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.

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.

Hifu focal therapy for prostate cancer using intraoperatory contrast enhanced ultrasound / Terapia focal con HIFU en cáncer de prostata utilizando ecografia con contraste intraoperatoria

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(R)) 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(R), 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

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.

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.

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.

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.

Minimally Invasive Salvage Prostatectomy After Primary Radiation or Ablation Treatment.

OBJECTIVE: To analyze oncologic, functional and morbidity outcomes for patients undergoing minimally invasive salvage prostatectomy (MISP) at our institution. PATIENTS AND METHODS: Between 2001 and 2015, 5841 patients underwent radical prostatectomy at our institution, out of which 28 were MISP. Indications for MISP were prostate-specific antigen nadir +2 ng/dL in radio-recurrent patients and biopsy-proven prostate cancer (PCa) in other ablative treatments. We analyzed primary cancer characteristics, surgical data, perioperative complications, oncologic and functional outcomes of MISP, and further compared results between MISP after primary whole-gland treatment (WT) and focal treatment (FT). RESULTS: Median age at salvage treatment was 65 (interquartile range [IQR] 61-68). Compared with WT, MISP after FT had significantly lower operative time (133 vs 176 min, P = .001) and fewer upstaging (≥pT3a) (28% vs 79%, P = .008) at final pathology. Overall, positive surgical margin (PSM) were noted in 4 patients (14%). Perioperative complications were observed in 9 patients with no difference between groups. At 12-months follow-up, 57% were continent and 33% had moderate to severe urinary leak. Potency was preserved in 6 out of 10 preoperatively potent patients. Over a median follow-up of 62 months (IQR 43-110), 11 patients relapsed with a median time to biochemical recurrence of 16 months (IQR 7-25). Recurrences were managed with salvage radiotherapy in 6 patients, 4 with hormone therapy and 1 castration-resistant prostate cancer. Overall, 24 patients are alive at last follow-up and 18 (72%) remain disease free. CONCLUSION: MISP after primary radiation or ablation for prostate cancer is feasible and safe with acceptable oncological outcomes. Compared with FT, MISP after WT appears to have longer operative time and more frequent upstaging.

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.

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.

Clinical utility of transperineal template-guided mapping biopsy of the prostate after negative magnetic resonance imaging-guided transrectal biopsy.

PURPOSE: We evaluated the prostate cancer detection with transperineal template-guided mapping biopsy in patients with elevated prostate-specific antigen and negative magnetic resonance imaging (MRI)-guided biopsy. MATERIALS AND METHODS: Totally 75 patients underwent transperineal template-guided mapping biopsy for prior negative MRI-guided (cognitive registration) biopsy during April 2013 to August 2014. Primary objective was to report clinically significant cancer detection in this cohort of patients. Significant cancer was defined using varying thresholds of MCL or Gleason grade 3+4 or greater or both. Cancers with more than 80% of positive core length anterior to the level of urethra were termed anterior zone cancer. Secondary objective was to evaluate the potential clinical and radiological predictors for significant cancer detection. RESULTS: The mean age was 61.6 ± 6.5 years and median prostate-specific antigen was 10.4 ng/dl (7.9-18) with a mean MRI target size of 7.2mm (4-11). Transperineal template-guided mapping biopsy identified cancer in 36% (27/75) patients and 66.6% (18/27) of them were anterior zone cancers. The rates of detection of clinically significant and insignificant cancer according to the several definitions used range from 22.7% to 30.7% and 5.3% to 13.3%, respectively. Multivariate analysis did not identify any predictors for finding clinically significant and anterior cancers in this group of patients. CONCLUSION: Transperineal template-guided mapping biopsy appears to be an excellent biopsy protocol for downstream management following negative MRI-guided biopsy. Most of the cancers detected were predominantly anterior tumors.

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.

T-helper 1 immunoreaction influences survival in muscle-invasive bladder cancer: proof of concept.

OBJECTIVE: To define immunoscore in bladder cancer studying T helper 1 (Th1) immunoreaction. To define a cancer-specific survival model based on Th1 cells infiltration. METHODS: A total of 252 patients underwent primary transurethral resection of bladder tumour at our Institution. A retrospective review of a selected cohort with pT1 and muscle-invasive bladder cancer (MIBC) lesions was performed. Pathology blocks were marked with CD3 and CD8 antibodies. Immune cells density in stromal reaction (SR) was measured on five distinct high-power field (HPF) by two dedicated uro-pathologist blinded for patients' evolution. STATISTICS: Student test or non-parametric Wilcoxon test as appropriate to compare means between two groups. Receiver operating characteristics (ROC) curve to define markers threshold. Cox model to assess survival's predictors. RESULTS: Ten pT1 and 20 MIBC consecutive cases were analysed. Median follow-up was 33.4 months. Immunohistological analysis for pT1 lesions featured limited SR. For MIBC, the mean density of lymphocytes in the SR was of 105/HPF (CD3) and 86/HPF (CD8). Survivors harboured higher lymphocytes densities versus non survivors (CD3: p = 0.0319; CD8: p = 0.0279). CD3 (p = 0.034) and CD8 (p = 0.034) lymphocytes densities were independently associated with cancer-specific survival on Cox model analyses. The retrospective design and small size of cohorts are the study limitations. CONCLUSIONS: High CD3 and CD8 lymphocytes SR densities are associated with better cancer-specific survival for MIBC. Th1 reaction against the tumour seems to be protective for bladder cancer. Further evaluation is warranted.

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.

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.

Current, new and novel therapy for castration-resistant prostate cancer.

Androgen deprivation therapy is the standard of care for the initial treatment of metastatic prostate cancer. However, the majority of these patients live long enough to experience disease progression despite castration. This scenario is defined as castration-resistant prostate cancer (CRPC) and has a poor outcome and limited options for treatment. First-line treatment after hormonal therapy failure include secondary hormonal manipulation and docetaxel. Advances in the understanding of the molecular mechanisms underlying CRPC have translated into a recent increase in the number of effective systemic agents, and some of them have been already approved as first and second-line treatment. Despite these advances, the median survival in the first-line setting of metastatic CRPC is approximately 20 months and in the postdocetaxel setting is approximately 15 months. Promising and necessary new therapies in Phase III trials include hormonal agents, new cytotoxics agents, as well as other immunotherapeutics and antiprostate-specific membrane antigen therapies.

Focal brachytherapy for selected low-risk prostate cancers: a pilot study.

PURPOSE: To evaluate the feasibility and the early toxicity of focal brachytherapy in highly selected localized prostate cancer patients. METHODS AND MATERIALS: Twenty-one patients underwent a focal brachytherapy between February 2010 and March 2012, representing 3.7% of the cases treated by our group during this period. Patient selection was based on (at least) two series of prostate biopsies and a high-resolution MRI. Only patients with very limited and localized tumors, according to strict criteria, were selected for the procedure. The technique used a real-time procedure with the implantation of free (125)I seeds and dynamic dose calculation. The prescribed dose for the focal volume was 145Gy. RESULTS: The treated volume corresponded to a mean value of 34% of the total prostatic volume (range, 20-48%). For the focal volume, the mean D90 and V100 was 183.2Gy (range, 176-188Gy) and 99.3% (range, 98.8-100%), respectively. The technique was performed in an hour and a half. When compared with a previous cohort treated by whole-prostate brachytherapy, urinary toxicity (International Prostate Symptom Score) was borderline reduced (p = 0.04) at 6 months only, whereas the recovery of the International Index of Erectile Function 5 was better (p = 0.014). The International Continence Score was nil in almost all cases as well as rectal toxicity. CONCLUSION: Focal treatment by brachytherapy is easily feasible with little acute toxicity. Further investigation is needed to assess the results in terms of tumor control and long-term toxicity.