Immediate versus delayed prostatectomy and the fate of patients who progress to a higher risk disease on active surveillance. / Prostatectomía inmediata versus demorada en pacientes que progresan a una enfermedad de mayor riesgo en vigilancia activa.

INTRODUCTION: Oncological outcomes of radical prostatectomy (RP) in patients progressing on active surveillance (AS) are debated. We compared outcomes of AS eligible patients undergoing RP immediately after diagnosis with those doing so after delay or disease progression on AS. METHODS: Between 2000 and 2014, 961 patients were AS eligible as per EAU criteria. RP within 6 months of diagnosis (IRP) or beyond (DRP), RP without AS (DRPa) and AS patients progressing to RP (DRPb) were compared. Baseline PSA, clinical and biopsy characteristics were noted. Oncological outcomes included adverse pathology in RP specimen and biochemical recurrence (BCR). Matched pair analysis was done between DRPb and GS7 patients undergoing immediate RP (GS7IRP). RESULTS: IRP, DRP, DRPa and DRPb had 820 (85%), 141 (15%), 118 (12.24%) and 23 (2.7%) patients respectively. IRP, DRPa and DRPb underwent RP at a median of 3, 9 and 19 months after diagnosis respectively. Baseline characteristics were comparable. DRP vs. IRP had earlier median time (31 vs. 43 months; p<.001) and higher rate of progression to BCR (7.6 vs. 3.9%;p=.045). DRPb showed higher BCR (19 vs. 5%;p=.021) with earlier median time to BCR, compared to IRP and DRPa (p=.038). There was no difference in adverse pathology and BCR rates, but time to BCR was significantly lesser in DRPb (49 vs. 6 months;p<.001), compared to GS7IRP. CONCLUSIONS: Patients progressing on AS had worst oncological outcomes. RP for GS7 progression and matched pair of GS7 patients had similar outcomes. Worse oncological outcomes in AS progressors cannot be explained by a mere delay in RP.

Oncological outcomes and pathological characteristics of cT1 upstaging to pT3a renal cell carcinoma compared with de novo pT3a tumors. / Resultados oncológicos y características patológicas de la sobrestadificación de cT1 a carcinoma de células renales pT3a en comparación con los tumores pT3a de novo.

INTRODUCTION: The significance of upstaging of cT1 renal tumors to pT3a is not clear. We evaluate the incidence of upstaging, identify predictors and analyze oncological outcomes of these patients versus those who did not upstage. We also compared the oncological outcomes of cT1 upstaging to pT3a with de novo pT3a renal tumors. METHODS: From a database of 1021 renal tumors with complete available follow-up data, 517 patients had cT1. Patients upstaging to pT3a were compared to those who did not. Baseline clinical, perioperative, histopathologic features and oncological outcomes were analysed. RESULTS: Out of 517 cT1 patients, 105 (20.3%) upstaged to pT3a and 412 (79.7%) did not. Proportion of patients in each group undergoing partial and radical nephrectomy, postoperative tumor size, histology, margin status and lymph node involvement were similar. Among upstaged, 9 patients (8.6%) developed first recurrence as compared to only 3 (0.7%) in those not upstaging (P <0.001). The median time to recurrence (57 vs. 107 months; P <0.001) was lesser in de novo pT3a renal tumors. CONCLUSIONS: Pathological upstaging from cT1 to pT3a and necrosis on histopathology were associated with recurrence. Advanced age, smoking, necrosis on histopathology, clear cell histology and higher Fuhrman grades contributed to pathological upstaging of cT1 tumors. De novo pT3a RCC had worse survival when compared to cT1 patients upstaging to pT3a RCC.

[Management of ablative therapies in prostate cancer]. / Traitements ablatifs pour cancer de prostate : modalités de prise en charge.

OBJECTIVES: To describe the specific modalities of ablative therapies management in prostate cancer. MATERIALS AND METHODS: A review of the scientific literature was performed in Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of keywords. Publications obtained were selected based on methodology, language and relevance. After selection, 61 articles were analysed. RESULTS: Development of innovations such as ablative therapies in prostate cancer induces specific modalities in their management, during pre-, per- and post-procedure. More than for classical and well-known treatments, the decision to propose an ablative therapy requires analysis and consensus of medical staff and patient's agreement. Patient's specificities and economical aspects must also be considered. Procedures and follow-up must be realized by referents actors. CONCLUSION: Indication, procedure and follow-up of ablative therapies in prostate cancer require specific modalities. They must be respected in order to optimize the results and to obtain a precise and objective evaluation for defining future indications.

Systematic review of perioperative outcomes and complications after open, laparoscopic and robot-assisted radical cystectomy. / Revisión sistemática de resultados perioperatorios y complicaciones después de cistectomía radical abierta, laparoscópica y asistida por robot.

Radical cystectomy and regional lymph node dissection is the standard treatment for localized muscle-invasive and for high-risk non-muscle-invasive bladder cancer, and represents one of the main surgical urologic procedures. The open surgical approach is still widely adopted, even if in the last two decades efforts have been made in order to evaluate if minimally invasive procedures, either laparoscopic or robot-assisted, might show a benefit compared to the standard technique. Open radical cystectomy is associated with a high complication rate, but data from the laparoscopic and robotic surgical series failed to demonstrate a clear reduction in post-operative complication rates compared to the open surgical series. Laparoscopic and robotic radical cystectomy show a reduction in blood loss, in-hospital stay and transfusion rates but a longer operative time, while open radical cystectomy is typically associated with a shorter operative time but with a longer in-hospital admission and possibly a higher rate of high grade complications.

High intensity focused ultrasound with Focal-One® device: Prostate-specific antigen impact and morbidity evaluation during the initial experience. / Ultrasonido focalizado de alta intensidad con el dispositivo Focal-One®: impacto sobre el antígeno prostático específico y evaluación de la morbilidad durante la experiencia inicial.

OBJECTIVE: We report our initial experience in the treatment of prostate cancer (PCa) with high-intensity focused ultrasound (HIFU) using the Focal-One® device. MATERIAL AND METHODS: Retrospective review of the prospectively populated database. Between June 2014 to October 2015, 85 patients underwent HIFU (focal/whole-gland) treatment for localized PCa. Preoperative cancer localization was done with multiparametric magnetic resonance imaging (mpMRI) and transperineal mapping biopsies. Treatment was carried out using the Focal-One® device under general anesthesia. Oncological follow-up: PSA measurement and control biopsy with mpMRI according to protocol. Questionnaire-based functional outcome assessment was done. Complications were reported using Clavien classification. RESULTS: The median PSA was 7.79ng/ml (IQR 6.32-9.16), with a median prostate volume of 38cc (IQR: 33-49.75). Focal and whole-gland therapy was performed in 64 and 21 patients respectively. Ten patients received salvage HIFU. Complications were encountered in 15% of cases, all Clavien 2 graded. Mean hospital stay was 1.8 days (0-7) and bladder catheter was removed on day 2 (1-6). Mean percentage reduction of PSA was 54%. Median follow-up was 3 months (IQR: 2-8). Functional outcomes: All patients were continents at 3 months and potency was maintained in 83% of the preoperatively potent. CONCLUSIONS: Focal-One® HIFU treatment appears to be a safe procedure with few complications. Functional outcomes proved no urinary incontinence and sexual function were maintained in 83%.

Evolution of prostate biopsy techniques. Looking back on a meaningful journey. / Evolución de las técnicas de biopsia prostática. Mirando hacia atrás en un viaje significativo.

BACKGROUND: The technique of prostate biopsy has evolved a long way since its inception to being a safe diagnostic procedure. The principles of the biopsy technique continue to improvise with the knowledge about prostate cancer and availability of newer treatment options like active surveillance and focal therapy. Currently, we depend on accurate cancer information from the biopsy more than ever for deciding the ideal treatment option. AIM: The aim of this review is to present the major milestones in prostate biopsy technique evolutions and its impact on the prostate cancer management. ACQUISITION OF EVIDENCE: We performed a detailed non-systematic literature review to present the historical facts on the transformations in prostate biopsy techniques and also the direction of present research to improve accurate cancer detection. SUMMARY OF EVIDENCE: There is a clear change in trend in biopsy technique before and after the introduction of transrectal ultrasound and prostate specific antigen. In the earlier era, the biopsies were aimed at palpable nodules and obtaining adequate prostatic tissue for diagnosis while the later era has moved towards detection of non-palpable and early prostate cancer. Recently, there is an increasing trend towards image guided targeted biopsies to extract maximum cancer information from minimum biopsy cores. CONCLUSION: Prostate biopsy techniques have seen major changes since its inception and have a major impact on prostate cancer management. There is a great potential for research which can further support the newer treatment options like focal therapy.

Robotics in urological surgery: evolution, current status and future perspectives.

CONTEXT: Robotic surgery is rapidly evolving and has become an essential part of surgical practice in several parts of the world. Robotic technology will expand globally and most of the surgeons around the world will have access to surgical robots in the future. It is essential that we are updated about the outcomes of robot assisted surgeries which will allow everyone to develop an unbiased opinion on the clinical utility of this innovation. OBJECTIVE: In this review we aim to present the evolution, objective evaluation of clinical outcomes and future perspectives of robot assisted urologic surgeries. ACQUISITION OF EVIDENCE: A systematic literature review of clinical outcomes of robotic urological surgeries was made in the PUBMED. Randomized control trials, cohort studies and review articles were included. Moreover, a detailed search in the web based search engine was made to acquire information on evolution and evolving technologies in robotics. SYNTHESIS OF EVIDENCE: The present evidence suggests that the clinical outcomes of the robot assisted urologic surgeries are comparable to the conventional open surgical and laparoscopic results and are associated with fewer complications. However, long term results are not available for all the common robotic urologic surgeries. There are plenty of novel developments in robotics to be available for clinical use in the future. CONCLUSION: Robotic urologic surgery will continue to evolve in the future. We should continue to critically analyze whether the advances in technology and the higher cost eventually translates to improved overall surgical performance and outcomes.

[Effect of wound infiltration of ropivacaine in postoperative pain after extraperitoneal laparoscopic radical prostatectomy]. / Effet de l'infiltration pariétale d'anesthésique local (ropivacaïne) sur la douleur postoperatoire après prostatectomie radicale laparoscopique sous-péritonéale.

PURPOSE: Evaluation of the efficiency of wound infiltration of ropivacaine in postoperative pain after extraperitoneal laparoscopic radical prostatectomy. MATERIAL AND METHODS: Prospective single institution study included 130 patients treated by extraperitoneal laparoscopic radical prostatectomy from January to March 2007. One hundred and two patients were included and randomised in two groups according to the year of birth (pair or impair). Only patients from the first group (year pair) had wound infiltration at the end of the procedure. The second group (year impair) was the control group. An analogic visual scale (EVA) permitted evaluation of pain at 30 minutes, 1, 6 and 12 hours after the procedure. Use of analgesics after procedure were noted for each patient. RESULTS: In the first group, the median of EVA was 1.44, 1.34, 1.72 and 1.51 respectively at 30 minutes, 1, 6 and 12 hours. In the second group, the median of EVA was 1.28, 1.36, 1.46 and 1.44. We found no statistically significant difference for pain and use of analgesic between the two groups (p=0.71, 0.96, 0.47 and 0.86 respectively at 30 minutes, 1, 6 and 12 hours). CONCLUSION: Ropivacaine in wound infiltration did not decrease significantly the postoperative pain and must not be used systematically.

High detection rate of circulating tumor cells in blood of patients with prostate cancer using telomerase activity.

BACKGROUND: Circulating tumor cells (CTCs) cannot be readily detected with currently available methods in the majority of patients with prostate cancer. Telomerase activation, one of the major immortalization events, is found in most cases of prostate cancer. We attempted to develop a method using telomerase activity to isolate CTCs in patients with prostate cancer. PATIENTS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood using Ficoll-Hypaque. Immunomagnetic beads coated with an epithelial cell-specific antigen antibody (BerEP4) were used to harvest epithelial cells from PBMCs. Telomerase activity was detected in harvested epithelial cells using the telomerase-PCR-enzyme-linked immunosorbent assay method. RESULTS: Blood samples from 107 patients with prostate cancer were studied. CTCs were detected in 19 of 24 (79%) patients with advanced prostate cancer. In contrast, CTCs were not detected in blood samples from 22 healthy male volunteers. CTCs were even identified in patients with an undetectable (<0.1 ng/ml) serum prostate-specific antigen (PSA). CTCs were detected in 55 of 70 (79%) patients with localized prostate cancer before radical prostatectomy (n = 30) or brachytherapy (n = 40). CTCs were also detected in 3 of 13 patients (23%) with an undetectable serum PSA measured at least 1 year after radical prostatectomy, which is consistent with the expected relapse rate in this setting. CONCLUSION: CTCs can be detected using telomerase activity in a large majority and a wide variety of patients with prostate cancer, including those with localized disease.

Detection of HER-2/neu-positive circulating epithelial cells in prostate cancer patients.

HER-2/neu may play a role in prostate carcinogenesis. The aim of this study was to use the expression of HER-2/neu as a molecular marker for the detection of circulating tumour cells (CTCs) in the blood of patients with prostate cancer (PC). Blood samples were collected from 42 patients with PC and nine healthy volunteers. Immunomagnetic beads were used to harvest epithelial cells from peripheral blood mononuclear cells. Total RNA was extracted and reverse transcribed before analysis by real-time PCR with HER-2/neu-specific primers. CTCs were HER-2/neu positive in six out of 11 (54%) patients with metastatic disease and in three out of 31 (9.6%) patients with localised PC (P=0.004). In blood samples from nine healthy volunteers, we detected no expression of HER-2/neu. The present method appears to be minimally invasive, highly sensitive and a specific approach for detecting CTCs in PC. Furthermore, it may help better target HER-2/neu in advanced PC.

[Competitive morbidity ant its impact on life expectancy: evaluation and inclusion in the therapeutic decision regarding localized prostatic cancer]. / La morbidité compétitive et son impact sur l'espérance de vie: évaluation et prise en compte dans la décision thérapeutique du cancer localisé de la prostate.

OBJECTIVES: The treatment decision taken by a multidisciplinary meeting for patients with localized prostate cancer must take into account the clinical stage of the cancer and its histological characteristics, but also the patient's age, general state and any concomitant diseases, as treatment is only beneficial when it induces a reduction of morbidity and specific mortality. The specific survival with or without recurrence after treatment for localized prostate cancer is long, at least more than 10 years. Curative treatment is generally not proposed to men with localized prostate cancer when his probability of survival related to a competitive morbidity (intercurrent medical disease) is estimated to be less than 10 years. The objective of this study was to measure the increase or reduction of the survival probability of a patient with localized prostate cancer according to his competitive morbidity, based on the mean life expectancy of the general population. METHODS: Review of the literature. RESULTS: Studies describing the natural history of prostate cancer show that the impact of treatment on morbidity of the cancer (local and/or metastatic) requires a life expectancy of about 8 to 10 years. The impact of a treatment on specific survival requires a life expectancy of about 13 to 15 years. The exact prevalence of diseases coexisting with prostate cancer is unknown. In the USA, The Index of Coexisting Disease (ICD), which takes into account 14 diseases, appears to be the most reliable tool to measure the competitive morbidity in patients with localized prostate cancer. Each disease is classified into 4 levels of severity (score 0 to 3). A table indicates estimated life expectancies by age-group and by ICD score. All men with a high score (2 to 3) die within 10 years after diagnosis, men with a score of 0 have a better estimated life expectancy according to age than that of the general population. CONCLUSION: The upper age limit, theoretically set at 70 years, in order to propose curative treatment for localized prostate cancer needs to be reviewed (the mean life expectancy for a 70-year-old man is 12.9 years in France). According to the ICD, the life expectancy at 70 years is 14.8 years in the case of a score of 0 and 8.4 years in the case of a score of 2. In the case of a score of 2, the impact of curative treatment on localized prostate cancer would be real on morbidity, but not on specific mortality.

[BCG therapy of superficial tumors of the bladder]. / La BCGthérapie des tumeurs superficielles de la vessie.

Superficial bladder tumor defined as pTa, pT1 and pTis stage is one of the most common cancer disease in the world. Intravesical BCGtherapy represents the best treatment when combined with transurethral resection to prevent tumor recurrence or progression and to lengthen the interval between recurrence. The toxicity is quite important but can be reduced by using the good procedure. Local or general immunostimulation is likely to be the exact mechanism of action but more data are needed.

MHC-dependent cytolysis of autologous tumor cells by lymphocytes infiltrating urothelial carcinomas.

Tumor-infiltrating lymphocytes (TIL) were grown from 23 urothelial carcinomas. Phenotyping analysis showed that the TIL cultures were mainly CD3+. Although CD4+ and CD8+ T-cell sub-sets were grown in culture, CD4+ T-cell sub-sets predominated over CD8+ T cells. Immunohistochemical studies performed on 5 tumor specimens confirmed this observation, and indicated that CD4+ T cells surrounded the tumor islets, whereas CD8+ T lymphocytes were localized among the tumor cells. Five short-term carcinoma cell lines established from these urothelial tumors were used as target cells in cytolysis assays in order to investigate the functional anti-tumor activity of autologous TIL. TIL from 4/5 tumors were lytic and 3 TIL lines displayed MHC-class-I-dependent cytotoxicity directed against autologous tumor cells. CD4+ T-cell-depletion experiments performed on TIL line 07 confirmed that CD8+ MHC-class-I-dependent CTL were the predominant effectors. Finally, experiments performed on 6 allogeneic urothelial-cancer cell lines matched for HLA-class-I molecules showed that TIL07 exhibited selective lytic activity toward tumor 07. These data indicate that CD8+ MHC-class-I-dependent CTL present in urothelial carcinomas are functional and may participate in the anti-tumor immune response.

Reaction of peripheral-blood lymphocytes to the human chorionic gonadotropin beta sub-unit in patients with productive tumors.

Human chorionic gonadotropin (hCG) and its beta sub-unit (hCG beta) are secreted by trophoblast cells during pregnancy, and by tumoral cells of trophoblastic and non-trophoblastic origin. In contrast to hCG, the free hCG beta sub-unit is consistently undetectable in healthy non-pregnant subjects. With this in mind, we sought to determine whether an immune response to hCG beta can be detected in patients with bladder or germ-cell testis cancers. Peripheral-blood mononuclear cells (PBMC) from 31% of patients with hCG beta-productive bladder cancers and 33% of testis-tumor-bearing patients displayed an hCG beta-specific proliferative response, whereas no patients with non-hCG beta-productive cancers had a proliferative response. PBMC from pregnant women and healthy controls did not elicit significant reactivity. By the use of overlapping synthetic peptides, the immunogenic regions of hCG beta were delineated within the central 20-65 portion. Moreover, in 2 bladder-cancer patients with the HLA DR7, DQ2 haplotype, the T-cell response to hCG beta was focused on the hCG beta (20-47) peptide. Taken together, these results indicate that hCG beta is a tumor-associated antigen capable of inducing a cell-mediated immune response in patients with productive tumors.

[Technique and results of the "Mini-Bricker" urinary tract diversion after total cystectomy for bladder tumors]. / Technique et résultats du "Mini-Bricker" dans la dérivation des voies urinaires après cystectomie totale pour tumeur de vessie.

The authors have performed a "Mini-Bricker" operation in 24 patients with bladder cancer. This technique consists of urinary diversion in which the size of the intestinal loop is reduced to an average of 4 cm and the ureteroileal anastomosis is performed end-to-end in order to allow subsequent endourological procedures, if necessary. The postoperative course was uneventful in 71% of cases. Seven early complications were reported: 3 infectious, 1 thromboembolic and 2 hernias. In the medium term, one case of disturbances and 2 stenoses of the ureteroileal anastomosis were treated by endoscopic dilatation. The median follow-up is 3 years and 5 patients have died. A retrospective survey of quality of life revealed that 86% of patients were satisfied with their diversion and rapidly acquired autonomy following cystectomy without the need for retraining and without having to get up at night.

Influence of preoperative positive seminal vesicle biopsy on the staging of prostatic cancer.

A total of 71 patients with clinically localized prostatic cancer underwent preoperative biopsy of each seminal vesicle. Group 1 (67 patients) underwent 2 seminal vesicle biopsies before lymph node dissection and vesiculo-prostatectomy, while group 2 (4 patients) underwent seminal vesicle biopsy and lymph node dissection before radiation therapy. In group 1 there were 11 positive biopsies (16.5%) with a median prostate specific antigen (PSA) level of 24 ng./ml. (range 11 to 45). Of the biopsies 56 were normal, with a median PSA level of 11.8 (range 3.5 to 88, p < 0.008). Histological examination of the seminal vesicles on the prostatectomy specimen revealed 18 cases of seminal vesicle invasion (sensitivity 61%, specificity 100%, positive predictive value 100% and negative predictive value 87.5%). A positive biopsy was correlated with the mean tumor volume (10.3 cc with positive biopsies versus 4.9 cc with negative biopsies) and local invasion (positive margins in 36% versus 9%, respectively, and capsular perforation in 81% versus 25%, respectively). In group 2 the 4 seminal vesicle biopsies and lymph node dissections were positive. Overall (groups 1 and 2), positive seminal vesicle biopsies were predictive of lymph node involvement in 47% of the cases versus 7% when biopsies were negative (p > 0.001). The postoperative course was significantly different (local recurrence and metastases in 45% versus 9%, respectively, and median interval 8.8 months versus 18.3 months, respectively, p < 0.001). Seminal vesicle biopsy appears to have a satisfactory yield only in cases with a PSA level of greater than 10 ng./ml. A positive seminal vesicle biopsy confirms the presence of extraprostatic invasion of clinically localized cancer in a given patient. Seminal vesicle biopsy allows for better staging of prostatic cancer.

Systematic prostatic biopsies in 100 men with no suspicion of cancer on digital rectal examination.

A total of 100 men with a mean age of 63 years underwent, in the following order, prostate specific antigen (PSA) assay (radioimmunometric assay, normal less than 2.5 ng./ml.), rectal examination, transrectal ultrasonography with a 7 MHz. probe, measurement of the prostatic volume, and 6 ultrasound-guided randomized biopsies and biopsies of any hypoechogenic zones. All men with a suspicious prostate on rectal examination (nodule, induration or firm zone) were excluded from the study. There were 14 prostatic cancers detected: 3 (8.5%) in men less than 60 years old, 4 (11%) in men between 60 and 70 years old and 7 (24%) in men more than 70 years old. No cancer was detected in men with a PSA level of less than 10 ng./ml., 5 (26%) were detected in 19 men with a PSA level of 10 to 19 ng./ml., 4 (40%) were detected in 10 men with a PSA of 20 to 29.9 ng./ml. and 5 (100%) were detected in 5 men with a PSA of 30 or more ng./ml. A total of 66 men (66%) had a PSA level of less than 10 ng./ml. There were 18 (18%) hypoechogenic zones detected: 2 (11%) were positive for cancer but, over-all, the hypoechogenic zones revealed cancer in only 2 of 100 cases (2%). In 12 of the 14 cancers detected (86%) with no clinical suspicion the PSA level was higher than the maximal PSA level related to the prostate weight. We conclude that systematic randomized prostatic biopsies are the best method of early diagnosis, detecting 41% of all prostatic cancers in men with a normal rectal examination when the PSA level is 10 ng./ml. or more. The real question is to determine whether this early diagnosis is useful for the patient, since presently, there is no certainty of the therapeutic benefit in terms of quantity and quality of life.

Seminal vesicle biopsies in the preoperative staging of prostatic cancer.

Twenty-five patients with localized prostate cancer underwent seminal vesicle biopsies before radical prostatectomy. A transrectal probe of 7 MHz, a 18-gauge needle and a biopsy gun were used. The preoperative biopsy established the absence of seminal vesicle invasion in 89% of cases. When the seminal vesicles are positive at biopsy, capsular penetration is observed in 100% of the cases and lymph node positivity in 50%. When seminal vesicles are negative at biopsy and the prostate-specific antigen level is less than 20 ng/ml (n less than 2.5), capsular penetration of greater than 1 cm is absent in 100% of cases and lymph nodes are positive in only 7% of cases. Biopsy of the seminal vesicle, as an outpatient procedure, improves the preoperative staging of prostate cancer before radical prostatectomy: negative biopsies are good predictors of the absence of lymph node invasion.