Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer.

Importance: Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited. Objective: To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis. Design, Setting, and Participants: This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023. Exposure: At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months. Main Outcomes and Measures: Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters. Results: A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months. Conclusions and Relevance: In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.

Non-timely clinically applicable ADC ratio in prostate mpMRI: a comparison with fusion biopsy results.

PURPOSE: The purpose of the study was to assess the diagnostic accuracy of ADC ratio and to evaluate its efficacy in reducing the number of false positives in prostatic mpMRI. MATERIALS AND METHODS: All patients who underwent an mpMRI and a targeted fusion biopsy in our institution from 2016 to 2021 were retrospectively selected. Two experienced readers (R1 and R2) independently evaluated the images, blindly to biopsy results. The radiologists assessed the ADC ratios by tracing a circular 10 mm2 ROI on the biopsied lesion and on the apparently benign contralateral parenchyma. Prostate cancers were divided into non-clinically significant (nsPC, Gleason score = 6) and clinically significant (sPC, Gleason score ≥ 7). ROC analyses were performed. RESULTS: 167 patients and188 lesions were included. Concordance was 0.62 according to Cohen's K. ADC ratio showed an AUC for PCAs of 0.78 in R1 and 0.8 in R2. The AUC for sPC was 0.85 in R1 and 0.84 in R2. The 100% sensitivity cut-off for sPCs was 0.65 (specificity 25.6%) in R1 and 0.66 (specificity 27.4%) in R2. Forty-three benign or not clinically significant lesions were above the 0.65 threshold in R1; 46 were above the 0.66 cut-off in R2. This would have allowed to avoid an equal number of unnecessary biopsies at the cost of 2 nsPCs in R1 and one nsPC in R2. CONCLUSION: In our sample, the ADC ratio was a useful and accurate tool that could potentially reduce the number of false positives in mpMRI.

Assessment of predictors of renal cell carcinoma progression after nephrectomy at short- and medium-term follow-up and implication on surveillance protocols.

BACKGROUND: Prediction of risk of RCC progression after surgery is important for follow-up planning. We identified predictors of progression-free survival (PFS) and cancer-specific survival (CSS) in a large single institutional cohort and investigated patterns and sites of progression according to stage and grade. METHODS: Node-negative non-metastatic clear-cell RCC (ccRCC) patients treated with radical or partial nephrectomy from 2000 to 2020 were included. Sites of progression were defined as thoracic, abdominal and others (bone/brain). Kaplan-Meier curves and multivariable Cox regression (MCR) models tested for PFS and CSS. RESULTS: Of 384 clear cell RCC N0M0 patients, 301 (78.4%) vs. 83 (21.6%) were pT1-2 vs. pT3-4, respectively; 253 (65.9%) vs. 130 (33.9%) were G1-G2 vs. G3-G4. Thoracic progressions occurred in 2.7% pT1-T2 vs. 21.7% pT3-T4 and 2.8% G1-G2 vs. 14.6% G3-G4 tumors. Abdominal progressions occurred in 4.0% pT1-T2 vs. 13.3% pT3-T4 and 4.3% G1-G2 vs. 9.2% G3-G4. Other progressions occurred in 0.3% pT1-T2 vs. 9.6% pT3-T4 and 0.8% G1-G2 vs. 5.4% G3-G4 (5.4%). Five-year PFS and CSS were 81.7 and 90.6%, respectively. At MCR models, pT3-4 (HR 9.1, P<0.001), G3-G4 (HR 2.7, P=0.003) and PSMs (HR 6.1, P<0.001) independently predicted PFS. Similarly, pT3-4 (HR 10.1, P<0.001), G3-G4 (HR 4.1, P=0.02), and PSMs (HR 5.2, P=0.04) independently predicted CSS. CONCLUSIONS: In ccRCC N0M0 patients, G3-G4, pT3-4, PSMs were independent predictors of progression after surgery. Lower stage and grade ccRCCs progress predominantly in the abdominal sites and may be followed with less frequent extra-abdominal imaging compared to more advanced/aggressive tumors.

Oncological outcomes of active surveillance and percutaneous cryoablation of small renal masses are similar at intermediate term follow-up.

BACKGROUND: Active surveillance (AS) and minimally invasive ablative therapies such as percutaneous cryoablation (PCA) are emerging as alternative treatment modalities in the management of small renal masses (SRMs). METHODS: Fifty-nine patients underwent PCA since 2011 and 75 underwent AS since 2010 at two different institutions. Only patients with follow-up ≥6 months were included. All patients were followed with a standardized protocol. Treatment failure was defined by dimensional progression for AS and renal recurrence for PCA, in addition to stage and/or metastatic progression for both groups. RESULTS: Treatment failure was observed in 14 cases (18.7%) during AS (mainly due to dimensional progression) and 12 patients (16%) underwent delayed intervention with a mean follow-up of 36.83 months. Seven patients (11.9%) in the PCA group experienced treatment failure with a mean follow-up of 33.39 months and three of them underwent re-ablation successfully. Cancer-specific-survival at 2 and 5 years was 100% and 95,8% in AS-group vs. 98.2% and 98.2% in PCA-group (P=0.831). One patient in both groups died from metastatic disease. Overall-survival at 2 and 5 years was 91.7% and 82.4% in the AS group vs. 96.5% and 96.5% in the PCA group (P=0.113). Failure-free survival at 2 and 5 years was 90.9% and 70.1% in the AS group vs. 93.1% and 70.9% in the PCA group (P=0.645). CONCLUSIONS: AS and PCA provide similar survival outcomes and are safe and valid treatment options for elderly and comorbid patients with SRMs.

Apoptotic and predictive factors by Bax, Caspases 3/9, Bcl-2, p53 and Ki-67 in prostate cancer after 12 Gy single-dose.

Radio-induced apoptosis is mediated by the activation of tumor protein p53, Bax and caspases. The purpose of this study was to investigate the early activation of this pathway in men receiving in vivo irradiation immediately before radical prostatectomy for locally advanced prostate cancer. We also investigated cell proliferation index (Ki-67), proto-oncogene (p53) and anti-apoptotic protein (Bcl-2) levels as potential predictive factors. We selected a homogeneous sample of 20 patients with locally advanced prostate cancer and candidate to radical prostatectomy. To assess the apoptotic pathways, Bax, is studied through immunofluorescence assay, before and after 12 Gy single dose intraoperative radiotherapy (IORT) to the prostate, on bioptic samples and on surgical specimens. Moreover, before and after IORT, Bcl-2, p53, and Ki-67 were also detected through immunohistochemistry. A count of positive Bax spots for immunofluorescence was performed on tumor cells, prostatic intraepithelial neoplasia (PIN), and healthy tissue areas before and after IORT. We also analyzed Caspases 3 and 9 expressions after IORT. Before IORT, Bcl-2 mean value in neoplastic cells was 2.23% ± 1.95, mean Ki-67 in neoplastic area was 4.5% ± 3.8, and p53 was 22.5% ± 6.8. After IORT, Bcl-2 mean value in neoplastic cells was 8.85 ± 8.92%, Ki-67 in neoplastic area was 7.8 ± 6.09%, and p53 was 24.9 ± 26.4%. After the irradiation, healthy areas expressed significantly lower levels of Bax (2.81 ± 1.69%) with respect to neoplastic cells (p < 0.0001), while in PIN areas, Bax positive cells were significantly more present than in neoplastic areas (p = 0.0001). At statistical analysis, it was observed that cancer cells with Ki-67 ≥ 8% had a trend toward greater expression of Bax (p = 0.0641). We observed an increase of Bcl-2 expression after IORT in neoplastic areas (p = 0.0041). Biopsy specimens with p53 ≥ 18% and Ki-67 ≥ 8% had worse post-operative staging with extracapsular invasion (p = 0.04 for both parameters) and nodal positivity (p = 0.04 for p53 and p = 0.0001 at pathology for ki-67). No correlation between IORT and Caspases activation was noted. In conclusion, after 12 Gy IORT, Bax was overexpressed in tumor and PIN cells. Pre-operative Ki-67 and p53 definition could be used in future studies to predict patients with worse pathological stage, while Bcl-2 activation after IORT might be a predictive factor for loco-regional failure.

Pathological, Oncologic and Functional Outcomes of a Prospective Registry of Salvage High Intensity Focused Ultrasound Ablation for Radiorecurrent Prostate Cancer.

PURPOSE: In this prospective registry we prospectively assessed the oncologic, functional and safety outcomes of salvage high intensity focused ultrasound for radiorecurrent prostate cancer. MATERIALS AND METHODS: A total of 81 men were prospectively recruited and evaluated at regular scheduled study visits to 6 months after high intensity focused ultrasound and thereafter as per standard of care. Transrectal ultrasound guided biopsy was performed at 6 months. The primary end point was absence or histological persistence of disease at 6-month biopsy. Secondary end points included quality of life, biochemical recurrence-free survival, overall survival, cancer specific survival and progression to androgen deprivation therapy. Survival analysis was performed according to the Kaplan-Meier method and multivariate analysis was performed using the log rank (Mantel-Cox) test. RESULTS: Mean ± SD prostate specific antigen before high intensity focused ultrasound was 4.06 ± 2.88 ng/ml. At 6 months 63 men underwent biopsy, of whom 22 (35%) had residual disease. At a mean followup of 53.5 ± 31.6 months median biochemical recurrence-free survival was 63 months. The 5-year overall and cancer specific survival rates were 88% and 94.4%, respectively. Nadir prostate specific antigen less than 0.5 ng/ml was a significant predictor of biochemical recurrence-free survival (p=0.014, 95% CI 1.22-5.87). I-PSS significantly increased (p <0.001) while IIEF-5 scores decreased and the SF-36 score did not change significantly. The rate of rectal fistulization and severe incontinence was 3.7% each. A total of 223 complications were recorded in the 180 days after high intensity focused ultrasound (Clavien-Dindo grade 1-195, grade II-20, grade III-7, grade IVa-1). CONCLUSIONS: Salvage high intensity focused ultrasound appears to be a viable treatment option for radiorecurrent prostate cancer, with acceptable morbidity.

Long-Term Oncologic Outcomes of Salvage Cryoablation for Radio-Recurrent Prostate Cancer.

PURPOSE: Management of localized radio-recurrent prostate cancer is not standardized, partly due to the absence of long-term data on oncologic control and the toxicity of various treatment modalities. We analyzed the long-term oncologic outcomes and morbidity of salvage cryoablation for radio-recurrent prostate cancer. MATERIALS AND METHODS: Patients undergoing salvage cryoablation for biopsy proven, localized radio-recurrent prostate cancer from 1995 to 2004 were prospectively accrued. Preoperative characteristics, perioperative morbidity and postoperative data were reviewed from a prospectively maintained database or via telephonic contact with the patient. The primary outcome was overall survival. Secondary outcomes were metastasis-free and biochemical disease-free survival. The Kaplan-Meier method was used for survival analysis and multivariable Cox regression analysis was performed. RESULTS: Of 187 patients 157 (84%) had records available for followup. Mean ± SD age was 69.4 ± 5.8 years and mean presalvage prostate specific antigen was 6.6 ± 5.7 ng/ml. Median followup was 117 months (IQR 55-154). Five and 10-year overall survival was 93% and 76%, respectively. Biochemical disease-free survival at 10 and 15 years was 35% and 22.6% whereas metastasis-free survival at 10 and 15 years was 86% and 71%, respectively. On multivariable analysis precryoablation and nadir prostate specific antigen values were significant predictors of metastasis-free and biochemical disease-free survival. Age at salvage cryoablation (p = 0.008) and nadir prostate specific antigen (p = 0.015) were significant predictors of overall survival. There were 157 Clavien-Dindo grade 1-2 and 22 grade 3 complications. CONCLUSIONS: A single center, long-term experience documented by a prospectively maintained database shows that cryoablation is a viable salvage option for radio-recurrent prostate cancer as it provides durable biochemical disease-free survival with acceptable morbidity.

Long-Term Outcomes of the Implant of a Periurethral Constrictor for Stress Urinary Incontinence Following Radical Prostatectomy.

OBJECTIVES: To assess morbidity, effectiveness and quality of life (QoL) of implant of Silimed periurethral constrictor (PC) in a consecutive series of patients who had stress urinary incontinence following radical prostatectomy. MATERIAL AND METHODS: A prospective non-randomized study designed on patients who underwent implant of Silimed PC. Primary end point was postoperative morbidity and secondary end points were effectiveness of implant and QoL. We performed a sub-analysis of men who received previous radiation and we compared the subpopulation with radiation-naïve patients. RESULTS: Nineteen patients (31.6%) received pelvic radiation therapy prior implant. All procedures were completed successfully with median operative time of 55 (IQR 50-62.5) min. We recorded 47 (78.3%) postoperative complications in 30 men. Twenty-three men (38.3%) developed urethral erosion at median follow-up of 27.5 (IQR 21-35) months, and 1 man (1.9%) had rectourethral fistula at 2 months. Risk of urethral erosion increased significantly among patients who received radiation (63.1 vs. 26.8%; p < 0.001). In 12 cases (20%), we recorded malfunctioning of the reservoir requiring replacement. CONCLUSION: The implant of Silimed device is not safe due to a high risk of urethral erosion. Careful patient selection and detailed counseling are mandatory when considering the implant of PC in adult patients.

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial.

BACKGROUND: Magnetic resonance imaging-guided transurethral ultrasound ablation (MRI-TULSA) is a novel minimally invasive technology for ablating prostate tissue, potentially offering good disease control of localized cancer and low morbidity. OBJECTIVE: To determine the clinical safety and feasibility of MRI-TULSA for whole-gland prostate ablation in a primary treatment setting of localized prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: A single-arm prospective phase 1 study was performed at three tertiary referral centers in Canada, Germany, and the United States. Thirty patients (median age: 69 yr; interquartile range [IQR]: 67-71 yr) with biopsy-proven low-risk (80%) and intermediate-risk (20%) PCa were treated and followed for 12 mo. INTERVENTION: MRI-TULSA treatment was delivered with the therapeutic intent of conservative whole-gland ablation including 3-mm safety margins and 10% residual viable prostate expected around the capsule. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end points were safety (adverse events) and feasibility (technical accuracy and precision of conformal thermal ablation). Exploratory outcomes included quality of life, prostate-specific antigen (PSA), and biopsy at 12 mo. RESULTS AND LIMITATIONS: Median treatment time was 36min (IQR: 26-44) and prostate volume was 44ml (IQR: 38-48). Spatial control of thermal ablation was ±1.3mm on MRI thermometry. Common Terminology Criteria for Adverse Events included hematuria (43% grade [G] 1; 6.7% G2), urinary tract infections (33% G2), acute urinary retention (10% G1; 17% G2), and epididymitis (3.3% G3). There were no rectal injuries. Median pretreatment International Prostate Symptom Score 8 (IQR: 5-13) returned to 6 (IQR: 4-10) at 3 mo (mean change: -2; 95% confidence interval [CI], -4 to 1). Median pretreatment International Index of Erectile Function 13 (IQR: 6-28) recovered to 13 (IQR: 5-25) at 12 mo (mean change: -1; 95% CI, -5 to 3). Median PSA decreased 87% at 1 mo and was stable at 0.8 ng/ml (IQR: 0.6-1.1) to 12 mo. Positive biopsies showed 61% reduction in total cancer length, clinically significant disease in 9 of 29 patients (31%; 95% CI, 15-51), and any disease in 16 of 29 patients (55%; 95% CI, 36-74). CONCLUSIONS: MRI-TULSA was feasible, safe, and technically precise for whole-gland prostate ablation in patients with localized PCa. Phase 1 data are sufficiently compelling to study MRI-TULSA further in a larger prospective trial with reduced safety margins. PATIENT SUMMARY: We used magnetic resonance imaging-guided transurethral ultrasound to heat and ablate the prostate in men with prostate cancer. We showed that the treatment can be targeted within a narrow range (1mm) and has a well-tolerated side effect profile. A larger study is under way. TRIAL REGISTRATION: NCT01686958, DRKS00005311.

Assessment of histopathological features of needle biopsy in recurrent prostate cancer following salvage high-intensity focused ultrasound.

INTRODUCTION: Local recurrence of prostate cancer (PCa) following radiotherapy may be treated with curative intent using salvage high-intensity focused ultrasound (s-HIFU). The interpretation of needle core biopsy specimens following s-HIFU is a daunting task, even for experienced pathologists. We describe various histopathological features encountered in biopsy specimens following whole-gland s-HIFU in one of the largest descriptive studies to date. METHODS: Fifty-five patients with biopsy-proven localized radio-recurrent PCa underwent s-HIFU and transrectal ultrasound (TRUS)-guided prostatic needle biopsies at 180 days post-treatment. All biopsies were reviewed by two genitourinary pathologists. RESULTS: PCa was detected in 11 (24%) biopsies. Radiation therapy-associated changes were identified in all cases. Additional findings included extensive coagulative stromal necrosis (100%), smudgy chromatin of cancer nuclei (82%), and markedly enlarged bizarre nuclei in the residual cancer (55%). Gleason grade assignment was possible in 10 (91%) of these biopsies and concordance of Gleason grading between pre- and post-therapy specimens was observed in six (60%) cases. CONCLUSIONS: The histological interpretation of needle biopsies following salvage HIFU is challenging and requires an understanding of the histopathological changes associated with this procedure in both tumoural and non-tumoural prostatic tissue. Accurate interpretation of the morphological changes following s-HIFU is instrumental for optimization of clinical decision-making and treatment planning in recurrent PCa.

Case Presentation: Kidney Cancer in Transplanted Kidney.

Management of metastatic renal cell carcinoma in kidney graft is challenging. A multidisciplinary team of experts plays a key role in the clinical decision making to balance quality of life and oncological outcome.

Comparative morbidity of ablative energy-based salvage treatments for radio-recurrent prostate cancer.

INTRODUCTION: We compared the morbidity of whole gland salvage ablation using cryotherapy (CRYO) and high-intensity focused ultrasound (HIFU) for radio recurrent prostate cancer at a single centre over a 17-year period. METHODS: Patients were divided in 3 cohorts. Group 1 included the first 65 patients treated with CRYO (1995-1998); Group 2 included the last 65 patients treated with CRYO (2002-2004), and Group 3 included 65 patients treated with HIFU (2006-2011). We analyzed the complications reported within at least 90 days of treatment or up to the last follow-up. RESULTS: We tallied Clavien grade complications. For Groups 1, 2 and 3, we recorded the following Clavien I-II complications: 78, 49 and 13, respectively. For Clavien grade IIIa, 2, 5 and 4 for Groups 1, 2 and 3, respectively. For Clavien grade IIIb, 8, 2 and 3 for Groups 1, 2 and 3, respectively. Clavien grade II complications were statistically higher in Group 1 versus Group 2 (p = 0.005) and in Group 2 versus Group 3 (p = 0.0001). The rate of mild-moderate incontinence was significantly higher in the CRYO group compared to the HIFU cohort (p ≤ 0.05). The rate of urinary retention was significantly higher in Group 2 compared to Group 3 (p = 0.0005). The rates of severe incontinence (range: 1.5%-5%), need for surgical intervention (uniform at 1.5%), and recto-urethral fistulae (range: 1.5%-3%) were not statistically different. CONCLUSIONS: CRYO was associated with higher overall morbidity. The morbidity during the early experience with HIFU was lower than both subgroups of CRYO. This may reflect the advancement of technology or cumulative learning experience.

Dovitinib: rationale, preclinical and early clinical data in urothelial carcinoma of the bladder.

INTRODUCTION: Bladder cancer (BC) is the third and fifth cancer in men in terms of incidence and mortality in the US. Overexpression and mutations of fibroblast growth factor receptor 3 (FGFR3) are frequently found in BC and can represent a very interesting therapeutic target. Different FGFR3-targeted strategies have been investigated through in vitro and in vivo settings, including FGFR3 tyrosine kinase inhibitors such as dovitinib . AREAS COVERED: The authors review the data that provide a scientific rationale for FGFR3-targeted therapy in BC. They also provide an evaluation of the currently available in vitro and in vivo data on the use of dovitinib in BC patients. EXPERT OPINION: The development and progression of BC rely on a very complex signaling network that involves many different receptors aside from FGFR3 and VEGFR2. The involved signaling network can also be very different from one BC to the other, and can also evolve through time in the same patient. Inhibiting only one single target may thus not be sufficient to achieve a complete downstream oncogenic signaling blockage. Additionally, in vitro data on the use of neutralizing monoclonal antibodies targeting FGFR3 show that it can be a more efficient strategy to reach the same goal, with the potential advantage of less toxicity.

Oncological outcomes of robotic-assisted radical prostatectomy after more than 5 years.

INTRODUCTION: In the last 10 years, robotic-assisted radical prostatectomy (RARP) has become increasingly popular as witnessed by an increased number of publications. However, there is still little known about the long-term oncologic outcomes of this technique. The aim of this study is to assess the oncologic outcomes of patients who underwent RARP at least 5 years ago, with an emphasis on biochemical recurrence-free survival (BCRFS). MATERIALS AND METHODS: In 2004, RARP was introduced at our institutions. Records of all patients having RARP were prospectively collected in a dedicated database as part of the NUVOLA-BAUS project. For the present study, we selected only patients who had a follow-up of at least 5 years. Endpoints were BCRFS rate and 5-year cancer-specific survival (CSS). RESULTS: Overall, we identified 175 patients; 61.7 % of patients had Gleason 7-9 disease and 26.9 % had pT ≥ 3 disease at final pathology. Eight patients (4.5 %) had biochemical recurrence at follow-up. Overall 5-year BCRFS rate was 95.4 %, while it was 97.6, 91 and 50 % in pT2, pT3 and pT4 diseases, respectively. Among the patients who recurred, the mean time to recurrence was 22.1 ± 8.8 months. These patients received salvage external beam radiation treatment combined with hormonal therapy (anti-androgen + LHRH analogue) or hormonal therapy alone. 5-year CSS was 98.3 % (172/175): in 2 cases, the specimen showed pT4 cancer, while lymph node metastasis was noted in one case. CONCLUSION: The 5-year BCRFS and CSS after RARP are encouraging even in a population with significant high-risk disease.

Transurethral resection of the prostate in kidney transplant recipients: urological and renal functional outcomes at long-term follow-up.

OBJECTIVES: To assess prospectively the safety and efficacy of transurethral resection of the prostate (TURP) for the treatment of lower urinary tract symptoms attributable to benign prostatic hyperplasia (BPH) in patients who have undergone renal transplantation (RT). To assess the impact of TURP on renal graft function. PATIENTS AND METHODS: Urological and renal functional outcomes of TURP performed in RT recipients for treatment of lower urinary tract obstruction attributable to BPH were prospectively assessed in a series of 32 consecutive patients with follow-up of ≥48 months. Maximum urinary flow rate (Qmax ) at uroflowmetry, International Prostate Symptom Score (IPSS), post-void residual urine volume (PVR), haemoglobin and serum creatinine (sCr) levels were recorded before TURP and 1, 6, 24 and 48 months after the procedure. The trends in these variables after TURP were evaluated. Early and delayed complications were assessed and graded according to the Clavien classification system. RESULTS: TURP was performed at a mean of 6 months after RT. No intraoperative complications occurred. Seven postoperative complications were observed (21.9%): two Clavien grade II and five Clavien grade IIIa. Qmax , IPSS and PVR improved significantly after surgery and the improvement was maintained until 48 months. No patient required a repeat TURP during follow-up. SCr levels significantly decreased 1 and 6 months after TURP and did not significantly increase at long-term follow-up. CONCLUSIONS: TURP for lower urinary tract obstruction attributable to BPH in RT recipients is safe and effective since it improves urinary flow, bladder emptying and related urinary symptoms. TURP allows an early significant improvement of graft function that is maintained at a follow-up of 48 months.

Design and evaluation of an image-guidance system for robot-assisted radical prostatectomy.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Systems for image guidance during laparoscopic surgery can be broadly defined as systems that enable the surgeon to refer to preoperatively gathered information during the procedure. For a laparoscopic system the preoperative information can be overlaid onto the laparoscopic video screen. Examples of surgical image-guidance systems and the results of early testing are not uncommon but the technical methodologies used vary widely as do the visualisation methods. This study reports our experience of using an image-guidance system on 13 patients. Furthermore, we use previously proposed methodology to form a development and evaluation framework specific to image-guided laparoscopic radical prostatectomy. Finally, we propose that if the system development process is properly designed, it should be possible to correlate system technical parameters with clinical outcomes. We present a possible plot for the key technical parameter of accuracy. Better understanding of this correlation should enable robust development and evaluation of surgical image-guidance systems to optimise patient outcomes. OBJECTIVE: To implement and test the feasibility of an image-guidance system for robot-assisted radical prostatectomy (RARP). Laparoscopic surgical outcomes may be improved through image guidance. However, to demonstrate improved outcomes rigorous evaluation techniques are required. Therefore we also present our work in establishing robust evaluation techniques. PATIENTS AND METHODS: Development work used three cadavers and an anatomy phantom. The system has been used on 13 patients. During surgery the surgeon can refer to the patient's magnetic resonance imaging (collected before the operation) overlaid on the endoscopic video image. The result of the overlay process was measured qualitatively by the surgeon with reference to the desired clinical outcomes. RESULTS: The use of the overlay system has not resulted in any measurable change in clinical outcomes. The surgeons found the system to be a useful tool for reference during surgery. A more rigorous evaluation method is proposed that will enable on-going development. CONCLUSION: Image guidance during RARP is feasible. We propose a series of measures that will improve further development and evaluation.

Recent advances in the diagnosis and treatment of bladder cancer.

Bladder cancer is the commonest malignancy of the urinary tract. In this review, we look at the latest developments in the diagnosis and management of this condition. Cystoscopy and urine cytology are the most important tools in the diagnosis and follow-up of bladder cancer. Various alternatives have been investigated, either to reduce the frequency of cystoscopy, or improve its sensitivity for detection of tumors. These include urine-based markers and point-of-care tests. Narrow-band imaging and photodynamic diagnosis/blue-light cystoscopy have shown promise in improving detection and reducing recurrence of bladder tumors, by improving the completion of bladder resection when compared with standard resection in white light. The majority of patients with a new diagnosis of bladder cancer have non-muscle-invasive bladder cancer, which requires adjuvant intravesical chemotherapy and/or immunotherapy. Recent developments in post-resection intravesical regimens are discussed. For patients with muscle-invasive bladder cancer, both laparoscopic radical cystectomy and robot-assisted radical cystectomy have been shown to reduce peri-operative morbidity, while being oncologically equivalent to open radical cystectomy in the medium term. Bladder-preserving strategies entail resection and chemoradiation, and in selected patients give equivalent results to surgery. The development, advantages, and disadvantages of these newer approaches are also discussed.

Minimally invasive cystectomy approaches in the treatment of bladder cancer.

Bladder cancer is the most frequently occurring tumor of the urinary system, with over 10,000 new diagnoses each year in the UK. Approximately 70% of these are non-muscle-invasive and limited to the mucosa (Ta) or submucosa (T1). These tumors are generally managed with transurethral resection followed by adjuvant intravesical chemo- or immuno-therapy and regular cystoscopic surveillance. The principal end points in the management of these tumors are prevention of recurrence and progression. Muscle-invasive bladder cancer is a life-threatening disease with overall 5-year mortality of 50%. Neoadjuvant chemotherapy, where possible followed by radical surgery, is currently considered the best standard of care. Open radical cystectomy is the gold-standard treatment for muscle-invasive or high-risk non-muscle-invasive (multifocal or recurrence after intravesical therapy) bladder cancer. Historically, this procedure has carried significant morbidity, although mortality of open radical cystectomy has reduced to 1-2% owing to improvements in anesthesia and intensive care facilities. Over the last 15 years, minimally invasive techniques in radical cystectomy have evolved, with the aim of reducing morbidity. In this article, we review the development of laparoscopic radical cystectomy and robot-assisted radical cystectomy, along with current evidence on perioperative morbidity and medium-term oncological outcomes.

Transmesenteric approach for left transperitoneal renal surgery: technique and experience.

INTRODUCTION: In the last few years laparoscopic surgery has become the gold standard for the treatment of several urological diseases such as renal cancer and ureteropelvic junction obstruction (UPJO). A transmesenteric approach for left laparoscopic pyeloplasty has been recently described in order to avoid bowel manipulation and the potentially related complications. The aim of the present study is to describe the surgical technique and the advantages of the transmesenteric approach for laparoscopic pyeloplasty, pyelolithotomy, and simple nephrectomy in our experience. SUBJECTS AND METHODS: From December 2007 to May 2010, 12 laparoscopic procedures for left renal diseases were performed using a transmesenteric approach. The indications were left UPJO in 9 cases, left pelvic-ureteral stones in 2 cases, and left end-stage kidney disease in one case. RESULTS: No conversions or intraoperative complications were observed. No blood transfusions were required. Resumption of oral intake and canalization occurred in all cases within 48 hours of the procedure. All patients had an uneventful postoperative course. CONCLUSIONS: The laparoscopic transmesenteric approach represents an interesting and advantageous technical improvement of minimally invasive surgery for the treatment of left renal diseases.

Chromophobe renal cell carcinoma (RCC): oncological outcomes and prognostic factors in a large multicentre series.

UNLABELLED: Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? About 80% of RCCs have clear cell histology, and consistent data are available about the clinical and histological characteristics of this histological subtype. Conversely, less attention has been dedicated to the study of non-clear cell renal tumours Specifically, published data show that chromophobe RCC (ChRCC) have often favourable pathological stages and better nuclear grades as well as a lower risk of metastasizing compared with clear cell RCC (ccRCC). Patients with ChRCC were shown to have significantly higher cancer-specific survival (CSS) probabilities compared with ccRCC. However, an independent prognostic role of RCC histotype was not confirmed in some large multicenter series and only a few studies have focused on the oncological outcomes of ChRCC. The present study is one of the few to evaluate cancer-related outcomes of ChRCC and represents to our knowledge the largest series of ChRCCs. Consequently, the present findings may assist in elucidating the natural history of surgically treated ChRCC. The present study confirms that ChRCCs have good prognosis and a low tendency to progress and metastasize. Only 1.3% of patients presented with distant metastases at diagnosis, and the 5- and 10-year CSS were 93% and 88.9%, respectively. However, although ChRCCs are generally characterised by an excellent prognosis, we observed that patients with locally advanced or metastatic cancers as well as those with sarcomatoid differentiation have a poor outcome. The study also investigated prognostic factors for recurrence-free survival (RFS) and CSS for this RCC histotype. The definition of outcome predictors can be useful for patient counselling, planning of follow-up strategies, and patient selection for clinical trials. In the present study, gender, clinical T stage, pathological T stage, and presence of sarcomatoid differentiation were significantly associated with RFS and CSS at multivariable analysis. We also identified N/M stage as an independent predictor of CSS. Notably, as Fuhrman grade was not an independent predictor of cancer-related outcomes, the present study confirms that this histological variable is not a reliable prognostic factor for ChRCC. OBJECTIVES: To investigate cancer-related outcomes of chromophobe renal cell carcinoma (ChRCC) in a large multicentre dataset. To determine prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS) for this RCC histological type. PATIENTS AND METHODS: In all, 291 patients with ChRCC were identified from a multi-institutional retrospective database including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007. Univariable and multivariable Cox regression models were used to identify prognostic factors predictive of RFS and CSS after surgery for ChRCC. RESULTS: At a median follow-up of 44 months, 25 patients (8.6%) had disease recurrence and 18 patients (6.2%) died from disease. The 5-year RFS and CSS rates were 89.3% and 93%, respectively. Gender (P= 0.014), clinical T stage (P= 0.017), pathological T stage (P= 0.003), and sarcomatoid differentiation (P= 0.032) were independent predictors of RFS at multivariable analysis. For CSS, there was an independent prognostic role for gender (P= 0.032) and T stage (P= 0.019) among the clinical variables and for T stage (P= 0.016), N/M stage (P= 0.023), and sarcomatoid differentiation (P= 0.015) among the pathological variables. CONCLUSIONS: Patients with ChRCC have a low risk of tumour progression, metastasis, and cancer-specific death. Patient gender, clinical and pathological tumour stage, and sarcomatoid differentiation are significant predictors of RFS and CSS for ChRCC.