Radical Prostatectomy after Vascular Targeted Photodynamic Therapy with Padeliporfin: Feasibility, and Early and Intermediate Results.

PURPOSE: Vascular targeted photodynamic therapy with TOOKAD® is a new therapeutic option for localized prostate cancer management. The objectives of this study were to assess the feasibility of radical prostatectomy after vascular targeted photodynamic therapy and describe functional and oncologic outcomes. MATERIALS AND METHODS: We retrospectively included in study 45 patients who underwent salvage radical prostatectomy after vascular targeted photodynamic therapy for recurrent prostate cancer at a total of 14 surgical centers in Europe between October 2008 and March 2017. Of the 42 radical prostatectomies performed 16 were robot-assisted, 6 were laparoscopic and 20 were open surgery. Primary end points were morbidity and technical difficulties. Secondary end points were early and intermediate postoperative functional and oncologic outcomes. RESULTS: Median operative time was 180 minutes (IQR 150-223). Median blood loss was 200 ml (IQR 155-363). According to the surgeons the surgery was easy in 29 patients (69%) and difficult in 13 (31%). Nerve sparing was feasible in 14 patients (33%). Five postoperative complications (12%) were found, including 2 Clavien I, 2 Clavien II and 1 Clavien IIIB complications. Of the cases 13 (31%) were pT3 and 21 (50%) were pT2c. Surgical margins were positive in 13 patients (31%). Prostate specific antigen was undetectable at 6 to 12 months in 37 patients (88%). Nine patients underwent complementary radiotherapy. Four patients had final prostate specific antigen greater than 0.2 ng/ml at a median followup of 23 months (IQR 12-36). At 1 year 27 patients (64%) were completely continent (no pads) and 10 (24%) had low incontinence (1 pad). Four patients (11%) recovered potency without treatment and 23 (64%) recovered potency with appropriate treatment. CONCLUSIONS: Salvage radical prostatectomy after vascular targeted photodynamic therapy treatment was feasible and safe without difficulty for most of the surgeons.

A Multicenter, Randomized, Placebo-Controlled Study Evaluating the Efficacy of a Combination of Propolis and Cranberry (Vaccinium macrocarpon) (DUAB®) in Preventing Low Urinary Tract Infection Recurrence in Women Complaining of Recurrent Cystitis.

OBJECTIVES: The purpose of the study was to compare the efficacy of a product containing cranberry and propolis (DUAB) to placebo for reducing frequency of cystitis in women with recurrent acute cystitis. METHOD: A multicenter, placebo-controlled, randomized study of women aged >18 years with at least 4 episodes of cystitis in the previous 12 months was performed. The number of cystitis episodes over a 6-month follow-up was the primary end point. RESULTS: Forty-two women were included in the cranberry + propolis group, and 43 women were in the placebo group. The mean age was 53 ± 18 years, with 6.2 ± 3.6 cystitis episodes in the previous year, with no differences between the 2 groups. The mean number of infections was lower in the propolis + cranberry group (respectively, 2.3 ± 1.8 vs. 3.1 ± 1.8). The total number of cystitis episodes in the first 3 months was lower in the propolis + cranberry group (0.7 ± 1.1 vs. 1.3 ± 1.1, p = 0.0257) after adjusting for water consumption. The mean time to onset of the first urinary tract infection (UTI) was also significantly longer in the propolis + cranberry group (69.9 ± 45.8 days vs. 43.3 ± 45.9, p = 0.0258). Tolerance to the treatments was good and comparable in both groups. CONCLUSIONS: We demonstrate for the first time that cranberry and propolis supplementation significantly reduces the incidence of UTIs during the first 3 months and delays the onset of an episode of cystitis.

Randomized Trial of Partial Gland Ablation with Vascular Targeted Phototherapy versus Active Surveillance for Low Risk Prostate Cancer: Extended Followup and Analyses of Effectiveness.

PURPOSE: The prospective PCM301 trial randomized 413 men with low risk prostate cancer to partial gland ablation with vascular targeted photodynamic therapy in 207 and active surveillance in 206. Two-year outcomes were reported previously. We report 4-year rates of intervention with radical therapy and further assess efficacy with biopsy results. MATERIALS AND METHODS: Prostate biopsies were mandated at 12 and 24 months. Thereafter patients were monitored for radical therapy with periodic biopsies performed according to the standard of care at each institution. Ablation efficacy was assessed by biopsy results overall and in field in the treated lobe or the lobe with index cancer. RESULTS: Conversion to radical therapy was less likely in the ablation cohort than in the surveillance cohort, including 7% vs 32% at 2 years, 15% vs 44% at 3 years and 24% vs 53% at 4 years (HR 0.31, 95% CI 0.21-0.46). Radical therapy triggers were similar in the 2 arms. Cancer progression rates overall and by grade were significantly lower in the ablation cohort (HR 0.42, 95% CI 0.29-0.59). End of study biopsy results were negative throughout the prostate in 50% of patients after ablation vs 14% after surveillance (risk difference 36%, 95% CI 28-44). Gleason 7 or higher cancer was less likely for ablation than for surveillance (16% vs 41%). Of the in field biopsies 10% contained Gleason 7 cancer after ablation vs 34% after surveillance. CONCLUSIONS: In this randomized trial of partial ablation of low risk prostate cancer photodynamic therapy significantly reduced the subsequent finding of higher grade cancer on biopsy. Consequently fewer cases were converted to radical therapy, a clinically meaningful benefit that lowered treatment related morbidity.

Transcutaneous tibial nerve stimulation: 2 years follow-up outcomes in the management of anticholinergic refractory overactive bladder.

PURPOSE: To evaluate long-term use, efficacy and tolerability of transcutaneous tibial nerve stimulation (TTNS) in the treatment of refractory overactive bladder (OAB). METHODS: We performed a prospective observational study and included all patients treated in a single center for OAB persisting after first-line anticholinergic treatment, with ≥ 24 months follow-up. The protocol consisted of daily stimulation at home. The primary outcome was treatment persistence. Amelioration was defined as an improvement in urinary symptom profile (USP) score. RESULTS: We assessed 84 consecutive patients. After a mean follow-up of 39.3 months and a mean treatment use of 8.3 months, almost two-thirds of patients (71.8%) had discontinued TTNS. Treatment continuation was > 12 months for 28 patients (33.3%) and > 18 months for 16 patients (19%). TTNS was successful following 3 months of treatment in 60 (71%) patients. Mean USP score stayed significantly lower than baseline until 12 months of treatment, but was not significant anymore after 18 months. Discontinuation therapy reasons were a lack of sufficient symptom relief for 59 (70%) patients, compliance difficulty for 5 (6%) patients and becoming asymptomatic for 6 (8%) patients. No serious adverse events occurred. CONCLUSIONS: The present study confirms the utility of TTNS as a treatment option for patients with resistant OAB. In the long-term use, few patients continued with therapy, mostly because of a decreased effectiveness with time.

Prostatic injection of botulinum toxin is not inferior to optimized medical therapy in the management of lower urinary tract symptoms due to benign prostatic hyperplasia: results of a randomized clinical trial.

OBJECTIVE: To explore efficacy and safety of Botulinum Neurotoxin Type A (BoNT-A) prostatic injection in patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperperplasia. MATERIALS AND METHODS: A phase 3 multicenter open-labeled study randomised patients to receive BoNT-A prostatic injection or optimized medical therapy. BoNT-A injection consisted in trans-rectal injections of 200 UI in the transitional zone of the prostate. Optimal medical therapy consisted in oral medication with any drug patented for LUTS. One month (M1) after randomisation patients in the BoNT-A group were asked to stop any medical therapy related to LUTS. The main judgment criterion was the IPSS score at M4. Per-protocol analysis was performed with a non-inferiority hypothesis (ΔIPSS < 3). RESULTS: 127 patients were randomised to BoNT-A (n = 64) or medical therapy (n = 63). At randomisation mean IPSS was 16.9 ± 7.2 in the BoNT-A group vs 15.7 ± 7.3 in control. In the BoNT-A group, 44 patients (73.3%) could interrupt medical therapy for LUTS from M1 to M4. At M4, mean IPSS score was 12.0 ± 6.7 in the BoNT-A group vs 11.8 ± 6.9 in control. After adjustment for baseline IPSS, delta IPSS between groups was 0.01; 95% CI [- 2.14; 2.11] leading to accept the non-inferiority hypothesis. CONCLUSIONS: Four months after BoNT-A injection, most of the patients could interrupt LUTS-related medical treatments. In these patients, IPSS improvement was not inferior to optimized medical treatment, but the study design did not allow to conclude that this improvement was related with study drug rather than with sustained placebo effect. TRIAL REGISTRATION: NCT01275521.

Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial.

BACKGROUND: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. METHODS: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894. FINDINGS: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). INTERPRETATION: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. FUNDING: Steba Biotech.

Vascular Targeted Photodynamic Therapy with Padeliporfin for Low Risk Prostate Cancer Treatment: Midterm Oncologic Outcomes.

PURPOSE: We assessed the midterm oncologic outcomes of vascular targeted photodynamic therapy with padeliporfin for low risk prostate cancer treatment. MATERIALS AND METHODS: We prospectively assessed all patients treated with vascular targeted photodynamic therapy for low risk prostate cancer at our center. Patients were followed every 6 months. All patients underwent prostate biopsies 6 months after treatment or when there was biological or clinical progression. The primary end point was progression-free survival. Secondary end points were absent clinically significant cancer in the treated lobes, radical therapy and the prostate specific antigen rate. Variables were compared with the chi-square, Mann-Whitney or Wilcoxon test. Progression-free survival is reported with Kaplan-Meier curves. RESULTS: A total of 82 men were treated with vascular targeted photodynamic therapy. Median followup was 68 months (range 6 to 89). Median progression-free survival was 86 months (95% CI 82-90). Median prostate specific antigen decreased significantly by 41% 6 months after treatment and it remained stable during followup (p <0.001). A total of 115 lobes were treated and absent clinically significant cancer was achieved in 94 (82%). Of the 82 patients 20 (24%) underwent radical therapy, including radical prostatectomy in 18 and brachytherapy in 2, at a median of 22 months (range 6 to 86). Study limitations include a single arm design, small population size and midterm followup. CONCLUSIONS: Padeliporfin vascular targeted photodynamic therapy for low risk prostate cancer achieved an 82% rate of absent clinically significant cancer in treated lobes and 76% of patients avoided radical therapy at a median followup of 68 months. However, longer followup is required to determine long-term outcomes.

Correlation between prostate volume and single nucleotide polymorphisms implicated in the steroid pathway.

OBJECTIVES: A few preliminary studies have suggested a link between some genetics variants and benign prostatic hyperplasia (BPH). Our goal was to study the link between a set of single nucleotide polymorphisms (SNPs) implicated in the steroid pathway and accurate measurement of prostate volume in a cohort of men who underwent radical prostatectomy. METHODS: Clinical and pathological data including prostate weight were obtained from 611 Caucasian patients with small volume, localized prostate cancer treated by radical prostatectomy. Patients were genotyped for 90 SNPs located inside or nearby genes implicated in the steroid pathway (Sequenom iPLEX). Correlation between prostate weight and genotypes from each SNP was studied by analysis of covariance, adjusted on age and tumor stage. A Bonferroni correction was applied, and the SNPs implicated were then incorporated in a multivariable model. RESULTS AND LIMITATIONS: Seven SNPs located in or nearby genes implicated in steroid hormone metabolism were significantly associated with prostate volume: HSD17B2 (rs1119933), ESR2 (rs8006145), SULT2B1 (rs279451), NQO1 (rs2917670), ESR1 (rs1569788), GSTP1 (rs1138272), and CYP19A1 (rs17523880). Significant association was maintained after multivariate analysis for four SNPs, indicating their independent association with prostate volume. The power of the association of each SNP with prostate volume was comparable to the effect of age. The strongest associations were found with variants in ESR1, ESR2, HSD17B2, and CYP19A1 genes, indicating a potential role of the estrogen signaling pathway in genesis of BPH. CONCLUSIONS: Our results are in favor of an implication of estrogen biotransformation and signaling pathways in the pathophysiology of BPH.

Final Results of a Phase I/II Multicenter Trial of WST11 Vascular Targeted Photodynamic Therapy for Hemi-Ablation of the Prostate in Men with Unilateral Low Risk Prostate Cancer Performed in the United States.

PURPOSE: Vascular targeted photodynamic therapy with WST11 (TOOKAD® Soluble) is a form of tissue ablation that may be used therapeutically for localized prostate cancer. To study dosing parameters and associated treatment effects we performed a prospective, multicenter, phase I/II trial of WST11 vascular targeted photodynamic therapy of prostate cancer. MATERIALS AND METHODS: A total of 30 men with unilateral, low volume, Gleason 3 + 3 prostate cancer were enrolled at 5 centers after local institutional review board approval. Light energy, fiber number and WST11 dose were escalated to identify optimal dosing parameters for vascular targeted photodynamic therapy hemi-ablation. Men were treated with photodynamic therapy and evaluated by posttreatment magnetic resonance imaging and biopsy. Prostate specific antigen, light dose index (defined as fiber length/desired treatment volume), toxicity and quality of life parameters were recorded. RESULTS: After dose escalation 21 men received optimized dosing of 4 mg/kg WST11 at 200 J energy. On posttreatment biopsy residual prostate cancer was found in the treated lobe in 10 men, the untreated lobe in 4 and both lobes in 1. At a light dose index of 1 or greater with optimal dosing in 15 men 73.3% had a negative biopsy in the treated lobe. Six men undergoing retreatment with the optimal dose and a light dose index of 1 or greater had a negative posttreatment biopsy. Minimal effects were observed on urinary and sexual function, and overall quality of life. CONCLUSIONS: Hemi-ablation of the prostate with WST11 vascular targeted photodynamic therapy was well tolerated and resulted in a negative biopsy in the treated lobe in the majority of men. Dosing parameters and the light dose index appear related to tissue response as determined by magnetic resonance imaging and biopsy. These parameters may serve as the basis for further prospective studies.

Multicentre prospective evaluation of the learning curve of holmium laser enucleation of the prostate (HoLEP).

OBJECTIVES: To describe the step-by-step learning curve of the holmium laser enucleation of the prostate (HoLEP) surgical technique. SUBJECTS/PATIENTS AND METHODS: A prospective, multicentre observational study was conducted, involving surgeons experienced in transurethral resection of the prostate and open prostatectomy but never having performed HoLEP. The main judgment criterion was the ability of the surgeon to perform four consecutive successful procedures, defined by the following: complete enucleation and morcellation within <90 min, without any conversion to standard transurethral resection of the prostate (TURP), with acceptable stress, and with acceptable difficulty (evaluated by Likert scales). Each surgeon included 20 consecutive cases. RESULTS: Of nine centres, three abandoned HoLEP before the end of the study due to complications, and one was excluded for treating patients off protocol. Only one centre achieved the main judgment criterion of four consecutive successful HoLEP procedures. Overall, the procedures were successfully performed in 43.6% of cases. Reasons for unsuccessful procedures were mainly operative time >90 min (n = 51), followed by conversion to TURP (n = 14), incomplete morcellation (n = 8), significant stress (n = 9), or difficulty (n = 14) during HoLEP. Ignoring operating time, 64% of procedures were successful and four out of five centres did four consecutive successful cases. Of the five centres that completed the study, four chose to continue HoLEP. CONCLUSION: Even in a prospective training structure, HoLEP has a steep learning curve exceeding 20 cases, with almost half of our centres choosing to abandon or not to continue with the technique. Operating time and difficulty of the enucleation seem the most important problems for a beginner. A more intensely mentored and structured mentorship programme might allow safer adoption of the procedure.

The subclassification of papillary renal cell carcinoma does not affect oncological outcomes after nephron sparing surgery.

OBJECTIVES: To evaluate the oncological outcomes of papillary renal cell carcinoma (pRCC) following nephron sparing surgery (NSS) and to determine whether the subclassification type of pRCC could be a prognostic factor for recurrence, progression, and specific death. MATERIALS AND METHODS: An international multicentre retrospective study involving 19 institutions and the French network for research on kidney cancer was conducted after IRB approval. We analyzed data of all patients with pRCC who were treated by NSS between 2004 and 2014. RESULTS: We included 486 patients. Tumors were type 1 pRCC in 369 (76 %) cases and type 2 pRCC in 117 (24 %) cases. After a mean follow-up of 35 (1-120) months, 8 (1.6 %) patients experienced a local recurrence, 12 (1.5 %) had a metastatic progression, 24 (4.9 %) died, and 7 (1.4 %) died from cancer. Patients with type I pRCC had more grade II (66.3 vs. 46.1 %; p < 0.001) and less grade III (20 vs. 41 %; p < 0.001) tumors. Three-year estimated cancer-free survival (CFS) rate for type 1 pRCC was 96.5 % and for type 2 pRCC was 95.1 % (p = 0.894), respectively. Three-year estimated cancer-specific survival rate for type 1 pRCC was 98.4 % and for type 2 pRCC was 97.3 % (p = 0.947), respectively. Tumor stage superior to pT1 was the only prognostic factor for CFS (HR 3.5; p = 0.03). CONCLUSION: Histological subtyping of pRCC has no impact on oncologic outcomes after nephron sparing surgery. In this selected population of pRCC tumors, we found that tumor stage is the only prognostic factor for cancer-free survival.

Partial nephrectomy after selective embolization of tumor vessels in a hybrid operating room: A new approach of zero ischemia in renal surgery.

It is established that partial nephrectomy is the standard of care for tumors confined to the kidney. Achieving a partial nephrectomy without renal ischemia and limiting operative bleeding is the subject of numerous researches. Since 2010, hybrid operating rooms have been used to perform both interventional radiology and surgical procedures at the same place and time. We used this latest technology to treat 3 patients with localized kidney tumors. The tumors were of moderate complexity and all were treated after immediate hyperselective embolization by laparoscopic surgery without dissection and clamping of the renal pedicle. The embolization of tumor vessels could be performed using image-stitching software. After embolization, operative time was 50, 70 and 80 minutes and blood loss was less than 100 ml for each case. Postoperative control 3D arteriography confirmed the respect of the vascularization of the healthy renal parenchyma. No postoperative complications occurred. Combined approach including hyperselective embolization and partial nephrectomy in the same time in a dedicated operating room is a new approach of zero ischemia during partial nephrectomy which reduces the difficulty of the surgery, limits injury to the kidney and increases patient safety.

Posterior Spinal Cord Syndrome after Flexible Ureteroscopy for Kidney Stones.

A 49-year-old woman was treated for right kidney stones using flexible ureteroscopy and laser lithotripsy. She was readmitted 2 weeks after the treatment with complaints of walking difficulties. On neurologic examination, it was found that she had a bilateral proprioceptive dysfunction. Spinal MRI revealed an intramedullary lesion at the T10-T11 level consistent with an intramedullary cavernoma. The final diagnosis was a spinal compression consecutive to the cavernoma bleeding associated with the prolonged lithotomy position. Symptoms have not been reversible and the patient continued to have walking difficulties. We report for the first time a major complication that arises as a result of using flexible ureteroscopy for treating kidney stones.

Vascular-targeted photodynamic therapy with TOOKAD® Soluble in localized prostate cancer: standardization of the procedure.

INTRODUCTION: Vascular-targeted photodynamic therapy with TOOKAD(®) Soluble is an innovative focal therapy procedure assessed in localized prostate cancer treatment. MATERIALS AND METHODS: This mini-invasive technique destroys targeted tissues using a photosensitizer [TOOKAD(®) Soluble (WST11), STEBA Biotech] activated by laser light in the presence of oxygen. Its application for prostate cancer requires intravenous infusion of TOOKAD(®) Soluble and the illumination of the targeted area by transperineal optical fibers inserted under trans-rectal ultrasound guidance under general anesthesia. CONCLUSION: Based on the experience gained through hundreds of procedures, we describe here the standardized technique of vascular-targeted photodynamic therapy with TOOKAD(®) Soluble defined during the phase II and III trials.

Feasibility, safety, and efficacy of salvage radical prostatectomy after Tookad® Soluble focal treatment for localized prostate cancer.

PURPOSE: To investigate feasibility, safety, and efficacy of salvage radical prostatectomy (RP) for recurrent prostate cancer (PCa) after focal treatment with TOOKAD(®) Soluble vascular-targeted photodynamic therapy (VTP). METHODS: Nineteen patients underwent RP after biopsy-proven PCa post-focal VTP. We reported: operation time, blood loss, transfusion, complications, urethral catheterization time, functional outcomes, and short-term oncologic outcomes. RESULTS: Median age was 64 years (58-70). Median PSA before VTP was 6.30 ng/ml (3.20-9.80). Median delay between VTP and RP was 17 months (8-48). Median blood loss was 400 ml (100-1,000). Median operation time was 150 min (90-210), median urethral catheterization time was 7 days (5-18), and median hospital stay was 7 days (4-21). There was no perioperative mortality. Three patients had related per-operative complications: one pelvic hematoma (150 cc) (Clavien IIIa), one per-operative transfusion (900 cc hemorrhage) (Clavien II), and one superficial wound infection (Clavien I). After a median follow-up of 10 months (1-46), 13 were completely continent (68 %), five needed ≤1 pad/day, and one needed 3 pads/day (Clavien I). Severe erectile dysfunction was observed before and after RP (respectively 8 and 18). Ten patients regained potency with appropriate treatment. Median postoperative PSA was 0.02 ng/ml (<0.01-0.38) and remained undetectable for 16 patients (84 %). Nine patients had positive margins and six underwent complementary radiotherapy. Positive margins were significantly associated with bilateral VTP [risk ratio = 4.3, 95 % confidence interval (1.6-11.7), p = 0.003]. CONCLUSION: Salvage RP after VTP treatment was feasible, safe, and efficient to treat most of the locally recurrent PCa. Short-term oncologic and functional outcomes were promising, but further studies are required.

Role of active surveillance and focal therapy in low- and intermediate-risk prostate cancers.

PURPOSE: Low-risk prostate cancer is found in about half of newly diagnosed men subjected to PSA screening. METHODS: To define the role of active surveillance and focal therapy in low- and intermediate-risk prostate cancers, an invited international panel of practicing physicians in the field of localized prostate cancer discussed the available literature in three consecutive meetings to come to a broad interpretation of the available data. RESULTS: The panel ("new prostate cancer management group," npm) agreed on the following observations. In most men with a low-volume Gleason 6 tumor, initial conservative management is appropriate. In men with a larger unifocal Gleason score 6 or 3 + 4 lesion, focal therapy, although still considered an investigational approach, appears to be a suitable option in early non-randomized comparison studies. Furthermore, in patients with multifocal small satellite Gleason 6 lesions in the presence of a larger index lesion, focal therapy of the index lesion is an option. For patients with high-grade, large-volume disease, or in young men with evidence of high-volume multifocal low-grade prostate cancer, whole-gland treatment should be considered. CONCLUSION: Active surveillance is a preferred and safe option for low-risk prostate cancer. Focal therapy is still under investigation, but the available phase II data are promising. Clinical benefits must be shown in prospective trials. With improved imaging, focal therapy may be an option for patients not choosing active surveillance with low-risk disease, progression upon active surveillance or intermediate-risk cancers with a localizable lesion.

Acute renal colic during pregnancy: management and predictive factors.

INTRODUCTION: The aim of this study was to identify predictive factors of urolithiasis etiology for acute renal colic (ARC) during pregnancy. MATERIALS AND METHODS: We performed a retrospective review of all pregnant women hospitalized for an ARC between January 2007 and October 2012 in the department of Obstetrics and Gynecology of a University Hospital. Univariate and multivariate regression models were used to assess potential predictive factors of urolithiasis etiology. RESULTS: We included 82 patients. A urolithiasis was identified in 24 (29.3%) patients. In univariate analysis, we identified the following predictive factors for a urolithiasis etiology: primiparity (p = 0.017), leukocyturia (p = 0.021), left hydronephrosis > 10 mm and > 15 mm (p = 0.009; p = 0.02) and right hydronephrosis > 15 mm (p = 0.019). In multivariate analysis, only left hydronephrosis > 10 mm remained predictive for a urolithiasis etiology (p = 0.036; HR 7.45). A ureteral stenting was necessary for 23 patients (28.0%). Three patients (3.7%) had a premature membrane rupture and two patients (2.4%) delivered prematurely. After delivery, 10 patients (12.2%) required surgical treatment. CONCLUSION: Left hydronephrosis was related to urolithiasic etiology for ARC. Obstetrical consequences of ARC were minor.

Impact of retrograde flexible ureteroscopy and intracorporeal lithotripsy on kidney functional outcomes.

OBJECTIVE: The aim of the study was to evaluate renal function and to identify factors associated with renal function deterioration after retrograde intrarenal surgery (RIRS) for kidney stones. MATERIALS AND METHODS: We retrospectively analyzed patients with renal stones treated by RIRS between January 2010 and June 2013 at a single institute. We used the National Kidney Foundation classification of chronic kidney disease (CKD) to classify Glomerular Filtration Rate (GFR) in 5 groups. The baseline creatinine level was systematically pre-operatively and post-operatively evaluated. All patients had a creatinine blood measurement in June 2013. A change toward a less or a more favorable GFR group following RIRS was considered significant. RESULTS: We included 163 patients. There were 86 males (52.8%) and 77 females (47.3%) with a mean age of 52.8±17 years. After a mean follow-up of 15.5±11.5 months, median GFR was not significantly changed from 84.3±26.2 to 84.9±24.5 mL/min (p=0.675). Significant renal function deterioration occurred in 8 cases (4.9%) and significant renal function amelioration occurred in 23 cases (14.1%). In univariate analysis, multiple procedures (p=0.023; HR: 5.4) and preoperative CKD (p=0.011; HR: 6.8) were associated with decreased renal function. In multivariate analysis these factors did not remain as predictive factors. CONCLUSION: Stone management with RIRS seems to have favorable outcomes on kidney function; however, special attention should be given to patients with multiple procedures and preoperative chronic kidney disease.

Neoadjuvant targeted molecular therapies in patients undergoing nephrectomy and inferior vena cava thrombectomy: is it useful?

OBJECTIVE: To assess the effect of neoadjuvant targeted molecular therapies (TMTs) on size and level of inferior vena cava tumor thrombi and to evaluate their impact on surgical management. METHODS: We retrospectively analyzed the data of 14 patients treated for a clear cell renal cell carcinoma with inferior vena cava thrombi by neoadjuvant TMT before nephrectomy. Clinical, pathological and perioperative data were gathered retrospectively at each institution. The primitive tumor size and the thrombus size were defined by computed tomography before TMT. The tumor thrombus level was defined according to the Novick's classification. RESULTS: Before TMT, thrombus level was staged I for 1 (7%), II for 10 (72%) and III (21%) for 3 patients. First-line therapy was sunitinib in 11 cases and sorafenib in 3 cases. Median therapy duration was two cycles (1-5). Three patients experienced major adverse effects (grade III) during TMT. Following TMT, 6 (43%) patients had a measurable decrease, 6 (43%) had no change, and 2 (14%) had an increase in the thrombus. One patient (7%) had a downstage of thrombus level, 12 (85%) had stable thrombi, and 1 (7%) had an upstage. Regarding primary tumor, 7 (50%), 5 (36%) and 2 (14%) patients had a decrease, stabilization and an increase in tumor size, respectively. CONCLUSION: Neoadjuvant TMT appears to have limited effects on renal tumor thrombi. This retrospective study failed to demonstrate a significant impact of neoadjuvant TMT on surgical management of clear cell renal cell carcinoma with inferior vena cava tumor thrombi.

Transcutaneous posterior tibial nerve stimulation: evaluation of a therapeutic option in the management of anticholinergic refractory overactive bladder.

INTRODUCTION AND HYPOTHESIS: This study evaluated the efficacy and tolerability of transcutaneous posterior tibial nerve stimulation (TPTNS) in the treatment of overactive bladder (OAB) after failure of a first-line anticholinergic treatment. MATERIALS AND METHODS: We performed a prospective observational study and included all patients treated in a single center for OAB persisting after first-line anticholinergic treatment from November 2010 to May 2013. The protocol consisted of daily stimulation at home. The efficacy end point was defined as improvement on the Urinary Symptom Profile (USP) and the French-validated urinary symptom score Mesure du Handicap Urinaire (MHU). RESULTS: We assessed 43 consecutive patients. TPTNS was successful following 1 month of treatment in 23 (53%) patients. Bladder capacity was the only predictive factor for treatment success (p = 0.044). For patients who showed improved symptoms (n = 23; 53%), mean MHU and USP decreased significantly, from 11.8 ± 2.8 to 5.6 ± 3 (p < 0.001) and from 14 ± 3.3 to 6.9 ± 3.2 (p < 0.001), respectively. After a mean follow-up of 10.8 ± 1.6 months, 21 (49%) patients continued the TPTNS. Mean MHU and USP scores were 4.4 ± 2.8 and 5.4 ± 3.5, respectively, and stayed lower than baseline (p < 0.001). Patients reported no adverse events. CONCLUSION: TPTNS is well tolerated and is effective in one half of the patients studied after they failed anticholinergic treatment. TPTNS could become a second therapeutic option before surgical treatment in the management strategy of OAB.