External validation of biochemical recurrence definition to predict oncologic outcomes following focal therapy for localized prostate cancer using high intensity focused ultrasound.

PURPOSE: This is an external validation of several biochemical recurrence definitions based on prostate specific antigen criteria (PSA). The purpose is to predict the need of additional treatment and failure after focal therapy using high intensity focused ultrasound (HIFU) for localized prostate cancer (PCa). MATERIALS AND METHODS: A total of 343 consecutive patients who underwent HIFU with Ablatherm® and Focal One® devices between June 2001 and November 2020 were identified. Treatment failure was defined as clinically significant PCa on postoperative biopsy, the need for salvage radical or systematic treatment, metastasis, or PCa-related death. The biochemical recurrence definitions tested were PSA nadir, time to PSA nadir, percentage of PSA reduction, Huber et al. criteria defined as PSA nadir + 1 ng/mL at 12 months or PSA nadir + 1.5 ng/mL at 24-36 months. Multivariable Cox regression analysis and decision-curve analysis were used to validate and compare criteria. Kaplan-Meier analysis was used to assess criteria associated with the highest accuracy. RESULTS: One hundred seventy-eight patients met the inclusion criteria and were analyzed. Overall, 61 (34%) and 41 (23%) patients had an additional treatment and failure with a median follow-up of 52 months. At multivariable analysis, model including Huber et al. criteria exhibited the highest Harrell's C-index for the prediction of the need of additional treatment (hazard ratio [HR]: 10, p < 0.001, c-index: 84%) and treatment failure (HR: 9.1, p < 0.001, c-index: 82%) as well as higher net benefit. The 60-months need of additional treatment and treatment failure-free survival were 89% and 98% compared to 26% and 49%, respectively, when stratified according to Huber et al. criteria (Log-rank test, p < 0.001). Similar results were found after excluding patient with non-clinically significant PCa at initial biopsy. CONCLUSIONS: We report an external validation of biochemical recurrence definitions predicting the need of additional treatment and failure after focal therapy using HIFU for localized PCa. Huber et al. criteria were identified as the most accurate and could be used to guide clinicians toward further evaluation and salvage treatments.

The role of perilesional and multiparametric resonance imaging-targeted biopsies to reduce the risk of upgrading at radical prostatectomy pathology: A retrospective monocentric study.

PURPOSE: To evaluate histopathologic upgrading between biopsy methods and whole-mount prostatectomy specimens in International Society of Urological Pathology grade group. METHODS: Overall, 134 patients, including 175 magnetic resonance imaging (MRI)-suspicious lesions, diagnosed on MRI-targeted (TB) and systematic (SB) biopsies before radical prostatectomy were retrospectively analyzed from a prospectively maintained database. Perilesional (PLB) and "extended" perilesional (ePLB) biopsies were defined as those taken within a circumferential zone of 5 and 10 mm around magnetic resonance imaging (MRI)-suspicious lesion respectively. Proportion of upgrading at prostatectomy pathology were compared between TB, TB + PLB, TP + ePLB and TB + SB. Uni- and multivariable logistic regressions assessed predictors of upgrading for TB + ePLB method. RESULTS: Focusing on index lesion, median (interquartile range) number of cores taken was 4 (3-4) for TB, 5 (4-6) for TB + PLB, 6 (5-8) for TB + ePLB and 12 (12-15) for TB + SB. A higher upgrading proportion was detected upon comparing TB and TB + PLB methods to TB + SB (32 vs. 19%, P = 0.001, 26 vs. 19%, P = 0.04, respectively). Conversely, no significant difference was found between TB + ePLB compared to TB + SB (23 vs. 19%, P = 0.2). Proportion of downgrading was similar regardless of biopsy method (all P > 0.1). At multivariable analysis, Prostate Imaging-Reporting and Data System Steering score, total number of positive ePLB cores and International Society of Urological Pathology Grade Group were independent predictors of upgrading (all P ≤ 0.03). Similar results were found by adding data from non-index lesions. CONCLUSION: Our finding suggest that MRI-targeted biopsies associated with perilesional sampling in a circumferential zone of 10 mm reduced upgrading proportion and showed similar accuracy as the current gold standard combination. Further prospective studies comparing biopsy methods are expected to validate this diagnostic strategy.

Salvage Hemiablation High Intensity Focused Ultrasound for unilateral radio-recurrent prostate cancer.

OBJECTIVE: To report the oncological and functional outcomes of salvage hemiablation high-intensity focused ultrasound (HIFU) in patients with unilateral radio-recurrent prostate cancer. PATIENTS AND METHODS: Patients with biochemical recurrence (BCR) after primary radiation therapy and evidence of unilateral organ confined recurrence based on a complete match between mpMRI and MRI targeted biopsies were included. Patients with distant metastasis were excluded. Patients were followed with serial serum PSA determinations. BCR were defined using the Phoenix criteria. Complications were graded according to the Clavien score. IIEF-5 questionnaire was used to assess erectile dysfunction. Urinary incontinence was reported using physician reported rates. RESULTS: A total of 10 consecutive patients (median age: 71 years, IQR: 69-76) were prospectively enrolled. The median pre-treatment PSA and post-treatment PSA nadir were 3.1ng/mL (IQR: 1.54-8.59) and 1.52ng/mL (IQR: 0.76-2.2), respectively. At a median follow-up of 41.5 (IQR: 18-58) months, 50% of patients experience BCR. BCR free-survival rates at 24 and 36 months were 75% (CI95%: 31-93) and 60% (CI95%: 20-85), respectively. Urinary in continence grade II occurred in two patients and the remaining patients were pad-free. One patient developed de novo erectile dysfunction requiring PDE5I. The erectile function scores decreased from a mean of 10.1 to 8.7. CONCLUSION: Hemiablation HIFU is an alternative to whole gland therapy in patients with unilateral radio- recurrent prostate cancer, which offers limited urinary and rectal morbidity, and preserves functional outcomes. LEVEL OF EVIDENCE: 3.

Focal Treatment for Unilateral Prostate Cancer Using High-Intensity Focal Ultrasound: A Comprehensive Study of Pooled Data.

BACKGROUND: Focal therapy for prostate cancer (PCa) remains experimental. Aim of the current study is to review available evidence and perform a pooled analysis exploring oncologic and functional results of high intensity focus ultrasound (HIFU) focal therapy for the treatment of unilateral PCa. METHODS: The National Library of Medicine Database was searched for relevant articles. A wide search was performed, including the combination of following words: "HIFU," "prostate," "cancer," and "focal." Overall, 167 articles were reviewed. Of these, seven articles were identified and eligible for the pooled analysis. Data on HIFU hemiablation or focal prostate ablation, oncologic and functional results were pooled from these seven studies that included 366 men with unilateral PCa. RESULTS: In the 366 analyzed cases, mean age was 67 years (95% confidence interval 66-69), and mean preoperative prostate-specific antigen was 6.4 ng/cc (5.5-7.4). Three studies included PCa up to Gleason 7 (3 + 4), three studies did include also Gleason 7 (4 + 3), whereas one study had no limitation in terms of Gleason score. Regarding early complications, low-grade Clavien-Dindo I-II were reported in 26% (16-37), whereas high-grade Clavien-Dindo ≥III were found in 3.8% (0-8.6). Analyzing oncologic outcomes mean follow-up was 26 months (23-31): at one year after HIFU, negative biopsy rate for clinically significant PCa was 87% (79-96), whereas salvage treatment-free survival rate was 92% (85-98). Regarding functional outcomes, reported potency rates were 74% (64-84), and continence 96% (91-100), although definitions of potency and continence were not homogenous across studies. CONCLUSIONS: This pooled analysis of the results of focal HIFU treatment of PCa shows promising oncologic and functional outcomes. Well-selected patients may be candidates for such a conservative partial treatment of the gland. Well-designed trials are awaited to compare HIFU focal treatment with current standard of care.

A Hard Ball for a Tennis Player: A Rare Case of Large Calcifying Sertoli Cell Testicular Tumor.

A 46 year old tennis player was addressed to our clinic after incidental finding of right testicular calcification on plain x-ray of the spine. Urologic consultation revealed a hard non-tender testicular mass which required inguinal orchiectomy. Final histology revealed large cell calcifying Sertoli cell tumor: we herein present the case and review current physiopathology of such rare testicular disease.

Management of Anastomosis Leakage Post-RALP: A Simple Trick for a Complex Situation.

A case of 74 years old male patient who underwent RALP with bladder neck reconstruction. Persistent vesicourethral anastomotic leak was seen at cystography. A self-made side fenestrated Foley catheter was used and on the day after, a complete reversal in fluid output between the Foley catheter and the drain was seen.

Clinical impact of 68 Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer with rising prostate-specific antigen after treatment with curative intent: preliminary analysis of a multidisciplinary approach.

OBJECTIVE: To assess the impact of a novel molecular imaging technique, 68 Ga-(HBED-CC)-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT), in the clinical management of patients with prostate cancer with rising prostate-specific antigen (PSA) after treatment with curative intent. PATIENTS AND METHODS: In all, 131 consecutive patients were referred to our centre for a 68 Ga-PSMA PET/CT in the setting of recurring prostate cancer. Of these patients, 11/131(8%) presented with persistent PSA after radical prostatectomy, while 120/131 (92%) were referred for biochemical recurrence after surgery, radiotherapy or both. The images where taken 1 h after injection of 2 MBq/kg of the 68 Ga-(HBED-CC)-PSMA ligand. All examinations were interpreted by two experienced nuclear medicine specialists. Using the results of the examination, a multidisciplinary oncology committee (MOC) reported on the treatment strategy. A positive impact on clinical management was considered if the examination determined a modification in the treatment strategy compared to the MOC decision before PSMA imaging. RESULTS: All patients completed the examination with no adverse reactions. The median (interquartile range) PSA level at the time of the examination was 2.2 (0.72-6.7) ng/mL. Overall, 68 Ga-PSMA PET/CT detected at least one lesion suspicious for prostate cancer in 98/131 (75%) patients. There was an impact on subsequent management in 99/131 patients (76%). The main modifications included continuing surveillance (withholding hormonal therapy), hormonal manipulations, stereotaxic radiotherapy, salvage radiotherapy, salvage node dissection or salvage local treatment (prostatectomy, high-intensity focussed ultrasound). CONCLUSION: Our preliminary experience suggests that performing 68 Ga-PSMA PET/CT in patients with prostate cancer with rising PSA after treatment with curative intent can be clinically useful as it changes the treatment strategy in a significant proportion of patients. However, larger prospective trials are needed to validate our present findings.

Comparing High-Intensity Focal Ultrasound Hemiablation to Robotic Radical Prostatectomy in the Management of Unilateral Prostate Cancer: A Matched-Pair Analysis.

INTRODUCTION: Although still experimental, focal treatment is being increasingly implemented in the management of prostate cancer (PCa). Aim of the current study was to compare functional and oncologic outcomes of high-intensity focal ultrasound (HIFU) hemiablation of the prostate to robot-assisted laparoscopic prostatectomy (RALP) in the management of unilateral PCa. MATERIALS: Fifty-five men with unilateral, clinically localized PCa underwent HIFU hemiablation of the affected prostatic lobe between 2007 and 2015. All patients were found to have unilateral disease on the basis on full concordance between multiparametric magnetic resonance imaging (MRI) and MRI-guided biopsies. These patients were matched 1:1 with patients who underwent RALP for PCa in which pT2a-b disease (unilateral) was found on final pathologic analysis. Matching criteria were Gleason score, prostate specific antigen (PSA), and cT stage. Treatment failure was defined as the need for salvage external beam radiotherapy or systemic androgen deprivation therapy (ADT) due to disease progression. Kaplan-Meier curves and log-rank tests were constructed to assess differences in salvage treatment free survival across surgical techniques. RESULTS: Matching was effective with no significant differences across the two groups, although men treated with HIFU were older (p < 0.001). Median follow-up was 36 months (interquartile range 16-56). HIFU was associated to better and faster recovery of continence, with most men (82%) showing no signs of urinary incontinence even right after surgery. Moreover, the risk of de novo erectile dysfunction was significantly lower after HIFU. No significant difference was found in the need for salvage external beam radiation therapy or ADT across the two surgical approaches: 7/55 men underwent salvage therapy in the HIFU vs 6/55 in the RALP group (p = 0.76). Nonetheless, seven more patients in the HIFU arm required a complementary treatment on the contralateral lobe during follow-up, after developing a contralateral PCa. No patient died of PCa on follow-up, while six men died of other causes (five HIFU vs one RALP, p = 0.11). CONCLUSION: In this matched pair analysis, HIFU hemiablation was comparable to RALP in controlling localized unilateral PCa, with no significant differences in the need for salvage therapies. HIFU was also associated to significantly better functional outcomes. Accurate patient selection remains vital, and larger prospective trials are needed to confirm our findings.

High Intensity Focused Ultrasound versus Brachytherapy for the Treatment of Localized Prostate Cancer: A Matched-Pair Analysis.

Purpose. To evaluate postoperative morbidity and long term oncologic and functional outcomes of high intensity focused ultrasound (HIFU) compared to brachytherapy for the treatment of localized prostate cancer. Material and Methods. Patients treated by brachytherapy were matched 1 : 1 with patients who underwent HIFU. Differences in postoperative complications across the two groups were assessed using Wilcoxon's rank-sum or χ (2) test. Kaplan-Meier curves, log-rank tests, and Cox regression models were constructed to assess differences in survival rates between the two groups. Results. Brachytherapy was significantly associated with lower voiding LUTS and less frequent acute urinary retention (p < 0.05). Median oncologic follow-up was 83 months (13-123 months) in the HIFU cohort and 44 months (13-89 months) in the brachytherapy cohort. Median time to achieve PSA nadir was statistically shorter in the HIFU. Biochemical recurrence-free survival rate was significantly higher in the brachytherapy cohort compared to HIFU cohort (68.5% versus 53%, p < 0.05). No statistically significant difference in metastasis-free, cancer specific, and overall survivals was observed between the two groups. Conclusion. HIFU and brachytherapy are safe with no significant difference in cancer specific survival on long term oncologic follow-up. Nonetheless, a randomized controlled trial is needed to confirm these results.

Evaluation of the single-knot running vesicourethral anastomosis 10 years after its introduction: results from an international survey.

OBJECTIVE: To evaluate the acceptance of the single-knot running vesicourethral anastomosis in a worldwide survey, 10 years after its introduction. MATERIALS AND METHODS: A survey composed of 13 multiple-choice questions was launched on the Internet. Urologists involved in minimally invasive surgery were invited to participate. Questions explored professional characteristics of the respondents, experience with the single-knot running vesicourethral anastomosis, complications (including technical, early, and late complications), and a general opinion on the technique. RESULTS: The 391 urologists who participated in the survey worked in academic, private, and community settings. Live surgeries appear to have been the most important tool to teach the technique. The global experience gained with this technique is vast: in the last 10 years we calculated over 120,000 anastomoses were performed by our cohort of respondents. Overall, technical, early (mainly uncomplicated early leakage), and late complications (mainly anastomotic stricture) were observed in <2% of cases by the majority of surgeons in the survey. Most urologists in the survey seem to accept the technique as a commonly used procedure in urologic surgery. CONCLUSIONS: Today, in 2014, the single-knot running anastomosis technique appears to have been well accepted by the urologic community. However, research should continue always in order to explore and invent better surgical solutions for our patients.

Single high intensity focused ultrasound session as a whole gland primary treatment for clinically localized prostate cancer: 10-year outcomes.

Objectives. To assess the treatment outcomes of a single session of whole gland high intensity focused ultrasound (HIFU) for patients with localized prostate cancer (PCa). Methods. Response rates were defined using the Stuttgart and Phoenix criteria. Complications were graded according to the Clavien score. Results. At a median follow-up of 94months, 48 (44.4%) and 50 (46.3%) patients experienced biochemical recurrence for Phoenix and Stuttgart definition, respectively. The 5- and 10-year actuarial biochemical recurrence free survival rates were 57% and 40%, respectively. The 10-year overall survival rate, cancer specific survival rate, and metastasis free survival rate were 72%, 90%, and 70%, respectively. Preoperative high risk category, Gleason score, preoperative PSA, and postoperative nadir PSA were independent predictors of oncological failure. 24.5% of patients had self-resolving LUTS, 18.2% had urinary tract infection, and 18.2% had acute urinary retention. A grade 3b complication occurred in 27 patients. Pad-free continence rate was 87.9% and the erectile dysfunction rate was 30.8%. Conclusion. Single session HIFU can be alternative therapy for patients with low risk PCa. Patients with intermediate risk should be informed about the need of multiple sessions of HIFU and/or adjuvant treatments and HIFU performed very poorly in high risk patients.

Primary Zonal High Intensity Focused Ultrasound for Prostate Cancer: Results of a Prospective Phase IIa Feasibility Study.

OBJECTIVES: To present the results of a prospective phase IIa study assessing the role of primary zonal High Intensity Focused Ultrasound (HIFU) for prostate cancer treatment. METHODS: 31 consecutive patients with unilateral organ confined prostate cancer primarily treated by zonal HIFU (from February 2007 to June 2011) were recruited into a single centre prospective phase IIa feasibility study. Complications were prospectively recorded and graded according to the Clavien-Dindo score. Postoperatively, patients were followed with serial serum PSA determinations and digital rectal examinations. An individual PSA nadir was identified in each patient. Followup also included whole gland biopsies performed in the event of a PSA rising>2.0 ng/mL above nadir value (Phoenix criteria). RESULTS: At a median followup of 38 months, biochemical recurrence free survival was 100%, 89%, and 82.7% at 1, 2, and 3 years, respectively, with overall and cancer specific survival of 100%. The procedure was safe and well tolerated with no major adverse events. All patients were continent at their last followup and 55.2% (16/29) had erectile function sufficient for penetration. CONCLUSION: Primary zonal HIFU is a valid focal therapy strategy, safe and feasible in day to day practice with good promising results [corrected].

Long-term evaluation of oncologic and functional outcomes after laparoscopic open-assisted radical cystectomy: a matched-pair analysis.

PURPOSE: To evaluate peri- and postoperative morbidity, and long-term oncologic and functional results of our laparoscopic radical cystectomy (LRC) technique, comparing it with our standard open approach. METHODS: Between 2000 and 2010, 54 patients underwent LRC for urothelial cell carcinoma of the bladder in two academic hospitals. The procedures were performed by two surgeons. Patients were matched 1:1 with patients who underwent open RC in the same years by the same surgical team. Differences in peri- and postoperative complications across the two groups were assessed using Wilcoxon's rank-sum or χ (2) test. Kaplan-Meier curves, log-rank tests and Cox regression models were constructed to assess differences in recurrence-free survival on long-term follow-up between the two groups. RESULTS: Laparoscopic radical cystectomy was significantly associated with lower blood loss (p < 0.0001) and less frequent postoperative ileus (p = 0.03). Regarding more serious postoperative complications, no difference was found across the two cohorts. Median oncologic follow-up was 42 months (IQR 12-72 months) in the LRC cohort and 18 months (IQR 8-27 months) in patients undergoing open radical cystectomy (ORC). No statistically significant difference in recurrence-free survival was observed between the two groups (log rank p = 0.677). On univariate Cox regression, the surgical approach used was not significantly associated with risk of recurrence. CONCLUSIONS: We found that LRC is safe and associated with lower blood loss and decreased postoperative ileus compared with ORC. Moreover, on long-term oncologic follow-up, LRC appeared non-inferior to ORC with no significant difference in recurrence-free survival. Nonetheless, these results must be confirmed by larger series and stronger long-term follow-up data are needed.

3D versus 2D Systematic Transrectal Ultrasound-Guided Prostate Biopsy: Higher Cancer Detection Rate in Clinical Practice.

Objectives. To compare prostate cancer detection rates of extended 2D versus 3D biopsies and to further assess the clinical impact of this method in day-to-day practice. Methods. We analyzed the data of a cohort of 220 consecutive patients with no prior history of prostate cancer who underwent an initial prostate biopsy in daily practice due to an abnormal PSA and/or DRE using, respectively, the classical 2D and the new 3D systems. All the biopsies were done by a single experienced operator using the same standardized protocol. Results. There was no significant difference in terms of age, total PSA, or prostate volume between the two groups. However, cancer detection rate was significantly higher using the 3D versus the 2D system, 50% versus 34% (P < 0.05). There was no statistically significant difference while comparing the 2 groups in term of nonsignificant cancer detection. Conclusion. There is reasonable evidence demonstrating the superiority of the 3D-guided biopsies in detecting prostate cancers that would have been missed using the 2D extended protocol.

[Renal complications of sickle-cell anaemia]. / Les complications rénales de la drépanocytose.

There are six described complications of sickle cell trait or disease : gross hematuria, renal infarction, papillary necrosis, nephrotic syndrome and urine concentration defects. Because of a high frequency of sickle cell trait patients among patients suffering from medullary kidney carcinoma, it has been called the seventh complication. We briefly review physiopatholgy and diagnosis of these complications.