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.

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.

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.

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.

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.

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.

The reconstruction of "complex" ureteral lesions.

A total of 13 patients with ureteral lesions wider than 12 cm in length and/or previous radiation treatment have been submitted to reconstructive treatment. Four patients with lesions after radiation therapy were treated with ileal ureter and contemporary bladder augmentation, one with ureteroneocystostomy combined with psoas hitch procedure and one combining psoas hitch and Boori Flap technique. The association of psoas hitch with Boari Flap technique were also used to treat two patients with the undesired outcome of vascular procedure. A patient after complete ureteral stripping following ureteroscopy was submitted to ileal bladder substitution. Two renal autotransplantations were performed in a patient with extensive stricture of the ureter following multiple endourological procedure and in a patient with negative outcome of previous attempt of open ureteral defect reconstruction following abdominal trauma.

Retropubic nerve and seminal sparing radical prostatectomy for recurrent bladder neck-prostatic urethra strictures.

OBJECTIVES: To verify if nerve and seminal sparing radical prostatectomy could represent surgical solution for iatrogenic bladder neck prostatic urethra contracture without external sphincter involvement. MATERIAL AND METHODS: At our institution 4 patients have been submitted to nerve and seminal sparing radical prostatectomy for recurrent bladder neck-prostatic urethra contracture following TURP for middle size adenoma. In all cases bladder neck was reconstructed and a 20F silicon catheter was left in place for two weeks to stint the vesico-urethral anastomosis. RESULTS: In all cases no significant perioperative complications were experienced. A normal voiding urethrogram preceded removal of the catheter 14 days postoperatively. Urinary continence was recovered by all of the patients. Uroflowmetry was persistently normal at periodic controls. With a mean follow-up of 36.3 months, no patient complained of symptomatic recurrence of urinary obstruction. In three previously potent patients, sexual activity with satisfactory intercourse was maintained. CONCLUSION: Even though our experience is very limited in terms of number of patients and length of follow-up, we think that nerve and seminal sparing radical prostatectomy, because of the limited risk of major complications and the good result in terms of preservation of both urinary continence and erectile function, can be a reasonable solution for iatrogenic bladder neck-prostatic contracture after prostatic surgery for BPH.