DDX5 mRNA-targeting antisense oligonucleotide as a new promising therapeutic in combating castration-resistant prostate cancer.

The heat shock protein 27 (Hsp27) has emerged as a principal factor of the castration-resistant prostate cancer (CRPC) progression. Also, an antisense oligonucleotide (ASO) against Hsp27 (OGX-427 or apatorsen) has been assessed in different clinical trials. Here, we illustrate that Hsp27 highly regulates the expression of the human DEAD-box protein 5 (DDX5), and we define DDX5 as a novel therapeutic target for CRPC treatment. DDX5 overexpression is strongly correlated with aggressive tumor features, notably with CRPC. DDX5 downregulation using a specific ASO-based inhibitor that acts on DDX5 mRNAs inhibits cell proliferation in preclinical models, and it particularly restores the treatment sensitivity of CRPC. Interestingly, through the identification and analysis of DDX5 protein interaction networks, we have identified some specific functions of DDX5 in CRPC that could contribute actively to tumor progression and therapeutic resistance. We first present the interactions of DDX5 and the Ku70/80 heterodimer and the transcription factor IIH, thereby uncovering DDX5 roles in different DNA repair pathways. Collectively, our study highlights critical functions of DDX5 contributing to CRPC progression and provides preclinical proof of concept that a combination of ASO-directed DDX5 inhibition with a DNA damage-inducing therapy can serve as a highly potential novel strategy to treat CRPC.

Radioisotope-guided Lymphadenectomy for Pelvic Lymph Node Staging in Patients With Intermediate- and High-risk Prostate Cancer (The Prospective SENTINELLE Study).

PURPOSE: Our aim was to prospectively evaluate the diagnostic accuracy of sentinel lymph node biopsy-guided lymph node dissection compared to extended pelvic lymph node dissection in patients with intermediate- or high-risk prostate cancer. MATERIALS AND METHODS: We conducted a prospective, single-arm, multicenter study at 3 tertiary centers in France between February 2012 and May 2019. Eligible patients had clinically localized intermediate- or high-risk prostate cancer. After intraprostatic injection of (99m)Tc-nanocolloid, the locations of the sentinel lymph nodes were defined by preoperative lymphoscintigraphy. Surgical excision of the sentinel lymph nodes was performed using intraoperative gamma probe guidance. After resection of the sentinel lymph nodes, extended pelvic lymph node dissection was performed in all patients. We assessed the diagnostic accuracy of the sentinel lymph node biopsy method using extended pelvic lymph node dissection as the reference standard. This trial was registered in ClinicalTrials.gov (NCT02732392). RESULTS: A total of 162 men cN0M0 (CT scan and bone scan) were enrolled: 106 (65.4%) and 56 (34.6%) patients had intermediate- and high-risk prostate cancer, respectively. The median number of nodes retrieved was 14 (mean 16, IQR 10-21) per patient. At final pathological analysis, 22 patients (13.6%) were pN+. Sensitivity, specificity, negative predictive value, and positive predictive value of sentinel lymph node biopsy method in detecting patients with at least 1 lymph node metastasis were 95.4% (95% CI, 75.1-99.7), 100% (95% CI, 96.6-100), 99.2% (95% CI, 95.5-99.9), and 100% (95% CI, 80.7-100), respectively. CONCLUSIONS: Our multicenter prospective study supports that sentinel lymph node biopsy is a very effective and sensitive method for pelvic lymph node staging in patients with intermediate- or high-risk localized prostate cancer.

Expanding inclusion criteria for active surveillance in intermediate-risk prostate cancer: a machine learning approach.

PURPOSE: To develop new selection criteria for active surveillance (AS) in intermediate-risk (IR) prostate cancer (PCa) patients. METHODS: Retrospective study including patients from 14 referral centers who underwent pre-biopsy mpMRI, image-guided biopsies and radical prostatectomy. The cohort included biopsy-naive IR PCa patients who met the following inclusion criteria: Gleason Grade Group (GGG) 1-2, PSA < 20 ng/mL, and cT1-cT2 tumors. We relied on a recursive machine learning partitioning algorithm developed to predict adverse pathological features (i.e., ≥ pT3a and/or pN + and/or GGG ≥ 3). RESULTS: A total of 594 patients with IR PCa were included, of whom 220 (37%) had adverse features. PI-RADS score (weight:0.726), PSA density (weight:0.158), and clinical T stage (weight:0.116) were selected as the most informative risk factors to classify patients according to their risk of adverse features, leading to the creation of five risk clusters. The adverse feature rates for cluster #1 (PI-RADS ≤ 3 and PSA density < 0.15), cluster #2 (PI-RADS 4 and PSA density < 0.15), cluster #3 (PI-RADS 1-4 and PSA density ≥ 0.15), cluster #4 (normal DRE and PI-RADS 5), and cluster #5 (abnormal DRE and PI-RADS 5) were 11.8, 27.9, 37.3, 42.7, and 65.1%, respectively. Compared with the current inclusion criteria, extending the AS criteria to clusters #1 + #2 or #1 + #2 + #3 would increase the number of eligible patients (+ 60 and + 253%, respectively) without increasing the risk of adverse pathological features. CONCLUSIONS: The newly developed model has the potential to expand the number of patients eligible for AS without compromising oncologic outcomes. Prospective validation is warranted.

HoSAGE: sarcopenia in older patient with intermediate / high-risk prostate cancer, prevalence and incidence after androgen deprivation therapy: study protocol for a cohort trial.

BACKGROUND: Sarcopenia is defined by a loss of muscle strength associated to a decrease in skeletal muscle mass. Ageing greatly contributes to sarcopenia as may many other factors such as cancer or androgen deprivation therapies (ADT). This cohort study aims to evaluate (1) the prevalence of muscle disorders and sarcopenia in older patients before initiation of intermediate to high risk prostate cancer treatment with ADT and radiotherapy, and (2) the occurrence and/or aggravation of muscle disorders and sarcopenia at the end of cancer treatment. METHODS: This cohort study is monocentric and prospective. The primary objectives are to determine the risk factor of sarcopenia prevalence and to study the relationship between ADT and sarcopenia incidence, in patients 70 years and older with histologically proven localized or locally advanced prostate cancer, addressed to a geriatrician (G8 score ≤14) for comprehensive geriatric assessment (CGA) in Marseille University Hospital. Secondary objectives encompass, measurement of sarcopenia clinical criteria along prostate oncological treatment; evaluation of the quality of life of patients with sarcopenia; evaluation of the impact of socio-behavioral and anthropological factors on sarcopenia evolution and incidence; finally the evaluation of the impact of ADT exposure on sarcopenia. Sarcopenia prevalence was estimated to be between 20 and 30%, therefore the study will enroll 200 patients. DISCUSSION: The current guidelines for older patients with prostate cancer recommend a pelvic radiotherapy treatment associated to variable duration (6 to 36 months) of ADT. However ADT impacts muscle mass and could exacerbate the risks of sarcopenia. Our study intends to assess the specific effect of ADT on sarcopenia incidence and/or worsening as well as to estimate sarcopenia prevalence in this population. The results of this cohort trial will lead to a better understanding of sarcopenia prevalence and incidence necessary to further elaborate a prevention plan. TRIAL REGISTRATION: The protocol was registered to the French drug and device regulation agency under the number 2019-A02319-48, before beginning the study (11/12/2019). The ClinicalTrials.gov identifier is NCT04484246, registration on the ClinicalTrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04484246 ).

Long-term results of endoscopic treatment in vesicoureteral reflux after kidney transplantation.

OBJECTIVES: To assess the long-term clinical outcomes and identify factors predicting success of endoscopic treatment for symptomatic vesicoureteral reflux (VUR) after kidney transplantation. PATIENTS AND METHODS: A retrospective chart review of all patients who had a symptomatic VUR after renal transplantation at our centre between January 2000 and December 2020 was performed. VUR was documented by retrograde cystography and was determined by at least one episode of acute graft pyelonephritis (AGPN). Endoscopic injections of polydimethylsiloxane (MacroPlastique™) or dextranomer/hyaluronic acid copolymer (Deflux™) were performed by expert urologists via rigid cystoscopy with a bevelled needle system. The results of endoscopic treatment were evaluated by cystography at three months. The primary endpoint was clinical efficacy as defined by the absence of AGPN during follow-up. Radiological success was defined by the absence of VUR at the three months follow-up cystography. RESULTS: Out of 2135 kidney transplantations, a total of 117 (5.5%) patients had symptomatic VUR: 100 (85.5%) underwent Deflux™ and 17 (14.5%) MacroPlastique™. Preoperative high-grade VUR was recorded in 71% of patients. One postoperative complication was observed, Clavien > II. After a median follow-up of 11.2 years (IQR 6.5-14.4), clinical success was achieved in 73 patients (62.4%). Radiological success was obtained in 42 patients (36%). Multivariable analysis failed to identify predictors of endoscopic treatment success, which was independent of the preoperative grade of VUR and the type of bulking agent used. CONCLUSION: Endoscopic treatment of VUR is a simple and well-tolerated procedure with long-term clinical efficacy.

Comparison between Zumsteg classification and Briganti nomogram for the risk of lymph-node invasion before radical prostatectomy.

PURPOSE: To evaluate the performance of the Zumsteg classification to estimate the risk of lymph-node invasion (LNI) compared with the Briganti nomogram (BN) in prostatectomy patients with intermediate-risk prostate cancer (IRPC). METHODS: We included consecutive patients who had extended pelvic lymph-node dissection associated with radical prostatectomy for IRPC. To be classified favorable intermediate risk (FIR), patients could only have one intermediate-risk factor, fewer than 50% positive biopsies and no primary Gleason score of 4. RESULTS: On the 387 patients included, 149 (38.5%) and 238 (54.3%) were classified FIR and unfavorable intermediate risk (UIR), respectively, and 212 (54.8%) had a BN inferior to 5%. Thirty-eight patients (9.8%) had LNI: 6 FIR patients (4.0%) versus 32 UIR patients (13.4%) and 14 patients (6.6%) with a BN inferior to 5% versus 24 patients (13.7%) with a BN superior to 5%. Eight patients with a BN inferior to 5%, but classified UIR, had LNI. Sensitivity to detect LNI was higher with the Zumsteg classification than with the BN: 84.2% (CI 95% [68-93]) versus 63.2% (CI 95% [46-78]). Both screening tests were concordant to predict LNI (kappa coefficient of 0.076, p < 0.05 for Zumsteg and Briganti) CONCLUSIONS: Zumsteg classification appeared to be more sensitive and as effective (despite the impossibility to make decision curve analysis) than the BN to estimate the risk of LNI. Regarding the modest number of pN+ patients, further studies are needed to see the interest of proposing ePLND for UIR patients only.

Diagnostic ureteroscopy prior to nephroureterectomy for urothelial carcinoma is associated with a high risk of bladder recurrence despite technical precautions to avoid tumor spillage.

PURPOSE: There have recent reports in the literature of increased rates of bladder recurrence (BR) after radical nephroureterectomy (RNU) when diagnostic flexible ureteroscopy (DFU) was performed before RNU. The technical heterogeneity of DFU was a major bias in these studies. Our purpose was to evaluate the impact of a standardized DFU technique before RNU on the risk of BR. METHODS: A retrospective monocenter study including patients who underwent RNU for upper tract urothelial carcinoma (UTUC) between 2005 and 2017. 171 patients were identified. 78 patients were excluded owing to a history of bladder cancer before RNU or neo-adjuvant/adjuvant chemotherapy. 93 included patients were stratified according to pre-RNU ureteroscopy (DFU + 70 patients) or no pre-RNU ureteroscopy (DFU-23 patients). The standardized DFU technique consisted of systematic ureteral sheath (ch9-10), flexible ureteroscopy, biopsy, and drainage with a mono-J/bladder catheter to avoid contact of contaminated urine of the upper tract with the bladder. RESULTS: Epidemiological, initial staging, and postoperative tumoral characteristics were similar in both groups. Mean follow-up was 35 months [2-166], 47(50%) BR occurred with 41(87%) in the DFU + group, and pre-RNU-DFU was an independent predictive factor of BR (OR = 4[1.4-11.9], P = 0.01) (Cox regression model). The characteristics of BR were similar in both groups, although BR occurred earlier in DFU + (427 days vs. 226 days (P = 0.07)). CONCLUSION: Bladder recurrence after diagnostic ureteroscopy + nephroureterectomy was high despite technical precautions to avoid contact of bladder mucosa with contaminated urine from the upper urinary tract. Post-DFU endovesical instillation should be investigated.

Extent of positive surgical margins following radical prostatectomy: impact on biochemical recurrence with long-term follow-up.

BACKGROUND: To assess the prognostic value of the extent of positive surgical margins (PSM) following radical prostatectomy (RP) on biochemical recurrence (BR) with long-term follow-up. METHODS: This retrospective study analyzed 1275 RPs performed between January 1992 and December 2013 in two university centers in Marseille (France). The inclusion criteria were: follow-up > 24 months, undetectable postoperative prostate-specific antigen (PSA), no seminal vesicle (SV) invasion, no lymph node invasion confirmed by surgery (pN0) or imaging (pNx), and no neoadjuvant or adjuvant treatment. BR was defined by PSA level ≥ 0.2 ng/mL on two successive samples. We included 189 patients, divided into two groups: - Focal PSM (fPSM): single PSM (sPSM) ≤3 mm; - Extensive PSM (ePSM): sPSM with linear length > 3 mm or several margins regardless of the length. RESULTS: The median follow-up was 101 months (18-283) and the median age was 63 years (46-76). BR occurred in only 12.1% (14/115) of cases involving fPSM and in 54.1% (40/74) of cases involving ePSM. In the multivariate model, ePSM patients were significantly associated with increased BR compared to fPSM (hazard ratio [HR] = 6.11; 95% confidence interval [CI] = 3.25-11.49). The ePSM significantly decreased BR-free survival (p < 0.001) for every patient and every subgroup (pT2, pT3a, pG ≤6, and pG ≥7). The median BR time following RP was significantly shorter for ePSM patients than fPSM (57.2 vs. 89.2 months p < 0.001). CONCLUSION: With a median 8-year follow-up, ePSM was strongly associated with BR compared to fPSM. Therefore, it seems legitimate to monitor patients with fPSM. In cases of ePSM, adjuvant treatment appears effective.

Clinicopathological characteristics of incidental prostate cancer discovered from radical cystoprostatectomy specimen: a multicenter French study.

PURPOSE: The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated. METHODS: We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa. RESULTS: Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7%). Most tumors (90.1%) were organ-confined (pT2), whereas 9.9% of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9%), 6 in 575 cases (61.7%), 7 (3 + 4) in 149 cases (16.0%), 7 (4 + 3) in 38 cases (4.1%), and >7 in 40 cases (4.3%). After a median follow-up of 25.5 months (interquartile range 14.2-47.4), 35.4% of patients had bladder cancer recurrence and 23.8% died of bladder cancer. Only 16 patients (1.9%) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa. CONCLUSIONS: The rate of incidentally diagnosed PCa in RCP specimens was 21.7%. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9% of cases during follow-up.

Clinical outcomes after salvage radiotherapy without androgen deprivation therapy in patients with persistently detectable PSA after radical prostatectomy: results from a national multicentre study.

PURPOSE: To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT). METHODS: Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses. RESULTS: Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8-10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030). CONCLUSIONS: In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.

Modified holmium laser enucleation for benign prostatic obstruction to preserve sexual and ejaculatory function.

INTRODUCTION: To report ejaculatory and urinary results in patients who underwent holmium laser enucleation of the prostate (HoLEP) with selective laser enucleation of the median lobe (MLHoLEP). METHODS: Patients with lower urinary tract symptoms (LUTS)/benign prostatic obstruction (BPO) who underwent MLHoLEP to preserve ejaculatory function in a single center were retrospectively identified. Urinary function was assessed using International Prostate Score Symptom (IPSS), IPSS-Quality of Life index (IPSS-QoL), peak urinary flow (Qmax) and postvoid residual (PVR). Erectile function was assessed using International Index of Erectile Function (IIEF-5). In patients with preoperative antegrade ejaculation, retrograde ejaculation was routinely screened at each follow-up visit. Sexual and urinary functions at 3 and 12 months were compared with baseline values. RESULTS: A total of 55 patients met our inclusion criteria. A significant improvement in the IPSS, IPSS-QoL, PVR and Qmax was found at 3 and 12 months, compared with baseline (all P<0.05). Eight patients (14.5%) required surgical reintervention due to persistant LUTS/BPO. No significant changes in the erectile function were found at 3 (P=0.3) and 12 months (P>0.9). In patients with preoperative antegrade ejaculation (n=32), only four cases of de novo retrograde ejaculation were recorded postoperatively. CONCLUSION: MLHoLEP represents a new alternative for men with LUTS/BPO who wish to preserve their ejaculatory function. Patients should be aware that improvement in urinary function may be inferior to the traditional technique, with a higher reintervention rate due to persistent LUTS. LEVEL OF EVIDENCE: Grade 4.

Salvage high-intensity focused ultrasound (S-HIFU) for recurrence after primary radiotherapy of prostate cancer.

OBJECTIVES: To evaluate functional and oncological outcomes of salvage high-intensity focal ultrasound (S-HIFU) after external beam radiotherapy (EBRT) failure in prostate cancer (PCa) patients. METHODS: This single-center study included patients who underwent S-HIFU for local recurrence after EBRT between 2006 and 2023. Cancer-specific survival, metastasis-free survival and progression-free survival were illustrated using Kaplan-Meier curves. Disease progression was defined by one of the following criteria: increase of 2ng/mL or more above the PSA nadir, positive post-S-HIFU biopsy or initiation of androgen deprivation therapy (ADT). Multivariable Cox proportional hazards model was used to identify predictors of disease progression after S-HIFU. RESULTS: A total of 52 S-HIFU sessions for 48 patients were performed. Median time between EBRT and S-HIFU was 6.5 years. Median PSA before S-HIFU was 3.2ng/mL and median PSA nadir after S-HIFU was 0.58ng/mL. A total of 39 (81.3%) complications was recorded, including 3 (6.3%) high grade complications according to the Clavien-Dindo classification. After a median follow-up period of 6 years, 14 (29.2%) patients developed metastatic disease. Eighteen (37.5%) patients had no recurrence, whereas 30 (62.5%) patients received ADT for disease progression. The estimated 5-yr cancer-specific survival (CSS), metastasis-free survival (MFS) and progression-free survival rates (PFSR) were 100%, 79.9% (95% CI 67-92) and 41.2% (95% CI 74-96), respectively. The estimated 10-yr CSS, MFS and PFSR were 80% (95% CI 45-100), 50.7% (95% CI 19.4-82.1) and 14% (95% CI 10.8-45), respectively. The hazard of progression increased with the intermediate (HR 3.8; 95% CI 0.99 to 15; p=0.049) and high pre-EBRT d'Amico-s risk group (HR 4.1; 95% CI 0.98 to 16.2; p=0.050). Also, the time between EBRT and S-HIFU was significantly associated with risk of progression (HR 0.61; 95% CI 0.43 to 0.86; p=0.004). No significant difference linked to the disease progression (DP) risk was found between focal vs whole-gland treatment (p=0.70). CONCLUSION: Physicians should consider HIFU as a local salvage treatment after failed EBRT, thus avoiding or delaying palliative androgen deprivation therapy. Further studies are needed to improve patient selection for this therapy.

Predictive factors of oncologic outcomes in patients who do not achieve undetectable prostate specific antigen after radical prostatectomy.

PURPOSE: We identified factors predicting oncologic outcomes in cases of persistently detectable prostate specific antigen. MATERIALS AND METHODS: We reviewed the charts of patients treated with radical prostatectomy between 1998 and 2011 at a total of 14 centers. Study inclusion criteria were radical prostatectomy for presumed localized prostate cancer, absent positive nodes and detectable prostate specific antigen, defined as prostate specific antigen 0.1 ng/ml or greater 6 weeks postoperatively. Of the 9,735 radical prostatectomy cases reviewed 496 (5.1%) were eligible for analysis. Predictive factors for oncologic outcomes were assessed in time dependent analyses using the Kaplan-Meier method and Cox regression models. RESULTS: At 6 weeks prostate specific antigen was 0.1 to 6.8 ng/ml. Biochemical progression was noted in 74.4% of patients and clinical metastasis was noted in 5%. The 2 most powerful predictors of general salvage treatment (vs radiotherapy) were postoperative prostate specific antigen greater than 1 ng/ml (OR 3.46, p=0.032) and prostate specific antigen velocity greater than 0.2 ng/ml per year (HR 6.01, p=0.001). Positive prostate specific antigen velocity was the single factor that independently correlated with the risk of failed salvage therapy (HR 2.6, p=0.001). The 5-year disease-free survival rate was 81.0% in patients with stable or negative prostate specific antigen velocity compared with 58.4% in those with positive prostate specific antigen velocity (p<0.001). CONCLUSIONS: Patients with detectable prostate specific antigen after radical prostatectomy have a poor biochemical outcome. We identified postoperative prostate specific antigen and prostate specific antigen velocity as independent predictors of progression and failed salvage treatment. In addition to pathological prognostic factors, these factors should be considered early to better stratify patients for adjuvant therapy.

Positive surgical margins and their locations in specimens are adverse prognosis features after radical cystectomy in non-metastatic carcinoma invading bladder muscle: results from a nationwide case-control study.

OBJECTIVE: To compare the prognoses associated with positive surgical margins (PSMs) according to their urethral, ureteric and/or soft tissue locations in patients with pN0 M0 bladder cancer who have not undergone neoadjuvant chemotherapy. PATIENTS AND METHODS: A retrospective, case-control study was conducted between 1991 and 2011 using data from 17 academic centres in France. A total of 154 patients (cases) with PSMs met the eligibility criteria and were matched according to centre, pT stage, gender, age and urinary diversion method with a population-based sample of 154 patients (controls) from 3651 patients who had undergone cystectomies. The median follow-up period was 23.9 months. Multivariable Cox regression analysis was used to test the effects of PSMs on local recurrence (LR)-free survival, metastatic recurrence (MR)-free survival and cancer-specific survival (CSS). RESULTS: The 5-year LR-free survival and CSS rates of patients with urethral and soft tissue PSMs were lower than those in the control group. A significant decrease in CSS was associated with soft tissue PSMs (P = 0.003, odds ratio = 0.425, 95% confidence interval 0.283-0.647). The prognosis was not affected in cases of ureteric PSMs. CONCLUSIONS: Soft tissue PSMs were associated with poor CSS rates in patients with pN0 M0 bladder cancer. A correlation between urethrectomy and a reduction of the risk of LR in a urethral PSM setting was observed.

[Radical prostatectomy in prostate cancer: indications and surgical approaches]. / Indications et voies d'abord de la prostatectomie radicale dans le cancer de la prostate.

Prostate cancer is the most frequent in men: 71000 new cases were diagnosed in France in 2011. Early diagnosis allows treatments with curative intent. Risk groups by D'Amico classification system were validated to estimate progression risk after radical prostatectomy, external beam radiotherapy and brachytherapy. Radical prostatectomy is one of the reference treatments for localized prostate cancer. There are many surgical approaches: open retropubic approach, perineal, trans peritoneal or extra peritoneal laparoscopic approach, robotic assisted or not. Main surgical steps are the same between retropubic or laparoscopic approaches. Regarding oncologic (positive surgical margins rate, progression free survival) and functional results (continence and erections), no difference was reported between different surgical approaches.

Patient Blood Management in Transurethral Resection Surgery: Overview and Strategy Analysis from a French Tertiary Hospital.

INTRODUCTION: Since Patient blood management (PBM) suggests a bundle of measures aiming to reduce perioperative blood transfusion because preoperative anemia and blood transfusion are associated with poor postoperative outcomes. There is a lack of data on the effect of PBM in patients undergoing transurethral resection of prostate (TURP) or bladder tumor (TURBT). We aimed to assess the bleeding risk in TURP and TURBT procedures and the effect of preoperative anemia on postoperative morbimortality. METHODS: A single-center retrospective observational cohort study was conducted in a tertiary hospital in Marseille, France. All patients undergoing TURP or TURBT were included in 2020 and divided into two groups: preoperative anemia (n = 19) and no preoperative anemia (n = 59). We recorded demographic characteristics, preoperative hemoglobin concentration, iron deficiency markers, preoperative initiation of a treatment for anemia, perioperative bleeding, and postoperative outcomes up to 30 days including blood transfusion, hospital readmission, reintervention, infection, and mortality. RESULTS: Baseline characteristics were comparable between groups. No patient had iron deficiency markers and no prescription of iron was initiated before surgery. No major bleeding was reported during surgery. Postoperative anemia was found in 21 patients, including 16 (76%) in the preoperative anemia group and 5 (24%) in the non-preoperative anemia group. One patient of each group received a blood transfusion after surgery. No significant differences in 30-day outcomes were reported. CONCLUSION: Our study suggests that TURP and TURBT are not associated with a high-risk of postoperative bleeding. In such procedures, adherence PBM strategies do not seem beneficial. Since recent guidelines recommend restricting preoperative testing, our results may help to improve preoperative risk stratification.

Life Cycle Assessment of Reusable and Disposable Cystoscopes: A Path to Greener Urological Procedures.

BACKGROUND: The environmental impact of reusable and disposable devices is unclear; reuse is expected to reduce the carbon footprint, but the environmental impact of reprocessing of reusable devices is increasingly being questioned. OBJECTIVE: The aim was to provide the first rigorous life cycle assessment of reusable and disposable flexible cystoscopes. DESIGN, SETTING, AND PARTICIPANTS: We performed a life cycle assessment of reusable flexible cystoscopes and the aS4C single-use cystoscope (aScope; Ambu, Ballerup, Denmark). For the aScope, the complete lifespan of the scope was evaluated, including raw material extraction, material formulation, component production, product assembly, distribution, transportation after use, and final disposal. For reusable cystoscopes, we limited our analysis to their reprocessing, using a model consisting of standard high-level disinfection with peracetic acid. The environmental impact was evaluated by an independent third-party consulting company APESA (Technopole Hélioparc, Pau, France) dedicated to such risk assessments. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The environmental footprint of both cystoscopes was assessed using five environmental impact categories, namely, climate change, mineral resource depletion, ecotoxicity, acidification, and eutrophication. To perform the life cycle assessment, Simapro v9.3.3 software was used and the Ecoinvent v3.5 database was employed as the primary life cycle inventory database. A Monte Carlo analysis was used to account for the inherent uncertainty in life cycle inventory data and the variability in material and energy consumption for each type of flexible cystoscope. RESULTS AND LIMITATIONS: By only comparing the disinfection reprocessing of reusable cystoscopes with the complete lifespan of the single-use cystoscope, the use of the aScope would allow a reduction of at least 33% in the climate change category, 50% in the mineral resources' depletion category, 51% in the ecotoxicity category, 71% in the acidification category, and 49% in the eutrophication category. Our results cannot be generalized to all health care facilities as we studied only one type of reprocessing method and one disposable flexible cystoscope. CONCLUSIONS: Disinfection reprocessing of reusable cystoscopes was found to have a significantly larger environmental footprint and impact than the whole lifespan of the single-use cystoscope aScope. PATIENT SUMMARY: Using a cradle-to-grave life cycle analysis, we showed that the environmental footprint of a flexible cystoscopy procedure can be reduced by using a disposable cystoscope instead of a reusable cystoscope.

TP53INP1 overexpression in prostate cancer correlates with poor prognostic factors and is predictive of biological cancer relapse.

BACKGROUND: Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a proapoptotic protein involved in cell stress response. Whereas there is an overexpression of TP53INP1 in numerous tissues submitted to stress agents, TP53INP1 is down-expressed in stomach, pancreatic, and inflammation-mediated colic carcinomas. In medullary thyroid carcinomas, TP53INP1 overexpression correlates with poor prognosis. TP53INP1 expression has never been reported in Prostate Cancer (PC). Our aim was to investigate variations of TP53INP1 expression and their correlation to clinicopathological parameters in PC. METHODS: Quantitative measurements of immunohistochemical expression of TP53INP1 using high-throughput densitometry, assessed on digitized microscopic tissue micro-array images, were correlated with clinicopathological parameters in 91 human PC. Treatment of LNCaP tumor cells in vitro with cytokines and with TP53INP1 antisense oligonucleotide (ASO) was also analyzed. RESULTS: In normal prostate tissues, TP53INP1 is only expressed in prostate basal cells. There is a de novo TP53INP1 expression in prostate luminal cells in inflammatory prostate tissues, high grade PIN lesions and in PC. Stimulation of LNCaP cells with inflammatory cytokines enhances the level of TP53INP1 mRNA. In PC, TP53INP1 overexpression correlates with high Gleason grade, unfavorable D'Amico score and lymph node invasion, and is an independent factor of biological cancer relapse. Moreover, treatment of LNCaP cells with a TP53INP1 ASO down-regulates TP53INP1 protein level, inhibits proliferation, and induces apoptosis. CONCLUSION: TP53INP1 overexpression in PC seems to be a worse prognostic factor, particularly predictive of biological cancer relapse. Results in vitro suggest that TP53INP1 could be considered as a relevant target for potential specific therapy.

Seminal vesicle invasion: what is the best adjuvant treatment after radical prostatectomy?

OBJECTIVE: • To evaluate the biochemical-failure free survival according to different adjuvant treatments in patients who underwent radical prostatectomy (RP) with seminal vesicle invasion (SVI). PATIENTS AND METHODS: • Between 1994 and 2008, 4090 men underwent RP in nine centres. Of these, 310 men had a SVI. • Exclusion criteria were: detectable postoperative prostate-specific antigen, lymph node metastases and follow-up <18 months. • Therefore, the study group included 199 patients. Of these, 41 received adjuvant radiotherapy (RT) only, 26 received adjuvant androgen deprivation therapy (ADT) only, 50 received adjuvant ADT combined with RT and 82 were monitored. The endpoint for this analysis was biochemical no evidence of disease (bNED). • Preoperative prostate-specific antigen level, specimen Gleason score, age, clinical stage, surgical margin status and adjuvant treatment were evaluated in a multivariable analysis with respect to bNED survival. RESULTS: • After a mean (range) follow-up of 60.3 (18-185) months, 88 (44.2%) patients had a biochemical relapse. • The estimated 5- and 7-year bNED survival were 32.6% and 25.9% for the observation group, 44.4% and 28.6% for the RT only group, 48.4% and 32.3% for the ADT only group and 82.8% and 62.1% for the adjuvant ADT combined with RT group. • On multivariate analysis, only adjuvant ADT combined with RT (P < 0.001) was an independent prognostic factor of biochemical relapse. CONCLUSIONS: • RP appeared to be insufficient as a single treatment for patients with SVI. • The findings of the present study suggest that adjuvant ADT combined with RT after RP for patients with SVI confers a substantial benefit on 5-year bNED survival.