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.

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.

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.

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.