprivation therapy and distant metastasis-free survival in men undergoing external beam radiotherapy with and without a brachytherapy boost for treatment of high-risk prostate cancer.

Head and neck cancer; Image guided radiotherapy; Squamous cell cancer Cáncer de cabeza y cuello; Radioterapia guiada por imagen; Cáncer de células escamosas Càncer de cap i coll; Radioteràpia guiada per imatge; Càncer de cèl·lules escamoses Squamous cell cancer of the head and neck (SCCHN) often requires adjuvant radiotherapy. Radiotherapy for SCCHN is a challenge because the head and neck contain several critical organs that should receive minimal doses of radiation. These organs include the eyes, parotid glands, brainstem, spinal cord, mandible, and thyroid gland. Approaches like image-guided radiotherapy (IGRT) combined with volumetric modulated arc therapy hold the promise to focus radiation to the planning target volume and spare nearby structures while observing potential changes to patient anatomy during treatment to determine whether replanning is required. IGRT, however, requires the frequent imaging of patients to update the treatment plan. In this retrospective study, we present our findings of SCCHN patients treated in a public hospital in Peru. The patients reflected overall demographic trends associated with SCCHN. Each patient was imaged using computed tomography once before radiotherapy and once by cone-beam computed tomography (CBCT) during treatment, for a total of two images. Tumor displacement, planning target volume, gross tumor volume, and neck diameter were compared between the two images. Among the measurements, only a small statistically significant increase in gross tumor volume was observed between the images. However, a minority of patients did experience changes to anatomy, which highlights the need for continued research into criteria to determine which patients are likely to benefit from treatment replanning due to intra-treatment anatomical changes. Alternatively, a lack of frequent CBCT imaging before each session, due to high patient flows and limited staff resources, made it difficult to observe transient changes and trends in each patient. We conclude that the treatment and outcome improvements associated with IGRT are likely associated with frequent imaging during radiotherapy and properly selecting which patients will benefit most from this resource-intensive technique.

Purpose: Docetaxel improves survival in patients with metastatic prostate cancer. This randomized phase 2 trial aimed to assess the activity of weekly docetaxel with radiation therapy (RT) plus androgen deprivation in patients with high-risk localized prostate cancer. The study examined the benefit of 9 weekly docetaxel administrations to RT plus 3 years of luteinizing hormone-releasing hormone analogues. Methods and Materials: A total of 132 patients were recruited for the study. Patients' characteristics included T3-T4 stage (81.1%), Gleason score >= 8 (77.3%), prostate-specific antigen level >20 ng/mL (28.9%), and pN+ (18.2%). All patients included in the trial received either the standard-of-care control arm with luteinizing hormone-releasing hormone analogues plus RT (arm A) or the experimental arm (RT + 9 weekly cycles of docetaxel + 3 years of androgen deprivation therapy, arm B). The primary objective was to achieve a high percentage of patients who were free of biochemical recurrence within 5 years of randomization. Secondary endpoints included biochemical recurrence-free survival (BRFS), progression-free survival (PFS), overall survival (OS), clinical response rate, biochemical response rate, and toxicity. Results: No difference between the arms of the study was found in biochemical recurrence (93.4% at 60 months for arm A vs 85.3% for arm B; P = .3297). PFS at 60 months was 93.4% and 83.7% in arms A and B, respectively (P = .2532). Five-year survival was 93.3% (95% confidence interval, 83.1-97.45) in arm A versus 93.6% (83.8-97.55) in arm B; median PFS and OS have not been reached. Prostate-specific antigen level

Bladder cancer is the fourth most common cancer in men and the ninth most common in women in the Western world. The management of bladder carcinoma requires a multidisciplinary approach. Optimal treatment depends on several factors, including histology, stage, patient status, and possible comorbidities. Here we review recent findings on the treatment of muscle-invasive bladder carcinoma, advanced urothelial carcinoma, upper tract urothelial carcinoma, non-urothelial carcinoma, and urologic complications arising from the disease or treatment. In addition, we present the recommendations of the Spanish Oncology Genitourinary Group for the treatment of these diseases, based on a focused analysis of clinical management and the potential of current research, including recent findings on the potential benefit of immunotherapy. In recent years, whole-genome approaches have provided new predictive biomarkers and promising molecular targets that could lead to precision medicine in bladder cancer. Moreover, the involvement of other specialists in addition to urologists will ensure not only appropriate therapeutic decisions but also adequate follow-up for response evaluation and management of complications. It is crucial, however, to apply recent molecular findings and implement clinical guidelines as soon as possible in order to maximize therapeutic gains and improve patient prognosis.

Background: Health-related quality of life (HRQoL) is greatly affected by prostate cancer (PCa) and associated treatments. This study aimed to measure the impact of radiotherapy on HRQoL and to further validate the Spanish version of the 16-item Expanded Prostate Cancer Index Composite (EPIC-16) in routine clinical practice.Methods: An observational, non-interventional, multicenter study was conducted in Spain with localized PCa patients initiating treatment with external beam radiotherapy (EBRT) or brachytherapy (BQT). Changes from baseline in EPIC-16, University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), and patient-perceived health status were longitudinally assessed at end of radiotherapy (V2) and 90 days thereafter (V3). Psychometric evaluations of the Spanish EPIC-16 were conducted.Results: Of 516 patients enrolled, 495 were included in the analysis (EBRT, n = 361; BQT, n = 134). At baseline, mean (standard deviation [SD]) EPIC-16 global scores were 11.9 (7.5) and 10.3 (7.7) for EBRT and BQT patients, respectively; scores increased, i.e., HRQoL worsened, from baseline, by mean (SD) of 6.8 (7.6) at V2 and 2.4 (7.4) at V3 for EBRT and 4.2 (7.6) and 3.9 (8.2) for BQT patients. Changes in Spanish EPIC-16 domains correlated well with urinary, bowel, and sexual UCLA-PCI domains. EPIC-16 showed good internal consistency (Cronbach’s alpha = .84), reliability, and construct validity.Conclusion: EPIC-16 scores worsened after radiotherapy in different HRQoL domains, regardless of patient-perceived health status. UCLA-PCI scores mostly recovered for EBRT patients at V3, while scores for BQT patients did not. The Spanish EPIC-16 questionnaire demonstrated sensitivity, strong discriminative properties and reliability, and validity for use in clinical practice.

Prostate cancer is the most frequent genitourinary tumor worldwide. Maintaining an optimum bone health throughout the natural course of prostate cancer is an important aspect in the management of this disease, particularly in this at risk population of older and frail patients who experience bone loss related to androgen-deprivation therapy (ADT) and/or patients who develop bone metastases. The number of treatment options for advanced prostate cancer that combine ADT with docetaxel, new hormonal agents and/or radiotherapy has increased substantially in recent years. Bisphosphonates and other bone targeted agents such as denosumab have shown an improvement in bone mineral density and are suited for patients with treatment-related osteoporosis and/or bone metastases with an increased risk of skeletal-related events (SREs). In this context, the aim of this review is to analyse key aspects of bone health and therapies that can prevent the occurrence of SREs throughout the clinical course of prostate cancer, and how to combine them with new available treatments in this setting.

Purpose/Objective(s) The optimal duration of androgen deprivation (AD) combined with high-dose radiotherapy (HDRT) in prostate cancer remains a matter of controversy. We did a phase 3 trial designed to determine whether long-term AD (LTAD) is superior to short-term AD (STAD) when combined with HDRT. In this report, we present the 10-year survival results. The hypothesis is that long-term AD (LTAD) compared to short-term AD (STAD) improves overall survival among high-risk patients receiving HDRT. Materials/Methods This open-label, phase 3 randomized controlled trial, recruited patients from ten university hospitals throughout Spain. Eligibility included patients with cT1c-T3aN0M0 adenocarcinoma of prostate with intermediate and high-risk factors according to NCCN criteria and PSA less than 100 ng/ml. All patients received 4 months of neoadjuvant and concomitant AD (STAD) + HDRT (median radiation dose 78 Gy) before randomization to adjuvant goserelin for two years (LTAD). Stratification was performed according to risk group (intermediate risk [IR] versus high risk [HR]). Study endpoints included overall survival (OS), metastasis free survival (MFS), disease free survival (DFS) and biochemical-disease free survival (bDFS). Survival analyses were done with Kaplan-Meier (KM) curves. Fine & Gray (FG FG FG F&G P = 0.057, HR, 1.12, 95% CI, 0.46 to 2.73). Only 11 patients died from PCa, all of them in the high-risk subgroup. Conclusion Long term results failed to show a significant benefit with LTAD compared to STAD in patients treated with HDRT. The subgroup of patients with high-risk PCa treated with LTAD had a non-significant improvement in bDFS, MFS and OS compared with STAD. The relatively small simple size, a low number of events and an effective salvage treatment could be responsible for the lack of a statistical significance. The trial is registered at ClinicalTrials.gov, number NCT 02175212.

Aim To analyze the effect of radiotherapy (RT) in patients with metastatic spinal cord compression (MSCC) and poor prognosis in our center. Background RT is an effective treatment for MSCC. Materials and methods Prospective evaluation on patients with MSCC and limited survival (according to Rades’ scale), and treated with single-dose 8 Gy RT (February 2013–August 2014). Pain, ambulatory status and sphincter control were recorded. Pain relief was evaluated following the International Bone Metastases Consensus Working Party Guidelines. Ambulatory status was evaluated with Frankel's scale. Spinal fracture and instability were recorded. Health aspects were evaluated via a short survey and measuring the time spent on RT. Results 35 patients were included. 51% had unfavorable histologies; 60% bone fracture and 17% spinal instability. Median Karnofsky score was 60; 100% were on high doses of opioids. Median survival was 1.5 months. 49% had a partial pain response at 2 weeks post-radiation, and 47% at one month. Significant reductions in pain intensity were present at 2 weeks (Visual analog scale, VAS score, from 8 ± 1.5 to 5 ± 1.9). Negligible effects were observed on motor and bladder function, along with side effects. KPS score was maintained during follow-up. 80% of patients spent ≤5% of their remaining lifetime on RT. A survey comparison between clinical judgment and the results according to treatment decision consider that these patients merit treatment evaluation. Conclusions A moderate pain response tailored to life expectancy can be obtained in patients treated with radiation. 8-Gy single-dose is an option for patients with limited survival.

Càncer de pròstata resistent a la castració; Oncologia de les radiacions; Consens Cáncer de próstata resistente a la castración; Oncología radioterápica; Consenso Castration-resistant prostate cancer; Radiation oncology; Consensus Background: The knowledge in the field of castration-resistant prostate cancer (CRPC) is developing rapidly, with emerging new therapies and advances in imaging. Nonetheless, in multiple areas there is still a lack of or very limited evidence, and clear guidance from clinicians regarding optimal strategy is required. Methods: A modified Delphi method, with 116 relevant questions divided into 7 different CRPC management topics, was used to develop a consensus statement by the URONCOR group. Results: A strong consensus or unanimity was reached on 93% of the proposed questions. The seven topics addressed were: CRPC definition, symptomatic patients, diagnosis of metastasis, CRPC progression, M0 management, M1 management and sequencing therapy, and treatment monitoring. Conclusions: The recommendations based on the radiation oncology experts' opinions are intended to provide cancer specialists with expert guidance and to standardise CRPC patient management in Spain, facilitating decision-making in different clinically relevant issues regarding CRPC patients.

5000 Background: Historically, androgen deprivation therapy (ADT) was the standard of care (SOC) for men with mCSPC. Since 2015, combining ADT with either docetaxel, novel hormonal therapies, or radiotherapy to the primary tumor (RXT) (for those with low burden metastases) was shown to improve overall survival (OS) and thus has become the new SOC. It is unknown whether combining these new treatments on top of ADT further increments outcomes. Methods: Men with de novo mCSPC were randomized to SOC, SOC + abiraterone acetate-prednisone (abiraterone), SOC + RXT, or SOC + abiraterone + RXT. SOC was initially ADT alone, then from Oct 2015 onwards the use of docetaxel was authorized as part of SOC (at the investigator’s discretion until 2017, then, following the publication of the LATITUDE and STAMPEDE trials, accrual was restricted to men receiving ADT+docetaxel). The trial has two co-primary endpoints of radiographic progression-free survival (rPFS) and OS with type I error of 0.1% and 4.9%, respectively. The required number of rPFS events to achieve 80% power has been reached for the abiraterone question (not yet for the RXT question). The interaction between abiraterone and RXT was first tested using a Cox model adjusted for stratification factors (performance status, type of castration, metastatic burden, and when applicable, docetaxel). A hierarchical testing was used to test the effect of abiraterone: overall population, then ADT+docetaxel population. Results: From Nov 2013 to Dec 2018, 1173 men were enrolled (SOC was ADT+docetaxel in 710 pts and ADT alone in 463 pts), median age 67y (IQR: 60-72), high volume 57%, low volume 43%. The median follow-up is 3.5y. No interaction was detected between the effect of abiraterone and that of RXT (p = 0.64), allowing to pool abiraterone arms for comparisons. rPFS was significantly improved in the abiraterone arm in the overall population (HR: 0.54 (0.46-0.64), p < 0.0001; medians: 2.2 vs 4.5 years) and in the ADT+docetaxel population: (HR: 0.50 (0.40-0.62), p < 0.0001; medians: 2.0 vs 4.5 years). bPFS (PFS including PSA progression as an event) also significantly favored abiraterone in the overall population (HR: 0.40 (0.35-0.47), p < 0.0001; medians: 1.5 vs 3.8 years) and in the ADT+docetaxel population (HR: 0.38 (0.31-0.47), p < 0.0001; medians: 1.5 vs 3.2 years). OS is maturing. Grade 3-4 adverse events reported in > 5% of pts within the first 6 months in the ADT+docetaxel population included neutropenic fever (4.5% vs 5.4%), liver toxicity (19.7% vs 13%), and hypertension (12.2% vs 8.6%) in the abiraterone and control arms, respectively. Conclusion: Adding abiraterone to ADT + docetaxel significantly improves rPFS in men with de novo metastatic prostate cancer, with about 2.5 years of absolute benefit in medians, and no meaningful additional short-term toxicity. Clinical trial information: NCT01957436.

BACKGROUND The optimal degree of testosterone suppression in patients with prostate cancer undergoing androgen deprivation therapy remains in question. Furthermore, serum free testosterone, which is the active form of testosterone, seems to correlate with intraprostatic testosterone. Here we compared free and total serum testosterone as predictors of survival free of castration resistance. METHODS Total testosterone (chemiluminescent assay, lower sensitivity 10 ng/dl) and free testosterone (analogue-ligand radioimmunoassay, lower sensitivity 0.05 pg/ml) were determined at 6 months of LHRH agonist treatment in a prospective cohort of 126 patients with prostate cancer. During a mean follow-up of 67 months (9–120), 75 (59.5%) events of castration-resistant progression were identified. Multivariate analysis and survival analysis according to total testosterone cutoffs of 50, 32, and 20 ng/dl, and free testosterone cutoffs of 1.7, 1.1, and 0.7 pg/ml were performed. RESULTS Metastatic spread was the most powerful predictor of castration resistance, HR: 2.09 (95%CI: 1.18–3.72), P = 0.012. Gleason score, baseline PSA and PSA at 6 months were also independents predictors, but not free and total testosterone. Stratified analysis was conducted on the basis of the status of metastatic diseases and free testosterone was found to be an independent predictor of survival free of castration resistance in the subgroup of patients without metastasis, HR: 2.12 (95%CI: 1.16–3.85), P = 0.014. The lowest threshold of free testosterone which showed significant differences was 1.7 pg/ml, P = 0.003. CONCLUSIONS Free testosterone at 6 months of LHRH agonist treatment seems to be a better surrogate than total testosterone to predict castration resistance in no metastatic prostate cancer patients. Prostate 77:114–120, 2017. © 2016 Wiley Periodicals, Inc.

Resumen Objetivos Determinar la influencia de la prostatectomia radical (PR) y de la radioterapia externa (RT) sobre el eje hipotalamo-hipofisario de 120 pacientes con cancer de prostata clinicamente localizado tratados con PR o RT exclusiva. Material y metodos Estudiamos 120 pacientes con cancer de prostata localizado. Noventa y dos pacientes recibieron PR y 28 RT exclusiva. Medimos los niveles sericos de hormona luteinizante, hormona foliculo estimulante (FSH), testosterona total (T), testosterona libre y estradiol basalmente y a los 3 y 12 meses tras completar el tratamiento. Resultados Los pacientes sometidos a PR eran mas jovenes y presentaban mayor volumen prostatico (64,3 vs. 71,1 anos, p Conclusiones El tratamiento del cancer de prostata influye en el eje hipotalamo-hipofisario. La influencia parece mas importante en los pacientes tratados con RT. Necesitamos mas estudios que eluciden el papel que la prostata puede jugar como organo endocrino.

The Vall d’Hebron multidisciplinary prostate cancer (PC) team reviews recent advances in the management of this neoplasm. Screening studies with long follow-up show a reduction in mortality, whereas active surveillance is emerging as a therapeutic approach of non-aggressive cancers. New markers increase the specificity of PSA and also allow targeting suspected aggressive cancers. Multiparametric magnetic resonance (mMRI) has emerged as the most effective method in the selection of patients for biopsy and also for local tumor staging. The paradigm of random prostatic biopsy is changing through the fusion techniques that allow guiding ultrasonography-driven biopsy of suspicious areas detected in mMRI. Radical prostatectomy (RP) and radiotherapy (RT) are curative treatments of localized PC and both have experienced significant technological improvements. RP is highly effective and the incorporation of robotic surgery is reducing morbidity. Modern RT allows the possibility of high tumor dose with minimal adjacent dose reducing its toxicity. Androgen deprivation therapy with LHRH analogues remains the treatment of choice for advanced PC, but should be limited to this indication. The loss of bone mass and adverse metabolic effects increases the frequency of fractures and cardiovascular morbimortality. After castration resistance in metastatic disease, new hormone-based drugs have demonstrated efficacy even after chemotherapy resistance.

The role of seizures and antiepileptic treatments associated with glioblastoma is a current topic of discussion. The objective of this study is to characterize and establish implications of epilepsy associated with glioblastoma.We retrospectively analyzed the medical history, focused on epileptic features of 134 histologically diagnosed glioblastoma over a period of 4 years.The sample group had an average age of 56 years and 66% were male. Complete tumor resection was performed in 66% and 64.2% received further radio-oncologic treatment. The average survival rate was 12.4 months and 11.5% survived to 5 years. Epileptic seizures were the presentation symptom in 27% of cases and 51% suffered seizures during the disease, 26% become drug-resistant. Focal evolving to a bilateral convulsive seizures were the most frequent type. Epileptic seizures at presentation independently predicted longer survival (p0.001). Furthermore, a history of epilepsy or seizures during disease improved survival. Late onset seizures, recurrences or status epilepticus during the course of the disease indicated tumor progression or the final stages of life. Prophylactic antiepileptic drugs did not prevent seizures. Similarly, there was no difference in survival between patients who did not use antiepileptic drugs and those using valproate or levetiracetam. Patients under 60 years, full oncologic treatment and secondary glioblastomas were factors that improved survival (p0.001).Previous history of epilepsy or the onset of seizures as a presentation symptom in glioblastomas predict longer survival. Half of patients have seizures during the course of the disease. Antiepileptic drugs alone do not increase survival in glioblastoma patients.

Therapeutic options for metastatic bladder cancer (BC) have seen minimal evolution over the past 30 years, with platinum-based chemotherapy remaining the mainstay of standard of care for metastatic BC. Recently, five immune checkpoint inhibitors (ICIs) have been approved by the FDA as second-line therapy, and two ICIs are approved as first-line treatment in selected patients. Molecular alterations of muscle-invasive bladder cancer (MIBC) have been reported by The Cancer Genome Atlas. About 15% of patients with MIBC have molecular alterations in the fibroblast growth factor (FGF) axis. Several ongoing trials are testing novel FGF receptor (FGFR) inhibitors in patients with FGFR genomic aberrations. Recently, erdafitinib, a pan-FGFR inhibitor, was approved by the FDA in patients with metastatic BC who have progressed on platinum-based chemotherapy. We reviewed the literature over the last decade and provide a summary of current knowledge of FGF signaling, and the prognosis associated with FGFR mutations in BC. We cover the role of FGFR inhibition with non-selective and selective tyrosine kinase inhibitors as well as novel agents in metastatic BC. Efficacy and safety data including insights from mechanism-based toxicity are reported for selected populations of metastatic BC with FGFR aberrations. Current strategies to managing resistance to anti-FGFR agents is addressed, and the importance of developing reliable biomarkers as the therapeutic landscape moves towards an individualized therapeutic approach.

496 Background: There is a growing interest in local treatment for metastatic solid tumors. Recently, retrospective studies have reported the potential benefit of RLT to primary bladder cancer in pts with metastatic disease. We tested the impact of previous RLT in pts with mUC treated with ICI. Methods: Data from pts with mUC treated with ICI collected between May 2013 and May 2019 using a multi-institutional database was evaluated. Stratification was made according to previous RLT with ICI versus no RLT with ICI. We defined RLT as radical surgery (RS) or ≥50 Gy of radiotherapy (RT) delivered to the bladder. The X2 test was used to determine differences in rates. Overall survival (OS) between previous RLT plus ICI (group A) versus no RLT plus ICI (group B) generated using Kaplan-Meier method was compared by log-rank test. OS was calculated from the date of initiation of ICI to the date of death. Analyses were performed using SPSS v21. Results: A total of 115 pts with mUC were treated with ICI, 62 (53.9%) previously were treated with RS, 7(6.1%) RT and 46 (40%) no received RLT. ICI prescribed were atezolizumab (55.7%), pembrolizumab (16.5%), durvalumab (11.3%), durvalumab/tremelimumab (7.8%), nivolumab (5.2%) and avelumab (3.5%). The disease control rate (CR [6.9%] +PR [9.6%] +SD [14.1%]) was higher for pts with previous RLT compared to those pts who did not receive RLT (CR [3.2%] + PR [5.8%] + SD [6.4%](P=0.325). Median OS was 11.23 mo (95% CI; 6.02-16.44) and 7.95 mo (95%IC; 5.15-10.75) for group A and group B, respectively (P=0.481). Conclusions: This multicenter cohort suggests that previous RLT might play an impact for control disease in pts with mUC treated with ICI. Although this is hypothesis generating, the true value of this approach remains to be demonstrated in prospective studies.

Serum testosterone measurement is recommended to assess the efficacy of androgen deprivation therapy (ADT) and to diagnose castration resistance in patients with prostate cancer (PCa). Currently, the accepted castrate level of serum testosterone is 50 ng/dL. Liquid chromatography and tandem mass spectrometry (LC MSMS) is the appropriate method to measure testosterone, especially at low levels. However, worldwide, chemiluminescent assays (CLIAs) are used in clinical laboratories, despite their lack of accuracy and reproducibility, because they are automatable, fast, sensitive, and inexpensive.We compared serum testosterone levels measured using LC MSMS and CLIAs in 126 patients with PCa undergoing luteinizing hormone-releasing hormone (LHRH) agonist therapy.The median serum testosterone level was 14.0 ng/dL (range, 2.0-67.0 ng/dL) with LC MSMS and 31.9 ng/dL (range, 10.0-91.6 ng/dL) with CLIA (P .001). The serum testosterone levels, measured using LC MSMS, were 20 ng/dL in 83 patients (65.9%), 20 to 50 ng/dL in 40 (31.7%), and50 ng/dL in 3 patients (2.4%). These ranges were found in 34 (27%), 72 (57.1%), and 20 (15.9%) patients when testosterone was measured using CLIA (P .001). The castrate level of serum testosterone using LC MSMS and CLIA was 39.8 ng/dL (95% confidence interval [CI], 37.1-43.4 ng/dL) and 66.5 ng/dL (95% CI, 62.3-71.2 ng/dL), respectively.We found that CLIA overestimated the testosterone levels in PCa patients undergoing LHRH agonist therapy. Thus, the castration level was incorrectly considered inadequate with CLIA in almost 15% of patients. The true castration level of serum testosterone using an appropriate method is 50 ng/dL.

4531 Background: Immune-checkpoints inhibitors (ICIs) represents the standard of care for platinum-pretreated advanced urothelial cancer patients (pts). By enhancing T-cell activation, a unique spectrum of inflammatory side effects has emerged, also known as immune-related adverse events (irAEs). Data regarding the association between irAEs and pts outcomes are conflicting. Here we conducted a retrospective analysis to investigate the association between irAEs profile and disease outcome in metastastic urothelial carcinoma (mUC) pts. Methods: Medical records from pts with mUC included in clinical trials between July 2013 and June 2018 and treated with ICIs were reviewed. Pts previously treated with platinum-based chemotherapy or cisplatin ineligible pts who had not been previously treated with chemotherapy were included. Clinical responses were assessed as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST v1.1. Adverse events were graded based CTCAE v4.03. Overall survival (OS) was calculated from the date of initiation of ICI to the date of death. X2 test was used to determine differences in rates. OS was estimated using Kaplan-Method and long rank test was used to assess differences between groups. All analyses were performed using SPSS v21. Results: From a total of 52 pts, 44 (84.6%) were treated with ICI monotherapy and 8 (15.3%) in combination (anti-CTLA4 or targeted therapy). Median age was 65 years, 42 pts (80.8%) were male, 44 patients (84.6%) had ECOG PS 0-1, 14 pts (26.9%) had liver metastasis. Overall irAEs were observed in 30 pts (57.7%) and 10 pts (19.2%) developed grade 3/4 irAES. Most common grade 3/4 irAEs were diarrhea (6.6%), rash (6.6%) and hepatitis (6.6%). Disease control rate (CR [26%]+PR[33%]+SD[20%]) was higher for patients with irAEs compared to those patients who did not developed irAEs (CR [13.6%]+PR[0%]+SD[22.7%], this difference was statically significant (P = 0.002). Median OS was 11.23 mo (CI 95%, 3.76-18.70) for the overall cohort, while median OS was 21.91 mo for those patients with irAEs compared to 6.47 mo in patients who did not developed irAEs (P = 0.004). Conclusions: In this analysis we found that the development of irAEs was a strong predictor of improved OS in mUC patients treated with ICI.

To evaluate the efficacy and toxicity of docetaxel regimen as second-line after failure of a platinum-based chemotherapy.Between May 2005 and June 2008, we retrospectively analyzed the data of 22 patients who had evidence of disease progression after one prior platinum-based regimen for metastatic urothelial carcinoma. Patients were treated with two different docetaxel dose schedules: (1) docetaxel 60 mg/m(2) every 21 days for unfit patients or (2) docetaxel 75 mg/m(2) every 21 days for fit patients.Median number of docetaxel cycles was three. Overall disease control rate was 18 %. Of the 22 patients, no patient achieved complete or partial response and four patients had stable disease. Median progression-free survival was 1.67 months and median overall survival was 3.12 months. Neutropenia was the most common adverse event.This study identifies that docetaxel as second-line chemotherapy has low activity and was associated with significant toxicity.

Initial therapy for metastatic prostate cancer consists of androgenic suppression. However, this is only a palliative treatment with an effective duration that usually lasts 12-24 months. Historically, castration-resistant prostate cancer (CRPC) had been considered a chemoresistant tumour. In 2004, docetaxel received USA Food and Drug Administration approval as a first-line treatment for metastatic prostate cancer, after two independent phase III trials showed an increased survival benefit. Recently, five new drugs have shown increased survival in CRPC: sipuleucel-T (assymptomatic or minimally symptomatic), abiraterone acetate (before and after docetaxel), cabazitaxel (after docetaxel), MDV3100 (after docetaxel) and radium-223 (not suitable for docetaxel or after docetaxel). The identification of antigens in normal prostate tissue or prostate cancer that are recognised by immune effectors cells has resulted in several new studies based on immunotherapy. Prostate cancer disease provides a test system to determine the efficacy of vaccines for different reasons. This cancer is a tumour that grows relatively slowly. Recurrence is often diagnosed early (with many patients presenting only with biochemical progression), there is a biological marker that can predict prognosis and outcome (PSA doubling time), various specific antigens have been identified and characterised, and vaccines can be used with a good safety profile combined with anti-androgen therapy, chemotherapy, or radiotherapy. Here we provide a review of the main important immune treatments in CRPC.

The optimal degree of testosterone suppression in patients with prostate cancer undergoing androgen deprivation therapy remains in question. Furthermore, serum free testosterone, which is the active form of testosterone, seems to correlate with intraprostatic testosterone. Here we compared free and total serum testosterone as predictors of survival free of castration resistance.Total testosterone (chemiluminescent assay, lower sensitivity 10 ng/dl) and free testosterone (analogue-ligand radioimmunoassay, lower sensitivity 0.05 pg/ml) were determined at 6 months of LHRH agonist treatment in a prospective cohort of 126 patients with prostate cancer. During a mean follow-up of 67 months (9-120), 75 (59.5%) events of castration-resistant progression were identified. Multivariate analysis and survival analysis according to total testosterone cutoffs of 50, 32, and 20 ng/dl, and free testosterone cutoffs of 1.7, 1.1, and 0.7 pg/ml were performed.Metastatic spread was the most powerful predictor of castration resistance, HR: 2.09 (95%CI: 1.18-3.72), P = 0.012. Gleason score, baseline PSA and PSA at 6 months were also independents predictors, but not free and total testosterone. Stratified analysis was conducted on the basis of the status of metastatic diseases and free testosterone was found to be an independent predictor of survival free of castration resistance in the subgroup of patients without metastasis, HR: 2.12 (95%CI: 1.16-3.85), P = 0.014. The lowest threshold of free testosterone which showed significant differences was 1.7 pg/ml, P = 0.003.Free testosterone at 6 months of LHRH agonist treatment seems to be a better surrogate than total testosterone to predict castration resistance in no metastatic prostate cancer patients. Prostate 77:114-120, 2017. © 2016 Wiley Periodicals, Inc.

We compared biochemical control and quality of life with intermittent (6 months) versus continuous (36 months) androgen deprivation therapy (ADT) in a non-inferiority randomized phase 3 trial in patients with biochemical failure (BF) after external beam radical radiotherapy (EBRT). Patients were stratified according to the Gleason score (GS) and were classified as low risk with a GS < 6 and 7 (3 + 4) and high risk with a GS of 7 (4 + 3) and > 7. Patients were followed with PSA determinations and quality-of-life assessments (QLQ C-30 and QLQ PR-25) every 6 months for a period of 3 years. BF after radiation was defined as a PSA level of nadir +2 ng/ml. Disease progression (DP) after ADT was defined as PSA >4 ng/ml (BF) and/or metastases. Seventy-seven patients were included in this multicenter phase 3 trial from 2005 to 2009. Thirty-eight and 39 patients were included in the intermittent and continuous groups, respectively. The median follow-up for both groups was 48 months (40-68). DP after ADT in the intermittent group was seen in three patients (distant metastases in one patient) versus 0 in the continuous group. The QLQ-C30 and QLQ PR-25 scores did not show any statistically difference between the two ADT groups. No significant differences were seen in DP and QLQ between intermittent (6 months) and continuous (36 months) ADT in patients with BF after EBRT.

Bladder cancer is one of the leading causes of death in Europe and the United States. About 25% of patients with bladder cancer have advanced disease (muscle-invasive or metastatic disease) at presentation and are candidates for systemic chemotherapy. In the setting of metastatic disease, use of cisplatin-based regimens improves survival. However, despite initial high response rates, the responses are typically not durable leading to recurrence and death in the vast majority of these patients with median overall survival of 15months and a 5-year survival rate of ⩽10%. Furthermore, unfit patients for cisplatin have no standard of care for first line therapy in advance disease Most second-line chemotherapeutic agents tested have been disappointing. Newer targeted drugs and immunotherapies are being studied in the metastatic setting, their usefulness in the neoadjuvant and adjuvant settings is also an intriguing area of ongoing research. Thus, new treatment strategies are clearly needed. The comprehensive evaluation of multiple molecular pathways characterized by The Cancer Genome Atlas project has shed light on potential therapeutic targets for bladder urothelial carcinomas. We have focused especially on emerging therapies in locally advanced and metastatic urothelial carcinoma with an emphasis on immune checkpoints inhibitors and FGFR targeted therapies, which have shown great promise in early clinical studies.