A multidisciplinary consensus statement on the optimal pharmacological treatment for metastatic hormone-sensitive prostate cancer.

Androgen deprivation therapy (ADT) is the mainstay treatment for metastatic hormone-sensitive prostate cancer (mHSPC). The addition of docetaxel or new hormone therapies (abiraterone, apalutamide, or enzalutamide) improves overall survival and is currently the standard of care. However, the decision on the specific regimen to accompany ADT should be discussed with the patient, considering factors such as possible associated toxicities, duration of treatment, comorbidities, patient preferences, as there is no sufficient evidence to recommend one regimen over the other in most cases. This paper summarizes the evidence on the management of mHSPC and provides consensus recommendations on the optimal treatment in combination with ADT in mHSPC patients, with special attention to the patient's clinical profile.

Hormone sensitive protocol for metastatic prostate cancer, an update.

To review and update last protocols in hormone sensitive metastatic prostate cancer for improving clinical management in routine. Evidence analysis available about recent updates protocols in hormone sensitive metastatic prostate cancer according to expert panel of clinicians about this field. A nominal consensus group for unify and improve the recommendations to the management of sensitive metastatic prostate cancer patients is currently needed. This document unifies and improve the management of patients with hormone sensitive metastatic prostate cancer, with a methodology that combines data quantitative and qualitative and based on the participation of a broad scientific committee appointed by the Spanish Association of Urology.

The impact of psychiatric pathology on the prognosis and survival of men with prostate cancer undergoing radical prostatectomy.

INTRODUCTION AND OBJECTIVE: Cancer-specific anxiety is the most frequently reported psychological response after radical prostatectomy (RP). We evaluated the prevalence of pretreatment psychiatric pathology in patients with prostate cancer undergoing RP and identified the effects of psychiatric diagnoses on their survival and prognosis. MATERIAL AND METHODS: Retrospective multicenter observational study including 1078 men treated with RP for organ-confined prostate cancer. Groups: GP: patients with psychiatric pathology prior to RP; GNP: patients without psychiatric pathology prior to RP. Urological, oncological and psychiatric variables, descriptive statistics and multivariate analysis were included. RESULTS: 37.94% of patients presented a psychiatric diagnosis. Adjuvant radiotherapy was required in 27.83% and hormone therapy in 23.38%; being more frequent in GP. Cancer-specific survival was higher in GNP. Anxiety, depression, insomnia, smoking, psychosis and alcoholism were the most frequent. Low TNM and low presence of LUTS and SUI increased the probability of absence of psychiatric pathology. Fatigue, erectile dysfunction and cognitive impairment after RP with RT and/or HT were higher in GP. Older age and higher PSA at diagnosis increased the relative risk of psychiatric pathology and worse outcome. The most frequently related factors were RP, PSA, age and survival time. CONCLUSIONS: Psychiatric pathology is present in patients undergoing radical prostatectomy for prostate cancer, with a high impact on survival and prognostic outcomes.

Non-metastatic castration-resistant prostate cancer: management recommendations.

INTRODUCTION AND OBJECTIVE: Survival and quality of life (QoL) of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) deteriorate significantly when they develop metastases. New generation antiandrogens (apalutamide, enzalutamide and darolutamide) can prolong metastasis-free survival (MFS) and overall survival (OS) in these patients, maintaining their QoL. MATERIAL AND METHODS: After the performance of a systematic review of the literature, a scientific committee reached a consensus on simple and practical recommendations to consolidate and improve the management of patients with nmCRPC in urology consultations. RESULTS: Recommendations are made on the frequency of PSA determination and imaging tests in patients with nmCRPC. The importance of co-morbidities in patients with nmCRPC is also highlighted, and recommendations are also made on functional and QoL assessment that can be carried out during urology consultations. The efficacy, safety, and effects on QoL of new generation antiandrogens are reviewed. CONCLUSIONS: To evaluate treatment of patients with nmCRPC, it is necessary to consider co-morbidities and QoL, in addition to age. New generation antiandrogens are a safe and effective treatment option for patients with nmCRPC. The recommendations of this review can be helpful in optimizing the management of nmCRPC patients in urology consultations.

Clinical drivers for imaging testing in non-metastatic castration-resistant prostate cancer in clinical practice: Results of the IDENTIFICA study. / Factores clínicos determinantes para la realización de pruebas de imagen en cáncer de próstata resistente a la castración no metastásico en la práctica clínica: resultados del estudio IDENTIFICA.

INTRODUCTION: The aim of the study was to describe the clinical drivers that lead physicians to perform imaging tests in search of metastasis in non-metastasic castration prostate resistant cancer (nmCRPC) patients. METHODS: Observational, cross-sectional study conducted at the Departments of Urology of 38 Spanish hospitals. The study included 188 patients diagnosed with nmCRPC who underwent an imaging test for the assessment of metástasis. In one study visit, physicians were requested to specify the clinical factors that led them to perform these tests. The results of the imaging tests and the clinical characteristics of the patients since the time of prostate cancer (PC) diagnosis, were reported. Regression analyses were used to determine predictors of imaging test results. RESULTS: Prostate-specific antigen (PSA) level was the most important driver to order imaging tests (57.1%), followed by regular follow-up (16.5%) and PSA doubling time (PSADT) (12.0%). Although these drivers were not associated to detection of metastasis, patients with PSA levels ≥20 ng/mL had a greater risk of metastasis than patients with PSA levels <4ng/mL (P=.004) and CRPC patients diagnosed with metastasis (mCRPC) had higher median PSA levels (20.9; interquartile range [IQR]: 6.7-38.6) than nmCRPC (9.1; IQR: 5.0-18.0) (P=.005). Sixty-six percent of the patients did not undergo any imaging test after CRPC diagnosis until the study visit (10.6, IQR: 4.0-19.5 months). Curative-intent treatment at PC diagnosis and Gleason score predicted longer time from PC to CRPC diagnosis. CONCLUSIONS: Physicians based their decisions to order imaging tests for metastasis detection in nmCRPC patients mainly on PSA and PSA kinetics, including the regular follow-up stated by guideline recommendations.

Advances in urologic oncology "OncoForum": The best of 2019. / Avances en uro-oncología «OncoForum¼: lo mejor del 2019.

OBJECTIVE: Review the latest evidence on urologic oncology on kidney, bladder and prostate tumors. METHODS: Abstracts on kidney, bladder and prostate cancer presented at the 2019 congresses (EAU, AUA, ASCO and ESMO) and the publications with the greatest impact in this period, with the highest evaluation by the OncoForum committee, are reviewed. RESULTS: In patients with metastatic kidney cancer, regimens including immunotherapy (nivolumab + ipilimumab, pembrolizumab) have been shown to be superior to sunitinib in terms of survival. In patients with non-muscle invasive bladder cancer, pembrolizumab has been shown to be an effective alternative in those refractory to bacillus Calmette-Guérin, while in patients with metastatic urothelial cancer, third-line enfortumab vedotin achieved a significant response rate (44%). In patients with localized prostate cancer (PCa), ultrafractionated external radiotherapy did not show any greater acute toxicity than fractionated or hypofractionated radiotherapy. The benefit of enzalutamide and apalutamide associated with castration has been confirmed in M1 PCa patients, regardless of disease volume. In patients with castration-resistant M0 PCa, treatment with enzalutamide, apalutamide or darolutamide has been associated with a delay in the occurrence of metastasis and prolonged survival. Cabazitaxel has demonstrated a survival benefit in patients with metastatic CRPC, while olaparib showed anti-tumor activity after chemotherapy in those tumors with mutations in DNA repair genes. CONCLUSIONS: These data show the implementation of immunotherapy as a novel alternative against renal and bladder cancer. The arrival of new agents for advanced urothelial carcinoma should be highlighted, and the efficacy of enzalutamide and apalutamide in de novo metastatic prostate cancer is established. In metastatic CRPC, cabazitaxel and olaparib (targeting mutations) are promising therapeutic options.

Liquid biopsy and prostate cancer. Current evidence applied to clinical practice. / Biopsia líquida y cáncer de próstata. Evidencia actual aplicada a la clínica.

CONTEXT: Despite being a validated source of biomarkers, liquid biopsy has not yet succeeded in becoming part of the standard clinical practice in prostate cancer patients. Few biomarkers undergo adequate validation, prospective and independent, of their predictive and/or prognostic value, which results in a lack of the different available tests in the clinical practice. OBJECTIVE: To carry out a pragmatic synthesis of current scientific evidence on liquid biopsy for prostate cancer patients. EVIDENCE ACQUISITION: Non-systematic literature review, narrowing the search to papers on liquid biopsy from blood samples in prostate cancer patients. We mainly selected works evaluating clinical endpoints in prostate cancer. EVIDENCE SYNTHESIS: The most clinically advanced forms of liquid biopsy are circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Both CTCs and ctDNA have demonstrated their prognostic value in metastatic disease. ARV7 determination is the first predictive biomarker of the disease. Its implementation into routine clinical practice requires methodological standardization and adequate clinical validation of the different available ways to detect it. The detection of CTCs in the early stages of the disease still depends on the optimization of the diagnostic methods and on the development of the biological characterization of these cells. The biological information provided by CTCs and ctDNA is different; therefore, the study of its adequate combination is the object of cutting-edge research. CONCLUSIONS: The absence of protocols and methodological standards is the limiting factor when aiming to reach conclusions that could have a potential impact on clinical practice. Therefore, the real short-term challenge for liquid biopsy is the establishment of consensus and common criteria.

Review of the experience and evidence of Pygeum africanum in urological practice. / Revisión sobre la experiencia y evidencias del Pygeum africanum en Urología.

CONTEXT: Pygeum africanum(P. africanum) is still being employed in urology practice for the treatment of lower urinary tract symptoms secondary to benign prostate hyperplasia. EVIDENCE ACQUISITION: A non-exhaustive review has been carried out about P. africanum, its mechanisms of action "in vitro" as well as "in vivo", clinical trials and routine clinical practice. EVIDENCE SYNTHESIS: The conclusions of the review and the reflections of the authors on the use of P. africanum are described. CONCLUSIONS: Although with an evidence level IV (based on expert opinion) the use of P. africanum seems to be an option in the urological therapeutic arsenal.

Factors related to early castration resistance in metastatic prostate cancer. Results from the National Prostate Cancer Registry in Spain. / Factores relacionados con la resistencia a la castración precoz en el cáncer de próstata metastásico. Resultados del Registro nacional de cáncer de próstata en España.

INTRODUCTION: The objective of the study was to determine the factors independently related with the development of castration resistance (CR) in prostate cancer (PC) in the medium term. MATERIAL AND METHODS: 155 patients diagnosed with metastatic PC with a follow-up of up to 39 months. Data taken from the National PC Registry. The evaluated variables were age, PSA, nadir PSA, Gleason, perineural invasion, TNM stages, and ADT type (intermittent/continuous). RESULTS: Mean follow-up 26,2±13,4 months. 47.1% developed early CR, with mean time until onset of 12,2±8,7 months. Univariate analysis the mean PSA was correlated with CR (290±905,1 ng/mL in non CR, 519,1±1437,2 ng/mL in CR, P<.001), mean age (73,3±8,3 years in non CR, 69,1±9,3 in CR P=.01), mean PSA nadir (15,5±57,3ng/mL in non CR, 15,9±23,7 ng/mL in CR, p<0,001), Gleason (in ≥8, HR:2,11. 95% CI: 1.22-3.65, p=0.006), and T stage (in T3-T4, HR: 2.85. 95% CI: 1.57-5.19, P<.001). Multivariate analysis the independent variables associated to CR are age (HR: 0.96. 95% CI: 0.94-0.99, P=.01), PSA nadir (HR: 1.65. 95% CI: 1,43-1,91, P<.001), and T3-T4 stage (HR: 2.11. 95% CI: 1.10-4.04, P=.02). CONCLUSIONS: PSA nadir and T3-T4 tumor stage at diagnosis are associated to an increased risk of developing CR. In addition, age at diagnosis is shown as a variable that decreases risk. Therefore, an older age would be associated with lower risk probability of CR in the medium term.

Current status of young urologists and residents' activity and academic training in Spain. National survey results. / Estado actual de la actividad y formación académica de residentes y urólogos jóvenes en España. Resultados de una encuesta nacional.

OBJECTIVE: To study the current status of the activity and academic training of residents and young urologists in Spain. MATERIAL AND METHODS: From the working group of residents and young urologists of the Spanish Association of Urology (AEU), an anonymous survey of 32 questions was designed. Its aim was to evaluate the academic activity of residents, defined by: number of communications to congresses, publications in national and international journals, clinical rotations within Spain and abroad, master's degree, Doctorate (PhD), applications to the European Board of Urology exam and language competences. The survey was sent via email and disseminated through social networks. RESULTS: Ninety-one respondents were obtained; 66% affirmed not having publications in scientific journals, 67% did not perform rotations abroad. Only 21% claimed to have taken the EBU exam. Only 2% of the respondents had completed a Fellowship. Although most of them (82%) had not done so, they would be interested. However, 67% of respondents believed that the relevance of academic/research activity is from high to very high. CONCLUSIONS: Our results indicate that academic activity, scientific production and publication of articles of the residents and young urologists in Spain is low. Moreover, participation in the EBU exam, the completion of a master's degree, PhD, rotations and fellowship is low. In contrast, the assessment of scientific activity is considered to be very relevant.

Radium-223 for the treatment of metastatic castration-resistant prostate cancer: A window of opportunity. / Radio-223 en el tratamiento del cáncer de próstata resistente a la castración metastásico: una ventana de oportunidad.

CONTEXT: The elimination of bone metastases, restoration and/or preservation of bone morphology and prevention and/or delay of skeletal events are a fundamental objective in the management of metastatic castration-resistant prostate cancer (mCRPC). Radium-223 is the first targeted alpha therapy with effects on bone that has been shown to increase survival in these patients, besides providing other bone-related benefits. OBJECTIVE: To analyze the impact of bone metastasis on mCRPC, and the benefits and the window of opportunity provided by radium-223 in the treatment of patients with mCRPC in the current treatment era. EVIDENCE ACQUISITION: A bibliographic search of PubMed and Spanish and international congresses on radium-223 and other first-line treatments for mCRPC was performed. Recent guidelines and recommendations by experts were also consulted. SUMMARY OF THE EVIDENCE: Evidence for the mechanism of action of radium-223 widen its effects to the tumor bone environment. Survival of patients treated with radium-223 is higher in those with mild symptoms as opposed to those with moderate-severe symptoms. The presence of visceral metastases even in the early stages of mCRPC supports starting radium-223 therapy before the symptoms become clinically relevant. A 3-year study has confirmed its good safety profile. Changes in tALP and LDH may be useful markers for monitoring the treatment with radium-223, but they are not predictors of overall survival. CONCLUSION: Radium-223 is a valuable therapeutic alternative in the treatment of patients with mCRPC in early stages of the disease, with a good safety profile. Its benefits extend to the bone environment.

Developments in urologic oncology "OncoForum": The best of 2017. / Avances en uro-oncología «OncoForum¼: lo mejor del 2017.

OBJECTIVE: To put forth new findings of urologic oncology with impact on clinical practice presented during 2017 in the main annual meetings. METHODS: This document reviews abstracts on prostate, kidney and bladder cancer presented at the congresses of 2016 (EAU, AUA, ASCO, ESMO and ASTRO) and publications with the highest impact in this period valued with the highest scores by the OncoForum committee. RESULTS: Among patients at high risk of recurrent renal cell carcinoma after nephrectomy, adjuvant sunitinib compared to placebo showed a benefit in patients at higher risk of recurrence. In cisplatin-ineligible advanced urothelial cancer, pembrolizumab elicits clinically meaningful, durable responses. Among patients with localized prostate cancer, treatment for disease progression was less frequent (absolute difference, 26.2 percentage pontis) and adverse events was more frequent with surgery than with observation. Among patients with locally advanced or merastatic prostate cancer, androgen-deprivation therapy plus abiraterone and prednisolone resulted in fewer deaths and fewer treatment-failure events (P<.001). Among patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate, enzalutamide median radiographic progression free survival was 8,1 months and enzalutamide median overall survival was not reached. CONCLUSIONS: Among patients at high risk of recurrent renal cell carcinoma after nephrectomy, adjuvant sunitinib showed a benefit across subgroups including patients at higher risk of recurrence. Among patients with localized prostate cancer, surgery was not associated with significantly lower all-cause or porstate-cancer mortality than observation. Among patients with locally advanced or merastatic prostate cancer, androgen-deprivation therapy plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure-free survival than androgen-deprivation therapy alone. In patients with metastatic castration-resistant prostate cancer previously treated with abiraterone enzalutamide remained active.

Developments in urologic oncology «OncoForum¼: The best of 2016. / Avances en uroncología «OncoForum¼: lo mejor de 2016.

OBJECTIVE: To put forth new findings of urologic oncology with impact on clinical practice presented during 2016 in the main annual meetings. ACQUISITION OF EVIDENCE: This document reviews abstracts on prostate, kidney and bladder cancer presented at the congresses of 2016 (EAU, AUA, ASCO, ESMO and ASTRO) and publications with the highest impact in this period valued with the highest scores by the OncoForum committee. SYNTHESIS OF EVIDENCE: In High-Risk Renal-Cell carcinoma after nephrectomy, disease-free survival was significantly greater for sunitinib than placebo group, with adverse events more frequents. In locally advanced and metastatic urotherial carcinoma patients, aletozumab achieved overall response rate in all subgroups of patients, included poor prognostic. In localized prostate cancer, the difference of prostate-cancer-specific mortality among active monitoring, radical prostatectomy and external-beam radiotherapy was not significant (P=0,48). In TERRAIN study, with castration-resistant prostate cancer patients, adverse events was reported in 31% and 23% of patients treated with enzalutamide and bicalutamide, respectively. Moreover, enzalutamide significantly improved median progression-free survival (15.7 months) compared bicalutamide (5.8 months) (P<.0001). In SRTIVE study, Enzalutamide reduced the risk of progression or death by 76% compared with bicalutamide (P<.001). CONCLUSIONS: In high-risk renal-cell carcinoma after nephrectomy, sunitinb has been considered as treatment choice. In localized prostate cancer, prostate-cancer-specific mortality was low irrespective of the treatment assigned (active monitoring, radical prostatectomy and external-beam radiotherapy). In metastatic castration-resistant prostate cancer new results of treatment with enzalutamide and abiraterone has been published, wich have been shown beneficial effects in metastatic and no metastatic patients.

Role of PET-CT with 18F-fluorocholine in biochemical recurrence after treatment of prostate cancer with curative intent. / Papel de la tomografía por emisión de positrones-tomografía computerizada con 18F-fluorocolina en la recidiva bioquímica tras tratamiento con intención curativa del cáncer de próstata.

OBJECTIVES: To analyse the ability of the PET-CT with 18F-fluorocholine (18F-FCH) to detect disease on biochemical recurrence after treatment with curative intent. To determine the clinical variables that would be able to optimise the test's diagnostic yield. MATERIAL AND METHODS: A retrospective study of PET-CTs with 18F-fluorocholine performed on 61 patients with prostate cancer who had undergone treatment with curative intent and met the criteria for biochemical recurrence. The results of the PET-CT were categorised into positive or negative and were validated using pre-established criteria. The relationship between the result of the PET-CT and the initial PSA nadir, PSA trigger, rising PSA velocity (PSAva) and PSA doubling time (PSAdt). The relationship between the metastatic sites on the PET-CT and the remaining variables was analysed. RESULTS: There was a 34.4% detection rate of the disease. The initial PSA, PSA nadir, PSA trigger and PSAva showed statistically significant differences according to the result of the PET-CT. The best discriminatory cut-off point between a positive or negative PET-CT for PSA trigger and PSAva was 3.5ng/ml and 0.25ng/ml/month respectively. The PSAdt was significantly lower in patients with remote disease compared to patients with localised disease (5.1 vs 16.8 months, P=.01). The probability that the PET-CT would detect remote disease vs localised disease was 3.2 times higher if the PSAdt was under 6 months (80% vs 20%, OR: 3.2, P=.02). In the multivariate analysis, only the initial PSA and not having undergone radical prostatectomy were demonstrated as independent predictive factors of a positive PET-CT result. CONCLUSIONS: The PET-CT with 18F-FCH can detect disease in a high percentage of patients with biochemical recurrence and provides information on its anatomical location. PSA kinetics and the patient's previous treatment are key variables in increasing the test's diagnostic.