Diagnostic Performance and Clinical Impact of PSMA PET/CT versus mpMRI in Patients with a High Suspicion of Prostate Cancer and Previously Negative Biopsy: A Prospective Trial (PROSPET-BX).

BACKGROUND: This prospective single-arm study is designed to compare in parallel 68Ga-PSMA PET/TRUS (transrectal or transperineal) fusion biopsy ("experimental test") with multiparametric MRI (mpMRI)/TRUS fusion prostate biopsy ("standard test") in men with a high suspicion of prostate cancer (PCa) after at least one negative biopsy. The primary objective was to evaluate the diagnostic performance of 68Ga-PSMA PET/TRUS fusion prostate biopsy in comparison to mpMRI/TRUS fusion prostate biopsy analyzed in parallel. Secondarily, we aimed to determine the relationship between the "experimental test" and the histopathological characteristics of the specimen, along with the clinical utility of the "experimental test" compared to the "standard test." SUMMARY: To test the superiority of 68Ga-PSMA PET/CT compared to mpMRI, we will enroll a minimum cohort of 128 patients. Inclusion criteria comprise: age >18 years; blood PSA level >4.0 ng/mL; free-to-total PSA ratio <20%; progressive rise of PSA levels in two consecutive blood samples despite antibiotics; serum blood tests suspicious for PCa; at least one previous negative biopsy; ASAP and/or high-grade PIN; negative digital rectal examination. All eligible patients will undergo 68Ga-PSMA PET/CT and mpMRI scans within 1 month's distance from each other, followed by biopsy session to be completed within 1 month's distance. Targeted TRUS fusion needle biopsy will be performed for all lesions detected with PET and mpMRI. The total duration of the study is 36 months. KEY MESSAGES: By comparing the "experimental test" and the "standard test" in parallel, we will be able to determine the superior diagnostic performance of 68Ga-PSMA PET/CT over mpMRI in detecting PCa, and in particular clinically significant PCa, in the specific cohort of patients with a high suspicion of PCa who are candidates to re-biopsy. The clinical impact of the "experimental test" will be subsequently analyzed in terms of the number of prostate biopsies that could be spared, time-consuming, patient friendliness, and cost-effectiveness.

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.

Early Catheter Removal After Robot-assisted Radical Prostatectomy: Results from a Prospective Single-institutional Randomized Trial (Ripreca Study).

BACKGROUND: The adoption of robotic technology in the treatment of prostate cancer (PCa) could lead to improvement in outcomes. OBJECTIVE: To evaluate feasibility, to compare functional outcomes, and to assess the economic benefits of removing catheter on the postoperative day (POD) 3 versus POD 5 after robot-assisted radical prostatectomy (RARP). DESIGN, SETTING, AND PARTICIPANTS: From September 2016 to May 2017, patients selected to undergo RARP for clinically localized PCa at a high-volume center were prospectively randomized into group 1 (POD 3; n=72) versus group 2 (POD 5, n=74). INTERVENTION: All patients underwent RARP with anatomical posterior and anterior reconstruction. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was to compare acute urinary retention (AUR) and urinary leakage rate in the two groups. The secondary endpoints were early and mid-term postoperative functional outcomes assessed through questionnaires (ICIQ-MLUTS, IPSS), early continence rate, and postoperative pain/discomfort (visual analog scale score). The economic impact of early catheter removal was also assessed. RESULTS AND LIMITATIONS: AUR was reported in two (1.4%) cases, one for each study group (p=0.9). One case of vesicourethral leakage was reported (0.7%) in group 1. Urethral discomfort and pain at discharge was significantly higher in group 2 (p=0.03). In our clinical practice, POD 3 catheter removal approach would determine a saving of approximately €80 000 and 405 d of hospitalization yearly. The main limitation is the small sample size. CONCLUSIONS: Early catheter removal after RARP does not lead to an increase in perioperative complications. No negative effect on early and mid-term functional outcomes was observed. A significant impact on saving economic resources was reported. PATIENT SUMMARY: We demonstrated that early catheter removal has no negative effect on spontaneous voiding, complications, or urinary continence recovery after robot-assisted radical prostatectomy.

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.

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 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.

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.

A prospective multicenter European study on flexible ureterorenoscopy for the management of renal stone.

PURPOSE: The aim of this study was to describe the outcomes and the complications of retrograde intrarenal surgery (RIRS) for renal stones in a multi-institutional working group. MATERIALS AND METHODS: From 2012 to 2014, we conducted a prospective study including all RIRS performed for kidney stones in 4 European centers. Demographic information, disease characteristics, and perioperative and postoperative data were gathered. Patients and stone data, procedure characteristics, results and safety outcomes were analyzed and compared by descriptive statistics. Complications were reported using the standardized Clavien system. RESULTS: Three hundred and fifty-six patients underwent 377 RIRS with holmium laser lithotripsy for renal stones. The RIRS was completed in all patients with a mean operative time of 63.5 min. The stone-free status was confirmed endoscopically and through fluoroscopic imaging after the first procedure in 73.6%. The second procedure was performed in twenty patients (5.6%) achieving an overall stone free rate of 78.9%. The overall complication rate was 15.1%. Intra-operative and post-operative complications were seen in 24 (6.7%) and 30 (8.4%) cases, respectively. CONCLUSIONS: RIRS is a minimally invasive procedure with good results in terms of stone-free and complications rate.

A prospective multicenter European study on flexible ureterorenoscopy for the management of renal stone

ABSTRACT Purpose The aim of this study was to describe the outcomes and the complications of retrograde intrarenal surgery (RIRS) for renal stones in a multi-institutional working group. Materials and Methods From 2012 to 2014, we conducted a prospective study including all RIRS performed for kidney stones in 4 European centers. Demographic information, disease characteristics, and perioperative and postoperative data were gathered. Patients and stone data, procedure characteristics, results and safety outcomes were analyzed and compared by descriptive statistics. Complications were reported using the standardized Clavien system. Results Three hundred and fifty-six patients underwent 377 RIRS with holmium laser lithotripsy for renal stones. The RIRS was completed in all patients with a mean operative time of 63.5 min. The stone-free status was confirmed endoscopically and through fluoroscopic imaging after the first procedure in 73.6%. The second procedure was performed in twenty patients (5.6%) achieving an overall stone free rate of 78.9%. The overall complication rate was 15.1%. Intra-operative and post-operative complications were seen in 24 (6.7%) and 30 (8.4%) cases, respectively. Conclusions RIRS is a minimally invasive procedure with good results in terms of stone-free and complications rate.

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.

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.

"En Bloc" Resection of Nonmuscle Invasive Bladder Cancer: A Prospective Single-center Study.

OBJECTIVE: To describe our "en bloc" technique for nonmuscle invasive bladder cancer (NMIBC), assess the quality of resection, and report the midterm oncological outcome. MATERIALS AND METHODS: This is an observational prospective longitudinal study, from June 2010 to February 2014, enrolling patients with clinically NMIBC, having tumors of ≤3 cm and ≤4 lesions who underwent electrical en bloc bladder resection. The primary study end point was recurrence-free survival. Secondary outcomes were feasibility, safety, the presence of detrusor muscle, and the recurrence rate at the first follow-up cystoscopy (3 months). Statistical analysis was complemented with multivariable analysis. RESULTS: Of 87 enrolled patients, 2 showed a nonurothelial carcinoma and 11 showed muscle invasive bladder carcinoma at the definitive pathology. The study cohort consisted of 74 transitional cell carcinoma NMIBC cases, mean age 71 years ± 8, presenting with a mean tumor diameter of 1.98 ± 0.59 cm and a median number of resected tumors per patients of 1 (range 1-4). The 2-year recurrence-free survival was 85.59%. All the en bloc resection of bladder tumor samples showed the presence of detrusor muscle and the recurrence rate at the first follow-up cystoscopy (3 months) was 5.4% (4/74). An extraperitoneal bladder perforation occurred in only one patient. At multivariable analysis, only gender and the presence of carcinoma in situ were independent predictors of recurrence. The midterm follow-up and the absence of a control group are the main limitations. CONCLUSION: Our findings confirmed the feasibility and safety of en bloc resection of bladder tumor, with a recurrence-free survival of 85% after 2 years.

Preoperative prostate health index is an independent predictor of early biochemical recurrence after radical prostatectomy: Results from a prospective single-center study.

BACKGROUND: The aim of this study was to test the hypothesis that preoperative prostate health index (PHI) levels could help to predict early biochemical recurrence (BCR) in a contemporary population of patients with prostate cancer treated with robot-assisted radical prostatectomy (RARP). METHODS: The study population consisted of 313 patients treated with RARP for clinically localized prostate cancer at a single institution between 2010 and 2011. Patients subjected to neoadjuvant or adjuvant therapies and patients with a follow-up of<2 years were excluded. BCR was defined as a postoperative level of total prostate-specific antigen ≥0.2 ng/ml and elevating after RARP. The minimum P-value method was used to determine the most significant PHI cutoff value to discriminate between patients with and without BCR. The Kaplan-Meier method was used to determine BCR-free survival rates. Finally, Cox regression models were fitted to determine the predictors of BCR, and the predictive accuracy (area under the curve) of each predictor was determined with the Harrell concordance index. RESULTS: Mean total prostate-specific antigen and mean PHI levels were 5.76 ng/ml (interquartile range: 4.2-8.7) and 46.0 (35-62), respectively. Biopsy Gleason score was 6 in 173 (55.3%), 7 in 121 (38.7%), and ≥8 in 19 (6.1%) patients. At final pathology, extracapsular extension was observed in 59 (18.8%), seminal vesicle invasion in 24 (7.7%), and lymph node invasion in 11 (3.5%) patients, whereas 228 (72.8%) patients had organ-confined disease. The 2-year BCR-free survival rate was 92.5% in the overall population and was 96.7% in patients with organ-confined disease. The most significant PHI cutoff value to discriminate between patients with and without BCR was 82. Specifically, the 2-year BCR-free survival rate was 97.7% in patients with a preoperative PHI level<82 relative to 69.7% in patients with a PHI level ≥82 (log-rank test: P<0.001). Finally, in multivariable Cox regression analyses, PHI level emerged as an independent predictor of BCR in both the preoperative and the postoperative settings and was more accurate than several established BCR predictors were. CONCLUSIONS: Preoperative PHI levels may discriminate between patients who are at a high risk vs. low risk of BCR after RARP. External validation of our findings within a larger population with a longer follow-up time is needed.

Single-session supine bilateral percutaneous nephrolithotomy.

OBJECTIVE: To evaluate the effectiveness and safety of supine bilateral percutaneous nephrolithotomy (BPCNL) performed in the same session in patients affected with bilateral renal calculi. METHODS: We retrospectively identified patients with bilateral renal stones with diameters >2 cm for each side, who had been treated with supine BPCNL in the same session, from November 2006 to April 2014. We reviewed demographic and stone characteristics, intraoperative and perioperative outcomes, and complications related to the procedure adopted. The stone size was calculated by measuring the maximum stone diameter by computed tomography scan. Stone-free rate was defined as clinically insignificant when residual fragments of ≤2 mm were detected by computed tomography scan. RESULTS: Twenty-five patients were included in the study; the mean age was 51.9 ± 11.4 years; the mean maximum stone diameter per renal unit was 3.1 ± 0.8 cm. Statistical significant differences in creatinine serum levels were detected at day 1 postoperatively compared with the baseline (P <.0001) values that became insignificant at 1 week and 1 month postoperatively (P >.05). The primary stone-free rate was 80%; ancillary procedures were performed in 3 of 25 patients (12%). Grade I complications occurred in 3 patients (12%), grade II in 4 patients (16%), and grade IIIA in 1 patient (4%). CONCLUSION: Supine BPCNL performed in the same session is a safe and effective procedure in patients affected with bilateral renal calculi. On the other hand, it is still a very challenging operation, and consequently, it should be performed only by experienced surgeons in a tertiary center.

Unclassified Renal Cell Carcinoma With Medullary Phenotype Versus Renal Medullary Carcinoma: Lessons From Diagnosis in an Italian Man Found to Harbor Sickle Cell Trait.

Medullary carcinoma is a rare malignant tumor of the kidney. It affects individuals of African descent and all cases reported show evidence of sickle cell trait. We reviewed an unusual carcinoma arising in a white man, the ninth in the literature. The tumor demonstrated features associated with renal medullary carcinoma, or unclassified renal cell carcinoma, medullary phenotype as recently described; the presence of sickle cell trait confirmed the diagnosis of medullary carcinoma. This case is helpful in the differential diagnosis with non-sickle cell associated "renal cell carcinoma, unclassified with medullary phenotype," and study of this spectrum of tumors is ongoing.

Sky is no limit for ureteroscopy: extending the indications and special circumstances.

PURPOSE: To critically review and synthesize data of ureteroscopy (URS) in different circumstances that all urologists may encounter during everyday clinical practice, such as pregnancy, obesity, bleeding diathesis, renal stones larger than 2 cm, calyceal diverticula, and kidney malformations. METHODS: According to PRISMA guidelines, a systematic literature review was performed to identify articles published between 1990 and December 2013 that reported different indications and special circumstances for URS. Articles were separated into the following categories: pregnancy, obesity, bleeding diathesis, stones larger than 2 cm in diameter, calyceal diverticula, and kidney malformations. We used a narrative synthesis for the analyses of the studies, including a description of the characteristics and main outcomes reported in the articles. RESULTS: Records identified through database searching were 1396; at the end of study selection, articles included were 57. The majority of these are retrospective studies and involve small cohorts of patients. There does not exist a consensus about important parameters in ureterorenoscopy like stone size, stone free status and complication rate. CONCLUSION: Ureteroscopy is effective and reliable tool capable of treating the majority of stones even in the most complicated clinical scenarios and will have more fundamental roles in endourology. The lack of definitive conclusions is due to the great heterogeneity in collecting study's results; multicentric randomized trials that define in advance the parameters to be studied should be encouraged.

Is retrograde intrarenal surgery for the treatment of renal stones with diameters exceeding 2 cm still a hazard?

INTRODUCTION: Major kidney stones have traditionally been treated with percutaneous nephrolithotomy. However, retrograde intrarenal surgery (RIRS), which until a few years ago was considered inappropriate for this purpose, is becoming a viable, attractive alternative. The aim of the current study was to assess the efficacy and safety of RIRS combined with holmium laser lithotripsy for the treatment of stones > 2 cm in diameter in a large series of patients, reporting complications according to the Clavien-Dindo classification. MATERIALS AND METHODS: By retrospective analysis, we identified a total of 162 patients who were affected by stones greater than 2 cm in diameter and who had undergone RIRS. We reviewed demographic and stone characteristics, intraoperative and postoperative outcomes, and complications. RESULTS: The mean stone size was 2.7 cm +/- 0.6 cm. The primary, secondary, and tertiary stone-free rates were 66%, 80.9%, and 87.7%, respectively. The mean number of procedures per patient was 1.48. The complication rates according to the Clavien-Dindo classification were Clavien I in 20.4% of patients, Clavien II in 0%, Clavien III in 4.9%, Clavien IV in 0.6%, and Clavien V in 0%. CONCLUSIONS: As an alternative to standard procedures for the treatment of renal calculi greater than 2 cm in diameter, RIRS is safe and effective, with a low complication rate.

Operative safety and oncologic outcome of laparoscopic radical nephrectomy for renal cell carcinoma >7 cm: a multicenter study of 222 patients.

OBJECTIVE: To evaluate the safety of laparoscopic radical nephrectomy (LRN) for renal cell carcinoma (RCC) >7 cm, addressing the issue of modality and risk factors for complications and open conversion, and to assess the oncologic outcome. METHODS: The data of 222 patients undergoing LRN for RCC >7 cm prospectively enrolled from 2002 to 2010 at 5 urologic centers were reviewed. Transperitoneal LRN was performed by 5 experienced laparoscopic surgeons. The Clavien-Dindo classification was used to assess complications. Multivariable analysis of factors predictive of conversions was performed. Oncologic outcomes for survival were estimated using the Kaplan-Meier method. RESULTS: Median tumor size was 8.5 cm, operative time was 180 minutes, and blood loss was 280 mL. Forty-two patients (19%) received a blood transfusion. Six (2.7%) patients had grade III-IV complications: 2 with postoperative bleeding requiring abdominal re-exploration and 1 each with adrenal injury, splenic injury, wound diastasis, and respiratory insufficiency. Twelve patients (5.4%) were converted to open surgery. The diameter was 11.9 in converted groups and 8.5 cm in nonconverted groups (P = .001). Multivariable analysis revealed that pathologic stage was the only independent predictor of conversion (P = .002). The 5-year overall (OS), cancer-specific (CSS), and progression-free (PFS) survival was 74%, 78%, and 66%, respectively. The 5-year stage-adjusted CSS was 89% in pT2 and 40% in pT3 patients (P <.0001). Limitations of this study were its retrospective nature and the relatively short follow-up period for oncologic outcome. CONCLUSION: LRN for large RCC is a safe operation. Stage pT3 is a risk factor for open conversion and is associated to significantly lower cancer-specific survival compared with pT2 stage.