Optimizing triple therapy in patients with metastatic hormone-sensitive prostate cancer.

Triple therapy with docetaxel, androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs) has demonstrated survival benefits in patients with metastatic hormone-sensitive prostate cancer (mHSPC), especially in those with high-risk disease. However, once the use of ADT and docetaxel is established, guidelines do not clearly specify which ARPI is most appropriate. In this work, a literature review to identify phase III clinical trials, systematic reviews, meta-analyses, and clinical practice guidelines on triple therapy in mHSPC was carried out. Evidence and recommendations were qualitatively reviewed to provide guidelines on the most suitable ARPI based on patient risk, disease volume, and nature of metastases (synchronous or metachronous). This review aims to update the previously published consensus on the optimal pharmacological treatment for mHSPC and to expose the opinions of hospital pharmacy, urology and medical and radiation oncology experts.

Development and implementation of an immunotherapy unit in a urology department.

INTRODUCTION: Immunotherapy is revolutionizing cancer treatment, with monoclonal antibodies directed against checkpoint regulatory molecules currently being the most widely used therapy. A total of six immune checkpoint inhibitor (CPI) drugs have been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for use in various solid tumors of the genitourinary tract. MATERIAL AND METHODS: The literature is reviewed and the methodology, as well as our own experience, are analyzed to establish treatment with CPIs in a urology department. RESULTS: The requirements recommended in terms of training, logistics and procedure are described in order to safely offer expert treatment with CPIs to patients with genitourinary tumors. CONCLUSIONS: Compliance with the proposed program ensures safe administration of immune checkpoint inhibitors in a hospital setting.

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.

Clinical and histological predictive factors of reclassification of prostate cancer patients on active surveillance.

INTRODUCTION AND OBJECTIVE: Active surveillance (AS) has been established as a therapeutic strategy in patients with low-risk prostate cancer. Demographic and anatomopathological factors that increase the probability of reclassifying patients have been identified. MATERIALS AND METHODS: Laboratory and histopathological data were collected from 116 patients included on AS since 2014. Univariate analysis was performed with Chi-square, t-student and Kendall's Tau, multivariate analysis according to logistic regression and Kaplan-Meier curves were calculated. RESULTS: Of the 116 patients in AS, the median age at diagnosis was 66 years and the median follow-up was 13 months (2-72). Of these, 61 (52.6%) are still on surveillance, while 55 (47.4%) have left the program, mostly due to histological progression (52 patients (45.2%)); radical prostatectomy was performed in 27 (49.1%). Prostate volume (PV)≤60cc and the number of positive cylinders >1 in diagnostic biopsy (P=.05) were associated with higher reclassification rate in univariate analysis (P<.05). Multivariate analysis showed that these two variables significantly correlated with higher reclassification rate (PV 60 cc: OR 4.39, P=.04; >1 positive cylinder at diagnostic biopsy: OR 2.48, P=.03). CONCLUSIONS: It has been shown that initial ultrasound volume and the number of positive cylinders in the diagnostic biopsy are independent risk factors for reclassification. Initial PSA, laterality of the affected cylinders and PSA density were not predictive factors of progression in our series.

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.

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.

Safety of nivolumab in metastatic renal cell carcinoma patients: A real-life experience in a Spanish urology setting. / Seguridad de nivolumab en pacientes con carcinoma de células renales metastásico: experiencia española en urología en la práctica clínica real.

INTRODUCTION AND OBJECTIVES: Nivolumab is an immunotherapy agent that has been an approved treatment for previously treated patients with advanced renal cell carcinoma (RCC). Experience in real-life settings, especially regarding immune- related adverse events, is scarce. We present our experience with reference to the safety of nivolumab in patients with metastatic RCC (mRCC) treated in 9 hospitals in Spain. MATERIAL AND METHODS: Retrospective, multicentre study of patients with mRCC treated with nivolumab between 2016 and 2018. Data on baseline socio-demographic and clinical characteristics and drug-related adverse events were collected. RESULTS: The mean age of the 26 patients included was 63.7±11.5 years; 96% were ECOG 0-1 and 78% had favourable or intermediate MSKCC risk scores; 73% had the clear cell histological subtype and 30% metastatic disease. Median follow-up was 9 months (range 1-14). All patients experienced an adverse event at different grades, with fatigue, fever and anaemia being the most common (27%). Grade 3 adverse events occurred in 23% of patients. Adverse reactions led to treatment suspension in 3 patients (11%). CONCLUSION: In the real-life clinical setting, nivolumab shows favourable outcomes, similar to those reported by other studies.

[Lasers as an alternative to the endoscopic surgery in BPH]. / Láser como alternativa a la cirugía endoscopica en la HBP.

Neodymium laser (Nd:YAG) has been used for prostatic coagulation. New contact tips have been developed in order to cause vaporization of the prostate. With the objective to examine the effectiveness and safety of 2 new laser procedures. ITT (interstitial thermotherapy) and Sidefocus Technique, in patients with BPH, we have participated in a prospective, international, multicenter study comparing these technique with TURP and prostatic incision. A total of 80 patients suffering from symptomatic BPH in our center were randomized for the four procedures as follow: ITT (18): sidefocus technique (21), incision (20) and TURP (21). Inclusion criteria were at least 50 years old, prostate between 20 and 60 g, maximum peak-flow < or = 12 ml/s, and I-PSS > or = 15. The patient's pretreatment evaluation consisted in World Health Organization symptom score and quality of life, digital rectal examination, transrectal, ultrasound, PSA, urine culture, prostatic biopsy if malignity suspected, uroflowmetric parameters and residual volume. Follow-up was performed using the same pretreatment parameters at one month, three months and six months. Statistical analysis was performed using ANOVA test and Student-Newman-Keul test. Symptom score decreased significantly in all groups. Peak flow rate increase was observed in the four groups but without statistical significance in both laser techniques. Results at the sixth month control comparing peak-flow rates are significantly more favourable for endoscopic surgical techniques (TURP and incision). Other flowmetric parameters, days of hospital stay, duration of catheter drainage, symptom scores and morbidity are analyzed.

[Verrucous carcinoma of the penis]. / Carcinoma verrucoso de pene.

Verrucous carcinoma includes approximately 5% of all neoplasias of the penis and is a tumoral variety of benign behaviour and differentiated histology. Our 10-case experience of penial verrucous carcinoma is reported here. In nearly all cases, partial penectomy was the definitive approach. No dissemination, locorregional or distant, was found in any of the report cases. Since prognosis of these tumours is good, we see no justification in performing lymphadenectomy, although it is advisable to adopt and expectant attitude when faced to inguinal adenopathies.

[Scrotal verrucous carcinoma]. / Carcinoma verrucoso escrotal.

Cancer of scrotum is of interest, despite its relative infrequency, because of its historical importance (was the first known occupational cancer) and also of its aggressive behavior. We report a rare case of verrucous carcinoma in a 67 years old man, without recrudescence six months after surgical treatment.

[Treatment of prostatic benign hyperplasia with endoscopically controlled laser fiber]. / Tratamiento de la hiperplasia benigna de próstata con fibra de láser bajo control endoscópico.

Between October 1992 and February 1993, 12 patients with benign prostate hyperplasia (BPH) were treated with Neodymium-YAG laser through an endoscopically-guided right angle fibre, and follow-up is now over 1 year. Follow-up consisted in the symptomatic assessment using I-PSS questionnaires, vesicoprostate ultrasound with flowmetry and residue measurement and urethrocystometry at least every 3 months. Mean time for suprapubic catheter withdrawal was 23.4 days (range 9-34), and one patient did not resumed micturition spontaneously. Symptomatology improved after the first month. remaining stable after 6 months, with a mean score decrease at one year of 11,2 (p < 0,001). All flowmetry parameters improved although only peak and mid-stream flow showed statistical differences, peak flow increasing at one year by an average of 5,9 ml/sec (P < 0,001). In 4 of the 12 patients surgery was performed; 1 underwent early surgery due to absence of spontaneous micturition and was excluded from the results assessment, and 3 due to persistence of symptomatology at 16, 18 and 21 months post-laser. In spite of the advantages presented by the laser when compared to conventional surgical approaches, such as short time application, absence of haemorrhage and likely used in an ambulatory setting, the major initial irritative symptomatology and the need for a suprapubic catheter during at least three weeks, are in general poorly tolerated and limit its use. The apparent improvement in symptomatology after one month is not accompanied by objective changes in flowmetry, since in our series only 1 patient presented Qmax greater than 15 ml/sec with no residues. Therefore, we consider that treatment with endoscopically-guided laser fibre in BPH has, with the technology currently available. a very limited use.

[Cystadenoma of seminal vesicles]. / Cistadenoma de vesículas seminales.

Cystadenoma of the seminal vesicles is a extremely rare pathology. To our knowledge only eight cases have been reported in the literature. We report a new case of this benign tumor, bilaterally located and incidentally found at surgery. Literature is reviewed and clinical, diagnostic and therapeutic aspects of these are discussed.

[Treatment of benign hyperplasia of the prostate using thermal transurethral needle ablation (TUNA)]. / Tratamiento de la hiperplasia benigna de próstata mediante ablación térmica transuretral con aguja (TUNA).

Transurethral needle ablation of the prostate (TUNA) is a new, fast and minimally invasive device that produce a selective necrosis of the prostatic gland by delivering low level radiofrequency energy. We describe our experience with this new technique. A total of 42 patients suffering from symptomatic BPH were treated with this procedure. The original generator was used in 27 patients (group 1). A new generator allowing a more homogeneous application of intraprostatic temperature was used in 15 patients (group 2). The patients pretreatment evaluation consisted of World Health Organization symptom score and quality of life, digital rectal examination, uroflowmetric parameters, residual volume, transrectal ultrasound and PSA. Follow-up was performed using the same pretreatment parameters at one month, three months, six months and twelve months. All patients were treated using urethral xylocaine with intravenous or intramuscular sedation (petidine clorhidrate) and tolerance was good. IPSS and quality of life decreased significantly in both groups at first month after treatment and kept low up to twelve-month control. Peak flow rate increased from 7.7 +/- 3.7 ml/sec to 10 +/- 4.1 ml/sec at the twelve-month control in group 1 (p > 0.05), and from 7.6 +/- 2 ml/sec to 9.8 +/- 3.3 ml/sec in group 2 (p > 0.05). Residual volume decrease was statistically significant in group 2 (p < 0.05). No significant complications were encountered. Five patients in group 1 and one patient in group 2 required TURP some time in the follow-up (14%). In our experience, after one year of follow-up, improvement in subjective parameters is evident, although uroflowmetric improvement is moderate and with no statistically significance. No differences were found between both groups of treatment.

[Extragonadal germinal tumors of retroperitoneal localization]. / Tumores germinales extragonadales de localización retroperitoneal.

Extragonadal germ cells tumors can arise primarily in the retroperitoneum. It has been suggested that these neoplasms might be metastasis from an occult testicular lesion which would have regressed later. We report our experience with seven retroperitoneal germ cell tumors without testicular involvement. The most frequent symptoms were lumbar or abdominal pain and paraneoplastic syndrome. Abdominal palpable mass was noticeable in 85% of patients. We point out the computerized tomography and echography as the most sensitive exploration for diagnosis. The confirmation of retroperitoneal tumor was achieved preoperatively in all cases. Surgical and chemotherapy treatment was performed. Radiotherapy was employed in two cases. The mean survival was 9.5 months (6-24 m.). Retroperitoneal lymphadenectomy after chemotherapy has not improved the survival. Relapses of the diseases were noticed after and apparently partial or complete response to chemotherapy.

[Genetic study of six chromophobic renal carcinomas]. / Estudio genético de 6 carcinomas renales cromófobos.

OBJECTIVES: To determine the role of tumor suppressor genes p53 and von Hippel-Lindau (VHL), and the specific loss of chromosomes 1, 2, 3, 6, 10, 13, 17 and 21 in the pathogenesis of Chromophobe Renal Cell Carcinomas (CrRCC). MATERIAL & METHODS: Renal tumor specimens and normal kidney tissue from 6 patients affected of CrRCC were obtained after radical nephrectomy and immediately snap-frozen. PCR-SSCP analysis for mutations of p53 (exons 5-8) and VHL genes was performed in all cases. All of the positive cases in SSCP analysis were further characterized by direct sequencing. Inactivation by VHL methylation were searched by Southern blot analysis. Microsatellite analysis using several markers covering both arms of chromosomes 1, 2, 6, 10, 13 and 17, as well as 3p and 21q, was performed to investigate specific loss of these chromosomes. RESULTS: Mutations of p53 were detected in 2 (33%) of the 6 CrRCCs, showing both tumors loss of heterocigosity (LOH) on 17p. VHL mutations and inactivation by methylation were not detected in any tumor. In 5 (83.3%) of the 6 CrRCCs, microsatellite analysis showed LOH at every informative marker on all the regions tested except 3p. Retention of heterozigosity on 3p was present in all cases. CONCLUSIONS: Mutations of p53 in CrRCCs are more frequent (33% in our series) than in clear cell renal cell carcinomas (< 2% in most series). Despite 65-75% of clear cell RCCs show VHL mutations (60%) and inactivation by methylation (5-20%), no CrRCC in our series showed these alterations. LOH in the specific chromosomes tested (1, 2, 6, 10, 13, 17 and 21) confirm cytogenetic findings that characterize CrRCCs (specific combinations of multiple chromosomal losses). Our results, similar to those reported by other authors, confirm that CrRCC is not only a histologic fenotype, but also a distinctive genotype from other RCCs. The specific combination of chromosomal losses allows a quick and easy diagnostic of this kind of neoplasms with a simple technique of microsatellite analysis.

[Post-transplantation renal rupture]. / Rotura renal postransplante.

INTRODUCTION: Renal allograft rupture in the transplanted patient represents a usually early postoperatory complication threatening graft and patient survival. Urgent management is often required. MATERIAL AND METHODS: Renal transplanted patients which had rupture of the renal allograft have been reviewed retrospectively. Between February 1980 and June 1996 a total of 868 renal transplants were performed, and 21 (2.41%) suffered from allograft rupture. Diagnosis was based mainly on the symptoms, blood analysis to test hematocrit value, and ultrasounds. RESULTS: Men age of the patients was 34 years old (21-49), 15 (71.4%) males and 6 (28.6%) females. Evolution was as follow: 4 patients underwent extracapsular nephrectomy due to non-functioning kidney; in 16 patients the graft could be preserved using different methods of renal corsetage (lyophilized human dura was applied in 8 cases, fascia lata in one, fascia lata and lyophilized human dura in 3 cases, and polyglycolic acid mesh in other 4 patients); and finally one patient was managed conservatively. There was no intra and post-operatory mortality. Four patients died lately of other causes not related to renal transplantation. Other 4 patients underwent chronic rejection and fail of the renal function. Two of these four patients have already received their second graft. A total of 13 patients have a good renal function (61.9%). CONCLUSIONS: Early diagnosis of the renal allograft rupture must be the main objective in order to initiate as soon as possible therapeutic measures that firstly should be aimed to preserve the graft (medically or surgically). Nephrectomy must be reserved for renal allograft rupture secondary to venous thrombosis and other situations threatening life.

[Urologic manifestations in patients with acquired immunodeficiency syndrome]. / Manifestaciones urológicas en pacientes con el síndrome de inmunodeficiencia adquirido.

In order to know the incidence and nature of urological conditions in the Acquired Immunodeficiency Syndrome, a revision was made of 223 clinical histories from patients admitted to our hospital between 1998 and 1992. Some 24.6% developed urological conditions with prevalence of unspecific urinary infections, though several types of specific infections, immunological, neoplastic, neurourological and nephrological changes were also found as well as other conditions not caused by the disease, such as renal lithiasis. We noted that, although involvement of urinary tract in AIDS is not well defined, its frequency is high, since up to one fourth of patients are affected by different disorders.

[The treatment of ureteral lithiasis with a pulsed dye laser]. / Tratamiento de la litiasis ureteral con láser pulsado colorante.

PURPOSE: Pulsed dye laser lithotripsy has shown to be an effective and safe procedure for treatment of ureteral calculi. We report our experience. MATERIAL AND METHODS: A total of 1000 patients were treated with pulsed dye laser between January 1990 and February 1996. In 450 patients the procedure was performed under general or regional anaesthesia; the remaining 550 patients were treated with the aid of a mild sedation. RESULTS: In the mild sedation group a total of 417 out of 550 patients (75.8%) had their calculi completely cleared (85.6% of effectiveness in women with pelvic lithiasis). Different facts caused the treatment to fail in the remaining patients: severe pain, vagal reaction and technical difficulties. In the anesthesia group the procedure was effective in 346 cases (76.9%). Laser failed to clear calculi in 104 patients in this group due to technical impossibility and persistence of ureteral fragments. Additional treatment options in order to achieve resolution of the calculi were: ESWL, both ESWL and laser, Dormia basket, Zeiss stent, three-prong grasping forceps, ureterolithotomy and nephrectomy. Morbidity was higher in the group treated under anesthesia, being haematuria the most frequent adverse effect. CONCLUSIONS: We believe that ureteroscopy and laser lithotripsy is an effective, safe and low morbidity procedure for the treatment of ureteral calculi in women with distal calculi. It is often suitable to perform it with mild sedation with the subsequent benefit for both the patient and health care system regarding to cost-effectiveness balance.

[Ruptures of double-J ureteral catheter. Our experience and review of the literature]. / Roturas de catéter ureteral doble-J. Nuestra experiencia y revisión de la literatura.

Ureteral double-J stents are currently being used widely in numerous urologic indications. Side effects are infrequent and usually related to the act of insertion per se. Complications with long-term indwelling stents are mainly due to stent incrustation and more rarely to spontaneous breakage. We report 3 cases of stent multiple fragmentation after and indwelling period superior to 22 months without evidence of stent incrustation. We reviewed the literature and analyzed the different etiologic factors that are thought to be involved. We believe that radiologic control post-insertion and stent substitution after an indwelling period of three months are mandatory.