Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

Modified videoendoscopic inguinal lymphadenectomy through suprafascial approach: Technical description and preliminary surgical outcomes.

INTRODUCTION: The videoendoscopic approach to inguinal lymph node dissection (VEIL) has been suggested as an excellent alternative carrying lower morbidity but equivalent oncological control. One of its most difficult steps is the development of an appropriate plane of dissection. A suprafascial approach would allow for better exposure. The objective of this study is to determine the feasibility, in terms of safety and oncological control, of a technical modification to the classical VEIL technique using a suprafascial plane of dissection in an initial series of patients. PATIENTS AND METHODS: A single institution retrospective review of patients undergoing VEIL technique using our modified suprafascial approach was conducted. A step-by-step surgical description is provided. Data collected included demographics; comorbid conditions; disease characteristics; intraoperative factors; and postoperative factors. RESULTS: A total of 7 patients (12 procedures) were included. Average age was 64.42 years old, and 71.42% of the patients were male. The procedure was performed bilaterally in 71.4% of the cases. Median estimated blood loss was 10 mL (range 10-25). Mean operative time was 185 min (range 120-170). Median number of nodes removed was 10.25 nodes (range 7-11). Only one of the patients (8.3%) experienced a Clavien-Dindo grade IIIa complication requiring delayed percutaneous drainage replacement. Median time until drainage removal was 13 days (range 10-16). Median length of stay was 48 hours but ranged from 24-96 hours within the series. CONCLUSIONS: The modified VEIL technique using a suprafascial plane of the dissection, allows a bilateral ILND in highly competitive operative times and with limited morbidity, without compromising its oncological efficacy.

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.

Diagnosis of metastasis in castration-resistant prostate cancer patients: decision algorithm in imaging tests. / Diagnóstico de metástasis en pacientes con cáncer de próstata resistente a la castración: algoritmo de decisión en pruebas de imagen.

INTRODUCTION: In castration-resistant prostate cancer (CRPC), early detection of metastases is essential for the selection of treatment, and prevention of bone complications. However detecting incipient metastases remains a challenge as the conventional radiological tests (bone scintigraphy or computerised tomography) lack sufficient sensitivity. Diagnostic imaging techniques are currently available that have greater sensitivity and specificity, but are little used due to shortfalls in the recommendations. OBJECTIVE: To create an algorithm that indicates the most suitable diagnostic imaging techniques for the different M0 CRPC patient profiles based on the scientific evidence. EVIDENCE ACQUISITION: Meetings were held with eight experts in Urology, Pathological Anatomy, Radiodiagnostics and Nuclear Medicine organised by the Andalusian Association of Urology, in which the recommendations and scientific evidence on each of the diagnostic imaging techniques were reviewed. SUMMARY OF THE EVIDENCE: We present the current recommendations for the detection of metastasis in M0 CRPC patients, the patients that would benefit from early detection, and summarise the evidence to support the use of each of the new techniques. CONCLUSIONS: Techniques such as 18F-Choline PET/CT or DWWB MRI and probably open MRI have been demonstrated to have good sensitivity and specificity for patients with low PSA (<10ng/ml). Their inclusion in routine clinical practice will help improve the early detection of metastasis in CRPC patients.

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.

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.

Radium-223 in the therapeutic sequence of metastatic castration-resistant prostate cancer. / Radio-223 en la secuencia terapéutica del cáncer de próstata resistente a la castración metastásico.

CONTEXT: Radium-223 is an □ -particle transmitter with specific action on bone metastases. The Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) study showed that radium-223 extended overall survival and delayed the onset of bone events in patients with symptomatic castration-resistant prostate cancer with bone metastases (mCRPC) and without visceral metastases, with a good safety profile. OBJECTIVE: To review the new scientific evidence on radium-223 based on prespecified and post-hoc analyses of the ALSYMPCA study and on early-access programs after the publication of the ALSYMPCA study, thereby providing new data on the management of patients with mCRPC. ACQUISITION OF EVIDENCE: We searched for evidence on PubMed and in the abstracts of international urology and oncology congresses, as well as ongoing clinical trials (ClinicalTrials.gov). SYNTHESIS OF THE EVIDENCE: The results of the reviewed studies offer promising results that will broaden the therapeutic benefits of radium-223 to patients with mild symptoms and those with no symptoms. The results also provide preliminary evidence on the benefit of radium-223 treatment after the failure of docetaxel, enzalutamide or abiraterone or the combination of radium-223 with these agents or other therapeutic agents such as bone-targeted agents and immunotherapy. CONCLUSION: Radium-223 can be a treatment option for patients with mild symptoms and can provide a therapeutic benefit after failure of currently available treatments or in combination with these treatments. This evidence should be corroborated in clinical trials before being added to clinical practice.

[Bladder hemangioma: a clinical case]. / Hemangioma vesical: caso clínico.

Contribution of a new case of vesical haemangioma in a 65-year old male. This is a benign and very rare tumour with not even 90 cases described in the urology literature to date. Haematuria was reported in all cases. This paper presents a review of the literature and a discussion of clinical and pathological features as well as diagnostic methods and recent changes in management approach.

[Primary lymphoma of the testicle]. / Linfoma primario de testículo.

Case report of a testicular lymphoma. A diagnosis of primary neoplasia of the testis was made since no involvement to the lymphoreticular system in any other organ was demonstrated. We review the clinical, diagnostic and therapeutical aspects and make a note on the rarity of our case, a type T tumour, due to the exceptional nature of this variety within primary lymphomas of the testis.

[Renal adenocarcinoma in a girl 13 years old]. / Adenocarcinoma renal en una niña de trece años.

Case report of a renal adenocarcinoma in a 13 year-old girl found during the study of a painless, gross haematuria of several months evolution. Apart from a review of signs and symptoms, diagnosis, therapeutical approach and other issues related to this tumour, the authors insist on the significance gross haematuria has in children presenting symptoms that should alert the medical profession about a possible neoplasia of this features, in spite of its rare occurrence.

[Primary nontransitional neoplasms of the bladder]. / Neoplasias primitivas no transicionales de vejiga.

Revision of all primitive tumours of the bladder diagnosed in our Service between July 1990 and July 1998. Among a total of 703 neoplasms of the bladder only 14 were non-transitional primitive tumours, accounting for just 1.98%. Eleven were malignant neoplasms with a diagnosis of epidermoid carcinoma in nine cases, one adenocarcinoma and one bladder adenocarcinoma. The other three were benign tumours: one haemangioma and two leiomyomas. From a clinical perspective, the predominant symptom was haematuria, followed by irritative symptoms. The two leiomyomas were accidental findings during a gynaecological examination (ultrasound) and a diagnostic examination for a nephritic colic (urography). The diagnostic means used and the extension studies were the same as used for transitional neoplasms. In general, treatment of benign neoplasms was partial cystectomy or transurethral resection while it was radical surgery for the malignant tumours when the existing criteria were an indication for that type of surgery (cystoprostatectomy with bypass), since there are no definite criteria with regards to therapy due to the low incidence of these tumours. Only three of the 11 patients with malignant neoplasms are still alive. All the others died within one year of diagnosis, an evidence of the aggressiveness of these tumours. These cases were considered primitive bladder tumours once it was concluded that there was no relation with any previous or simultaneous transitional neoplasms and that there had been no primitive tumour in a different organ.

[Melanoma of the female urethra: a very infrequent tumor]. / Melanoma de uretra femenina: un tumor muy infrecuente.

Case report of a melanoma of the urethra in a 75-year old female patient. A few months after diagnosis the patient died of multiple lung metastasis. This is a review of the clinical and diagnostic aspects of the neoplasia highlighting the therapeutical options that albeit debatable seem to be quite clear as to the master lines to follow.

[Bladder carcinosarcoma: case report with immunohistologic study]. / Carcinosarcoma vesical: aportación de un caso con estudio inmunohistológico.

We present a new case of carcinosarcoma of the bladder. This tumor is generally considered to be a rare one, has an uncertain aetiology and very poor prognosis, composed by mesenchymal and epithelial elements. It is an aggressive tumor with a short clinical course. At present radical cystectomy is the treatment of choice.

[Congenital bladder diverticulum and Ehlers-Danlos syndrome: an unusual association]. / Divertículo vesical congénito y síndrome de Ehlers-Danlos: una rara asociación.

The existence of a vesical diverticulum in the context of a congenital connective tissue disorder such as Ehlers-Danlos syndrome led us to consider the possibility of a relationship. Four types of diverticula can be found in the literature: congenital, acquired, iatrogenic and syndrome-associated. Within the later, Ehlers-Danlos syndromes type IV and IX, even type V, are associated to the existence of vesical diverticula. The potential spontaneous rupture of the diverticulum is a typical feature, as well as post-surgery relapse. The attitude towards such diverticula should be one of watchful waiting, and simple, plasty-free diverticulectomy on the bladder's neck is indicated when performing a surgical procedure.

[Glandular cystic cystitis]. / Consideraciones sobre la cistitis quística glandular.

Cystic-glandular cystitis is considered as part of the urothelial pre-neoplastic proliferative abnormalities. This group includes atypical hyperplasia. Von Brunn's nidus, and cystitis cystica. They are a consequence of the changes experienced at the urothelium level in response to inflammation, irritation or carcinogens. Diagnosis is mainly based in the pathoanatomical study of the biopsy obtained following endoscopic resection. The signs and symptoms it presents are varied and show a clear relationship to distribution and extension of cysts. Treatment is based in the removal of irritative factors. Cystectomy with urinary by-pass may be necessary if required by clinical evolution.

[C.F.C.-type ureterosigmoidostomy. Results]. / Ureterosigmoidostomía tipo C.F.C. Aportación de resultados.

This paper presents the results obtained with a C.F.C. type ureterosygmoidostomy technique described by us. A total of 25 patients aged between 52 and 74 years (mean age, 65 years), 23 (23/25) male and 2 (2/25) female were evaluated. 24 of the total 25 patients had infiltrant neoplasia of the bladder (pT2: 8; pT3a: 12; pT3b: 4) which was graded as moderately differentiated (G2: 10) or undifferentiated (G3: 14). The remaining patient, a female, had tuberculous microbladder. Male patients underwent radical cystoprostatectomy (23/25); while in two females traditional cystectomy was performed (2/25). Patients with neoplasia of the bladder (24/25) were performed bilateral lymphadenectomy prior to radical surgery. All 25 patients were performed C.F.C. type ureterosygmoidostomy (Actas Urol Esp 20: 324, 1996). Follow-up of patients was carried out over a mean period of 27 months (July 1994-October 1997). The complications reported were 4 cases of ureterointestinal stricture and one stercoral fistula. The strictures were resolved with endoscopic techniques and the fistula through discharge colostomy. Death (6/25) occurred as a result of the tumour progression, and in no case was related to the surgical technique. All patients showed daytime continence (100%), and 22/25 were also continent during the nighttime (88%): there were occasional leaks in 5/25 (20%). No metabolic disorders were seen in any of the patients. (All patients were given drug therapy to prevent metabolic acidosis).

[Histologic-ultrasonographic correlation of gland asymmetry and "pseudoruptures" of the prostatic capsule]. / Correlación histoecográfica de la asimetría glandular y de las "pseudorupturas" de la cápsula prostática.

An histo-ultrasound correlation was carried out between the information obtained with pre-operative transrectal ultrasound and that obtained with the histopathological study of 29 prostate specimens from patients with mean age 63 years (range, 52 to 71 years), who underwent radical cystoprostatectomy for infiltrant neoplasia of the bladder (22/29) and radical prostatectomy for prostate cancer (7/29). The (extrinsic and intrinsic) ultrasound parameters were analyzed focusing in the study of the prostatic capsule or "pseudocapsule". With this comparative, echographic and histological study the concept of capsular "pseudorupture" that results from the presence of (arterial and/or venous) vessels, nerves and fibromuscular folds at the periprostatic fat tissue is introduced. The interruption of the capsular echogram was seen as an indication of tumoral involvement of the capsule, and extracapsular spread. Our results allow us to suggest that this assertion should be reconsidered since these capsular "interruptions", "irregularities" or "pseudoruptures" are present in the normal prostate. Similarly, glandular asymmetry in relation with an heterogenous growth in one lobe in defined to differentiate it from that seen in neoplastic processes.