(18)F-FACBC (anti1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid) versus (11)C-choline PET/CT in prostate cancer relapse: results of a prospective trial.

PURPOSE: To compare the accuracy of (18)F-FACBC and (11)C-choline PET/CT in patients radically treated for prostate cancer presenting with biochemical relapse. METHODS: This prospective study enrolled 100 consecutive patients radically treated for prostate cancer and presenting with rising PSA. Of these 100 patients, 89 were included in the analysis. All had biochemical relapse after radical prostatectomy (at least 3 months previously), had (11)C-choline and (18)F-FACBC PET/CT performed within 1 week and were off hormonal therapy at the time of the scans. The two tracers were compared directly in terms of overall positivity/negativity on both a per-patient basis and a per-site basis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for both the tracers; follow-up at 1 year (including correlative imaging, PSA trend and pathology when available) was considered as the standard of reference. RESULTS: In 51 patients the results were negative and in 25 patients positive with both the tracers, in eight patients the results were positive with (18)F-FACBC but negative with (11)C-choline, and in five patients the results were positive with (11)C-choline but negative with (18)F-FACBC. Overall in 49 patients the results were false-negative (FN), in two true-negative, in 24 true-positive (TP) and in none false-positive (FP) with both tracers. In terms of discordances between the tracers: (1) in one patient, the result was FN with (11)C-choline but FP with (18)F-FACBC (lymph node), (2) in seven, FN with (11)C-choline but TP with (18)F-FACBC (lymph node in five, bone in one, local relapse in one), (3) in one, FP with (11)C-choline (lymph node) but TP with (18)F-FACBC (local relapse), (4) in two, FP with (11)C-choline (lymph nodes in one, local relapse in one) but FN with (18)F-FACBC, and (5) in three, TP with (11)C-choline (lymph nodes in two, bone in one) but FN with (18)F-FACBC. With (11)C-choline and (18)F-FACBC, sensitivities were 32 % and 37 %, specificities 40 % and 67 %, accuracies 32 % and 38 %, PPVs 90 % and 97 %, and NPVs 3 % and 4 %, respectively. Categorizing patients by PSA level (<1 ng/ml 28 patients, 1 - <2 ng/ml 28 patients, 2 - <3 ng/ml 11 patients, ≥3 ng/ml 22 patients), the number (percent) of patients with TP findings were generally higher with (18)F-FACBC than with (11)C-choline: six patients (21 %) and four patients (14 %), eight patients (29 %) and eight patients (29 %), five patients (45 %) and four patients (36 %), and 13 patients (59 %) and 11 patients (50 %), respectively. CONCLUSION: (18)F-FACBC can be considered an alternative tracer superior to (11)C-choline in the setting of patients with biochemical relapse after radical prostatectomy.

Sexual function in adult life following Passerini-Glazel feminizing genitoplasty in patients with congenital adrenal hyperplasia.

PURPOSE: We assessed external genitalia sensitivity and sexual function in adults with congenital adrenal hyperplasia who had undergone Passerini-Glazel feminizing genitoplasty as children, and compared them to a control group of healthy counterparts. MATERIALS AND METHODS: Inclusion criteria were congenital adrenal hyperplasia, Passerini-Glazel feminizing genitoplasty, adult age and penetrative vaginal intercourse. Thermal and vibratory sensitivity of the clitoris, vagina and labia minora were analyzed using the Genito Sensory Analyzer (Medoc Ltd., Minnetonka, Minnesota). Psychosexual outcome was assessed with the Beck Depression Inventory, Zung Self-Rating Anxiety Scale, Female Sexual Distress Scale and Female Sexual Function Index. Matched analyses were performed to compare outcomes in patients to controls (healthy medical students). All statistical tests were performed using SPSS®, version 18.0 RESULTS: A total of 12 patients (10%) entered the study. Thermal and vibratory clitoral sensitivity was significantly decreased in all patients compared to healthy controls (p <0.01). There was no difference in thermal or vibratory vaginal sensitivity between patients and controls. On the Female Sexual Distress Scale 11 patients (91.6%) and 11 controls (91.6%) described a stable satisfactory relationship. All patients reported active sexual desire, good arousal, adequate lubrication and orgasm. No significant difference in Female Sexual Function Index global score or single domain scores was observed between patients and controls. CONCLUSIONS: Although clitoral sensitivity in sexually active patients with congenital adrenal hyperplasia treated with Passerini-Glazel feminizing genitoplasty is significantly reduced compared to controls, sexual function in those patients is not statistically or clinically significantly different from their healthy counterparts. Finally, 1-stage Passerini-Glazel feminizing genitoplasty seems to allow normal adult sexual function.

The number of cores taken in patients diagnosed with a single microfocus at initial biopsy is a major predictor of insignificant prostate cancer.

PURPOSE: Patients with a single microfocus of prostate cancer at initial biopsy represent the ideal candidates for active surveillance. We investigate whether the number of cores taken affects the concordance rate between microfocus of prostate cancer and the confirmation of a pathologically insignificant prostate cancer at radical prostatectomy. MATERIALS AND METHODS: Data were analyzed from 233 patients with a single microfocus of prostate cancer at initial transrectal prostate biopsy (a single focus of Gleason 6 involving 5% or less of the core) subsequently treated with radical prostatectomy. The chi-square test, cubic spline analyses and logistic regression analyses were used to depict the relationship between the number of cores taken and the probability of confirming the presence of an indolent disease (pathologically confirmed insignificant prostate cancer defined as radical prostatectomy Gleason score 6 or less, tumor volume 0.5 ml or less and organ confined disease). RESULTS: Overall 65 patients (27.9%) showed pathologically confirmed insignificant prostate cancer at radical prostatectomy. The rate of pathologically confirmed insignificant prostate cancer was 3.8%, 29.6% and 39.4% in patients who underwent biopsy of 12 or fewer cores, 13 to 18 cores and 19 or more cores, respectively (p <0.001). After adjusting for the available confounders, age (p = 0.04), number of cores taken (p <0.001) and prostate specific antigen density (p <0.02) were independent predictors of pathologically confirmed insignificant prostate cancer. CONCLUSIONS: Of patients diagnosed with a single microfocus of prostate cancer the number of biopsy cores taken was a major independent predictor of having pathologically confirmed insignificant prostate cancer at radical prostatectomy. Therefore, when active surveillance is considered as a possible alternative in patients with microfocus of prostate cancer, the number of cores taken should be taken into account in decision making.

Nerve-sparing approach during radical prostatectomy is strongly associated with the rate of postoperative urinary continence recovery.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Urinary incontinence and erectile dysfunction are the most bothersome sequelae affecting health-related quality of life in patients treated with radical prostatectomy for prostate cancer. While it has been widely reported that a nerve-sparing approach significantly improves postoperative erectile function, the impact of neurovascular bundle preservation on urinary continence recovery is still a matter of controversy. Our study clearly demonstrates that patients treated with nerve-sparing radical prostatectomy have higher chances of recovering full continence after surgery. The results indicate that, when technically and oncologically feasible, an attempt at a nerve-sparing approach should be planned in order to increase the probability of achieving full continence after radical prostatectomy. OBJECTIVE: To demonstrate that nerve-sparing radical prostatectomy (NSRP) is associated with higher rates of urinary continence (UC) recovery compared with non-nerve-sparing procedures in patients with surgically treated organ-confined prostate cancer. PATIENTS AND METHODS: The study included 1249 patients treated with radical prostatectomy between 2003 and 2010. Patients were divided into three preoperative risk groups: low (PSA < 10 ng/mL, cT1, biopsy Gleason sum ≤ 6), high (cT3 or biopsy Gleason 8-10 or PSA > 20 ng/mL) and intermediate (all the remaining). Postoperative UC recovery was defined as the absence of any protection device. The association between nerve-sparing status and UC recovery was assessed in univariable and multivariable Cox regression analyses after accounting for age at surgery, Charlson Comorbidity Index and preoperative risk group. RESULTS: At a mean follow-up of 42.2 months (range 1-78), 993 patients (79.5%) recovered UC. Overall, UC recovery rate at 1 and 2 years was 76% and 79%, respectively. On univariable Cox regression analysis, age at surgery, preoperative risk group, medical comorbidities and nerve-sparing status were significantly associated with UC recovery (all P ≤ 0.001). On multivariable analysis, age, risk group and nerve-sparing status were also independently associated with UC recovery (all P < 0.003). Patients treated with bilateral NSRP had a 1.8-fold higher chance of full UC recovery. CONCLUSIONS: Patients treated with bilateral NSRP have significantly higher chances of recovering full continence. Therefore, when oncologically and technically feasible, a nerve-sparing procedure should be attempted.

Radical prostatectomy represents an effective treatment in patients with specimen-confined high pathological Gleason score prostate cancer.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: To date, only a few studies have addressed the long-term oncological outcomes of radical prostatectomy (RP) in patients with pathological Gleason score ≥ 8 prostate cancer. According to these reports, some individuals with pathological Gleason score ≥ 8 may benefit from RP, with cancer-control outcomes comparable with those of patients with low- and intermediate-risk prostate cancer. The presence of pathological Gleason score 8-10 represents a poor prognostic factor in the outcome of men with prostate cancer. However, in patients with specimen-confined disease, RP and bilateral PLND provided long-term cancer-control outcomes similar to those of patients with more favourable disease characteristics. OBJECTIVES: To evaluate the outcomes of patients with pathological Gleason score 8-10 prostate cancer subjected to radical prostatectomy (RP). To determine the prognostic factors associated with cancer-specific survival (CSS) in this subset of patients. PATIENTS AND METHODS: The study included 580 consecutive patients with pathological Gleason sum 8-10 prostate cancer treated with RP and pelvic lymph node dissection (PLND) at a single European institution between July 1988 and April 2010. All patients had detailed pathological and follow-up data. Pathological Gleason score was determined by a single expert genitourinary pathologist. Biochemical recurrence (BCR) was defined PSA concentration of ≥ 0.2 ng/mL and rising. Kaplan-Meier plots were used to graphically explore BCR-free survival as well as CSS and overall survival (OS) rates. Moreover, univariable and multivariable Cox regression models were fitted to test the predictors of CSS. RESULTS: The mean (median, range) age at surgery was 66.1 (66.4, 41-85) years. The mean (median, range) total PSA concentration was 29.6 (11.1, 0.5-1710) ng/mL. Pathological Gleason score was 8 in 238 (41.0%), 9 in 330 (56.9%) and 10 in 12 (2.1%) patients. Overall, 119 (20.5%), 124 (21.4%), 281 (48.4%) and 56 (9.7%) patients had pT2, pT3a, pT3b and pT4 prostate cancer, respectively. Overall, 275 (47.4%) had LN invasion, while 150 (25.1%) patients had specimen-confined disease (defined as pT2cR0 pN0 or pT3aR0 pN0 prostate cancer). The mean (median, range) follow-up was 53 (47, 1-226) months. At 5 and 10 years after RP, BCR-free survival was 76.7% and 49.6%, respectively. Similarly, the 5- and 10-year CSS rates were 87.3% and 69.5%, respectively. Patients with specimen-confined disease (P < 0.001) and patients with negative LNs (P = 0.012) had significantly better CSS rates than their counterparts with less favourable pathological characteristics. In multivariable Cox regression models, only the presence of specimen-confined disease achieved independent predictor status (P = 0.001). CONCLUSION: Presence of high Gleason score at RP represents a poor prognostic factor in the outcome of patients with prostate cancer. However, RP provides excellent long-term cancer control outcomes in the subset of patients with specimen-confined disease.

A novel tool to assess the risk of urinary incontinence after nerve-sparing radical prostatectomy.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Urinary incontinence is one of the most important morbidities after radical prostatectomy that has detrimental effect on the postoperative quality of life. The present study provides an accurate and dynamic multivariable risk stratification tool that predicts the postoperative urinary incontinence risk after radical prostatectomy based on patient-related as well as surgeon-related variables. OBJECTIVE: To develop a multivariable risk classification tool to estimate postoperative urinary incontinence (UI) risk as UI represents one of the most disabling surgical sequelae after radical prostatectomy (RP). PATIENTS AND METHODS: We evaluated 1311 patients treated with nerve-sparing RP between 2006 and 2010 at our institution. Regression tree analysis was used to stratify patients according to their postoperative UI risk. Kaplan-Meier curve estimates were used to assess the UI rate in the novel UI-risk groups. The discrimination of the novel tool was measured with the area under the curve method. RESULTS: At 3, 6 and 12 months, the UI rates were 44%, 26% and 12%, respectively. Regression tree analysis stratified patients into high risk (International Index of Erectile Function - Erectile Function domain [IIEF-EF] = 1-10), intermediate risk (IIEF-EF > 10 and age ≥ 65 years), low risk (IIEF-EF > 10, age < 65 years and body mass index [BMI] ≥ 25 kg/m(2) ) and very low risk (IIEF-EF > 10, age < 65 years and BMI < 25 kg/m(2) ) groups. The 3-month UI rates in these groups were 37%, 43%, 45% and 48%, respectively. The 6-month UI rates were 19%, 23%, 29% and 34%, respectively. The 12-month UI rates were 7%, 13%, 14% and 15%, respectively (log-rank P < 0.001). The area under the curve was 71%, 70% and 68% at 3, 6 and 12 months, respectively. CONCLUSIONS: We developed the first risk classification tool that predicts patients at high risk of UI after RP. These consisted mainly of individuals who were impotent before RP, elderly and/or overweight. This tool can be used for patient counselling.

Spatial distribution of positive cores improves the selection of patients with low-risk prostate cancer as candidates for active surveillance.

OBJECTIVE: To test the hypothesis that spatial distribution of positive cores at biopsy is a predictor of unfavourable prostate cancer characteristics at radical prostatectomy (RP) in active surveillance (AS) candidates. PATIENTS AND METHODS: We examined the data of 524 patients treated with RP, between 2000 and 2012. All fulfilled at least one of four commonly used AS criteria. Regression models tested the relationship between positive cores spatial distribution, defined as the number of positive zones at biopsy (PBxZ) and tumour laterality at biopsy and two endpoints: (i) unfavourable prostate cancer at RP (Gleason score ≥ 4 + 3, and/or pT3 disease), and (ii) clinically significant prostate cancer (tumour volume ≥ 2.5 mL). RESULTS: Unfavourable prostate cancer and clinically significant prostate cancer rates were 8 and 25%, respectively. Patients with more than one PBxZ had a 3.2-fold higher risk of harbouring unfavourable prostate cancer, and a 2.3-fold higher risk of harbouring clinically significant prostate cancer compared with their counterparts with one PBxZ (both P = 0.01). Patients with bilateral tumour at biopsy had a 3.3-fold higher risk of harbouring unfavourable prostate cancer and a 1.7-fold higher risk of harbouring clinically significant prostate cancer compared with their counterparts with unilateral tumour at biopsy (both P ≤ 0.04). Some of these results did not reach a statistically significant level, when the analyses were restricted to patients that fulfilled the most stringent AS criteria. CONCLUSIONS: Positive cores spatial distribution at biopsy should be considered, when advising patients about AS. The addition of this predictor to AS inclusion criteria can help identifying patients at a higher risk of progression, and reduce the rate of inappropriate surveillance of aggressive tumours. However, the most stringent AS criteria (namely John-Hopkins criteria and Prostate Cancer Research International: Active Surveillance criteria) might not benefit from the addition of this predictor. This point warrants further investigation in future studies.

Impact of the introduction of a robotic training programme on prostate cancer stage migration at a single tertiary referral centre.

OBJECTIVE: To evaluate the trend in robot-assisted radical prostatectomy (RARP) and open retropubic radical prostatectomy (RRP) use over time and to compare preoperative and pathological characteristics of patients treated with RARP or RRP at a single centre. PATIENTS AND METHODS: Between 2006 and 2010, 2511 consecutive patients treated with RP, with or without pelvic lymph node dissection (PLND), for prostate cancer (PCa) at a single tertiary care centre were analysed. Baseline patient characteristics and PCa risk distribution were compared according to treatment type (RRP vs RARP) in the overall population, as well as in three surgeons' initial 50 RARP and three surgeons' initial 50 RRP cases (n = 300). We used a chi-squared trend test to evaluate the differences in treatment type administration over time according to PCa characteristics. Logistic regression analyses focused on the prediction of PLND and adjuvant radiotherapy (RT) use. RESULTS: Overall, 1873 (74.6%) and 638 (25.4%) patients underwent RRP and RARP, respectively. Men treated with RARP were younger (mean age: 62 vs 65 years), less obese (mean BMI: 24.8 vs 26.4 kg/m(2) ), healthier (Charlson comorbidity index = 0: 68.7 vs 53.3%) and more likely to harbour clinical low-risk PCa (51 vs 30%) than their RRP counterparts (all P < 0.001). Similar findings were observed in sub-analyses focusing on six surgeons' 50 initial patients (all P ≤ 0.02). A significant increase in the rate of patients with low-risk PCa treated with RARP vs RRP was reported over time (5 vs 95% and 66 vs 34% in 2006 and 2010, respectively). Conversely, 76% of patients with high risk PCa were still treated with RRP in 2010. Patients treated with RARP were less likely to receive PLND at RP and adjuvant RT (all P ≤ 0.01), even after adjusting for clinical and PCa characteristics. CONCLUSIONS: The introduction of a robotic training programme at a high volume centre led to significant patient selection in terms of clinical and PCa characteristics. When both RRP and RARP facilities are available within the same centre, patients with the most favourable clinical and cancer profile are selected to undergo RARP. Use of RARP negatively influenced the rates and the extent of PLND as well as the use of adjuvant RT after surgery. Thus, baseline patient selection, surgical and treatment biases make any comparisons of RARP with RRP problematic.

Inhibition of phosphodiesterase 4 enhances clitoral and vaginal blood flow responses to dorsal clitoral nerve stimulation or PGE1 in anesthetized female rats.

INTRODUCTION.: Cyclic adenosine 3'5' monophosphate (cAMP) is produced by adenylate cyclase after activation by, e.g., vasoactive intestinal polypeptide or prostaglandin E1 (PGE1). The cAMP-degrading phosphodiesterase 4 (PDE4) is expressed in the vagina and clitoris, but no information is available on the functional role for PDE4-related signals in the female neurovascular genital response. AIM.: The aim of this study is to study the effect of inhibition of PDE4 with rolipram on nerve- and PGE1-induced vaginal and clitoral blood flow responses of rat. METHODS.: Measure of clitoral and vaginal blood flow and blood pressure in anesthetized rats during activation of the dorsal clitoral nerve (DCN) before and after intraperitoneal administration of rolipram or sildenafil (phosphodiesterase type 5 inhibitors [PDE5]) and nitro-L-arginine (L-NNA) (nitric oxide synthase inhibitor). Effect by topical administration of PGE1 on genital blood flow was also evaluated. MAIN OUTCOME MEASURE.: Blood flow was recorded as tissue perfusion units (TPU) by a Laser Doppler Flowmeter. Mean arterial blood pressure (MAP) was recorded (cmH2 O) in the carotid artery. Blood flow responses are expressed as TPU/MAP. Unpaired t-test and an analysis of variance were used. RESULTS.: Compared with control stimulations, rolipram (0.3 mg/kg) caused a twofold increase in peak blood flow (P < 0.05) and fourfold increase of the rate of clitoral blood flow during activation of the DCN (P < 0.05). Simultaneously, a twofold increase in peak blood flow and threefold increase in rate of blood flow were noted in the vagina (P < 0.05). Similar effects were noted for sildenafil (0.2 mg/kg) (P < 0.05). Inhibitory effects by L-NNA (60 mg/kg) on blood flow responses to DCN activation were significantly lower for rats treated with rolipram than with sildenafil (P < 0.05). PGE1-induced (10 µg) blood flow responses were significantly higher (P < 0.05) in rats treated with rolipram than with sildenafil. CONCLUSIONS.: These findings suggest that the cAMP/PDE4 system may be of similar functional importance as the nitric oxide/cyclic guanosine monophosphate/PDE5 pathway for neurovascular genital responses of the female rat.

Circulating sex steroids and prostate cancer: introducing the time-dependency theory.

PURPOSE: We sought whether serum total testosterone (tT), estradiol (E2), tT/E2 ratio, and sex hormone-binding globulin (SHBG) significantly fluctuate throughout time in men with prostate cancer (PCa). METHODS: Circulating hormones were measured in a cohort of 631 candidates for radical prostatectomy. Hormone levels were analyzed according to either patient age, stratified into quartiles, or body mass index (BMI). Linear regression analyses tested the association between sex steroids and continuously coded patient age and BMI values. RESULTS: No significant differences were found among age quartiles regarding serum tT levels and tT/E2 ratio. Conversely, E2 and SHBG levels significantly increased throughout time (all, p ≤ 0.001). Total T did not linearly change according to continuously coded patient age; in contrast, E2 and SHBG linearly increased (all, p ≤ 0.001), whereas tT/E2 decreased (p = 0.016) with aging. Rate of hypogonadism significantly increased with aging (p = 0.04). Total T, T/E2 ratio, and SHBG linearly decreased along with BMI increases (all p ≤ 0.02), whereas serum E2 did not significantly change. Rate of hypogonadism significantly increased with BMI increases (p < 0.001). CONCLUSIONS: In contrast with longitudinal studies in the general male population, these data indirectly suggest that serum tT levels could be stable over time in PCa patients. This finding led to formulation of a "time-dependency theory", which postulates that the endocrine biology of prostate tissue is dependent on the exposure time at a given concentration of sex steroid, which, in turn, fluctuates throughout the lifespan of the individual.

Preoperative sex steroids are significant predictors of early biochemical recurrence after radical prostatectomy.

PURPOSE: We sought the association of preoperative serum total testosterone (tT), hypogonadism, 17ß estradiol (E2), and sex hormone-binding globulin (SHBG) with early biochemical recurrence (BCR) after radical prostatectomy (RP). METHODS: Sex steroids were assessed the day before surgery (7-11 a.m.) in a cohort of 605 patients with a median follow-up of 24 months following RP. Cox regression models tested the association between predictors [including age, body mass index (BMI), prostate-specific antigen (PSA), clinical stage, biopsy Gleason scores, tT, hypogonadism, E2, and SHBG] and early BCR (defined as a PSA ≥ 0.1 ng/ml that occurred within 24 months after RP). RESULTS: Early BCR was found in 34 (5.6 %) patients. Patients with BCR did not differ in terms of age, BMI, serum PSA, tT, E2, and SHBG levels, rate of hypogonadism, and clinical stage as compared with those without BCR (all p ≥ 0.05). Conversely, patients with BCR showed a greater prevalence of biopsy Gleason scores ≥4 + 3 (all p ≤ 0.001). At multivariable Cox regression analysis, tT [hazard ratio (HR): 1.43; p = 0.03] E2 (HR: 1.05; p = 0.04), SHBG (HR: 1.29; p = 0.02), and biopsy Gleason scores equal to 4 + 3 (HR: 3.37; p = 0.04) and ≥8 (HR: 20.06; p < 0.001) achieved independent predictor status for early BCR. Conversely, no significant associations were found for all the other predictors. CONCLUSIONS: Current findings show that preoperative serum sex steroids are independent predictors of early BCR in a homogeneous, large cohort of nonscreened patients treated with RP.

Ureteral endometriosis: proposal for a diagnostic and therapeutic algorithm with a review of the literature.

INTRODUCTION: The ureteral involvement in deep pelvic endometriosis in usually asymptomatic and might lead to a silent loss of renal function. As a matter of fact, the diagnosis and the treatment modalities are still a matter of debate. MATERIALS AND METHODS: We performed a literature review by searching the MEDLINE database for articles published in English between 1996 and 2010, using the key words urinary tract endometriosis, ureteral endometriosis, diagnosis and treatment. We found more than 200 cases of ureteral endometriosis (UE). RESULTS: The disease most commonly affects a single distal segment of the ureter, with a left predisposition in most of the patients. Two major pathological types of UE may be distinguished: intrinsic and extrinsic. The symptoms are usually nonspecific and owing to secondary obstruction. The diagnosis has to be considered as a step- by-step procedure, starting from physical examination to highly detailed imaging methods. Nowadays, the treatment is usually chosen according to the type of UE, the site lesion and the distance to the ureteral orifice, with the use of JJ stents remaining a matter of debate. CONCLUSIONS: A close collaboration between the gynecologist and the urologist is advisable, especially in referral centers. Surgical treatment can lead to good results in terms of both patient compliance and prognosis.

Postoperative phosphodiesterase type 5 inhibitor administration increases the rate of urinary continence recovery after bilateral nerve-sparing radical prostatectomy.

OBJECTIVES: To investigate the effect of phosphodiesterase type 5 inhibitor on urinary continence recovery after bilateral nerve-sparing radical prostatectomy. METHODS: We analyzed data of 393 open bilateral nerve-sparing radical prostatectomies carried out between 2005 and 2010. Patients who recovered urinary continence within the first month after catheter removal (n = 52) were excluded. This resulted in 341 evaluable patients. Urinary continence recovery was defined as being completely pad free over a period of 24 h. Patients were stratified according to postoperative daily (n = 58; 17%), on-demand (n = 112; 32.8%) and no (n = 171; 50.1%) phosphodiesterase type 5 inhibitor use. The effect of phosphodiesterase type 5 inhibitor use on urinary continence was assessed using the Kaplan-Meier method. Uni- and multivariable Cox regression analyses were used to test the association between phosphodiesterase type 5 inhibitor and urinary continence recovery after adjusting for cofounders. RESULTS: At a mean follow up of 36.4 months after surgery (median: 33), 288 patients (84.5%) recovered urinary continence after bilateral nerve-sparing radical prostatectomy. Patients who did not use phosphodiesterase type 5 inhibitor after surgery had lower rates of urinary continence recovery at 1- and 2-year follow up as compared with patients taking phosphodiesterase type 5 inhibitor (67.1 vs 86.7% and 76 vs 94.4%, respectively; P < 0.001). After adjusting for all confounders, multivariable analysis showed that phosphodiesterase type 5 inhibitor use, either on demand or daily, had a positive impact on urinary continence recovery (P = 0.03). CONCLUSIONS: Patients taking phosphodiesterase type 5 inhibitor have higher urinary continence recovery rates as compared with patients left untreated after bilateral nerve-sparing radical prostatectomy. An improvement in sphincteric and pelvic floor blood supply might be responsible for this beneficial effect associated with the use of phosphodiesterase type 5 inhibitor.

Effect of number and location of distant metastases on renal cell carcinoma mortality in candidates for cytoreductive nephrectomy: implications for multimodal therapy.

OBJECTIVE: To test whether the combination of number and location of distant metastases affects cancer-specific survival in patients with metastatic renal cell carcinoma. METHODS: Overall, 242 metastatic renal cell carcinoma patients with synchronous metastases at diagnosis underwent cytoreductive nephrectomy at a single institution. Combinations of number and location of distant metastases were coded as: single metastasis and single organ affected, multiple metastases and single organ affected, single metastasis for each of the multiple organs affected, and multiple metastases for each of the multiple organs affected. Covariates included age, symptoms, performance status, American Society of Anesthesiologists score, hemoglobin, lactate dehydrogenase, tumor size, Fuhrman grade, T stage, lymph node status, necrosis, sarcomatoid features and metastasectomy at the time of nephrectomy. RESULTS: The median survival was 34.7 versus 32.3 versus 29.6 versus 8.5 months for single metastasis and single organ affected, multiple metastases and single organ affected single metastasis for each of the multiple organs affected, and multiple metastases for each of the multiple organs affected patients, respectively. At multivariable analyses, the combination of number and location of distant metastases resulted in one of the most informative and independent predictors of cancer-specific survival in metastatic renal cell carcinoma patients. The lung was the location with the highest rate of single organ affected (50.3% vs 35.1% in other sites; P < 0.001). Considering only patients with a single metastasis, no statistically significantly different cancer-specific survival rates were recorded (P > 0.3) among different metastatic organs. CONCLUSIONS: Among metastatic renal cell carcinoma patients undergoing cytoreductive nephrectomy, the combination of the number and location of distant metastases is a major independent predictor of cancer-specific survival. Patients with multiple organs affected by multifocal disease are more likely to have poorer survival.

Assessing the risk of lymph node invasion in patients with intermediate risk prostate cancer treated with extended pelvic lymph node dissection. A novel prediction tool.

BACKGROUND: Controversy exists regarding the need for extended pelvic lymph node dissection (ePLND) in patients with intermediate risk prostate cancer (PCa). MATERIALS AND METHODS: The study included 982 consecutive men with intermediate risk PCa (PSA 10­20 ng/ml or cT2b-c or biopsy Gleason 3 + 4/ 4 + 3) treated with ePLND and radical prostatectomy (RP) at a single center. All patients underwent an anatomically defined ePLND. A novel risk stratification tool was developed by applying the nonparametric tree modeling technique of classification and regression tree analysis (CART) which relied on pre-operative PSA, clinical stage, biopsy Gleason score, and percentage of positive cores. The area under the receiver characteristic curve (AUC) method was used to quantify the accuracy of the model. RESULTS: Lymph node invasion (LNI) was found in 81 (8.2%) patients. The CART analyses identified three risk groups of having LNI: a) Low risk: Gleason 3 + 3, cT1c/cT2, PSA 10-20 ng/ml, or Gleason 3 + 4/4 + 3, ≤ 63% of positive cores and PSA < 5 ng/ml (risk of LNI:3.7 and 5.2%, respectively; 64.8% of patients included); b) Moderate risk: Gleason 3 + 4/4 + 3, ≤ 63% of positive cores and PSA ≥ 5 ng/ml (risk of LNI:14.4%; 23% of patients included); c)High risk: Gleason 3 + 4/4 + 3, % positive cores >63% (risk of LNI:20.1%; 12.% of patients included; P < 0.001). The accuracy of the model was 71%. CONCLUSIONS: The risk of having LNI varies significantly (3.7­20.1%) in patients with intermediate risk PCa. Our predictive tool might help selecting those patients suitable fore PLND, allowing to spare this approach in about 60% of intermediate risk patients.

Lymphatic spread of nodal metastases in high-risk prostate cancer: The ascending pathway from the pelvis to the retroperitoneum.

BACKGROUND: The aim of this study was to map the nodal metastases distribution in patients with high-risk prostate cancer (PCa) treated with extended pelvic lymph node dissection (ePLND) and retroperitoneal lymph node dissection (rLND) at the time of radical prostatectomy (RP). MATERIALS AND METHODS: This prospective mapping study included 19 patients with high-risk PCa (sharing at least two out of the three following parameters: PSA >20 ng/ml, cT3, biopsy Gleason score ≥8). All patients were treated with RP, ePLND (removal of the obturator, hypogastric, external iliac, presacral, and common iliac lymph nodes) and rLND (removal of para-aortal/para-caval and inter-aorto-caval lymph nodes) by a single surgeon. All patients signed an informed consent highlighting the absence of clinical data supporting the benefit of this surgical approach. RESULTS: Overall, 18 out of 19 patients (94.7%) had pelvic lymph node invasion. The most commonly affected pelvic nodal landing site was obturator (88.8%), followed by external iliac (83.3%), common iliac (77%), hypogastric (44.4%), and presacral (33.3%). Moreover, 14 (77.8%) patients also had involvement of retroperitoneal lymph nodes. Only patients with positive common iliac lymph nodes having at least five positive lower pelvic lymph nodes (n = 14), also had invariably positive retroperitoneal lymph nodes. No patients with negative common iliac lymph nodes had positive retroperitoneal lymph nodes. CONCLUSIONS: PCa lymphatic spread ascends from the pelvis up to the retroperitoneum invariably through common iliac lymph nodes. PCa lymphatic spread can be divided in two main levels: pelvic and common iliac plus retroperitoneal lymph nodes.

There is no way to identify patients who will harbor small volume, unilateral prostate cancer at final pathology. implications for focal therapies.

BACKGROUND: The aim of this study was to assess the clinical characteristics of the potentially ideal candidates for focal therapy, that is, patients with unilateral, small volume (namely, pT2a) prostate cancer (PCa) at radical prostatectomy (RP). MATERIALS AND METHODS: We evaluated 2,503 consecutive pT2 PCa patients treated with RP between 2002 and 2009 at a single center. Within this population, the clinical characteristics of patients with pT2a and pT2b/c disease were compared. Univariable and multivariable logistic regression models were fitted to assess clinical predictors of pT2a at RP. RESULTS: Overall, 349 patients (14%) had pT2a PCa, while the remaining patients had either pT2b (n = 334; 15.5%) or pT2c disease (n = 1,820 patients; 84.5%). Patients with pT2a PCa had a significantly lower mean PSA value, lower mean percentage of positive biopsy cores and lower biopsy Gleason score distribution (all P ≤ 0.03). However, at multivariable analyses, only percentage of positive cores maintained an independent predictor status (P = 0.01). Even when considering only patients sharing all the most favorable PCa characteristics (namely, clinical stage T1, PSA ≤ 4, Gleason score ≤6 and percentage of positive cores ≤25%), the rate of pT2a disease was only 24%. CONCLUSIONS: The rate of small volume, unilateral PCa even among patients with extremely favourable PCa characteristics was remarkably low (roughly 25%). This suggests that: (1) Three quarters of the best candidates for focal therapy would ultimately show adverse pathological features; (2) At present, accurate identification of the ideal candidate for focal therapy is not possible with current clinical-pathologic parameters.

Age-adjusted validation of the most stringent criteria for active surveillance in low-risk prostate cancer patients.

BACKGROUND: The authors tested the performance of the currently used clinical criteria reported in populations studied by van den Bergh et al and Carter et al for the selection of patients with prostate cancer (PCa) for active surveillance (AS) according to age. METHODS: Data were analyzed from 893 patients who underwent with radical prostatectomy (RP). The authors investigated the rates of unfavorable PCa at RP (extracapsular extension, seminal vesicle or lymph node invasion, or Gleason score 7-10) in patients who fulfilled AS criteria according to age tertiles (ages ≤ 63 years, 63.1 to 69 years, and >69 years). Area under the curve (AUC) [corrected] analyses tested the criteria for predicting unfavorable PCa. Then, the patients were stratified according to the cutoff age of 70 years. Multivariate analyses were used to test the role of age in predicting unfavorable PCa. RESULTS: The rate of unfavorable PCa characteristics was between 24% and 27.8%. In the van den Bergh et al population, after age 70 years, the rate of unfavorable PCa characteristics was 41% compared with 23.2% and 24.1% in patients in the previous age tertiles (ages ≤ 63 years and 63.1 to 69 years, respectively). In the Carter et al population, the rate of unfavorable PCa was 41.2% compared with 17.3% and 18.6% in the previous age tertiles (ages ≤ 63 years and 63.1 to 69 years, respectively). When the 70-year age cutoff was used, unfavorable PCa was identified in 17.9% to 23.6% of patients aged <70 years versus 4% to 41.2% of patients aged >70 years (all P < .001). AUC analyses revealed significantly lower performance in older patients. In multivariate analyses, after adjustment for prostate-specific antigen, prostate volume, and the number of cores, age represented an independent predictor of unfavorable PCa. CONCLUSIONS: The currently used AS criteria performed significantly better for patients aged <70 years. The authors concluded that the current results should be taken into account when deciding whether to offer active surveillance to patients with low-risk PCa.

National Comprehensive Cancer Network practice guidelines 2011: Need for more accurate recommendations for pelvic lymph node dissection in prostate cancer.

PURPOSE: The 2011 NCCN (National Comprehensive Cancer Network) guidelines for prostate cancer recommend pelvic lymph node dissection at radical prostatectomy in all individuals with a nomogram predicted lymph node invasion probability of 2% or greater. We examined the ability of these guidelines to correctly predict lymph node invasion in patients treated with extended pelvic lymph node dissection. MATERIALS AND METHODS: We examined 3,064 consecutive patients treated with radical prostatectomy and extended pelvic lymph node dissection between 2000 and 2010. We formally validated the NCCN guideline nomogram using discrimination, calibration and decision curve analysis as benchmarks. Moreover the performance characteristics of the 2% nomogram cutoff as well as other cutoff values (range 1% to 10%) were tested. RESULTS: Overall 10.0% of patients had lymph node invasion. The discrimination accuracy of the NCCN guideline nomogram was 79.8%, with a maximum underestimation of the lymph node invasion risk of 41.2%. On decision curve analysis the NCCN nomogram fared better than not performing pelvic lymph node dissection in all patients. However, in the prediction range between 0% and 9% the nomogram did not fare better than performing pelvic lymph node dissection in all patients. The use of the 2% cutoff would allow the avoidance of 49.3% of pelvic lymph node dissections, at the cost of missing 20.3% of patients with lymph node invasion. CONCLUSIONS: The NCCN nomogram tends to significantly underestimate the real lymph node invasion rate. Moreover the use of the currently recommended cutoff of 2% to trigger pelvic lymph node dissection might not be appropriate.

Preoperative erectile function represents a significant predictor of postoperative urinary continence recovery in patients treated with bilateral nerve sparing radical prostatectomy.

PURPOSE: The association between baseline functional status and urinary continence recovery after radical prostatectomy remains controversial. We tested the hypothesis that baseline erectile and urinary function predicts urinary continence recovery after bilateral nerve sparing radical prostatectomy. MATERIALS AND METHODS: The study included 752 patients with prostate cancer treated with bilateral nerve sparing radical prostatectomy between 2003 and 2009. All patients had preoperative functional and oncological data available, including age at surgery, body mass index, prostate specific antigen, and erectile and urinary function. Preoperatively erectile and urinary function was assessed by the erectile function domain of the International Index of Erectile Function and the International Prostatic Symptoms Score. Urinary continence was defined as wearing no pads. Univariate and multivariate Cox regression models were used to test the association between predictors and urinary continence recovery after surgery. RESULTS: At a mean postoperative followup of 30.7 months (median 29, range 1 to 80) 611 patients (81.3%) had recovered urinary continence. Overall the urinary continence recovery rate at 1 and 3 years was 73.9% and 82.2%, respectively. On univariate Cox regression analysis patient age and the preoperative score on the erectile function domain of the International Index of Erectile Function were significantly associated with urinary continence recovery (each p ≤ 0.04). On multivariate analysis age at surgery and the preoperative erectile function domain of the International Index of Erectile Function were the only independent predictors of urinary continence recovery after bilateral nerve sparing radical prostatectomy (each p ≤ 0.04). CONCLUSIONS: Age and preoperative erectile function should be considered for urinary continence predictions after bilateral nerve sparing radical prostatectomy and for accurate patient counseling before surgery. Preoperative erectile function might be a marker of pelvic vascular disease, which may affect the status of the external urinary sphincter.