Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study.

BACKGROUND: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). METHODS: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (ß-CTX) were analysed. RESULTS: Patients with RCC who died or progressed had higher baseline ß-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline ß-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that ß-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. CONCLUSION: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

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.

[Economic evaluation of medical treatment of benign prostatic hyperplasia (BPH) in the specialised care setting in Spain. Application to the cost-effectiveness of two drugs frequently used in its treatment]. / Evaluación económica del tratamiento médico de la hiperplasia benigna de próstata (HBP) en España en atención especializada. Aplicación al coste- efectividad de dos fármacos habitualmente utilizados en su tratamiento.

OBJECTIVES: To develop a pharmacoeconomic study in order to know the average cost of BPH diagnosis and follow-up in Spain in the Urology Department setting from the perspective of the public health system, considering two frequently used drugs in the Spanish Healthcare environment, an alpha-blocker (tamsulosin) and the lipido-sterolic extract of Serenoa repens (Permixon). MATERIAL AND METHODS: Direct healthcare costs of BPH diagnosis and treatment were determined for each clinical stage according to the International Prostate Symptom Score (IPSS): mild, moderate and severe. Data on the usage and unit costs of healthcare resources were obtained from a semi-structured interview with clinical experts. The clinical efficacy of the medical treatments was obtained from the PERMAL clinical study, where therapeutic equivalence between the two studied drugs was observed. RESULTS: For patients treated in the Urology Department setting, the average annual cost of diagnostic tests and medical visits related to mild, moderate or severe BPH symptoms were, respectively, Euro 124, Euro 207, and Euro 286. The average annual cost of the drugs, including adverse effects treatment, was Euro 211 for Permixon and Euro 346 for tamsulosin. DISCUSSION: Costs of medical care of BPH increases with symptom intensity. Pharmacological treatment makes up a significant part of the disease's cost. According to the model used, treatment with Permixon is considerably more cost-effective than with tamsulosin, offering average yearly savings of Euro 135 per patient.

Consensus statement on definition, diagnosis, and management of high-risk prostate cancer patients on behalf of the Spanish Groups of Uro-Oncology Societies URONCOR, GUO, and SOGUG.

PURPOSE: Prostate cancer (PCa) is the most prevalent malignancy in men and the second cause of mortality in industrialized countries. METHODS: Based on Spanish Register of PCa, the incidence of high-risk PCa is 29%, approximately. In spite of the evidence-based beneficial effect of radiotherapy and androgen deprivation therapy in high-risk PCa, these patients (pts) are still a therapeutic challenge for all specialists involved, in part due to the absence of comparative studies to establish which of the present disposable treatments offer better results. RESULTS: Nowadays, high-risk PCa definition is not well consensual through the published oncology guides. Clinical stage, tumour grade, and number of risk factors are relevant to be considered on PCa prognosis. However, these factors are susceptible to change depending on when surgical or radiation therapy is considered to be the treatment of choice. Other factors, such as reference pathologist, different diagnosis biopsy schedules, surgical or radiotherapy techniques, adjuvant treatments, biochemical failures, and follow-up, make it difficult to compare the results between different therapeutic options. CONCLUSIONS: This article reviews important issues concerning high-risk PCa. URONCOR, GUO, and SOGUG on behalf of the Spanish Groups of Uro-Oncology Societies have reached a consensus addressing a practical recommendation on definition, diagnosis, and management of high-risk PCa.

Diagnosis and treatment for clinically localized prostate cancer. Adherence to the European Association of Urology clinical guidelines in a nationwide population-based study - GESCAP group. / Diagnóstico y tratamiento del cáncer de prostata clínicamente localizado. Adherencia a las guías clínicas en un estudio poblacional nacional ­ GESCAP.

OBJECTIVE: To assess the adherence to European Association of Urology (EAU) guidelines in the management of prostate cancer (PCa) in Spain. PATIENTS AND METHODS: Epidemiological, population-based, study including a national representative sample of 3,918 incident patients with histopathological confirmation during 2010; 95% of the patient's sample was followed up for at least one year. Diagnosis along with treatment related variables (for localized PCa -low, intermediate, high and locally-advanced by D'Amico risk stratification) was recorded. Differences between groups were tested with Chi-squared and Kruskal-Wallis tests. RESULTS: Mean (SD) age of PCa patients was 68.48 (8.18). Regarding diagnostic by biopsy procedures, 64.56% of all patients had 8-12 cores in first biopsy and 46.5% of the patients over 75 years, with PSA<10ng/mL were biopsied. Staging by Computer Tomography (CT) or Bone Scan (BS) was used for determining tumor extension in 60.09% of high-risk cases and was applied differentially depending on patients' age; 3,293 (84.05%) patients received a treatment for localized PCa. Radical prostatectomy was done in 1,277 patients and 206 out of these patients also had a lymphadenectomy, being 4.64% low-risk, 22.81% intermediate-risk and 36.00% high-risk patients; 86.08% of 1,082 patients who had radiotherapy were treated with 3D or IMRT and 35.77% received a dose ≥75Gy; 419 patients were treated with brachytherapy (BT): 54.81% were low-risk patients, 22.84% intermediate-risk and 12.98% high-risk. Hormonotherapy (HT, n=521) was applied as single therapy in 9.46% of low-risk and 17.92% of intermediate-risk patients. Additionally, HT was combined with RT in 14.34% of lower-risk patients and 58.26% of high-risk patients, and 67.19% low-intermediate risk with RT and/or BT received neoadjuvant/concomitant/adjuvant HT. Finally, 83.75% of high-risk patients undergoing RT and/or BT also received HT. CONCLUSIONS: Although EAU guidelines for PCa management are easily available in Europe, the adherence to their recommendations is low, finding the highest discrepancies in the need for a prostate biopsy and the diagnostic methods. Improve information and educational programs could allow a higher adherence to the guidelines and reduce the variability in daily practice. (Controlled-trials.com: ISRCTN19893319).

Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy. / Estudio retrospectivo de diferentes opciones de tratamiento conservador con Bacilo de Calmette-Guèrin en el carcinoma urotelial vesical T1G3: terapia de mantenimiento.

OBJECTIVE: To compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumours; however, a number of experts still question the need for maintenance BCG. MATERIAL AND METHODS: We retrospectively analysed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumour (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n=108), re-TURBT (n=153), induction with 27mg of BCG (Connaught strain) (n=87), induction with 81mg of BCG (n=489) or induction with 81mg of BCG+maintenance (n=202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan-Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. RESULTS: The mean follow-up was 62±39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81mg of BCG than in the other treatment groups (P<.001). The risk of tumour progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27mg of BCG (P=.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; P=.003). CONCLUSIONS: In the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance.

Treatment trends for clinically localised prostate cancer. National population analysis: GESCAP group. / Tendencias de tratamiento en el cáncer de próstata clínicamente localizado. Análisis poblacional a nivel nacional: grupo GESCAP.

OBJECTIVES: To describe the established therapies for localised prostate cancer (PC) in Spain and to assess compliance with the 2010 UAE guidelines. PATIENTS AND METHODS: This was an epidemiological, observational, prospective and multicentre study. Of the 3,918 patients diagnosed with PC during 2010, only those patients with localised PC were included. Follow-up was ultimately conducted for a minimum of one year from the diagnosis for 3,713 patients (94.77%). The treatment groups assessed were as follows: radical prostatectomy, radiation therapy, hormone therapy, brachytherapy, active surveillance or observation and experimental local treatment (cryotherapy or other treatment). Compliance with the recommendations of the EAU guidelines was studied, describing the treatment groups according to D'Amico risk stratification criteria (localised [low, intermediate and high risk] and locally advanced), age, PSA and Gleason score. RESULTS: By applying the D'Amico criteria, we included 3,641 (92.93%) patients. Based on the UAE recommendations: 1) 68.87% of the patients at low-intermediate risk aged≤65 years underwent radical prostatectomy; 2) 34.51% of the patients>65 years at high risk with locally advanced disease were administered radiation therapy and hormone therapy; 3) 30.36% of the patients at high risk with locally advanced disease were only treated with hormone therapy; 4) 15.20% of the patients at low risk were only treated with brachytherapy; 5) active surveillance or observation was selected for 2.44% of the patients aged≤65 years and for 10.63% of the patients at low-intermediate risk who were>65 years. Lastly, 86.5% of the patients at low risk underwent a single treatment, and 43.62% of the patients at high risk with locally advanced disease underwent combined treatments. CONCLUSIONS: This is the first national European study to evaluate the therapeutic management of localised PC based on the risk group to which the patient belonged. Most young patients (≤65 years) with low-intermediate risk localised PC were treated with surgery, which adheres to the recommendations of the 2010 UAE guidelines. Various therapeutic combinations have been employed for patients with high-risk, locally advanced localised tumours, revealing the need for a multidisciplinary approach (Controlled-trials.com number: ISRCTN19893319).

Intravesical immunoprophylaxis in recurrent superficial bladder cancer (Stage T1): multicenter trial comparing bacille Calmette-Guérin and interferon-alpha.

OBJECTIVES: To estimate and compare recurrence rates, index of recurrence, and disease-free interval in patients with superficial recurrent bladder cancer receiving bacille Calmette-Guérin (BCG) or interferon (IFN) for immunoprophylaxis. METHODS: One hundred twenty-two patients with recurrent superficial Stage pT1, grade 1 to 3 tumors were enrolled in a randomized, prospective, multicenter trial with two treatment arms of endovesical immunoprophylaxis: 150 mg of BCG versus 54 MU of recombinant IFN-alpha-2a. Administration was weekly during the first month, biweekly for 2 months, and monthly for 9 months. Both groups were similar with regard to tumor stage, grade, size, and number. RESULTS: Sixty-one patients were evaluable in the BCG group and 49 in the IFN group. Tumors recurred in 34 (69.4%) of 49 patients in the IFN group (890 months of follow-up) and in 24 (39.3%) of 61 in the BCG group (1272 months of follow-up). The total number of recurrences (28 for BCG, 47 for IFN), disease-free interval (mean 19.3 months for BCG, 15.3 months for IFN), and index of recurrence (2.2 for BCG, 5.5 for IFN) were statistically significant (P = 0.001) in favor of BCG. Progression to invasive carcinoma was similar in both study arms. Neither systemic nor local side effects were seen in the IFN group. However, the previously reported toxicity of BCG was confirmed. CONCLUSIONS: According to our trial, BCG remains the most efficacious agent for immunoprophylaxis of recurrent superficial bladder tumors.

[Lateral cysts of the prostate]. / Quistes laterales de la próstata.

Description and differential diagnosis of lateral cysts of the prostate gland which during their growth may invade its central section. Most cases, sized below 0.8 cm, are diagnosed by accident. A symptomatic prostate cyst is, in fact, a very uncommon condition. Presentation of one case of prostate cystadenoma which presented as a low urinary obstruction in a middle-age adult subject.

[Testicular mesothelioma. Report of a case]. / Mesotelioma testicular. Aportación de un caso.

Contribution of one case of malignant testicular mesothelioma. A highly malignant tumour the diagnosis and specific treatment of which is not clearly defined. The correct diagnosis should be based on a series of features not only clinical (quick re-accumulation of liquid in the inverted hydrocele) but also gross (multiple paratesticular nodes) and microscopic, supported by immunohistochemical techniques. The latter is based both in ruling an adenocarcinoma out (CEA-, LeuM1-, Vimentine- to tumoral cells), and in the reactivity of more specific antigens (CAM5.2(K-8)+ and Vimentine+ to stromal cells). The choice treatment is inguinal orchiectomy with adjuvant chemotherapy. No standard chemotherapeutical approaches have been defined.

Influence of the true number of Bacillus Calmette-Guérin instillations on the prognosis of non-muscle invasive bladder tumors.

OBJECTIVES: To analyze if the true number of BCG instillations applied in non-muscle invasive bladder tumors has any influence on their prognosis as well as other tumor and clinical characteristics: age, sex, different protocols, BCG dose, whether primary or recurrent, solitary or multiple, tumor size G3 or Cis. PATIENTS AND METHODS: A total of 324 high grade NMIBC (15 TaG3, 184 T1G3, 125 Cis) out of 1491 cases included in the CUETO database were analyzed. Following 6 post transurethral resection (RTU) BCG instillations, the patients were scheduled to receive one instillation every two weeks (3-6 times), for a total of 9-12 instillations. One third of the dose (27 mg) (112 cases) or total dose of 81 mg (212 cases). Mean follow-up was 59.6 months. Statistical Analysis: Kaplan-Meier, Cox-regression (uni-multivariate). RESULTS: A higher level of recurrence (p = 0.032) and progression (P = .013) risk as well as worse Ca-specific survival (P = .005) were obtained if there were fewer than 12 instillations with the Kaplan-Meier and Cox-regression multivariate analysis. A 27 mg (P = .008) dosage and being a female (P < .001) were independent factors for a higher recurrence risk, but not for progression or Ca-specific survival. The remaining characteristics studied were not statistically significant. CONCLUSIONS: In accordance with the results obtained, we can conclude that the number of BCG instillations applied has some influence on the outcome of high grade NMIBC. The optimum number of instillations as well as their time of application must still be determined. A dose of 27 mg and being a female are predictive factors of recurrence.

Factors that predict the development of bone metastases due to prostate cancer: Recommendations for follow-up and therapeutic options.

CONTEXT: Prostate cancer is a public health problem in Spain and in the Western world. Bone involvement, associated to significant morbidity, is practically constant in the advanced stages of the disease. This work aims to review the prognostic factors used in the usual clinical practice that predict the development of bone metastases and to analyze the follow-up and treatment option in these patient profiles. ACQUIRING OF EVIDENCE: We performed a review of the literature on the useful factors in the context of therapy with intention to cure. We included the classical clinical values in the diagnosis (PSA, clinical stage, Gleason score on the biopsy) pathological factors (pT stage, margins, bladder invasion, tumor volume, lymph node involvement) and PSA kinetics in their different contexts and the histological and molecular parameters. SYNTHESIS OF EVIDENCE: The tumor differentiation "Gleason" score and PSA are the most important predictive factors in the prediction of bone metastases in patients with intention to cure. Kinetic factors such as PSA doubling time (TDPSA) < 8 months or PSA > 10 ng/ml in the case of castration-resistant prostate cancer (CPRC), are predictive factors for the development of metastasis. Zoledronic acid and denosumab have demonstrated their effectiveness for the treatment of bone disease in randomized studies. CONCLUSIONS: There are predictive factors within the usual clinical practice that make it possible to recognize the "patient at risk" to develop bone metastatic disease. The currently available treatments, zoledronic acid or denosumab, can help us in the management of the patient at risk of developing metastasis or metastatic patient, increasing the quality of life and decreasing skeletal events.

Consenso multidisciplinar sobre idoneidad farmacológica en cáncer de próstata hormono-sensible metastásico / A multidisciplinary consensus statement on the optimal pharmacological treatment for metastatic hormone-sensitive prostate cancer

La terapia de privación androgénica (TPA) es el pilar del tratamiento del cáncer de próstata hormono-sensible metastásico (CPHSm). La adición de docetaxel o de nuevas terapias hormonales (abiraterona, apalutamida o enzalutamida) mejora la supervivencia global (SG) y es en la actualidad el estándar de tratamiento. Sin embargo, la decisión sobre el régimen específico que acompañe a la TPA debe ser discutida con el paciente teniendo en cuenta factores como las posibles toxicidades asociadas, la duración del tratamiento, las comorbilidades o sus preferencias, pues no hay evidencia suficiente para recomendar un régimen sobre otro en la mayoría de los casos. En este trabajo se resume la evidencia sobre el manejo del CPHSm y se aportan recomendaciones consensuadas sobre el tratamiento óptimo para añadir a la TPA en pacientes con CPHSm con especial atención al perfil clínico del paciente (AU)

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 (AU)