Active Surveillance for Low Risk Nonmuscle Invasive Bladder Cancer: A Confirmatory and Resource Consumption Study from the BIAS Project.

PURPOSE: We investigated predictive factors of failure and performed a resource consumption analysis in patients who underwent active surveillance for nonmuscle invasive bladder cancer. MATERIALS AND METHODS: This prospective observational study monitored patients with a history of pathologically confirmed stage pTa (grade 1-2) or pT1a (grade 2) nonmuscle invasive bladder cancer, and recurrent small size and number of tumors without hematuria and positive urine cytology. The primary end point was the failure rate of active surveillance. Assessment of failure predictive variables and per year direct hospital resource consumption analysis were secondary outcomes. Descriptive statistical analysis and Cox regression with univariable and multivariable analysis were done. RESULTS: Of 625 patients with nonmuscle invasive bladder cancer 122 with a total of 146 active surveillance events were included in the protocol. Of the events 59 (40.4%) were deemed to require treatment after entering active surveillance. Median time on active surveillance was 11 months (IQR 5-26). Currently 76 patients (62.3%) remain under observation. On univariable analysis only time from the first transurethral resection to the start of active surveillance seemed to be inversely associated with recurrence-free survival (HR 0.99, 95% CI 0.98-1.00, p = 0.027). Multivariable analysis also revealed an association with age at active surveillance start (HR 0.97, 95% CI 0.94-1.00, p = 0.031) and the size of the lesion at the first transurethral resection (HR 1.55, 95% CI 1.06-2.27, p = 0.025). The average specific annual resource consumption savings for each avoided transurethral bladder tumor resection was €1,378 for each intervention avoided. CONCLUSIONS: Active surveillance might be a reasonable clinical and cost-effective strategy in patients who present with small, low grade pTa/pT1a recurrent papillary bladder tumors.

68Ga-PSMA Positron Emission Tomography/Computerized Tomography for Primary Diagnosis of Prostate Cancer in Men with Contraindications to or Negative Multiparametric Magnetic Resonance Imaging: A Prospective Observational Study.

PURPOSE: 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography may represent the most promising imaging modality to identify and risk stratify prostate cancer in patients with contraindications to or negative multiparametric magnetic resonance imaging. MATERIALS AND METHODS: In this prospective observational study we analyzed 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography in a select group of patients with persistently elevated prostate specific antigen and/or Prostate Health Index suspicious for prostate cancer, negative digital rectal examination and at least 1 negative biopsy. The cohort comprised men with equivocal multiparametric magnetic resonance imaging (Prostate Imaging-Reporting and Data System, version 2 score of 2 or less), or an absolute or relative contraindication to multiparametric magnetic resonance imaging. Sensitivity, specificity and CIs were calculated compared to histopathology findings. ROC analysis was applied to determine the optimal cutoff values of 68Ga labeled prostate specific membrane antigen uptake to identify clinically significant prostate cancer (Gleason score 7 or greater). RESULTS: A total of 45 patients with a median age of 64 years were referred for 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography between January and August 2017. The 25 patients (55.5%) considered to have positive positron emission tomography results underwent software assisted fusion biopsy. We determined the uptake values of regions of interest, including a median maximum standardized uptake value of 5.34 (range 2.25 to 30.41) and a maximum-to-background standardized uptake value ratio of 1.99 (range 1.06 to 14.42). Mean and median uptake values on 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography (ie the maximum standardized uptake value or the maximum-to-background standardized uptake value ratio) were significantly higher for Gleason score 7 lesions than for Gleason score 6 or benign lesions (p <0.001). On ROC analysis a maximum standardized uptake value of 5.4 and a maximum-to-background standardized uptake value ratio of 2 discriminated clinically relevant prostate cancer with 100% overall sensitivity in each case, and 76% and 88% specificity, respectively. CONCLUSIONS: Our findings support the use of 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography for primary detection of prostate cancer in a specific subset of men.

Active surveillance for low-risk non-muscle-invasive bladder cancer: mid-term results from the Bladder cancer Italian Active Surveillance (BIAS) project.

OBJECTIVE: To report the oncological safety and the risk of progression for patients with non-muscle-invasive bladder cancer (NMIBC) included in an active surveillance (AS) programme after the diagnosis of recurrence. PATIENTS AND METHODS: This is a prospective study enrolling patients with history of pathologically confirmed low grade pTa-pT1a NMIBC and diagnosed with a tumour recurrence. Inclusion criteria consisted of negative urine cytology, presence of ≤5 lesions with a diameter of ≤10 mm, absence of carcinoma in situ (CIS) or persistent gross haematuria. The primary outcome of interest was adherence to AS. Need to proceed with treatment was defined as progression in number/dimension/positive cytology/symptoms (gross haematuria persistent) or any further intervention (resection or electro-fulguration). Finally, we assessed the up-grading and up-staging when transurethral resection of bladder tumour was performed. RESULTS: The study population consisted of 55 patients with a previous diagnosis of NMIBC (70 AS events) prospectively recruited since 2008. The mean patient age was 69.8 years. The median follow-up was 53 months. The median time patients remained under AS was 12.5 months. There was disease progression in 28 patients (51%). No patient progressed to muscle-invasive disease. In all, 15 patients (27.3%) had an increase in the number and/or size of the tumour, nine (16.4%) had haematuria, and four (7.3%) had a positive cytology. Only five (9%) patients in the whole series progressed to a high-grade tumour (Grade 3) or presented with associated CIS. The overall adherence to the follow-up schedule was 95%. CONCLUSION: Our data show that an AS protocol for NMIBC could be a reasonable option in a select group of patients with small, recurrent cancers.

Evaluation of Semen Self-Sampling Yield Predictors and CTC Isolation by Multi-Color Flow Cytometry for Liquid Biopsy of Localized Prostate Cancer.

Liquid biopsy (LB) for prostate cancer (PCa) detection could represent an alternative to biopsy. Seminal fluid (SF) is a source of PCa-specific biomarkers, as 40% of ejaculate derives from the prostate. We tested the feasibility of an SF-based LB by evaluating the yield of semen self-sampling in a cohort of >750 patients with clinically localized PCa. The overall SF collection yield was 18.2% (39% when considering only compliant patients), with about a half of the patients (53.15%) not consenting to SF donation. Independent favorable predictors for SF collection were younger age and lower prostate volume. We implemented a protocol to enrich prostate-derived cells by multi-color flow cytometry and applied it on SF and urine samples from 100 patients. The number of prostate-enriched cells (SYTO-16+ PSMA+ CD45-) was variable, with higher numbers of cells isolated from SF than urine (p value < 0.001). Putative cancer cells (EpCAMhigh) were 2% of isolated cells in both specimens. The fraction of EpCAMhigh cells over prostate-enriched cells (PSMA+) significantly correlated with patient age in both semen and urine, but not with other clinical parameters, such as Gleason Score, ISUP, or TNM stage. Hence, enumeration of prostate-derived cells is not sufficient to guide PCa diagnosis; additional molecular analyses to detect patient-specific cancer lesions will be needed.

Male awareness of prostate cancer risk remains poor in relatives of women with germline variants in DNA-repair genes.

Abstract. Objective: The aim of this study is to evaluate male awareness of developing prostate cancer (PCa) in families with germline DNA-repair genes (DRG) variants. Materials and methods: Data were collected from a prospective, monocentric cohort study. The study was conducted in a university hospital with a multidisciplinary approach to the patient (collaboration of the Departments of Oncology, Urology, Pathology, Radiology, and Medical Genetics Laboratory). We recruited healthy males, relatives of families of women with breast or ovarian cancer who tested positive for pathogenic variants (PVs) or likely pathogenic variants (LPVs) in DRGs. A dedicated PCa screening was designed and offered to men aged 35 to 69 years, based on early visits with digital rectal examination (DRE), prostate health index (PHI) measurement, multiparametric magnetic resonance imaging (mpMRI) and, if necessary, targeted/systematic prostate biopsies. The primary endpoint was to evaluate the willingness of healthy men from families with a DRG variants detected in female relatives affected with breast and/or ovarian cancer to be tested for the presence of familial PVs. The secondary endpoints were the acceptance to participate if resulted positive and compliance with the screening programme. Results: Over 1256 families, of which 139 resulted positive for PVs in DRGs, we identified 378 'healthy' men aged between 35 and 69 years old. Two hundred sixty-one (69.0%) refused to be tested for DRG variants, 66 (17.5%) declared to have been previously tested, and 51 (13.5%) males were interested to be tested. Between those previously tested and those who accepted to be tested, 62 (53.0%) were positive for a DRG variant, and all of them accepted to participate in the subsequent surveillance steps. The main limitation is that is a single-centre study and a short follow-up. Conclusions: All men tested positive for a DRG variants agreed to go under the surveillance scheme. However, only 31% of 'men at risk' (i.e., relative of a DRG variant carrier) expressed their willingness to be tested for the familial DRG variant. This observation strongly supports the urgent need to implement awareness of genetic risk for PCa within the male population.

Prospective evaluation of the role of imaging techniques and TMPRSS2:ERG mutation for the diagnosis of clinically significant prostate cancer.

Objectives: To test the hypothesis of a relationship between a specific genetic lesion (T2:ERG) and imaging scores, such as PI-RADS and PRI-MUS, and to test the effectiveness of these parameters for the diagnosis of prostate cancer (PCa) and clinically significant PCa (csPCa). Materials and methods: This is a prospective study of men with suspected PCa enrolled between 2016 and 2019 at a high-volume tertiary hospital. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they were presenting with >=1 suspicious lesion (PI-RADS>2) at mpMRI or PR-IMUS >2 at micro-ultrasound assessment. For each patient, one core from the highest PI-RADS or PRI-MUS lesion was collected for T2:ERG analysis. Multivariable logistic regression models (LRMs) were fitted for csPCa with a clinical model (age, total PSA, previous biopsy, family history for PCa), a clinical plus PI-RADS, clinical plus T2:ERG, clinical plus PI-RADS plus T2:ERG, and T2:ERG plus PI-RADS alone. Results: The cohort consists of 158 patients: 83.5% and 66.2% had respectively a diagnosis of PCa and csPCa after biopsy. A T2:ERG fusion was found in 37 men and 97.3% of these patients harbored PCa, while 81.1% were diagnosed with csPCa. SE of T2:ERG assay for csPCa was 28.8%, SP 87.0%, NPV 38.8%, and PPV 81.1%. Of 105 patients who performed mpMRI 93.% had PIRADS ≥3. SE of mpMRI for csPCa was 98.5%, SP was 12.8%, NPV was 83.3%, and PPV was 65.7%. Among 67 patients who were subjected to micro-US, 90% had a PRI-MUS ≥3. SE of micro-US for csPCa was 89.1%, SP was 9.52%, NPV was 28.6%, and PPV was 68.3%. At univariable LRM T2:ERG was confirmed as independent of mpMRI and micro-US result (OR 1.49, p=0.133 and OR 1.82, p=0.592, respectively). At multivariable LRM the clinical model alone had an AUC for csPCa of 0.74 while the clinical model including PI-RADS and T2:ERG achieved an AUC of 0.83. Conclusions: T2:ERG translocation and imaging results are independent of each other, but both are related csPCa. To evaluate the best diagnostic work-up for PCa and csPCa detection, all available tools (T2:ERG detection and imaging techniques) should be employed together as they appear to have a complementary role.

Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling.

UNLABELLED: What's known on the subject? and What does the study add? Transrectal gray-scale ultrasonography guided prostate biopsy sampling is the method for diagnosing prostate cancer (PC) in patients with an increased prostate specific antigen level and/or abnormal digital rectal examination. Several imaging strategies have been proposed to optimize the diagnostic value of biopsy sampling, although at the first biopsy nearly 10-30% of PC still remains undiagnosed. This study compares the PC detection rate when employing Colour Doppler ultransongraphy with or without the injection of SonoVue™ microbubble contrast agent, versus the transrectal ultrasongraphy-guided systematic biopsy sampling. The limited accuracy, sensitivity, specificity and the additional cost of using the contrast agent do not justify its routine application in PC detection. OBJECTIVE: • To compare prostate cancer (PC) detection rate employing colour Doppler ultrasonography with or without SonoVue™ contrast agent with transrectal ultrasonography-guided systematic biopsy sampling. PATIENTS AND METHODS: • A total of 300 patients with negative digital rectal examination and transrectal grey-scale ultrasonography, with PSA values ranging between 2.5 and 9.9 ng/mL, were randomized into three groups: 100 patients (group A) underwent transrectal ultrasonography-guided systematic bioptic sampling; 100 patients (group B) underwent colour Doppler ultrasonography, and 100 patients (group C) underwent colour Doppler ultrasonography before and during the injection of SonoVue™. • Contrast-enhanced targeted biopsies were sampled into hypervascularized areas of peripheral, transitional, apical or anterior prostate zones. • All the patients included in Groups B and C underwent a further 13 systematic prostate biopsies. The cancer detection rate was calculated for each group. RESULTS: • In 88 (29.3%) patients a histological diagnosis of PC was made, whereas 22 (7.4%) patients were diagnosed with high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. • No significant differences were found among the three groups for cancer detection rate (P= 0.329). • Additionally, low sensitivity, specificity and accuracy of colour Doppler with or without SonoVue™ contrast agent were found. CONCLUSIONS: • Prostate cancer detection rate does not significantly improve with the use of colour Doppler ultrasonography with or without SonoVue™. • Although no collateral effects have been highlighted, the combined use of colour Doppler ultrasonography and SonoVue™ determines adjunctive costs and increases the mean time for taking a single prostate biopsy.

Prospective Evaluation of 68Ga-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography in Primary Prostate Cancer Diagnosis.

BACKGROUND: Positron emission tomography (PET)/computed tomography (CT) with 68Ga-labeled prostate-specific membrane antigen ligand (68Ga-PSMA) may represent the most promising alternative to multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) diagnosis. OBJECTIVE: To test the diagnostic performance of 68Ga-PSMA PET/CT in this clinical context. DESIGN, SETTING, AND PARTICIPANTS: From January 2017 to December 2018 we prospectively enrolled 97 patients with persistently elevated prostate-specific antigen and/or Prostate Health Index score, negative digital rectal examination, and previous negative biopsy. We also included patients with either negative mpMRI or contraindications to or positive mpMRI but previous negative biopsy. INTERVENTION: Patients underwent 68Ga-PSMA PET/CT with additional pelvic reconstruction. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint of the study was the diagnostic performance of 68Ga-PSMA PET/CT in detecting malignant lesions and clinically significant PCa (Gleason score [GS] ≥7). RESULTS AND LIMITATIONS: 68Ga-PSMA PET/transrectal ultrasound fusion biopsy was performed in 64 of 97 patients (66%) for 114 regions of interest (ROIs). Forty patients (41%) had already undergone mpMRI with either a negative result for PCa (n = 15; 22 ROIs) or a positive mpMRI result but a previous negative biopsy. According to pathology, 23 patients (36%) had evidence of PCa: eight (16 ROIs) with GS 6, 13 (21 ROIs) with GS 7 (3 + 4 or 4 + 3), one (2 ROIs) with GS 8, and one (2 ROIs) with GS 10. Clinically significant PCa was identified in four patients with previous negative mpMRI (25%). PET/CT demonstrated PCa in seven patients (14 ROIs) with previous positive mpMRI and negative biopsy. The median maximum standardized uptake value (SUVmax) and median SUV ratio were significantly higher for PCa lesions than for benign lesions (p < 0.001). Optimal cutoff points obtained for SUVmax (>5.4) and SUV ratio (>2.2) could identify clinically significant PCa with accuracy of 81% and 90%, respectively. CONCLUSIONS: In our cohort of patients with high suspicion of cancer,68Ga-PSMA PET/CT was capable of detecting malignancy and accurately identifying clinically relevant PCa. PATIENT SUMMARY: Positron emission tomography/computed tomography with a 68Ga-labeled ligand for prostate-specific membrane antigen is capable of detecting prostate cancer in patients with a high suspicion of cancer and a previous negative biopsy.

Hope for Ostomates: A Carbon and Zeolite Impregnated Polyester Fabric Inhibits Urine Odor in Cancer Patients: A Randomized Experimental Study.

OBJECTIVE: Many individuals with bladder cancer have undergone a surgical urostomy and often complain of being self-conscious of the unpleasant smell of their own urine. The focus of this study was to test the efficacy of a pouch cover made of a carbon and zeolite containing polyester material to inhibit the smell of urine by comparing two trained dogs' response time in detecting volatile organic compounds (VOCs) in urine, with and without the fabric covering the samples. METHODS: This study used a randomized, blinded experimental design to evaluate the efficacy of a fabric to interfere with two highly trained dogs' ability to detect specific VOCs present in the urine of prostate cancer patient. Ninety urine samples were analyzed in this study. RESULTS: Prior to the experiment, both dogs accurately detected VOCs in the uncovered test urine samples of men with prostate cancer with a sensitivity and specificity of nearly 100%. Both dogs recognized the "uncovered" urine samples of men with prostate cancer within two seconds. When the test sample was covered with the study fabric, the test urine samples were detected within 30-40 seconds and in some instances the dogs were not able to identify the covered samples, whatsoever. CONCLUSION: The findings of this study demonstrate that the carbon and zeolite containing polyester fabric did significantly interfere with the ability of the dogs to detect VOCs in urine of men with prostate cancer. The fabric may show promise as a pouch cover in controlling offensive urine odor which many ostomates experience.

Bladder metastases of appendiceal mucinous adenocarcinoma: a case presentation.

BACKGROUND: Appendiceal adenocarcinoma is rare with a frequency of 0.08% of all surgically removed appendices. Few cases of appendiceal carcinoma infiltrating the bladder wall for spatial contiguity have been documented. CASE PRESENTATION: A case is reported of a 45-years old woman with mucinous cystadenocarcinoma of the appendix with bladder metastasis. Although ultrasonography and voided urinary cytology were negative, abdomen computed tomography (CT) scan and cystoscopy and subsequent pathological examination revealed a mass exclusively located in the anterior wall of the bladder. Histopathology of the transurethral bladder resection revealed a bladder adenocarcinoma [6 cm (at the maximum diameter) x 2,5 cm; approximate weight: 10 gr] with focal mucinous aspects penetrating the muscle and perivisceral fat. Laparotomy evidenced the presence of a solid mass of the appendix (2,5 cm x 3 cm x 2 cm) extending to the loco-regional lymph nodes. Appendectomy and right hemicolectomy, linfoadenectomy and partial cystectomy were performed. The subsequent pathological examination revealed a mucinous cystadenocarcinoma of the appendix with metastatic cells colonising the anterior bladder wall and several colic lymph nodes. CONCLUSIONS: The rarity of the appendiceal carcinoma invading the urinary bladder and its usual involvement of nearest organs and the posterior bladder wall, led us to describe this case which demonstrates the ability of the appendiceal cancer to metastasize different regions of urinary bladder.

Corporoplasty by plication: out patient surgery for the correction of penile curvature.

OBJECTIVE: Corporoplasty using plication of the albuginea is a simple technique but considered by many Authors at high risk for recurrence in respect to other corrective techniques using excision of the albuginea tunica. The aim of this study was to assess long-term functional and cosmetic results of this approach done in an outpatient environment. MATERIAL AND METHODS: From January 1997 to December 2008 we submitted 217 patients presenting induratio penis plastica (183) or congenital curvature (34) to corporoplasty with albuginea plication. All patients were assessed preoperatively with history, physical examination and photographic documention of the erectile penis. These patients, all with vaginal penetration problems, were submitted to corporoplication with 2-4 sutures 2/0 (polyglycolic) contralateral to the curvature, using local anaesthesia on outpatient basis. Follow-up included functional and cosmetic results, eventual complications and level of patient satisfaction. RESULTS: Median follow-up of our study was 44 months (range 2-58). Complete correction of curvature was achieved in 206 patients (95%) whereas 87% reported good erectile function (IIEF-5 > 21). 145 patients (67%) reported penis shortening and 41% complained of palpating the sutures. Two patients required reoperation for recurring curvature. No perioperative complications or altered sensitivity of the glans were reported. CONCLUSIONS: Simple plication of the corpora cavernosa can be done on an outpatient basis using local anaesthesia with optimal functional and cosmetic results. The success of this minimally invasive approach makes it a valid alternative to standard excision of the tunica albuginea procedure. Detailed preoperative information concerning procedure expectations and treatment course are extremely important in obtaining complete functional and cosmetic patient satisfaction.

Tubeless percutaneous nephrolithotomy: Our experience.

PURPOSE: To evaluate safety and outcomes of tubeless PCNL in comparison with standard PCNL. MATERIALS AND METHODS: Since June 2002 we have performed 99 tubeless PCNL. Tubeless technique involves antegrade placement of a 6Fr double-J stent without nephrostomy tube at the end of the procedure. This series has been compared with a total of 110 patients in which revision of operative reports ruled out the presence of intraoperative conditions necessary to candidate a patient to tubeless procedure but standard PCNL was performed because prior to its introduction or because of surgeon's attitude afterward. Mean stone burden was 5.4 for standard group and 4.9 cm2 for tubeless group respectively. Mean BMI was 24.1 in the first group and 23.6 in the second one. In this retrospective study, complications rate, postoperative pain, length of hospitalization and convalescence were evaluated by chart review. RESULTS: Hematocrit drop did not differ significantly between tubeless PCNL and standard PCNL (5.5% vs 5.90%). Conversely, there was statistically significant difference between tubeless and standard PCNL in terms of the amount of analgesics (49.5 vs. 84.2 mg), immediate postoperative patients' discomfort, hospitalization (2.2 vs 5.3 days) and time to resume normal activities (11.0 vs 16.5 days). CONCLUSIONS: In our series, tubeless approach did not determine increase in complication rate. Conversely, tubeless PCNL reduced analgesics' requirement, patients' discomfort, hospitalization and time to recovery. As such, at our Institution, tubeless PCNL has become routine procedure that actually is feasible in almost 2/3 of renal calculi suitable for percutaneous treatment.

Percutaneous nephrolithotomy: tubeless or not tubeless?

The objective of this study is to evaluate the safety and outcomes of tubeless PCNL in comparison with standard PCNL. Since June 2002, we have performed 99 tubeless PCNL. Tubeless technique involves antegrade placement of a 6Fr double-J stent without nephrostomy tube at the end of the procedure. This series has been compared with a total of 110 patients in which revision of operative reports ruled out the presence of intraoperative conditions necessary to candidate a patient to tubeless procedure but standard PCNL was performed because prior to its introduction or because of surgeon's attitude afterward. Mean stone burden was 5.4 for standard group and 4.9 cm(2) for tubeless group, respectively. Mean BMI was 24.1 in the first group and 23.6 in the second one. In this retrospective study, complications rate, postoperative pain, length of hospitalization and convalescence were evaluated by chart review. Hematocrit drop did not differ significantly between tubeless PCNL and standard PCNL (5.5 vs. 5.9%). Conversely, there was statistically significant difference between tubeless and standard PCNL in terms of the amount of analgesics (49.5 vs. 84.2 mg), immediate postoperative patients' discomfort, hospitalization (2.2 vs. 5.3 days) and time to resume normal activities (11.0 vs. 16.5 days). In conclusion, in our series, tubeless approach did not determine increase in complication rate. Conversely, tubeless PCNL reduced analgesics' requirement, patients' discomfort, hospitalization and time to recovery. As such, at our institution, tubeless PCNL has become routine procedure that actually is feasible in almost two-third of renal calculi suitable for percutaneous treatment.

PSA repeatedly fluctuating levels are reassuring enough to avoid biopsy?

INTRODUCTION: Prostate-specific antigen (PSA) levels can show wide fluctuations when repeatedly measured. Here we investigatewd if: (a) biopsy timing influences the prostate cancer (PC) detection rate in patients with fluctuating PSA (flu-PSA) in comparison with patients with steadily increasing PSA (si-PSA); (b) PSA slope estimated in patients with flu-PSA predicts a different risk of cancer detection; (c) flu-PSA and si-PSA patients develop PC in topographically different sites; (d) the behaviour of pre-operative PSA is an expression of a disease with defferent characteristics to the following radical prostatectomy. METHODS: The study involved 211 patients who underwent at least a second biopsy after a first negative prostate biopsy. PSA Slope, PSA velocity (PSAV) and PSA doubling time (PSADT) were estimated. Flu-PSA level was defined as a PSA series with at least one PSA value lower than the one immediately preceding it. RESULTS: 82 patients had flu-PSA levels and 129 si-PSA levels. There were no significant differences between the two groups in terms of cancer detection, clinical or pathological stage, but the si-PSA group with cancer had a higher Gleason score. No difference was found for PSA Slope between flu-PSA patients with cancer and those without. CONCLUSIONS: Our study demonstrates no difference in PC detection rate at repeat biopsy between patients with flu or si-PSA levels. PSA Slope, PSAV and PSADT were not found helpful tools in cancer detection.

Predictive factors for progression of patients with carcinoma in situ of the bladder at long-term follow-up: pure versus non-pure CIS.

BACKGROUND: The aim of this study was to identify the predictive factors for progression defined as any event that shifted the management of the disease from a bladder sparing approach, by comparing patients with pure versus non-pure carcinoma in situ (CIS) of the bladder. METHODS: A retrospective analysis was carried out in consecutive patients affected by newly-diagnosed pure CIS and non-pure CIS (excluding cases with concomitant muscle invasive cancer). All patients were enrolled a in our institution from 1998 to 2010. Data was prospectively collected. Main end point was progression-free survival. RESULTS: Overall, 149 patients with CIS were identified for the analysis. A total of 98 patients had pure CIS (66%). Median follow-up was 103 months (range: 40-206 months). Progression occurred in 29 patients (19%). A total of 30 patients died during the follow-up (20%). In 13 cases (9%), the death was cancer specific. Progression-free survival estimate was 181 months (95% CI: 169-193 months) and 154 months (95% CI: 133-176 months) respectively for pure and non-pure CIS population (P=0.03). Among examined variables (age, gender, symptoms, smoking habit, ASA score, number of bacillus Calmette-Guérin [BCG] instillations), multivariate analysis disclosed that only CIS type was an independent predictor of progression (P=0.03) with a relative risk of 0.37 in favor of pure CIS. CONCLUSIONS: Pure and non-pure CIS are efficiently treated by BCG therapy combined with trans-urethral resection and/or radical cystectomy, with relatively low rate of progression. CIS type was the only significant predictor of progression.

Long-term outcomes of high-grade T1 bladder cancer treated with intravesical bacillus Calmette-Guérin: experience of a single center.

BACKGROUND: To assess the outcomes of patients with high-grade (HG) pT1 bladder cancer (BC) treated with intravesical BCG therapy. METHODS: The study population consisted of 185 patients with HG pT1 BC treated between 1998 and 2010. We aimed to determine recurrence-free (RFS) and progression-free survival (PFS), as well as the predictors of RFS and PFS. RESULTS: Overall, 143 (77.3%) patients were males. Median age was 72 years (IQR: 66-78). Tumor size was ≥3 cm in 100 (54.1%) individuals. Most patients had single tumors (125; 67.6%). Primary, progressive and recurrent patterns of presentation were observed in 146 (78.9%), 21 (11.4%), and 18 (9.7%) cases, respectively. After 2nd-look TURB, 127 (68.6%) patients had no residual disease, 44 (23.8%) had Ta/CIS, and 14 (7.6%) had T1 HG BC. Twenty-two (11.9%) patients experience early recurrence after BCG. Of these, 12 patients (54.5%) were diagnosed with Ta/CIS, while 10 (45.5%) were diagnosed with HG pT1 BC. The median follow-up was 93 months (IQR: 63-147). Ten-year RFS and PFS rates were 69.6 and 79.2%. In multivariable Cox regression models, female gender (HR=2.41; P=0.001), progressive (HR=2.03; P=0.030) and recurrent (HR=3.87; P<0.001) pattern of presentation emerged as independent predictors of RFS, while age ≥70 years (HR=2.13; P=0.027), presence of multiple tumors (HR=2.06; P=0.019), and early recurrence (HR=3.88; P<0.001) emerged as independent predictors of PFS. CONCLUSIONS: Intravesical BCG appears to be an effective treatment for HG pT1 BC. Caution should be used in patients aged ≥70 years, with multiple tumors or experiencing early recurrence.

Nephron sparing surgery of parenchymal kidney tumours in solitary kidney.

INTRODUCTION: The aim of this study is to assess the therapeutic efficacy of nephron sparing surgery (NSS) in our experience applied to patients with either bilateral renal cancer or patients with cancer in a solitary functioning kidney, from an oncological viewpoint as well as renal function. MATERIALS AND METHODS: From January 1997 to March 2006 we submitted 185 patients to NSS. Twenty-seven presented absolute indications with disease in functionally or anatomically solitary kidney. All but six patients presented with preoperative creatinine levels lower than 2 mg/dL. Access was always lombotomic. Nineteen patients underwent renal artery clamping and cold ischemia. Lesions were between 2 and 14 cm in size. In six cases the collecting system was formally opened. RESULTS: Follow-up was between 2 and 108 months. Final histology showed 17 patients with clear cell renal carcinoma, six papillary cell carcinomas, one chromophobe carcinoma, one oncocytoma and two angiomyolipomas. No major perioperative complications were recorded. Two patients died of lung metastases. Two patients present secondary tumours (lung and liver), whereas one patient is being treated with chemotherapy for colon cancer Twenty-two patients are disease-free. None of the 10 patients discharged with creatinine levels >2 mg/dL, were submitted to dialytic therapy during follow-up. None of the patients discharged with normal renal function developed kidney failure. CONCLUSIONS: Conservative surgery for patients with absolute indications, is a valid alternative to radical surgery that obviously commits patients to long-term dialysis or renal transplantation. Our cases showed minimal surgical complications, brief hospital stay and limited invasiveness for patients with small incidence of kidney failure associated to the all important cancer control.

Targeted 11C-choline PET-CT/TRUS software fusion-guided prostate biopsy in men with persistently elevated PSA and negative mpMRI after previous negative biopsy.

BACKGROUND: We evaluated the feasibility and accuracy of 11C-choline PET-CT/TRUS fusion-guided prostate biopsy in men with persistently elevated PSA and negative mpMRI or contraindication to MRI, after previous negative biopsy. Clinical data were part of a prospective on-going observational clinical study: "Diagnostic accuracy of target mpMRI/US fusion biopsy in patients with suspected prostate cancer after initial negative biopsy". Patients with a negative biopsy and negative mpMRI (PI-RADS v.2 < 3) or absolute contraindications to MRI and persistently elevated PSA, were included. All patients underwent 11C-choline PET with dedicated acquisition of the pelvis and PET-CT/TRUS-guided prostate biopsy by Bio-Jet™ fusion system (D&K Technologies, Germany). The primary endpoint was to assess the accuracy of 11C-choline PET-CT to determine the presence and the topographical distribution of PCa. RESULTS: Overall, 15 patients (median age 71 yrs. ± 8.89; tPSA 13.5 ng/ml ± 4.3) were analysed. Fourteen had a positive PET scan, which revealed 30 lesions. PCa was detected in 7/15 patients (46.7%) and four patients presented a clinically significant PCa: GS > 6. Over 58 cores, 25 (43.1%) were positive. No statistically significant difference in terms of mean and median values for SUVmax and SUVratio between benign and malignant lesions was found. PCa lesions with GS 3 + 3 (n = 3) showed a median SUVmax and SUVratio of 4.01 and 1.46, compared to 5.45 and 1.57, respectively for lesions with GS >6 (n = 4). CONCLUSION: Software PET-CT/TRUS fusion-guided target biopsy could be a diagnostic alternative in patients with a suspected primary PCa and negative mpMRI, but its specificity appeared low.

Single small focus of prostate adenocarcinoma (< or = 1 mm and too small for grading) and clinical significant disease after radical prostatectomy.

OBJECTIVES: To determine whether a clinical significant adenocarcinoma of the cinoma (defined as a lesion < or =1 mm. and too small for grading) at needle biopsy, even repeated, and through prostate specific antigen (PSA), PSA density (PSAD) and free-to-total PSA ratio (f/t ratio). METHODS: Retrospectively 79/1610 consecutive patients undergoing prostatic needle biopsies presented one small focus of prostatic adenocarcinoma < or =1 mm and too small for grading. All patients underwent PSA, PSAD and f/t ratio to evaluate positive predictive value for clinically significant disease. All patients were submitted to radical retropubic prostatectomy (RRP) and were divided into three groups: group A (28/79 patients, 35.4%) submitted to RRP after diagnosis of just one small focus of adenocarcinoma at first biopsy; group B (26/79 patients, 32.9%) submitted to RRP after two successive diagnoses of small focus of adenocarcinoma; group C (25/79 patients, 31.6%) submitted to RRP after diagnosis of adenocarcinoma larger than 1 mm at successive biopsy in which Gleason score had been applied. RESULTS: The three groups resulted comparable for age, PSA, f/t ratio and PSAD. Clinically significant disease was found in 48 of 79 patients (60.7%); 16 patients of group A (33.3%), 15 patients of group B (31.2%) and 17 patients of group C (35.4%) respectively. Finally, PSA, f/t ratio, and PSAD showed no predictive value neither globally nor in the single groups. CONCLUSIONS: No selective criteria with consolidated predictive values emerge from our study and this is in agreement with data in the literature, where the risk to find no significant clinical disease is 9-48% approximately. The aim of this retrospective study is to analyze the correlation between a single small focus of adenocarcinoma by prostatic biopsy, even repeated, and the clinical significant disease on the following radical retropubic prostatectomy. Furthermore, we verified whether some preoperative parameters could be helpful to identify the subgroups of patients which could need a more or less aggressive and/or timely treatment. Our data show that 30-40% of patients did not harbor a clinically significant disease at the following RRP. Furthermore, the assumed predictive value of repeat biopsies has not been confirmed in these patients and no other preoperative predictive values can be helpful.

Managing chronic bladder diseases with the administration of exogenous glycosaminoglycans: an update on the evidence.

Although the pathophysiology of acute chronic cystitis and other 'sensory' disorders, i.e. painful bladder syndrome (PBS) or interstitial cystitis (IC), often remains multifactorial, there is a wide consensus that such clinical conditions may arise from a primary defective urothelium lining or from damaged glycosaminoglycans (GAGs). A 'cascade' of events starting from GAG injury, which fails to heal, may lead to chronic bladder epithelial damage and neurogenic inflammation. To restore the GAG layer is becoming the main aim of new therapies for the treatment of chronic cystitis and PBS/IC. Preliminary experiences with GAG replenishment for different pathological conditions involving the lower urinary tract have been reported. There is a range of commercially available intravesical formulations of these components, alone or in combination. Literature evidence shows that exogenous intravesical hyaluronic acid markedly reduces recurrences of urinary tract infections (UTIs). Patients treated with exogenous GAGs have fewer UTI recurrences, a longer time to recurrence and a greater improvement in quality of life. Exogenous intravesical GAGs have been used for the treatment of PBS/IC. Despite the limitations of most of the studies, findings confirmed the role of combination therapy with hyaluronic acid and chondroitin sulfate as a safe and effective option for the treatment of PBS/IC. To prevent and/or treat radiotherapy and chemotherapy induced cystitis, GAG replenishment therapy has been used showing preliminary encouraging results. The safety profile of exogenous GAGs has been reported to be very favourable, without adverse events of particular significance.