Michele Innocenzi

The emerging role of targeted therapy in renal cell carcinoma (RCC): is it time for a neoadjuvant or an adjuvant approach?

PURPOSE We address whether rational and significant clinical data exist on using angiogenic targeted therapies as neoadjuvant or adjuvant options to nephrectomy in non-metastatic RCC. METHODS We reviewed the recent international literature by carrying out a PUBMED search. RESULTS Neoadjuvant: a possible indication for a neoadjuvant targeted therapy approach is to facilitate surgery, reducing risks for patients and increasing the possibility of removing the mass and improving oncological results. Adjuvant: three major phase III clinical trials are currently ongoing. The ASSURE trial (1 year on oral sunitinib, sorafenib or placebo), the SORCE trial (3 years on placebo versus 1 year on sorafenib, followed by 2 years on placebo versus 3 years on sorafenib), and the S-TRAC trial (1 year on sunitinib or placebo) analyze patients who are at high risk of relapse. CONCLUSIONS Rationale and needs for the neoadjuvant or adjuvant use of targeted therapies in RCC are relevant. Significant phase III trials on the adjuvant use of targeted therapy in RCC are ongoing.

Predictors for response to intermittent androgen deprivation (IAD) in prostate cancer cases with biochemical progression after surgery

OBJECTIVE To define characteristics of the first cycle of intermittent androgen deprivation (IAD) that would predict for outcomes in a long term follow-up. MATERIAL AND METHODS In 1996 we started a prospective study of IAD for the treatment of biochemical progression (BP) after radical prostatectomy (RP) for prostate cancer (PC). The end-points of the trial were time to clinical progression (CP) and time to castration resistance PC (CRPC). Eighty-four cases were included in the study. In all cases, after an initial induction period, an acceptable nadir to switch from on-to-off-phase of IAD was considered to be a serum PSA < 1.0 ng/ml. MEASUREMENTS As possible predictors for time to CP and CRPC, we analyzed pretreatment parameters such as age, Gleason Score, serum PSA, testosterone, chromogranina A (CgA) levels, and characteristics from the first cycle of IAD. RESULTS Mean follow-up during IAD was 88.6 ± 16.7 months; 29.7% of patients developed CRPC and 14.2% of cases showed a CP with a mean time of 88.4 ± 14.3 months and 106.5 ± 20.6 months, respectively. At univariate and multivariate analysis, the PSA nadir during the first on-phase period and the first off-phase interval resulted in significant and independent predictors (P < 0.001) of the time to CRPC and CP. In particular for cases with a PSA nadir > 0.4 ng/ml and for those with an off-phase interval ≤ 24 weeks, the risk of CRPC and CP during IAD was 2.7-2.5 and 3.0-3.1 times that for patients with a PSA nadir ≤ 0.1 ng/ml and with an off-phase interval > 48 weeks, respectively. CONCLUSIONS Cases with BP after RP selected to IAD that show at the first cycle a PSA nadir ≤ 0.1 ng/ml and a off-phase interval ≥ 48 weeks may identify candidates who will experience better response to IAD treatments and delayed CP or CRPC development.

A meta-analysis and systematic review of randomized controlled trials with degarelix versus gonadotropin-releasing hormone agonists for advanced prostate cancer.

AbstractOur aim was to systematically evaluate the benefits of degarelix as antagonist versus agonists of gonadotropin-releasing hormones (GnRH) for the treatment of advanced prostate cancer (PC). This comparison was performed either in terms of biochemical or oncological or safety profiles. To this end we, carried out a systematic review and meta-analysis of the literature.We selected only studies directly and prospectively analyzing the two treatments in the same population (randomized phase III studies). We followed the Preferred Reporting Items for Systematic Reviews and meta-analyses process for reporting studies.After we eliminated studies according to the exclusion criteria, 9 publications were considered relevant to this review. These articles described 5 clinical trials that were eligible for inclusion. The follow-up duration in all trials did not exceed 364 days. This meta-analysis and review comprised a total of 1719 men, 1061 randomized to degarelix versus 658 to GnRH agonists treatment for advanced PC. Oncological results were evaluated only in 1 trial (CS21:408 cases) and they were not the primary endpoints of the study. Treatment emerging adverse events were reported in 61.4% and 58.8% of patients in the degarelix and GnRH agonists group, respectively (odds ratio, OR = 1.17; 95% confidence interval, 95% CI: 0.78–1.77, P > 0.1). Treatment related severe cardiovascular side effects were reported (trial CS21-30-35) in 1.6% and 3.6% of patients in the degarelix and GnRH agonists group, respectively (OR = 0.55, 95% CI: 0.26–1.14, P > 0.1).Our analysis evidences relevant limitations in particular for the comparative evaluation of the efficacy and the oncological results related to degarelix.

Urethral pseudodiverticulum secondary to penile fracture and complete urethra dissection

A 22-year-old man reported cracking sound and acute pain during sexual intercourse followed by rapid penile detumescence and ecchymosis. He experienced more pain because he could not urinate and had a palpably full bladder. Moreover, his urethra was bleeding. Physical examination revealed swollen, ecchymotic and deviated penis and penis ultrasonography showed an injury of the tunica albuginea and Bucks fascia with an expanding hematoma. Suprapubic catheter was positioned. Surgical exploration revealed a tear of tunica albuginea of both corpora cavernosa and complete urethral dissection. End-to-end urethral anastomosis and suture of corpora cavernosa lesion were performed. Vescical catheter was mantained for 6 days and suprapubic catheter for 3 months to allow a complete urethral healing. A pseudodiverticulum was found at anastomosis level on the urethrocistography 1 month after surgery. It disappeared by allowing micturition via the suprapubic catheter. The patient presented regular urinary flow and physiological erections 30 days later. In our experience, prompt surgical repair preserved erectile function and keeping the suprapubic catheter protected the urethra; this was the correct management for repairing the urethral lesion.

Role of neuroendocrine cells in prostate cancer progression

Neuroendocrine (NE) cells represent the third epithelial cell type on normal prostatic tissue (in addition to basal and secretory cells). They are localized in all regions of the human prostate at birth but rapidly decrease in the peripheral prostate after birth, and then reappear at puberty. After puberty, their number seems to increase until an apparently optimum level is reached, which persists between the age of 25 and 54. NE cells were defined by Pearse as APUD to refer to chemical characteristics of amine precursor uptake and decarboxylation, common to the cells of this system. The most predominant product of prostatic NE cells is Chromogranin A, but they also produce serotonin, CgB, secretogranin or CgC, thyroid-stimulating hormone-like peptide, calcitonin, katacalcin, PTHrP and α-human chorionic gonadotropin-like peptide. NE cells in normal and neoplastic prostates are devoid of androgen receptors, but they express epidermal growth factor (EGF) receptor and c-erbB-2. For these reason NE cells are androgen-insensitive. The NE component of prostate adenocarcinoma is resistant to hormone therapy; some studies showed that the number of NE tumor cells and CgA serum levels increase with the recovery of human prostate tumor from hormonal therapy. Currently there are no clinical data available to support an active role of radiotherapy in NE differentiation.

Rare case of multiple adenomatoid tumors arising from tunica vaginalis of testis and epididymis

Los tumores adenomatoides suelen presentarse como masas extratesticulares. La mayor parte de estas pequeñas masas paratesticulares, de crecimiento lento, se pueden diagnosticar mediante exploración fı́sica. La ecografı́a también ayuda al diagnóstico de este tumor benigno al demostrar la localización extratesticular de la masa. Los tumores adenomatoides del epidı́dimo se suelen identificar bien y es preciso diferenciarlos de las lesiones parenquimatosas testiculares. Un varón de 40 años acudió a nuestro servicio de urologı́a con antecedentes, desde un año antes, de masa escrotal izquierda, indolora y dura. El paciente negaba antecedentes de trastornos o intervenciones quirúrgicas genitourinarias, traumatismos recientes y sı́ntomas generales. La exploración fı́sica demostró múltiples masas paratesticulares de pequeño tamaño. La ecografı́a de escroto reveló 3 masas paratesticulares sólidas y bien definidas, hipoecoicas, de 5, 6 y 10mm respectivamente, localizadas en la superficie anterior del testı́culo. Todos los marcadores tumorales séricos, como alfafetoproteı́na, gonadotropina coriónica humana beta y lactato deshidrogenasa, estaban dentro de los lı́mites normales. Se realizó una exploración testicular mediante abordaje inguinal con escisión local de las masas paratesticulares (fig. 1). El análisis intraoperatorio de cortes congelados de las muestras no mostró signos de malignidad. El estudio histológico posterior confirmó la presencia de tejido fibroso benigno con elementos celulares reunidos en nidos y cordones sólidos y un moderado estado inflamatorio (fig. 2). El postoperatorio cursó sin incidencias y, hasta la fecha, el paciente se encuentra bien, sin signos de recidiva transcurridos 8 meses. El cáncer de testı́culo suele presentarse como una masa sólida palpable; el 90–95% de las masas testiculares palpables son tumores de células germinativas malignas. La ecografı́a de alta resolución detecta con fiabilidad las masas intratesticulares sólidas, aunque no diferencia entre lesiones benignas y malignas. Las opciones terapéuticas consisten en orquiectomı́a radical, biopsia diagnóstica por escisión y conducta expectante. Los tumores paratesticulares son procesos poco frecuentes y por lo general benignos que, si se diagnostican correctamente, son susceptibles de extirpación local. Los tumores adenomatoides de epidı́dimo son el subgrupo más frecuente y representan el 60–70% de las neoplasias benignas de estas estructuras. Se ha señalado que la inflamación puede intervenir en su aparición, debido a su asociación ocasional con periorquitis e hidroceles, ası́ como a la presencia de células inflamatorias en su interior. Se producen sobre todo en los tejidos paratesticulares en los varones y en el útero y las trompas de Falopio en las mujeres. En su mayor parte proceden del epidı́dimo y, rara vez, de túnica testicular, cordón espermático, conductos eyaculatorios, próstata o zonas suprarrenales. www.elsevier.es/acuro Actas Urológicas Españolas

Supernumerary kidney laparoscopically treated

Congenital anomalies of the kidney and urinary tract are part of a family of diseases with different anatomical origins. Duplicated collecting systems can be defined as a renal unit containing 2 pyelocalyceal systems associated with a single ureter or with double ureters. The supernumerary kidney is a definitive accessory organ with its own collecting system, blood supply, and distinct encapsulated parenchima. The true incidence of supernumerary kidney remains unknown, but most cases are in males, are unilateral and on the left side. We present a case of an adult woman with a hypoplastic supernumerary kidney with a complete ureteral duplication and an ectopic junction. The case has been laparoscopically treated. We demonstrate that a laparoscopic nephro-ureterectomy is feasible and that the management of the complication (urinoma and fistula) can be managed conservatively.

Neuroendocrine target therapies for prostate cancer

It is important to determine whether an increase in Chromogranin A levels and neuroendocrine (NE) cell activation are associated with progression towards on hormone-independent prostate-cancer. We proposed a combination of estrogens and somatostatin analogues as therapy of NE activation in hormone-independent prostate cancer. The combined therapy with ethinyl estradiol and lanreotide offered objective and symptomatic responses in patients with limited treatment options and refractoriness to conventional hormonal therapy strategies; in particular, it offered a median overall survival that was superior to the 10–month median survival in patients with hormone refractory disease. This combined therapy also sustains the new concept in cancer treatment in which therapies may target not only cancer cells but also its microenvironment, which can yield protection against apoptosis.

Intermittent androgen deprivation in prostate cancer cases with biochemical progression after radical prostatectomy: Are we ready to treat?

PURPOSE To evaluate clinical data from published trials on the use of intermittent androgen deprivation (IAD) therapy in patients with biochemical relapse after radical prostatectomy (RP). METHODS We searched the Medline and Cochrane Library databases for literature published on IAD and biochemical progression after radical prostatectomy. RESULTS To date, we have oncological and functional data from phase 3 studies focused on metastatic and locally advanced stages that confirmed IAD as a valid option treatment. For the aim of this review, only Tunn study, was specifically focused on patients who relapsed after surgery but clear and mature results are still missed. CONCLUSIONS The use of IAD in cases who relapse after RP is common in the clinical practice. Although specific recommendation on the use of IAD in this setting of patients are not available, we concluded that the real benefit of IAD in terms of long survival and quality of life is mainly for patients treated with surgery.

2055 USE OF MULTIPARAMETRIC MR WITH NEUROVASCULAR BUNDLE EVALUATION TO OPTIMIZE THE ONCOLOGICAL AND FUNCTIONAL MANAGEMENT OF PATIENTS CONSIDERED FOR NERVE SPARING RADICAL PROSTATECTOMY

Introduction. To obtain the best results with radical prostatectomy, either from an oncological or a functional point of view, a correct selection of cases and planning of surgery are crucial. Multiparametric magnetic resonance imaging (MRI) promises to make it a successful imaging tool for improving many aspects of prostate cancer management. Aim. The aim of this study is to evaluate whether a modern multiparametric MRI can help either to better select prostate cancer cases for a nerve-sparing radical prostatectomy or to improve the functional evaluation related to neurovascular bundles preservation. Main Outcome Measures. The effect of preoperative MRI on neurovascular bundle management was examined for the frequency and the appropriateness of changes of the surgical plane on the basis of MRI indications. Methods. In a prospective study, 125 consecutive patients with biopsy proven prostate cancer who were scheduled to undergo bilateral nerve-sparing surgery. All patients included into the study were submitted to a preoperative multiparametric MRI. On the basis of MRI evaluation, patients were divided into two groups. Patients in group A were then submitted to a bilateral nerve-sparing (NS) radical prostatectomy (RP), whereas patients in group B were submitted to unilateral NS or non-NS RP. Results. In group A, the confirmation from the MRI study to perform a bilateral NS procedure was appropriate in 70 of 73 cases (95.9%), whereas in group B, the surgical plan was appropriate in 28 of 32 cases (87.5%). On the contrary, MRI findings suggested a change in the initial surgical plan (group B) for 32 of 105 cases (30.5%). Of these 32 cases in group B, MRI suggested to perform a unilateral NS procedure in 21 of 32 cases (65.6%) and a non-NS procedure in 11 of 32 cases (34.4%). Conclusions. Multiparametric MRI analysis can significantly improve the standard selection and management of prostate carcinoma cases considered for an NS RP. Panebianco V, Salciccia S, Cattarino S, Minisola F, Gentilucci A, Alfarone A, Ricciuti GP, Marcantonio A, Lisi D, Gentile V, Passariello R, and Sciarra A. Use of multiparametric MR with neurovascular bundle evaluation to optimize the oncological and functional management of patients considered for nerve-sparing radical prostatectomy. J Sex Med 2012;9:2157-2166.