Long-term functional and oncological outcomes of nerve-sparing and prostate capsule-sparing cystectomy: a single-centre experience.

OBJECTIVES: To evaluate the technical feasibility, oncological and functional outcomes of nerve sparing cystoprostatectomy (NSCP) and prostate capsule-sparing cystectomy (PCSC) for the treatment of organ-confined bladder cancer at a single referral centre. PATIENTS AND METHODS: From April 2001 to June 2012, 60 patients underwent PCSC and 47 were treated with NSCP. Inclusion criteria for PCSC were: fully informed consent for the well-motivated patient; negative transurethral resection of the bladder neck; normal prostatic specific antigen (PSA) level (defined as <4 ng/dL during the first year of the study, which was later lowered to 2.5 ng/dL); and normal transrectal ultrasonography, with biopsy for any suspicious nodule. Patients received a complete oncological and functional follow-up. The Kaplan-Meier method was used to depict survival outcomes after surgery. RESULTS: After a median follow-up of 73 and 62 months for PCSC and NSCP, respectively, the 5-year cancer-specific survival was 90% for the PCSC group and 78% for the NSCP group (P = 0.055). Considering complications within 30 days after surgery, 13% and 21% patients had Clavien ≥III complications in the PCSC and NSCP groups, respectively (P = 0.2). For functional outcomes, at 3 months after surgery, 54 (90%) and 24 (51%) patients reported full recovery of daytime urinary continence in the PCSC and NSCP groups, respectively (P < 0.001); and for erectile function recovery, 32 (53%) and four (9%) patients in the PCSC group and in the NSCP group were respectively potent without any treatment (P < 0.001). CONCLUSIONS: NSCP and PCSC are appropriate for a subset of patients with bladder cancer, with excellent oncological and functional results. These surgical procedures should be proposed to well-motivated patients.

Switch from abiraterone plus prednisone to abiraterone plus dexamethasone at asymptomatic PSA progression in patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: To evaluate the effects of switching from prednisone (P) to dexamethasone (D) at asymptomatic prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). MATERIALS AND METHODS: Among 93 patients treated with AA between January 2013 and April 2016 in our institution, 48 consecutive asymptomatic patients with mCRPC, who experienced biochemical progression on treatment with AA+P 10 mg/day, were included. A corticosteroid switch to AA+D 0.5 mg/day at PSA increase was administered until radiological and/or clinical progression. The primary endpoint was progression-free-survival (PFS). A prognostic score based on independent prognostic factors was defined. RESULTS: The median time to PSA progression on AA+P was 8.94 months. The median PFS on AA+D and AA+corticosteroids (P then D) was 10.35 and 20.07 months, respectively. A total of 56.25% of patients showed a decrease or stabilization in PSA levels after the switch. In univariate analysis, three markers of switch efficiency were significantly associated with a longer PFS: long hormone-sensitivity duration (≥5 years; median PFS 16.62 vs 4.17 months, hazard ratio [HR] 0.30, 90% confidence interval [CI] 0.16-0.56); low PSA level at the time of switch (<50 ng/mL; median PFS 15.21 vs 3.86 months, HR 0.33, 90% CI 0.18-0.60); and short time to PSA progression on AA+P (<6 months; median PFS 28.02 vs 6.65 months, HR 0.41 (90% CI 0.21-0.81). In multivariate analysis, hormone sensitivity duration and PSA level were independent prognostic factors. CONCLUSION: A steroid switch from P to D appears to be a safe and non-expensive way of obtaining long-term responses to AA in selected patients with mCRPC. A longer PFS has been observed in patients with previous long hormone sensitivity duration, and/or low PSA level and/or short time to PSA progression on AA+P.

Biochemical recurrence-free conditional probability after radical prostatectomy: A dynamic prognosis.

OBJECTIVE: To estimate the conditional biochemical recurrence-free probability and to develop a predictive model according to the disease-free interval for men with clinically localized prostate cancer treated with minimally invasive radical prostatectomy. METHODS: The study population consisted of 3576 consecutive patients who underwent laparoscopic radical prostatectomy and 2619 men treated with robotic radical prostatectomy in the past 15 years at Institute Mutualiste Montsouris, Paris, France. Biochemical recurrence was defined as serum prostate-specific antigen ≥0.2 ng/dL. Univariable and multivariable survival analyses were carried out to identify the prognostic factors for overall free-of-biochemical recurrence probability and conditional survival with respect to the years from surgery without recurrence. A detailed nomogram for the static and dynamic prognosis of biochemical recurrence was developed and internally validated. RESULTS: The median follow-up period was 8.49 years (interquartile range 4.01-12.97), and 1148 (19%) patients experienced biochemical recurrence. Significant variables associated with biochemical recurrence in the multivariable model included preoperative prostate-specific antigen, positive surgical margins, extracapsular extension, pathological Gleason ≥4 + 3 and laparoscopic surgery (all P < 0.001). Conditional survival probability decreased with increasing time without biochemical recurrence from surgery. When stratified by prognosis factors, the 5- and 10-year conditional survival improved in all cases, especially in men with worse prognosis factors. The concordance index of the nomogram was 0.705. CONCLUSIONS: Conditional survival provides relevant information on how prognosis evolves over time. The risk of recurrence decreases with increasing number of years without disease. An easy-to-use nomogram for conditional survival estimates can be useful for patient counseling and also to optimize postoperative follow-up strategies.

First off-time treatment prostate-specific antigen kinetics predicts survival in intermittent androgen deprivation for prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) doubling time is relying on an exponential kinetic pattern. This pattern has never been validated in the setting of intermittent androgen deprivation (IAD). Objective is to analyze the prognostic significance for PCa of recurrent patterns in PSA kinetics in patients undergoing IAD. METHODS: A retrospective study was conducted on 377 patients treated with IAD. On-treatment period (ONTP) consisted of gonadotropin-releasing hormone agonist injections combined with oral androgen receptor antagonist. Off-treatment period (OFTP) began when PSA was lower than 4 ng/ml. ONTP resumed when PSA was higher than 20 ng/ml. PSA values of each OFTP were fitted with three basic patterns: exponential (PSA(t) = λ.e(αt)), linear (PSA(t) = a.t), and power law (PSA(t) = a.t(c)). Univariate and multivariate Cox regression model analyzed predictive factors for oncologic outcomes. RESULTS: Only 45% of the analyzed OFTPs were exponential. Linear and power law PSA kinetics represented 7.5% and 7.7%, respectively. Remaining fraction of analyzed OFTPs (40%) exhibited complex kinetics. Exponential PSA kinetics during the first OFTP was significantly associated with worse oncologic outcome. The estimated 10-year cancer-specific survival (CSS) was 46% for exponential versus 80% for nonexponential PSA kinetics patterns. The corresponding 10-year probability of castration-resistant prostate cancer (CRPC) was 69% and 31% for the two patterns, respectively. Limitations include retrospective design and mixed indications for IAD. CONCLUSION: PSA kinetic fitted with exponential pattern in approximately half of the OFTPs. First OFTP exponential PSA kinetic was associated with a shorter time to CRPC and worse CSS.

Evolution from laparoscopic to robotic nephron sparing surgery: a high-volume laparoscopic center experience on achieving 'trifecta' outcomes.

OBJECTIVE: To evaluate the transition from laparoscopic (LPN) to robotic partial nephrectomy (RPN) in our institution using 'trifecta' outcomes as surrogate marker of efficacy. PATIENTS AND METHODS: We identified 347 patients (LPN = 303, RPN = 44) in our prospectively maintained PN database between 2000 and 2014. The patients were chronologically divided into G1-first 151 LPN cases, G2-subsequent 152 LPN cases and G3-all RPN patients. Trifecta outcomes were defined as warm ischemia time (WIT) ≤25 min, no positive surgical margin (PSM) and complications ≤Clavien 2. Multivariable logistic model was used to analyze the predictors of the trifecta outcomes. RESULTS: The tumor complexity significantly increased from G1 to G3. We achieved lower WIT and less high-grade complication (Clavien ≥ 3) from G1 to G2, and the trend continued even with transition to RPN. PSM was consistently low throughout the transition. Renal functional outcomes always showed a significant positive trend, and with RPN, we achieved improved recovery of renal function (44 vs 57 vs 82 %, p < 0.05). The overall 'trifecta' rates increased significantly from G1 to G2 and reached 81.8 % in RPN (48 vs 75.6 vs 81 %, p < 0.01). Multivariate analysis has shown that the use of robot has significant effect on achieving overall trifecta. The limitations of the study are being retrospective and non-randomized, and the trifecta definitions were not externally validated. CONCLUSIONS: Our transition to RPN was essentially a continuation of our previous LPN experience as we continue to achieve higher 'trifecta' rates inspite of increasing tumor complexity.

Transperineal template-guided mapping biopsy of the prostate.

Accurate diagnosis of prostate cancer has eluded clinicians for decades. With our current understanding of prostate cancer, urologists should devise and confidently present the available treatment options ­ active surveillance/radical treatment/focal therapy to these patients. The diagnostic modalities used for prostate cancer have the dual problem of false negativity and overdiagnosis. Various modifications in the prostate biopsy techniques have increased the accuracy of cancer detection, but we are still far from an ideal diagnostic technique. Transperineal template-guided mapping biopsy of the prostate is an exhaustive biopsy technique that has been improvised over the past decade, and has shown superior results to other available modalities. We have carried out a PubMed search on the available experiences on this diagnostic modality, and along with our own experiences, we present a brief review on transperineal template-guided mapping biopsy of the prostate.

Positive surgical margins after minimally invasive radical prostatectomy in patients with pT2 and pT3a disease could be considered pathological upstaging.

OBJECTIVE: To assess the prognostic significance of positive surgical margins (PSMs) after minimally invasive radical prostatectomy (MIRP) in interaction with other established prognosis factors. PATIENTS AND METHODS: We retrospectively analysed data prospectively collected between 1998 and 2010 for 4628 consecutive patients who underwent MIRP for clinically localized prostate cancer. The impact of PSM on biochemical recurrence (BCR), defined as prostate-specific antigen (PSA) >0.2 ng/mL, was evaluated using multivariable Cox proportional hazards regression. Estimates of BCR-free survival were generated using the Kaplan-Meier method and compared among groups using the log-rank test. RESULTS: The median follow-up was 55 months. On multivariable analysis, PSM was an independent prognostic factor for BCR (adjusted hazard ratio: 2.14 for PSMs vs negative surgical margins (NSMs); 95% confidence interval [CI]: 1.86-2.45; P < 0.001). Other independent predictors for BCR were preoperative PSA, date of surgery, pT stage, Gleason score and lymph node involvement (all P < 0.001). The 5-year BCR-free probability was 80.6% (95% CI: 79-82.2) for NSMs vs 51% (95% CI: 47-55) for PSMs (log-rank P < 0.001). Patients with pT2 and pT3a PSMs had a similar prognosis to those with pT3a and pT3b NSMs, respectively (log-rank P ≥ 0.05). CONCLUSION: A PSM after MIRP is associated with 2.14-fold increased risk of BCR. In patients with pT2 and pT3a disease, a PSM could be considered a pathological upstaging.

Oncologic outcomes after minimally invasive radical prostatectomy in patients with seminal vesicle invasion (pT3b) without adjuvant therapy.

PURPOSE: To evaluate the long-term outcomes of patients with prostate cancer who have pathological pT3b N0-Nx, with postoperative PSA < 0.1 ng/ml and no systematic adjuvant treatment. MATERIALS AND METHODS: Using a monocentric prospectively maintained database, we identified among 2,142 men who underwent minimally invasive radical prostatectomy, 104 pT3b N0-Nx patients, with postoperative PSA < 0.1 ng/ml and at least 5 years of follow-up. Patients were considered for salvage treatment at biochemical recurrence (PSA ≥ 0.2 ng/ml). RESULTS: The median time of follow-up was 83.5 months (interquartile range [IQR]: 69-99). Overall, 102 patients (98 %) had T2 clinical stage or less. Specimen Gleason score was 7 in 71 patients (68 %) and <7 in 15 (14 %). Thirty-eight patients (37 %) were upgraded for Gleason score after radical prostatectomy. The overall 5-year probability of freedom from biochemical recurrence for the entire cohort was 55.8 % (95 % CI 45.8-65.8) and 73.3 % for patients who had specimen Gleason score <7 (p = 0.005). In univariate analysis, specimen Gleason score and surgical margin status were significant predictors for biochemical failure after radical prostatectomy (p = 0.05 and 0.007, respectively). In multivariate analysis, only specimen Gleason score >7 was significantly associated with biochemical failure (p = 0.009). CONCLUSION: SVI is an adverse prognostic factor, but it is not associated with a uniformly poor prognosis. Specimen Gleason score and surgical margin status are significant predictors of recurrence after radical prostatectomy in patients with prostate cancer and SVI.

Evaluation of erectile function after laparoscopic radical prostatectomy in a single center.

INTRODUCTION: To evaluate erectile function among men who had undergone laparoscopic radical prostatectomy and received postoperative medical therapy for erectile dysfunction. MATERIALS AND METHODS: We performed a prospective study in men who underwent laparoscopic radical prostatectomy between September 2003 and November 2005 at our center and who received penile rehabilitation after surgery. All patients had antegrade interfascial dissection. They received 10 mg tadalafil on the fifth postoperative day and continued to receive it every other day, regardless of erectile function. Intracavernous injection of alprostadil was initiated at 3 or 6 months depending on response to treatment with tadalafil. Follow up evaluations were done at 3, 6, 12, 18 and 24 months. Oncologic and functional outcomes and compliance were assessed. Patients filled in International Index of Erectile Function-5 (IIEF-5) questionnaires. RESULTS: Of 1078 men who underwent laparoscopic radical prostatectomy during this time, 586 patients met inclusion criteria, complied with the study medication, and had complete data for 24 months. The patients had a median preoperative baseline IIEF-5 score of 22. A total of 150 patients (26%) underwent unilateral nerve-sparing surgery, while 436 patients (74%) had bilateral nerve-sparing surgery. At 24 months, 35% of patients who underwent unilateral nerve-sparing surgery and 68% of patients who underwent bilateral nerve-sparing surgery reported having sufficient erectile function for intercourse without using intracavernous injection of alprostadil. At 24 months after surgery, the median IIEF-5 score was 13 (1-25) for the whole cohort, 5 (1-25) for patients who had undergone unilateral nerve-sparing surgery, and 15 (1-25) for patients who had undergone bilateral nerve-sparing surgery. CONCLUSIONS: The findings suggest that adequate patient selection and postoperative medical intervention allows the preservation or recovery of erectile function after laparoscopic radical prostatectomy. Inaccurate selection of patients and postoperative assessment might explain inferior erectile function results following this surgery.

Focal therapy with high-intensity focused ultrasound for prostate cancer in the elderly. A feasibility study with 10 years follow-up.

PURPOSE: To evaluate the long-term efficacy of prostate cancer control and complication rates, in the elderly, after focal therapy with high-intensity focused ultrasound (HIFU). MATERIALS AND METHODS: Between June 1997 and March 2000, patients with localized prostate cancer were included into a focal therapy protocol. Inclusion criteria were: PSA ≤ 10 ng/mL, ≤ 3 positive biopsies with only 1 lobe involved, clinical stage ≤ T2a, Gleason score ≤ 7 (3+4), negative CT scan and bone scan. Hemi-ablation of the prostate was performed with the Ablatherm® device. Survival, complication rates and urinary continence were evaluated. Control biopsies were performed at 1 year. Treatment failure was defined as a positive biopsy or need for salvage therapy. RESULTS: Twelve patients with a mean age 70 years were included. Median follow-up was 10 years. Control prostate biopsies were negative in 11/12 (91%) patients. Overall survival was 83% (10/12) and cancer specific survival was 100% at 10 years. Two patients died from other causes. Recurrence free survival was 90% (95% CI; 0.71-1) at 5 years, and 38% (95% CI; 0.04-0.73) at 10 years. Five patients had salvage therapy with repeat HIFU (n = 1) or hormonal therapy (n = 4) and all salvage patients were alive at 10 years. No patients developed lymph node or bone metastasis. No patients suffered from urinary incontinence. International Prostate Symptom Score was stable at 1 year. Complications included two urinary tract infections and one episode of acute urinary retention. CONCLUSIONS: Hemi-prostate ablation with HIFU can be safely performed in selected elderly patients with adequate long-term cancer control and low complication rates. Results from larger prospective studies using improved imaging techniques and extensive biopsy protocols are awaited.

Laparoscopic radical prostatectomy is feasible and effective in 'fit' senior men with localized prostate cancer.

OBJECTIVE To assess the effect of age and comorbidity on short-term complications, long-term continence and oncological outcome after laparoscopic radical prostatectomy (LRP) for localized prostate cancer. PATIENTS AND METHODS In all, 2048 consecutive men underwent LRP for localized prostate cancer in one institution. Comorbidity was assessed using the Charlson index. Short-term postoperative complications, transfusion rate, duration of hospital stay, long-term continence and oncological outcome were analysed by age and comorbidity classes. RESULTS Of the 2048 men, 297 were aged ≥ 70 years and 281 had a Charlson index of >0 (mainly diabetes 31%, chronic pulmonary disease 26%, prior other nonmetastatic cancer 16%, prior myocardial infarction 12%). Compared with younger men, senior men had significantly higher pathological stages and tumor grades. Of those 297 men aged ≥ 70 years, 90 (30.3%) developed biochemical relapse, none died from prostate cancer and five (1.7%) died from another cause over a median follow-up of 5 years. The occurrence and severity of short-term postoperative complications were more strongly related to comorbidity than chronological age. Multivariate analysis with stepwise regression confirmed that most important predictors of short-term postoperative complications were a Charlson index of ≥ 2, prostate weight of >80 g, obesity and age of ≥ 70 years. Postoperative continence significantly declined with age (ranging from 87% in men aged <60 years to 67.5% in men aged ≥ 70 years). Predictors of long-term incontinence were age of ≥ 70 years, obesity and need for perioperative transfusion. CONCLUSIONS LRP is feasible and effective in fit senior men (aged ≥ 70 years) with localized prostate cancer, including those at high risk of dying from it.

A 16-year clinical experience with intermittent androgen deprivation for prostate cancer: oncological results.

OBJECTIVE: To present oncological results with intermittent androgen deprivation (IAD) in a single center. METHODS: Between 1992 and 2008, 566 patients with prostate cancer (PC) were selected for a non-randomized study of IAD. Two hundred and eighteen patients had biochemical recurrence (BCR) after local treatment for PC and 348 patients had micro- or macro-metastatic disease. On-treatment period (ONTP) consisted of three-monthly injections of gonadatropin-releasing hormone (GnRH) agonist combined with daily oral androgen receptor antagonist. Off-treatment period (OFTP) was indicated when prostate-specific antigen (PSA) was <4 ng/ml. Criteria for resumption of hormonal therapy were PSA >20 ng/ml or clinical symptoms. Cancer specific survival curves were computed according to the Kaplan-Meier method. RESULTS: Median follow-up was 81 months (12-230). Median age was 74.7 years (52-92). Median Gleason score at diagnosis was 7 (3-9). Median initial PSA was 17 ng/ml (0.4-433). Cycle duration decreased progressively from 23 months for the 1st cycle to 10 months at 12th cycle. The number of patients who became hormone resistant was 182 (32%). Median cancer specific survival probability for the series is 12 (10.8-infinity) years. No previous treatment group showed a higher cancer specific survival probability (log rank test, CI 95%, P = 0.003) versus BCR group. Multivariate analysis of cancer specific survival demonstrates age, initial Gleason score and initial PSA level as significant factors affecting mortality (P < 0.05). CONCLUSIONS: Intermittent androgen deprivation is an acceptable treatment in different stages of PC. Duration of cycle decreased progressively during therapy. Age, Gleason score and PSA are factors predicting mortality.

[Intermittent androgen deprivation (IAD) for advanced prostate cancer. Why not the standard of therapy?]. / Bloqueo androgénico intermitente (BAI) en cáncer de próstata avanzado. Por qué no el tratamiento estándar?

SUMMARY OBJECTIVES: To review the literature and present a contemporary image of androgen deprivation for prostate cancer. METHODS: We conducted a PubMed search on intermittent androgen deprivation. Articles obtained on intermittent androgen deprivation (IAD) and the experiences at Institut Montsouris were used for the review. RESULTS: IAD is an approach to hormonal deprivation that holds effective cancer control while preventing the morbidity associated with continuous androgen blockade. IAD nuances have been assessed by urological community teams in order to verify its possible potential benefits. Evidence based approach supports the idea of IAD as a standard of therapy for advanced prostate cancer requiring hormone deprivation. Variation among medical teams' criteria for the treatment and surveillance await standardization. CONCLUSIONS: Reassessing the gold standard of hormonal blockade in advanced prostate cancer is mandatory.The undeniable evolution of IAD needs to be embraced by the urological community.

Comprehensive Evaluation of Focal Therapy Complications in Prostate Cancer: A Standardized Methodology.

Purpose: Today, up to one-third of newly diagnosed prostate cancer (PCa) cases may be suitable for focal treatment. The lack of data about the toxicity profiles of lesion-targeting therapies, however, has made it difficult to compare treatment modalities. The aim of the present study was to evaluate comprehensively the incidence, severity, and timing of onset of complications for PCa patients undergoing focal high-intensity focused ultrasound (HIFU) and focal cryosurgical ablation of the prostate (CSAP). Materials and Methods: A total of 336 patients were included who underwent focal HIFU or focal CSAP as a primary treatment for PCa between January 2009 and December 2017. Mean follow-up was 11 months (standard deviation: 3.0). All complications were captured and graded according to severity, and classified by timing of onset. Univariate and multivariate analysis was performed to identify predictors of the most common side effects. Results: There were 98 complications in 79/210 patients (38%) undergoing focal HIFU and 34 complications in 27/126 patients (21%) undergoing focal CSAP. In terms of severity, 95% of the complications of focal HIFU and 91% of the complications of focal CSAP were minor. Most complications presented in the early postoperative period. On multivariate analysis, subtotal HIFU was associated with acute urinary retention (AUR), while a smaller prostate size and longer catheterization time with dysuria. In CSAP patients, longer catheterization time was associated with AUR and urethral sloughing. The main limitation is the nonrandomized and retrospective nature. Conclusions: Focal HIFU and focal CSAP provide a tolerable toxicity, with primarily minor complications presenting in the early postoperative period.

HIFU focal therapy for prostate cancer using intraoperatory contrast enhanced ultrasound.

OBJECTIVE: High-intensity focused ultrasound (HIFU) Focal therapy appears to have encouraging oncologic outcomes and urinary and erectile function. The control of the treated area can be done using contrast enhanced ultrasound with sulfur hexafluoride (Sonovue®) at the end of the procedure. We report oncological and functional outcomes in HIFU focal therapy (FT) for prostate cancer (PCa) management using sonovue. METHODS: A total of 274 HIFU procedures were found in our registry in the period between June 2014 and July 2018. Prospective data of 59 consecutive patients after focal high-intensity focused ultrasound (HIFU) using Sonovue were collected. FT failure was defined as positive biopsy Gleason score (GS) ≥ 7 in- or out-field, local or systemic salvage treatment, PCa-metastasis or PCa-specific death. RESULTS: A total of 59 patients submitted to HIFU with median follow-up of 18 months were included in the analysis. Median age was 66.7 yr (IQR 59.1-74.3). Median preoperative prostate-specific antigen (PSA) was 7.6 ng/ml (IQR 5-10.2) and preoperative biopsies GS 6, 7(3+4), 7(4+3) were found in 26 (44%), 30 (50.8%) and 3 (5%), respectively. Failure was found in 16 (27.1%) patients. Failure-free survival (FFS) in 2 and 4yr was 83% and 74% respectively (Figure 1). No PCa-specific death was registered in the period of study. Median nadir PSA after FT was 2.67 ng/ml. Sexual potency was achieved in 75% of previous potent patients and urinary continence in 93.4% of patients at 3 months. Fourteen (23%) patients presented with complications. Four (6.7%) patients have presented complications grade 1 and 10 (16.9%) patients have presented complications grade 2. Six (10.1%) patients have presented acute urinary retention. CONCLUSIONS: Our study shows that the use of Sonovue after HIFU FT was safe. Patients present a significant proportion of failure after HIFU FT but with good functional outcomes and without incidence of severe complications.

OBJETIVOS: La terapia focal con HIFU (High-intensity focused ultrasound) parece tener unos resultados oncológicos y de función urinaria y eréctil prometedores. El control del área tratada puede realizarse al final de la intervención utilizando Sonovue®, el contraste de ecografía con hexafluoruro de azufre. Presentamos los resultados oncológicos y funcionales de la terapia focal con HIFU en el tratamiento cáncer de próstata utilizando Sonovue.MÉTODOS: Se encontraron en nuestro registro un total de 274 intervenciones con HIFU entre Junio 2014 y Julio 2018. Se recogieron los datos prospectivamente en 59 pacientes consecutivos después de HIFU utilizando Sonovue. Se define fracaso de la terapia focal como biopsia positiva con puntuación de Gleason (GS) >7 dentro o fuera del campo, tratamiento de salvamento local o sistémico, metástasis del CaP o muerte cáncer específica por CaP. RESULTADOS: Se incluyeron en el análisis un total de 59 pacientes sometidos a HIFU con una mediana de seguimiento de 18 meses. La mediana de edad fue 66,7 años (Rango intercuartílico (RIC) 59,1-74,3). La mediana de PSA preoperatorio fue 7,6 ng/mL (RIC 5-10,2) y las biopsias fueron GS 6, 7 (3+4) y 7 (4+3) en 26 (44%), 30 (50,8%) y 3 (5%) casos, respectivamente. En 16 pacientes (27,1%) fracasó el tratamiento. La supervivencia libre de fracaso del tratamiento a 2 y 4 años fue 83% y 74% respectivamente (Figura 1). No se ha registrado ninguna muerte cáncer específica por el CaP en el periodo de estudio. La mediana del nadir de PSA después de la terapia focal fue 2,67 ng/ml. El 75% de los pacientes previamente potentes consiguieron mantener su potencia sexual y el 93,4% eran continentes a los 3 meses. Catorce pacientes (23%) presentaron complicaciones. Cuatro (6,7%) presentaron complicaciones grado 1 y 10 (16,9%) grado 2. Seis pacientes (10,1%) presentaron retención aguda de orina. CONCLUSIONES: Nuestro estudio muestra que el uso de Sonovue después de terapia focal con HIFU es seguro. Los pacientes presentan una proporción significativa de fracasos después de terapia focal con HIFU aunque tiene buenos resultados funcionales y sin incidencia de complicaciones graves.

Architectural Patterns are a Relevant Morphologic Grading System for Clear Cell Renal Cell Carcinoma Prognosis Assessment: Comparisons With WHO/ISUP Grade and Integrated Staging Systems.

We developed and validated an architecture-based grading for clear cell renal cell carcinoma (ccRCC) in an observational retrospective cohort study including 506 tumors (principal cohort, n=254; validation cohort, n=252). Study endpoints were disease-free survival (DFS) and cancer-specific survival (CSS). Relationships with outcome were analyzed using Harrell concordance index, time-dependent receiver operating characteristic curve, area under curve, and Cox regression model. An architecture-based grading was devised on positive likelihood ratio (LR+) for DFS at 50 months as follows: grade 1 (LR+<0.8), cystic, compact, acinar, clear cell papillary RCC-like, and/or regressive patterns; grade 2 (1.2≤LR+<5), large nest, alveolar, papillary, chromophobe/oncocytic cell-like, eosinophilic hyaline globule, and/or intratumoral inflammatory reaction patterns; grade 3 (5≤LR+<10), rhabdoid, tumor giant cell, enlarged vascular space, and/or hereditary leiomyomatosis renal cell carcinoma (HLRCC)-like patterns; grade 4 (LR+≥10), sarcomatoid, infiltrative growth patterns, and lymphatic invasion. In the principal cohort, 3-tier (grades 1-2, 3, and 4) and 4-tier architectural scores outperformed World Health Organization/International Society of Urological Pathology, and World Health Organization/ International Society of Urological Pathology+necrosis gradings for DFS and CSS, and constituted an independent predictor for DFS (hazard ratio [HR]=5.91; P<6.7E-10) and CSS (HR=4.49; P=2.2E-03), retained in the localized (pT1-3N0M0) ccRCC subgroup (HR=6.10; P=1.3E-07 for DFS, and HR=20.09; P=9.4E-05 for CSS). On comparing with integrated staging systems, architectural grade with 1 morphologic datum remained an independent predictor of CSS, as did University of California Los Angeles Integrated Staging System and SSIGN, and was associated with the highest HR (HR=2.60; P=9.1E-04 in all patients; HR=4.38; P=2.0E-05 in the localized ccRCC subgroup). Architecture-based score for ccRCC outperforms all other morphologic grading systems and constitutes an independent predictor for DFS and CSS. As the predictive values of 3-tier and 4-tier architecture-based scores were similar throughout the study, we proposed to keep the simplified version as the final score, and to define 3 risk groups as follows: low risk (grades 1 to 2), intermediate risk (grade 3), and high risk (grade 4).

Grade Group Underestimation in Prostate Biopsy: Predictive Factors and Outcomes in Candidates for Active Surveillance.

OBJECTIVE: We intended to analyze the outcomes and predictive factors for underestimating the prostate cancer (PCa) grade group (GG) from prostate biopsies in a large monocentric cohort of patients treated by minimally invasive radical prostatectomy (RP). MATERIALS AND METHODS: Using a monocentric prospectively maintained database, we included 3062 patients who underwent minimally invasive RP between 2006 and 2013. We explored clinicopathologic features and outcomes associated with a GG upgrade from biopsy to RP. Multivariate logistic regression was used to develop and validate a nomogram to predict upgrading for GG1. RESULTS: Biopsy GG was upgraded after RP in 51.5% of cases. Patients upgraded from GG1 to GG2 or GG3 after RP had a longer time to biochemical recurrence than those with GG2 or GG3 respectively, on both biopsy and RP, but a shorter time to biochemical recurrence than those who remained GG1 after RP (P < .0001). In multivariate analyses, variables predicting upgrading for GG1 PCa were age (P = .0014), abnormal digital rectal examination (P < .0001), prostate-specific antigen density (P < .0001), percentage of positive cores (P < .0001), and body mass index (P = .037). A nomogram was generated and validated internally. CONCLUSIONS: Biopsy grading system is misleading in approximately 50% of cases. Upgrading GG from biopsy to RP may have consequences on clinical outcomes. A nomogram using clinicopathologic features could aid the probability of needing to upgrade GG1 patients at their initial evaluation.

Learning curve of minimally invasive radical prostatectomy: Comprehensive evaluation and cumulative summation analysis of oncological outcomes.

BACKGROUND AND OBJECTIVE: The primary objective was to evaluate the learning curve of minimally invasive radical prostatectomy (MIRP) in our institution and analyze the salient learning curve transition points regarding oncological outcomes. METHODS: Clinical, pathologic, and oncological outcome data were collected from our prospectively collected MIRP database to estimate positive surgical margin (PSM) and biochemical recurrence (BCR) trends during a 15-year period from 1998 to 2013. All the radical prostatectomies (laparoscopic prostatectomy [LRP]/robot-assisted laparoscopic radical prostatectomy [RARP]) were performed by 9 surgeons. PSM was defined as presence of cancer cells at inked margins. BCR was defined as serum prostate-specific antigen >0.2ng/ml and rising or start of secondary therapy. Surgical learning curve was assessed with the application of Kaplan-Meier curves, Cox regression model, cumulative summation, and logistic model to define the "transition point" of surgical improvement. RESULTS: We identified 5,547 patients with localized prostate cancer treated with MIRP (3,846 LRP and 1,701 RARP). Patient characteristics of LRP and RARP were similar. The overall risk of PSM in LRP was 25%, 20%, and 17% for the first 50, 50 to 350, and>350 cases, respectively. For the same population, the 5-year BCR rate decreased from 30% to 16.7%. RARP started 3 years after the LRP program (after approximately 250 LRP). The PSM rate for RARP decreased from 21.8% to 20.4% and the corresponding 5-year BCR rate decreased from 17.6% to 7.9%. The cumulative summation analysis showed significantly lower PSM and BCR at 2 years occurred at the transition point of 350 cases for LRP and 100 cases for RARP. In multivariable analysis, predictors of BCR were prostate-specific antigen, Gleason score, extraprostatic disease, seminal vesicle invasion, and number of operations (P<0.05). Patients harboring PSM showed higher BCR risk (23% vs. 8%, P< 0.05). CONCLUSIONS: Learning curve trends in our large, single-center experience show correlation between surgical experience and oncological outcomes in MIRP. Significant reduction in PSM and BCR risk at 2 years is noted after the initial 350 cases and 100 cases of LRP and RARP, respectively.

[Morbidity/mortality reviews: assessment of their implementation in one hospital]. / Bilan de la mise en place de revues de mortalité morbidité au sein d'un établissement hospitalier.

OBJECTIVES: The objective of this study was to describe the steps involved in establishing a morbidity/mortality review committee (MMRC) to analyze the causes of avoidable deaths or life-threatening complications and the development of plans and protocols to avoid their recurrence. METHODS: The MMRC included physicians from each hospital department. Each member was responsible for organizing departmental meetings to analyze its avoidable deaths and life-threatening complications. RESULTS: During its meetings three times a year, the MMRC developed a method for analysis of these serious events. Each department organized 3 (range: 1-12) meetings a year and analyzed 1-3 cases at each. Over 30 months, 35,817 patients were admitted to the hospital and 341 (1%) died. The unexpected mortality rate varied by department and specialty (median: 27%, range: 6-65%). In all, 92 cases were referred to MMRC meetings (27%; range: 6-70% of hospital deaths), and 30% of them involvement nosocomial diseases. Heart disease was the primary cause of unexpected deaths. DISCUSSION: The principal improvements involved medical and surgical strategies, surgical techniques, drug prescriptions, and patient monitoring.

Focal High-intensity Focused Ultrasound Targeted Hemiablation for Unilateral Prostate Cancer: A Prospective Evaluation of Oncologic and Functional Outcomes.

BACKGROUND: In selected patients with unilateral, organ-confined prostate cancer (PCa), hemiablation of the affected lobe might be feasible to achieve acceptable cancer control with fewer complications. OBJECTIVES: To assess the oncologic and functional outcomes of focal high-intensity focused ultrasound (HIFU) hemiablation in unilateral organ-confined PCa. DESIGN, SETTING AND PATIENTS: Single-center prospective evaluation of HIFU hemiablation for unilateral organ-confined PCa was performed from July 2009 through December 2013. INTERVENTION: Cancer localization was done with transrectal ultrasound-guided biopsy and multiparametric magnetic resonance imaging followed by HIFU hemiablation. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS: Oncologic outcomes were analyzed with control biopsies and prostate-specific antigen (PSA) measurement. Functional outcomes were assessed with validated questionnaires for genitourinary symptoms. RESULTS AND LIMITATIONS: Of 71 HIFU hemiablation patients, 67 completed the study protocol. The mean age was 70.2 yr (standard deviation: 6.8 yr), and median PSA was 6.1 ng/ml (interquartile range [IQR]: 1.6-15.5 ng/ml). Median maximum cancer-core length was 3 mm (IQR: 2-10 mm), and total cancer length was 6.5 mm (IQR: 2-24 mm). Gleason score was 6 (3+3) in 58 patients (86.6%) and 7 (3+4) in 9 patients (13.4%). Median follow-up was 12 mo (IQR: 6-50 mo), and at 12 mo, 56 of 67 patients had a negative control biopsy in the treated lobe. At 3 mo, all patients were continent, and potency was maintained in 11 of 21 preoperatively potent patients (confidence interval, 0.18-0.69). Complications included 8% Clavien-Dindo grade 2 and 2.8% grade 3 events. CONCLUSIONS: Focal HIFU hemiablation appears to achieve acceptable oncologic outcomes with low morbidity and minimal functional changes. Longer follow-up will establish future considerations. PATIENT SUMMARY: This study showed that high-intensity focused ultrasound hemiablation in selected patients with unilateral organ-confined prostate cancer can be used for satisfactory cancer control with minimal effect on genitourinary functions.