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.

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.

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.

Pathological Outcomes for Patients Who Failed To Remain Under Active Surveillance for Low-risk Non-muscle-invasive Bladder Cancer: Update and Results from the Bladder Cancer Italian Active Surveillance Project.

BACKGROUND: It has been shown that active surveillance (AS) is feasible and effective in a subset of patients with recurrent low-grade (LG) non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To update a previous preliminary series and investigate pathological outcomes for patients who failed to remain on AS. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study started in February 2008, and currently still active, at a tertiary university hospital, including patients with pathologically confirmed NMIBC who experienced recurrence during follow-up. INTERVENTION: AS monitoring consisted of cytology and in-office flexible cystoscopy every 3 mo for the first year, and every 6 mo thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was pathological results for patients who failed to remain on AS. The secondary outcome was an update of clinical results from our previous series. Data were complemented by descriptive statistical analysis and univariable and multivariable proportional hazards Cox regression. RESULTS AND LIMITATIONS: Overall, 167 patients were included. Of 181 AS events, 61 (33.7%) were deemed to require treatment because of positive cytology (n=10), gross haematuria (n=11), and increases in the tumour number (n=15), or size (n=17), or both (n=8). The median time on AS was 12 mo (interquartile range 4-26). Pathological specimens from AS failures did not show any malignancy in 20 cases. Histopathology identified urothelial hyperplasia and oedema, submucosal vascular ectasia, mucosal erosion, polypoid cystitis, von Brunn nest hyperplasia, and squamous metaplasia. The time from first transurethral resection to AS start was inversely associated with recurrence-free survival (hazard ratio 0.97, 95% confidence interval 0.96-1.00; p=0.024). The study lacks statistical subanalyses focusing on patients with failure and negative neoplastic pathological outcomes. CONCLUSIONS: AS might be a reasonable strategy in patients presenting with small LG pTa/pT1a recurrent bladder tumours. Approximately 30% of patients deemed to have AS failure did not harbour any neoplastic lesion, strengthening the role of AS. PATIENT SUMMARY: Patients with small low-grade pTa/pT1a recurrent papillary bladder tumours could benefit from an active surveillance protocol with no significant risk of pathological progression to muscle-invasive cancer.

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.

Safety and Feasibility of Salvage Endoscopic Combined Intrarenal Surgery in Embolized Kidney.

BACKGROUND: Although endoscopic combined intrarenal surgery (ECIRS) is well established as primary approach to complex lithiasis, no evidences are still available on its use in salvage context. CASE PRESENTATION: A male patient, of 55 years of age, underwent many unsuccessful surgical procedures to treat large and multiple right kidney stones, including percutaneous nephrolithotomy (PCNL). The latter was complicated by severe postoperative hemorrhage, managed with super-selective renal artery embolization (SRAE). Therefore he came to our institution to achieve a complete resolution of the urolithiasis. Preoperative evaluation included CT scan and renal scintigraphy to establish kidney and stone morphologic features and residual renal function. Salvage ECIRS was performed and postoperative assessment showed a complete resolution of lithiasis and absence of renal function impairment. CONCLUSION: To our knowledge, this is the first case of salvage ECIRS reported in literature after previous failed PCNL. Even after SRAE, this procedure appears as safe and as efficacious as standard salvage PCNL when performed by experienced hands.

Clinical performance of prostate health index in men with tPSA>10ng/ml: Results from a multicentric European study.

BACKGROUND: Evidence regarding the diagnostic accuracy of a [-2]proPSA derivative, namely, the prostate health index (PHI), to predict the presence of prostate cancer (PCa) in individuals with high total prostate-specific antigen (tPSA) levels is lacking. We tested the hypothesis that these markers could assist clinicians in the biopsy decision path of patients with tPSA>10ng/ml. METHODS: The primary endpoint was to evaluate the sensitivity, specificity, and diagnostic accuracy of PHI in determining the presence of PCa at biopsy in comparison to tPSA, free PSA, and % of free to total PSA. We calculated the number of prostate biopsies that could have been spared by using this marker to decide whether or not to perform a biopsy. A secondary endpoint was to determine the relationship between PHI and PCa characteristics. RESULTS: The PCa was diagnosed in 136 of 262 patients (51.9%). Total PSA and PHI values were significantly higher (P<0.005) and % of free to total PSA values significantly lower (P<0.0001) in patients with PCa relative to those with a negative biopsy. In multivariable logistic regression models, PHI achieved the independent predictor status and significantly increased the accuracy of the base multivariable model by an extent of 8.2% (P = 0.0005). The inclusion of PHI in the biopsy decision path would decrease the number of unnecessary biopsies by an extent of 50.0%, while missing only few cases with clinically significant PCa. Finally, Gleason score was significantly related to PHI levels. CONCLUSIONS: The results of our study support the diagnostic effectiveness of PHI even in patients with tPSA >10ng/ml. Further validation studies with larger sample size are needed to corroborate our findings.