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Purpose To assess the diagnostic accuracy of iXip, a novel biomarker for prostate cancer detection at initial biopsy based on an algorithm including patient age, prostate volume, PSA and PSA-IgM levels,. Materials and methods This was a prospective multicenter study involving 426 consecutive men undergoing initial prostate biopsy with at least 12 cores in a real-life clinical setting. Diagnostic accuracy of iXip for prostate cancer detection was calculated with AUC and compared to that of prostate volume, PSA and PSA-IgM levels. The correlation of iXip with tumor aggressiveness, defined as any cancer with Gleason score ≥7, was evaluated by Spearman ρ coefficient analysis. Results Prostate cancer was diagnosed in 193/426 patients (45%), of which 65 (35%) had Gleason score ≥7. iXip values were significantly higher in patients with cancer than in those without cancer (median value 55% vs. 39%, p Conclusions Our prospective multicenter study suggests that the novel biomarker iXip may be used with a 20% cut-off value in order to reduce the proportion of prostate biopsies by approximately 5%, without missing a single case of cancer. Moreover, higher iXip values are significantly correlated with tumor aggressiveness.

An increased risk of renal cell cancer (RCC) has been reported in overweight persons. The authors aimed to clarify which anthropometric measures are associated with risk of RCC and whether risk may vary according to selected variables. Between 1992 and 2004, they carried out an Italian multicenter case-control study including 767 (494 men, 273 women) incident cases of RCC and 1,534 hospital controls, frequency-matched to cases. To estimate odds ratios and 95% confidence intervals, they used conditional logistic regression matched on study center, sex, and age and adjusted for period of interview, years of education, smoking habits, and family history of kidney cancer. Using body-size measurements taken 1 year prior to diagnosis/interview, the authors found an odds ratio of 1.3 (95% confidence interval (CI): 1.0, 1.7) among obese persons (body mass index (BMI; weight (kg)/height (m) 2 ) � 30) versus normal-weight persons (BMI

Background: An increased risk of renal cell cancer (RCC) has been reported in subjects with hypertension. Whether this association may vary according to sex, smoking, obesity, or RCC clinical presentation is unclear. Results on the link between diabetes mellitus and RCC are inconclusive. Patients and methods: We conducted an Italian multicenter case–control study, including 767 (494 men, 273 women) incident cases of RCC, under 80 years of age, and 1534 hospital controls, frequency-matched to cases. Multiple logistic regression models, conditioned to center, sex, and age, and adjusted for period of interview, education, smoking, and body mass were used to estimate odds ratios (OR). Results: Compared with subjects never treated, patients with a history of treated hypertension [OR = 1.7, 95% confidence interval (CI) 1.4–2.1] reported an excess risk of RCC. This pattern was confirmed in different strata of sex, education, smoking habits, body mass, tumor histological type, stage, or grade. The attributable risk of RCC for treated hypertension in this population was 16%. A slight, nonsignificant increased risk was found for history of diabetes mellitus (OR = 1.3, 95% CI 0.9–1.7). Conclusion: A possible causal role of hypertension in renal cell carcinogenesis is supported by the consistency of the direct association.

To evaluate the impact of tobacco smoking on specific histological subtypes of transitional cell carcinoma of the bladder (TCC). Between 2003 and 2009, we conducted a hospital-based case-control study in Italy, enrolling 531 incident TCC cases and 524 cancer-free matched patients. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated through multiple logistic regression models. Compared to never smokers, TCC risk was threefold higher in former smokers (95% CI 2.07–4.18) and more than sixfold higher in current smokers (95% CI 4.54–9.85). TCC risk steadily increased with increasing intensity (OR for ≥25 cigarettes/day 8.75; 95% CI 3.40–22.55) and duration of smoking (OR for ≥50 years 5.46; 95% CI 2.60–11.49). No heterogeneity emerged between papillary and non-papillary TCCs for smoking intensity and duration, but the risk for those who had smoked for ≥50 years was twice for non-papillary TCC (OR 10.88) compared with papillary one (OR 4.76). Among current smokers, the risk for a 10-year increase in duration grew across strata of intensity (p-trend = 0.046). Conversely, the risk for a 5-cigarette/day increase in smoking intensity was quite steady across strata of duration (p-trend = 0.18). Study results suggested that duration of smoking outweighs intensity in determining TCC risk, with limited differences across histological subtypes. Elimination of tobacco smoking may prevent about 65 % of TCCs.

BACKGROUND The optimal management of high-risk prostate cancer remains uncertain. In this study we assessed the safety and efficacy of a novel multimodal treatment paradigm for high-risk prostate cancer. METHODS This was a prospective phase II trial including 35 patients with newly diagnosed high-risk localized or locally advanced prostate cancer treated with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel-based chemotherapy and long-term androgen deprivation therapy. Primary endpoint was acute and late toxicity evaluated with the Common Terminology Criteria for Adverse Events version 3.0. Secondary endpoint was biochemical and clinical recurrence-free survival explored with the Kaplan-Meier method. RESULTS Acute gastro-intestinal and genito-urinary toxicity was grade 2 in 23% and 20% of patients, and grade 3 in 9% and 3% of patients, respectively. Acute blood/bone marrow toxicity was grade 2 in 20% of patients. No acute grade ≥ 4 toxicity was observed. Late gastro-intestinal and genito-urinary toxicity was grade 2 in 9% of patients each. No late grade ≥ 3 toxicity was observed. Median follow-up was 63 months (interquartile range 31-79). Actuarial 5-year biochemical and clinical recurrence-free survival rate was 55% (95% confidence interval, 35-75%) and 70% (95% confidence interval, 52-88%), respectively. CONCLUSIONS In our phase II trial testing a novel multimodal treatment paradigm for high-risk prostate cancer, toxicity was acceptably low and mid-term oncological outcome was good. This treatment paradigm, thus, may warrant further evaluation in phase III randomized trials.

Purpose: We evaluated the potential of PET/CT and [F-18] fluoromethylcholine (FCH) in the assessment of suspected recurrence of prostate cancer after treatment. Methods: One hundred consecutive prostate cancer patients with a persistent increase in serum PSA (> 0.1 ng/ml) after radical prostatectomy ( 58 cases), radiotherapy ( 21 cases) or hormonal therapy alone ( 21 cases) were investigated. After injection of 3.7 - 4.07 MBq/kg of FCH, both early ( at < 15 min) and delayed ( at > 60 min) PET/CT scans were performed in 43 patients, delayed PET/CT scans in 53 patients and early PET/CT scans in four patients. Results: Of the 100 patients, 54 ( PSA 0.22 - 511.79 ng/ml) showed positive FCH PET/CT scans. Thirty-seven patients had bone and/or abdominal lymph node uptake, while 17 showed pelvic activity. Malignant disease was confirmed in all but one. Delayed SUVmax of bone metastases was significantly higher (p< 0.0001 by paired t test) than that measured at < 15 min, whereas no differences were observed between early and delayed SUVs of malignant lymph nodes or pelvic disease. Forty-six patients ( PSA 0.12 - 14.3 ng/ml) showed negative FCH PET/CT scans. Of the negative PET/CT scans, 89% were obtained in patients with serum PSA < 4 ng/ml and 87% in patients with a Gleason score < 8. In none of these cases could recurrent tumour be proven clinically during a follow-up of 6 months. Conclusion: FCH PET/CT is not likely to have a significant impact on the care of prostate cancer patients with biochemical recurrence until PSA increases to above 4 ng/ml. However, in selected patients, FCH PET/CT helps to exclude distant metastases when salvage local treatment is intended.

A series of patients with concurrent transitional cell carcinoma involvement of the prostate and bladder is reviewed to define the impact of prostate involvement pathways and the degree of prostate invasion on survival rate.A total of 72 patients who underwent radical cystectomy for pathological stage pT4a (D1) cancer was divided into contiguous--stage pT4a, transitional cell carcinoma of the bladder extended into the prostate through the bladder wall and noncontiguous--stage pT4a simultaneous transitional cell carcinoma of the prostate and bladder carcinoma that did not directly infiltrate into the prostate through the bladder wall. In the latter group the degree of prostate invasion was classified as urethral mucosal involvement, ductal/acinar involvement, stromal invasion and extracapsular extension. The survival rate was estimated by the Kaplan-Meier and Cox proportional hazards methods. Comparisons between curves were performed by univariate log rank and multivariate L-ratio tests.The overall 5-year survival rate for stage pT4a was 21.5% (median followup 64 months). Furthermore, 46% and 7% of patients in noncontiguous and contiguous pT4a groups, respectively, were estimated to be alive (p0.000). Those with positive nodes experienced a poor outcome in both groups. Of patients with noncontiguous pT4a stage 100% with urethral mucosal involvement, 50% with ductal/acinar involvement and 40% with stromal invasion were estimated to be alive. The major prognostic factors were bladder tumor stage, nodal involvement and degree of prostate invasion.The invasion pathways of the prostate in patients with transitional cell bladder carcinoma have a statistically significant prognostic role. Contiguous and noncontiguous involvements are 2 distinct clinicopathological features and they should not be included in the same stage. In the noncontiguous stage pT4a group bladder and prostate transitional cell carcinoma should be separately staged, and prostate involvement also should be staged according to invasion degree.

Radical cystectomy is the most common treatment for deeply invasive bladder cancer; due to reported operative risks, concerns have been expressed regarding the suitability of this operation in elderly patients. We reviewed the morbility and mortality rates in 50 patients aged 70 years and over (elderly group), undergoing radical cystectomy and urinary diversion, to verify if this procedure could be considered as initial treatment in older-age patients. The findings were compared with those observed in 50 patients aged 40 to 69 years (control group). In the elderly group there was no operative mortality; however 2 patients (4%) died post-operatively due to pulmonary embolism and multi-organ-failure syndrome respectively. Four patients (8%) were re-operated due to intestinal obstruction (2 pts), pelvic hematoma (1 pt) and wound dehiscence (1 pt). Wound separation was the more frequent complication (15%); 6% of patients experienced extended intestinal atonia. The length of hospital stay was 17.1 days. In the control group, surgical complications were comparable to those observed in the elderly group: furthermore medical complications were more frequent. In conclusion, these data suggest that radical cystectomy and urinary diversion can be safely performed in the elderly. Radical surgery is an effective treatment modality for elderly individuals who are in reasonably good general health. A higher incidence of medical complications must be expected in elderly patients.

Shortly after Morales' original report, several phase II trials confirmed the effectiveness of intravesical bacillus Calmette-Guérin (BCG) in superficial bladder cancer therapy. Concerns have been expressed about the toxicity related to this new therapeutic modality. These phase II trial data led European urologists to try to answer some questions related to BCG therapy, such as the optimal schedule and dose, the most effective BCG strain and the value of BCG compared with current chemotherapeutic drugs. To date, phase III trials have shown that BCG is more effective than thiotepa and doxorubicin in reducing tumour recurrences and progression and that BCG seems to be as effective as mitomycin C. Toxicity is significantly higher with BCG compared to chemotherapeutic drugs; no strain of BCG seems to be superior in this respect. Further studies are required to identify the optimal schedule and dose, as well as the best therapeutic efficacy/toxicity ratio.

Bacillus Calmette-Guerin (BCG) intravesical therapy represents a major advance in the treatment of superficial transitional cell carcinoma of the bladder. To date, however, the optimal treatment schedule must be defined and the toxicity related to the treatment is significant. The preliminary results of a randomized ongoing study performed to evaluate the effectiveness and relative toxicity of a low dose (75 mg.) BCG regimen in the treatment of superficial bladder cancer therapy are reported. A total of 126 patients (70 for prophylaxis of recurrent stages Ta and T1 papillary tumors and 56 for treatment of carcinoma in situ or with microinfiltration of the subepithelial connective tissue) underwent a 6-week course of 75 mg. BCG (Pasteur vaccine). An additional course was given in patients who failed to respond to the induction course. Maintenance therapy was administered in complete responders monthly for 1 year and then quarterly for 1 year. The prophylaxis group (transurethral resection plus BCG) was randomized versus transurethral resection alone (63 patients, control group). A complete response in the prophylaxis, control and therapy groups was observed in 74, 17 and 57% of the patients, respectively, while 4, 17 and 12.5%, respectively, experienced tumor progression. The additional course of therapy increased the response rate. On the contrary, previous unsuccessful intravesical chemotherapy did not affect the response rate. In regard to toxicity, irritative disturbances (27%) and fever (17%) appeared to be significantly decreased compared with the rates reported in the literature. No major complications were experienced. In conclusion, a low dose (75 mg.) Pasteur strain BCG regimen was effective as prophylaxis against recurrent superficial papillary tumors and as treatment of carcinoma in situ or with microinfiltration of the subepithelial connective tissue. Toxicity related to the treatment appeared to be low.

At the Institute of Urology, University of Padova, 125 patients with multifocal superficial bladder cancer underwent treatment with intravesical Mitomycin C (MMC; 1 weekly instillation of 40 mg for 8 consecutive weeks) between January 1982 and December 1988. Eighty-four patients had multifocal papillary tumors (stages Ta-T1) and 41 patients had carcinoma in situ of the bladder. At 6 and 36 months the tumor free percentage in the group with papillary tumors was 69 and 36%, respectively; for carcinoma in situ the complete response percentage at the same intervals was 80 and 36%. Thirty-one patients previously unsuccessfully treated with adriamycin did not show any difference compared to untreated ones. The authors emphasize the efficacy and low toxicity of intravesical MMC in multiple superficial bladder cancer. The possibility of long-term relapse suggests maintenance therapy.

423 Background: The soprachiasmatic nucleus represents the pacemaker coordinating circadian rhythm. Its dysregulation in neoplastic patients (pts) can be an important inducer/promoter of cancer progression. It is a potential mediator of cancer immunosuppressive effect and quality of life (QoL) impairment. CHI allows concentration of time active treatment with possible impact on QoL and immune and hormone set-up. Aim of this study was to evaluate feasibility, dose limiting toxicity and activity of CHI IL-2 in mRCC. Methods: 22 pts were enrolled, 14 were naive and 8 pretreated (chemo/immunotherapy in 6 and targeted in 6). M/F ratio was 16/6, median age 68 y. IL-2 CHI was administered iv in 8 h (peak 1 am, 9 am, 5 pm) from 2 MUI/m2 with escalated dose ( Fibonacci scale) x 3 days/q 2 wks for 4 cycles. Four maintenance cycles were performed in responsive/stable pts. Results: from January 2005 to July 2009, out of 22 pts, 3 were treated onto each Le (I-V ) and 7 in the VI. G3-4 toxicity was reported in four pts (hypotension in 2, renal in 2 and diarrhoea in 1) on the VI Le ( DLT 18,6 MUI/m2). Response: 1 CR, 2 PR, 9 SD, 10 PD. ORR was 25%%. DCR on overall/ good-intermediate group (MSKCC) was 54%/69%. Median PFS and OS were 4,5 and 14,5 mos respectively. In a univariate analysis dose Le (4-6 vs. 1-3), PS (0 vs 1-2), gender (M vs F) and cD3, cD4, cD8 count (gain vs drop) were statistically significant for OS. In a univariate analysis age (< 65 y vs. >65y), Motzer score (0-1-2 vs 3) increase/reduction of cD19, cD16, HLA-DR, cD4/cD8, increase/reduction of prolactine, reduction/increase of ACTH-Cortisol showed a trend of survival improvement. Conclusions: IL-2 CHI aappeared safe in a standard care unit, moderately toxic and active in mRCC. Phase 2 study with dose Le V is now ongoing.

Bladder pathologic features related to intravesical bacillus Calmette-Guerin (BCG) therapy in superficial bladder cancer (Ta, T1, Tis) were evaluated and related to clinical outcome. A total of 105 patients were treated with 75 mg Pasteur BCG weekly for six consecutive weeks. When tumor was not demonstrated a maintenance course was given. An additional six-week course was given when tumor recurrence or persistence, without progression, was observed after the induction course. An inflammatory change in the bladder was the most common pathologic finding. Granuloma was the only specific BCG-related feature and did not appear to be a prognostic factor because of low incidence (24%) and lack of correlation with clinical course. Dysplasia occurred more frequently (57%) in nonresponder patients and (26%) in responder patients, often heralding recurrence of tumor. All patients showing concurrent squamous and/or glandular metaplasia were unresponsive to BCG therapy. Histology and cytology did not correlate perfectly: cytology was ineffective in low-grade tumors and improved diagnostic accuracy, particularly when dysplasia was histologically evident.

Preoperative prostate-specific antigen (PSA) values were determined in 73 patients with clinically localized prostatic cancer and candidates for a radical procedure. Correlation of preoperative PSA with a final pathological stage was attempted. Only in 44.8% of our 22 patients with organ-confined disease was the PSA value within the normal range; in 17.3% of cases PSA values were higher than 20 ng/ml. 18.2% of the patients with locally advanced disease showed normal PSA values, while 45.5% had concentrations above 20 ng/ml. In the case of lymph node involvement, PSA values were normal in 22.7% of the cases. Our data indicate that no strict relationship can be suggested between PSA and the final pathological stage and grading of the tumor in patients who underwent radical prostatectomy.

Endourologic treatment was used for transitional cell carcinoma of the upper urinary tract in 16 patients. The presenting symptom was hematuria in 13 patients and flank pain in 1; in 2 cases, the diagnosis was made by chance at intravenous urography (IVU). Ureterorenoscopy (URS) was attempted in 11 cases, with removal of superficial transitional tumors of the ureter in 6 cases. In five cases, URS was diagnostic only. The remaining 10 patients were treated percutaneously. Pathological examination revealed 11 Ta Grade 1-2 papillary tumors, 4 T1 Grade 1-2 lesions, and 1 inverted papilloma. A single-J ureteral catheter was left in place after the procedure in 10 cases for 48 to 72 hours. In six cases, a nephrostomy tube was left in place in order to perform BCG immunotherapy (five cases) or mitomycin C chemotherapy (one case). Cytologic, radiographic, and endoscopic studies were negative after a median follow-up of 17 months in 10 patients. Four patients underwent nephroureterectomy for recurrence of tumor at...

e16091 Background: HRPC criteria include stage T2b-T2c according to the AJCC classification, PSA ≥ 10 ng/ml, Gleason score (GS) 7–10 with 12, 6% 7-year cancer specific mortality rate (D'Amico AV, Cancer. 2006). Several small nonrandomized NA chemotherapy studies were performed in this setting (Kim N. Chi J Urol. 2008; Prayer-Galletti T. Br J Urol. 2007; Konety BR. J Urol. 2004) with DFS of 42%-70%. Aim of this study: to evaluate the feasibility, efficacy, and toxicity of NA-CHT followed by RP and postoperative RT. Methods: Histological diagnosis of LA HRPC (T2b-T4), GS > 8, PSA > 10 ng/ml, age < 65 years, PS 0–1. Treatment: group A) paclitaxel 80 mg/sqm/weekly and estramustine phosphate (EP) 10 mg/Kg/day for 5 days/week for 4 months. Group B) carboplatin (AUC 5) i.v day 1 q 21 plus docetaxel 30 mg/sqm i.v day 1,8 and EP day -1-+4 and 7–11 q 21 for 4 cycles. Thereafter, the responsive and stable patients (pts) were submitted to RP and adjuvant RT (60–70Gy/30–35 fr) or to radical (R) RT (78 Gy/39 fr) respectively. Primary endpoint: disease-free survival (DFS); secondary endpoint: PSA relapse-free survival (RFS), overall survival (OS). Results: Between 2002 and 2008, 29 pts entered onto the studies. The toxicity was mild. The down-staging was obtained on 2 group A pts and on 1 group B pt respectively. Conclusions: NA-CHT with both regimens was been shown feasible and nontoxic in LAHRPC. Although a clinical response was documented, the pathological response was anecdotal.The DFS and OS are encouraging considering the historical data but warrant a randomized study. [Table: see text] No significant financial relationships to disclose.

We reviewed 261 patients who underwent a radical operation at a single institution as definitive treatment of invasive bladder cancer to evaluate the survival and accuracy of the tumor, nodes and metastasis system in characterizing the prognosis. Between January 1979 and June 1987 the 261 evaluable patients underwent 1-stage radical cystectomy with pelvic node dissection and urinary diversion. No chemotherapy and/or radiation therapy was given before or after the operation. The postoperative mortality rate was 1.8%. The over-all staging error between clinical and pathological stages was as high as 44%. The over-all actuarial 5-year survival rate was 54.5%. The 5-year survival rates were 75% for stage pT1, 63% for stage pT2, 31% for stage pT3 and 21% for stage pT4 disease. A significant difference in the survival (p less than 0.002) was observed in stage pT3 by dividing tumors confined within the bladder wall (pT3a, 50%) from those extending throughout the bladder wall (pT3b, 15%). A careful evaluation of transitional cell involvement of the prostate in stage pT4a cancer led to the identification of 2 different patterns: 1) contiguous when a bladder tumor extended directly into the prostate through the bladder wall and 2) noncontiguous when a bladder tumor and a transitional cell carcinoma of the prostate were found simultaneously. These patterns had completely different (p less than 0.05) survival rates (6 versus 37%). The patients with high grade tumors had a worse prognosis in comparison with those with grades 1 and 2 tumors (41 versus 56%, p less than 0.005). The over-all 5-year survival of patients with positive nodes was 4% in comparison with 60% of those without nodal involvement (p less than 0.001). Despite current optimal surgical treatment, nearly 50% of all patients with invasive bladder cancer continue to die. The need for a modification of the current tumor, nodes and metastasis tumor classification to provide the clinician a more reliable staging system for planning treatment modalities is indeed mandatory.

A new technique for detubularized and originally reshaped ileal total bladder replacement following radical cystectomy for bladder cancer is described and named 'Vescica Ileale Padovana'. 16 patients have been clinically, radiologically and urodynamically evaluated with a follow-up ranging from 4 to 18 months (mean 10 months). The complication rate was low: 1 ureteroileal stenosis; 2 urethroileal strictures. Daytime continence was perfect in 87% (14 of 16 patients). Nighttime continence was perfect (dry sleep for 6-7 h) in 81% (13 of 16 patients). The reservoir features were: high capacity (400-650 ml); low pressure (mean pressure at capacity 17 cm H2O no pressure waves in 50% of patients 30-50 cm H2O wide pressure waves with 250-ml threshold volume in 50%); absence of reflux; complete voiding by abdominal straining, and perineal relaxation.

A retrospective study was carried out on 200 consecutive superficial transitional cell carcinomas of the bladder in order to identify which factors could influence the recurrence and/or progression of the tumor. Many parameters were considered, such as stage, grade, number, size, site, tumor-free interval and bladder mucosa mapping. A careful histological study of the initial tumor was employed and the tumors confined to the stromal core of the papillary tumor (T1a) were separated from those with invasion of the lamina propria of the bladder wall (T1b). The behavior of the T1b lesions observed in our study will be discussed in a forthcoming article. Recurrence occurred in 83% of our patients, and it was influenced by number and grade of the tumor and by the presence of dysplasia in normal-appearing mucosa. In 20% of our patients tumor progression occurred. Tumor progression was correlated with invasion of the lamina propria of the bladder wall, high-grade neoplasias, tumor-free interval, dysplasia or carcinoma in situ in normal-appearing mucosa. The results of our study suggest that, by these risk factors, a better prediction of the behavior of superficial transitional cell carcinoma and, as a consequence, more appropriate treatment can be provided.

A case of bladder herniation through the abdominal wall as a late complication of retropubic prostatic adenomectomy is reported. The computed tomographic scan gave the diagnosis and a complete recovery was obtained with herniorraphy.

From January 1979 to June 1982, 141 consecutive patients with bladder transitional cell carcinoma were treated with a single stage lymphadenectomy plus radical cystectomy. The survival rate observed in our patients, based on the TNM classification, was comparable with that reported for other groups employing contemporary surgery. Survivorship for patients with deep invasive tumors was also estimated by breaking down the pT3 stage, and patients with tumor confined to the bladder wall (pT3a) were separately evaluated from those with tumor extended outside (pT3b). The results obtained with this subdivision showed that pT3a patients have almost the same survival rate as pT2 patients. From these results it is concluded that radical cystectomy is a satisfactory curative treatment of bladder cancer confined to the bladder wall, whatever the extension of the muscular involvement. Such considerations suggest that, in order to achieve a more objective analysis of the results after radical cystectomy for invasive bladder cancer, a modification of clinical staging is necessary. Moreover, a simplification of the classification methods should provide a better identification of the elements required to assess the prognosis and to improve treatment planning.