Antimicrobial for 7 or 14 Days for Febrile Urinary Tract Infection in Men: A Multicenter Noninferiority Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

BACKGROUND: The optimal duration of antimicrobial therapy for urinary tract infections (UTIs) in men remains controversial. METHODS: To compare 7 days to 14 days of total antibiotic treatment for febrile UTIs in men, this multicenter randomized, double-blind. placebo-controlled noninferiority trial enrolled 282 men from 27 centers in France. Men were eligible if they had a febrile UTI and urine culture showing a single uropathogen. Participants were treated with ofloxacin or a third-generation cephalosporin at day 1, then randomized at day 3-4 to either continue ofloxacin for 14 days total treatment, or for 7 days followed by placebo until day 14. The primary endpoint was treatment success, defined as a negative urine culture and the absence of fever and of subsequent antibiotic treatment between the end of treatment and 6 weeks after day 1. Secondary endpoints included recurrent UTI within weeks 6 and 12 after day 1, rectal carriage of antimicrobial-resistant Enterobacterales, and drug-related events. RESULTS: Two hundred forty participants were randomly assigned to receive antibiotic therapy for 7 days (115 participants) or 14 days (125 participants). In the intention-to-treat analysis, treatment success occurred in 64 participants (55.7%) in the 7-day group and in 97 participants (77.6%) in the 14-day group (risk difference, -21.9 [95% confidence interval, -33.3 to -10.1]), demonstrating inferiority. Adverse events during antibiotic therapy were reported in 4 participants in the 7-day arm and 7 in the 14-day arm. Rectal carriage of resistant Enterobacterales did not differ between both groups. CONCLUSIONS: A treatment with ofloxacin for 7 days was inferior to 14 days for febrile UTI in men and should therefore not be recommended. CLINICAL TRIALS REGISTRATION: NCT02424461; Eudra-CT: 2013-001647-32.

Operative and Midterm Oncological Outcome of Focal Salvage Cryotherapy for Localized Prostate Cancer.

BACKGROUND: Local recurrence after radiation therapy for prostate cancer is a major clinical issue. Various local treatments are available with mitigated functional and oncological outcomes. The aim of the present study was to evaluate perioperative and oncological results of salvage cryotherapy (CT) as treatment of local recurrence of prostate cancer. METHODS: We retrospectively reviewed all patients treated with hemi-prostatic salvage CT for local recurrence of prostate cancer in 1 academic hospital between November 2011 and April 2019. Local recurrence was defined according to the Phoenix criteria (prostate-specific antigen [PSA] nadir + 2 ng/mL), associated with a prostatic MRI target lesion and confirmed by biopsy. Perioperative and functional complications were collected. Cox regression was conducted to assess factors associated with time to initiation of androgen deprivation therapy (ADT). Statistical analyses were conducted using R Studio. RESULTS: A total of 29 patients were treated with an average follow-up of 37.6 months. Median age at CT was 77 years. Median PSA before CT was 5.1 ng/mL (min-max: 2.74-18). 17.2% of patients displayed a high D'Amico risk group. Median hospital stay was 1.4 days. Four patients (13.8%) experienced postoperative acute urinary retention. Nineteen patients (65.5%) experienced late functional complications (3 erectile dysfunctions, 3 stress incontinence, and 13 urinary frequency). Fourteen patients displayed recurrence after salvage treatment (48.2%). Median time to introduction of ADT was 15.1 months. ADT-free survival at 1 and 2 years was, respectively, 74% and 61%. In multivariate analysis, ISUP score 4 and PSA nadir <1 ng/mL after CT were significantly associated with time to ADT initiation. CONCLUSIONS: Salvage focal CT may delay the use of ADT in locally recurrent prostate cancer after RT and offers an alternative for eligible patients. The technique was feasible with acceptable perioperative morbidity and acceptable midterm oncological outcome.

Complications and Discharge after Radical Cystectomy for Older Patients with Muscle-Invasive Bladder Cancer: The ELCAPA-27 Cohort Study.

Radical cystectomy is the standard of care for localized bladder cancer but is associated with high morbidity and mortality rates-especially among older patients with comorbidities. The association between geriatric assessment parameters on post-operative complications and discharge has not previously been investigated. The present analysis of the Elderly Cancer Patient (ELCAPA) prospective cohort included all patients aged ≥70 having undergone a geriatric assessment and then radical cystectomy for localized muscle-invasive bladder cancer between 2007 and 2018. The primary endpoint was the proportion of patients with one or more complications in the first 30 days after cystectomy. The secondary endpoints were the length of hospital stay (LOS), the 30-day mortality, and discharge rates. Sixty-two patients (median age: 81; range: 79-83.8) were included. The 30-day complication rate was 73%, and 49% of the patients had experienced a major complication, according to the Clavien-Dindo classification. The 30-day mortality rate was 4%. None of the geriatric, oncological, or laboratory parameters were significantly associated with the occurrence or severity of complications. The median (interquartile range) LOS was 18 days (15-23) overall and was longer in patients with complications (19 days vs. 15 days in those without complications; p = 0.013). Thirty days after cystectomy, 25 patients (53%) had been discharged to home and 22 (47%) were still in a rehabilitation unit. In a univariate analysis, a Geriatric-8 score ≤ 14, a loss of one point on the Activities of Daily Living Scale, anemia, at least one grade ≥ 3 comorbidity on the Cumulative Illness Rating Scale-Geriatric, and an inpatient geriatric assessment were associated with a risk of not being discharged to home. In older patients having undergone a geriatric assessment, radical cystectomy is associated with a high complication rate, a longer LOS, and functional decline at 30 days.

Adherence to Treatment Guidelines and Associated Survival in Older Patients with Prostate Cancer: A Prospective Multicentre Cohort Study.

The guidelines on prostate cancer treatment in older men recommend evaluating the patient's underlying health status before treatment selection. We aimed to evaluate the frequency of a guideline-discordant treatment (GDT), identify factors associated with GDT, and assess the relationship between GDT and overall survival. We studied patients with prostate cancer aged 70 or older included in the ELCAPA cohort between 2010 and 2019. Multivariable logistic regression assessed GDT-associated factors. The restricted mean survival time (RMST) assessed the 24- and 36-month OS using stabilized inverse probability of treatment weighting of propensity scores. We included 356 patients (median age: 81 years), and 164 (46%) received a GDT (95% confidence interval (CI) = (41-51%)). Patients with metastases were less likely to receive a GDT (adjusted odds ratio (95% CI) = 0.34 (0.17-0.69); p = 0.003). After weighting, the RMST at 24 months was shorter in the GDT group (13.9 months, vs. 17 months for compliant treatments; difference (95% CI): -3.1 months (-5.3, -1.0); p = 0.004). RMST at 36 months was 18.5 months, vs. 21.8 months (difference: -3.3 months (-6.7, 0.0); p = 0.053). GDT is common in older patients with prostate cancer and especially those with non-metastatic disease. GDT was associated with worse survival, independently of health status and tumour characteristics.

Perioperative outcomes of transurethral resection for t1 bladder tumors: quality evaluation based on patient, tumor and surgeon criteria.

INTRODUCTION: Transurethral resection of bladder tumor (TURBT) is a fundamental but challenging step in the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC). The first- and second-look TURBT are central in the management of T1 tumors. MATERIALS AND METHODS: We retrospectively reviewed all patients treated with TURBT for T1 urothelial cell carcinoma (UCC) of the bladder in one academic institution between 2007 and 2017. Quality of TURBT was evaluated based on the presence/absence of muscle on pathology report, the presence/absence of residual tumor on the second look and the occurrence of complications. Patient-, surgeon- and tumor-related factors were investigated for their association with TURBT quality. RESULTS: 283 patients were included. Second-look resection was performed after a mean delay of 54 days. Muscle was observed in 85.9% of the samples on the first TURBT. On the second-look resection, UCC was observed in 52.3% of the samples. 38 complications were reported after the first TURBT (13.4%). Surgeon's experience was the only factor significantly associated with occurrence of post-operative complications (OR = 0.40; p = 0.04). Location of the tumor at the bottom of the bladder was a risk factor for not finding muscle at pathological analysis (OR = 0.20; p = 0.06). Male gender, multiplicity and tumor located at the bottom of the bladder were significantly associated with residual disease on reTURBT. In multivariate analysis, only male gender (OR = 4.71; p = 0.02) and tumor multiplicity remained significant (OR for unique tumor = 0.36; p = 0.02). CONCLUSION: TURBT is a challenging procedure and surgeon's experience is crucial in reducing the rate of post-operative complications. Technical difficulties resulting from patient's gender, tumor location or number of tumors may be as important as oncological factors in deciding whether or not to perform a second-look resection.

Impact of the COVID-19 pandemic on oncological and functional robotic-assisted surgical procedures.

The COVID-19 pandemic led to a decrease in surgical activity to avoid nosocomial contamination. Robotic-assisted surgery safety is uncertain, since viral dissemination could be facilitated by gas environment. We assessed the impact and safety of the COVID-19 pandemic on robotic-assisted surgery. Data were collected prospectively during lockdown (March 16th-April 30th 2020) in 10 academic centres with robotic surgical activity and was compared to a reference period of similar length. After surgery, patients with suspected COVID-19 were tested by RT-PCR. During the COVID-19 lockdown we evidenced a 60% decrease in activity and a 49% decrease in oncological procedures. However, the overall proportion of oncological surgeries was significantly higher during the pandemic (p < 0.001). Thirteen (7.2%) patients had suspected COVID-19 contamination, but only three (1.6%) were confirmed by RT-PCR. The COVID-19 pandemic resulted in a significant decrease in robotic-assisted surgery. Robotic approach was safe with a low rate of postoperative COVID-19 contamination.

Fosfomycin-trometamol (FT) or fluoroquinolone (FQ) as single-dose prophylaxis for transrectal ultrasound-guided prostate biopsy (TRUS-PB): A prospective cohort study.

OBJECTIVES: The increasing incidence of fluoroquinolones (FQ) resistance may lower its efficacy in preventing UTI following transrectal ultrasound-guided prostate biopsy (TRUS-PB). We assessed the efficacy and safety of FQ and fosfomycin-trometamol (FT) in patients undergoing TRUS-PB. METHODS: A prospective observational study was conducted between April 2017 and June 2019 and enrolled men undergoing TRUS-PB and receiving a single-dose of FQ (FQ-arm) or FT (FT-arm) for UTI prophylaxis per physician's choice. The primary efficacy endpoint was self-reported TRUS-PB UTI. We assessed baseline factors associated with UTI with logistic regression. RESULTS: A total of 222 men were enrolled, 141/222 (64%) received FQ, and 81/222 (36%) FT. The median age was 67.6 years [IQR, 61.4-72.1] and the Charlson score was 3 [IQR, 3-5]. The overall incidence of self-reported TRUS-PB UTI was 12% (24/197, (95%CI, 8%-17%)): 15% (17/116, (95% CI, 10%-17%)) in FQ-arm, versus 9% (7/81, 95% CI (5%-13%)) in FT-arm (RR = 0.55 (95% CI, 0.22-1.40), p-value = 0.209). No baseline characteristic was significantly associated with TRUS-PB UTI. Safety was similar between the arms: the rate of the reported adverse event was 31% (36/116, (95% CI, 25%-37%) in the FQ-arm versus 36% (28/81, (95% CI, 28%-41%)) in the FT-arm (RR = 1.17 (95% CI, 0.64-2.15), p = 0.602). CONCLUSIONS: TRUS-PB UTI prophylaxis with FT and FQ has similar efficacy and safety. A randomized comparison of these two antibiotics is warranted.

Operative and oncological results and impact on treatment strategy of systematic renal tumor biopsy: Comparison between patients < and >75 years old.

BACKGROUND: Proper usage of renal tumor biopsy (RTB) remains to be determined in the setting of renal tumors diagnosis, particularly in the elderly population. The aim of the study was to evaluate the perioperative and pathological results of RTB in a population of patients over 75 and to compare the performance of the procedure to their younger counterparts. MATERIAL AND METHODS: Systematic RTB were prospectively performed in a single center between 2009 and 2012. Patients' and tumor characteristics, operative and pathological results were collected. Data were compared between patients under and over 75 years old. Particular attention was paid to influence of RTB on treatment decision-making. RESULTS: A total of 180 patients were included (137 patients <75 years and 43 > 75 years). Size of tumor, clinical stage, radiological aspect and RENAL score were not statistically different between patients under or over 75 years. No difference was observed between the 2 groups regarding complication rate (2.9% vs. 0%, respectively, P = 0.625). One hundred fifty-seven patients (87.2%) had a positive diagnosis at first RTB, with no difference between the 2 groups regarding histology (P = 0.942). After biopsy, only 73.1% of patients <75 years and 70.7% of patients >75 years had concordance between radiological and histological findings (P = 0.919). Treatment decision was challenged after RTB in 21.8% of patients <75 years and in 25.0% of patients >75 years. CONCLUSIONS: RTB was as safe and accurate in the eldest population, as it is in the general population, and should be performed routinely considering its influence on patient management strategy.

Stromal osseous metaplasia in urothelial carcinoma of the bladder: a rare case report and literature review.

BACKGROUND: The bone formation within bladder tumors could be encountered in 3 conditions. These might consist of malignant bone formation in mesenchymal tumors; mixed mesenchymal and epithelial tumors; and epithelial tumors with stromal osseous metaplasia (SOM). This last is relatively rare. According to the English literature, only 12 cases have been reported in primary tumor and 7 in metastatic deposits of bladder primaries. Herein, we presented an additional case. CASE PRESENTATION: An 83-year-old man was admitted 13 years ago for prostatic adenocarcinoma, treated with radical prostatectomy. Biochemical recurrence was detected 2 years after surgery (prostate-specific-antigen (PSA) level: 4.60 ng/mL) and progressively normalized (<1.0 ng/mL) after adjuvant radiotherapy and annual injection of leuprorelin (enantoneR). He was referred after 8 years for hematuria, PSA level having slightly increased (0.60 ng/ml). Cystoscopy showed a nodular growth in the bladder wall, visualized as a calcified tumor on computed tomography (CT) and removed with transurethral resection. Histologically, the tumor consists of a non-muscle-invasive high grade papillary urothelial carcinoma with metaplastic bone within the stroma. Immunohistochemical analysis particularly demonstrated positive expression of respectively CD56 on osteoblasts, and CD68 on osteoclasts. MDM2 and CDK4 were negatives on osteoid and bone tissue. Six courses of Bacillus Calmette-Guerin (BCG) therapy have been administered. Two local recidives have occurred during an 8-month follow-up period after immunotherapy and were treated with six further courses of BCG therapy. At one-month follow-up, the patient was well without remaining symptoms. CONCLUSION: SOM is a rare benign condition whose pathogenesis remains uncompletely defined. Sarcomatoïd carcinoma represents the main differential diagnosis that influences therapeutic procedures. Prognosis depends essentially on the extent of the carcinomatous component .

Long-term functional outcomes of augmentation cystoplasty in adult spina bifida patients: A single-center experience in a multidisciplinary team.

AIM: To report the very long-term functional outcomes of augmentation cystoplasty (AC) in adult spina bifida patients. METHODS: All consecutive adult spina bifida patients who underwent AC between 1991 and 2008 were enrolled. Early postoperative complications (Clavien-Dindo classification) and long-term outcomes (voiding modalities, urodynamic parameters, renal function, continence, and quality of life) were assessed. RESULTS: Twenty-eight patients with a median age of 20 years (IQR 17-25) were included. They all underwent AC with a supratrigonal cystectomy (SC). The median follow-up was 13.6 years (IQR 6-16.5). Thirteen early postoperative complications (12 grade I-II, 1 grade III) were observed in 11 patients (39%). Eight patients (29%) had upper urinary tract infections managed with antibiotics, with 2 patients requiring ureteral stents. Bladder stones occurred in 2 patients (7%) and were managed with endoscopy and cystostomy. One bladder perforation was reported. One bladder cancer was observed 26 years after surgery. Creatinine clearance and all urodynamic parameters were significantly improved post-operatively. The overall complication and reoperation rates were 57% and 14%, respectively. At last follow up, the continence rate was 71% (n = 20), with 93% (n = 26) performing intermittent self-catheterization. Quality of life was improved for 71% of patients. CONCLUSION: In adult spina bifida population, AC is a high-risk procedure with an overall complication rate of 57% and a reoperation rate of 14%. However, AC is beneficial to the overall health of the patients since it provides a satisfying continence rate, an improvement of quality of life, and long-term protection of the upper urinary tract.

French recommendations for osteoporosis prevention and treatment in patients with prostate cancer treated by androgen deprivation.

Androgen-deprivation therapy (ADT) in patients with prostate cancer can be achieved surgically or chemically, notably by prescribing LHRH analogs. Major bone loss occurs rapidly in both cases, due to the decrease in testosterone levels, and can increase the fracture risk. The objective of developing these recommendations was to achieve a practical consensus among various scientific societies, based on a literature review, about osteoporosis prevention and treatment in patients on ADT. The following scientific societies contributed to the work: Société française de rhumatologie (SFR), Groupe de recherche et d'information sur les ostéoporoses (GRIO), Groupe européen d'études des métastases osseuses (GEMO), Association francophone pour les soins de support (AFSOS), Association française d'urologie (AFU), Société française de radiothérapie oncologique (SFRO). Medication prescription and reimbursement modalities in France were taken into account. The recommendations state that a fracture-risk evaluation and interventions targeting risk factors for fractures should be provided to all patients on ADT. Those patients with a history of severe osteoporotic fracture and/or a T-score < -2.5 should receive osteoporosis therapy. Patients whose T-score is between -1.5 and -2.5 should be treated if they exhibit at least two other risk factors among the following: age ≥ 75 years, history of non-severe fracture after 50 years of age, body mass index < 19 kg/m2, at least three comorbidities (e.g., cardiovascular disease, depression, Parkinson's disease, and dementia), current glucocorticoid therapy, and repeated falls. When the decision is difficult, FRAX® score determination and an assessment by a bone disease specialist may be helpful. When osteoporosis therapy is not indicated, general measures should be applied, and bone mineral density measured again after 12-24 months. The anti-tumor effects of bisphosphonates and denosumab fall outside the scope of these recommendations.

Urinary function and quality of life after radiotherapy for prostate cancer in patients with prior history of surgical treatment for benign prostatic hyperplasia.

BACKGROUND: To evaluate long-term IPSS score and urinary quality of life after radiotherapy for prostate cancer, in patients with prior history of surgical treatment for benign prostatic hyperplasia (BPH). METHODS: In this retrospective study, we reviewed medical records of patients treated in our department, between 2007 and 2013 with surgery for BPH followed by radiotherapy for localized prostate cancer. Patients were contacted to fill in IPSS questionnaire and they were also asked for urinary quality of life. Predictive factors known to be associated with bad urinary function were also analysed. RESULTS: Fifty-nine patients were included in our study. Median age was 70 years. Median follow-up was 4.6 years. Median radiotherapy dose was 78 Gy (5 × 2 Gy/week). Thirty patients (48.5%) received hormone therapy in combination with RT. Main surgery indications were urinary symptoms (65%) and urinary retention (20%). Five-year biochemical-disease free survival was 75% and 5-year clinical relapse free survival was 84%. At the time of the study, the IPSS after radiotherapy was as follows: 0-7: 77.6%; 8-19:20.7%; 20-35: 1.7%. Urinary quality of life was satisfactory for 74.2% of patients. After multivariate analysis, a high dose of RT and a medical history of hypertension were associated with a poorer quality of urinary life (p = 0.04). CONCLUSION: External radiotherapy remains an appropriate treatment option without a major risk for deterioration in urinary function in patient with antecedent surgery for BPH. High dose of RT and a medical history of hypertension were associated with a poorer quality of urinary life.

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).

Curative Treatment for Muscle Invasive Bladder Cancer in Elderly Patients: A Systematic Review.

CONTEXT: The incidence of muscle invasive bladder cancer (MIBC) increases with age. With increased life expectancy the number of elderly MIBC patients is expected to increase. Existing guidelines on management of MIBC do not preclude curative treatments for elderly patients. However, it is necessary to assess the risks and benefits of a treatment to avoid overtreatment that results in decreased health-related quality of life without prolonging survival. OBJECTIVE: To report on overall survival (OS), cancer specific survival (CSS), and morbidity after curative treatment in elderly patients, defined as age >70 yr, with nonmetastatic MIBC and to compare this with the outcome of younger MIBC patients. EVIDENCE ACQUISITION: A systematic review was performed using Medline, PubMed, and Embase databases. Articles were included if they addressed one of the three research questions: Only articles including >100 patients and with a clear age-stratification were included. EVIDENCE SYNTHESIS: Forty-two articles were retrieved for review. No article directly addressed the use of geriatric assessment. OS and CSS worsen significantly with age both after radical cystectomy and radiotherapy regimens. While POM significantly increases with age, morbidity seems comparable between younger and older patients. CONCLUSIONS: Although a proportion of elderly patients with MIBC will benefit from curative treatment, we observed worse OS, CSS, and POM with age. The impact of age on late morbidity is less clear. Prospective studies evaluating geriatric assessments are critically needed to optimize MIBC management in the elderly. PATIENT SUMMARY: We performed a systematic review to evaluate the outcome and complication rate in elderly patients with muscle invasive bladder cancer. We observed that overall survival and cancer specific survival significantly decrease and perioperative mortality significantly increases with age. The impact of age on late morbidity is less clear. There is a need for geriatric assessments to select those patients that will benefit from curative treatment.

Primary adenocarcinoma of the seminal vesicle.

Primary adenocarcinoma of the seminal vesicle is a rare condition with only about 60 cases described in the literature. The unusual characteristics of this disease makes diagnosis difficult and treatment strategies differ as there are no specific guidelines available. This report presents a case of adenocarcinoma of the seminal vesicle with lung metastases in which surgical and chemotherapeutic treatments have been carried out. The MVAC dose dense regimen following local resection seems effective in this scenario and may be used in the treatment of this disease.

[Management of prostate cancer in patients older than 75 years]. / Prise en charge diagnostique et thérapeutique des cancers de la prostate chez l'homme de plus de 75 ans.

Prostate cancer is a disease of the elderly men. Prostate cancer in the elderly men is often poorly managed and under-treated. The digital rectal examination is an effective screening test for elderly prostate cancer patients. In order to choose the appropriated therapeutic option, evaluation of life-expectancy is essential to offer an optimal individualized treatment. It is essential to take into account the patients' aspirations before starting any diagnostic and therapeutic approach. Therapeutic options should be adapted in elderly prostate cancer patients according to their comorbidities and needs. Elderly patients should be included in clinical trials specifically designed for this population.

Improved decision making in intermediate-risk prostate cancer: a multicenter study on pathologic and oncologic outcomes after radical prostatectomy.

BACKGROUND: Prognoses for intermediate-risk prostate cancer (PCa) remain heterogeneous. Improved substratification could optimize treatment and monitoring strategies. The objective was to validate this subclassification in a radical prostatectomy (RP) series. METHODS: Between 2000 and 2011, 4038 patients who underwent RP for intermediate-risk PCa in seven French academic centers were included. Unfavorable intermediate-risk (UIR) PCa was defined as having a primary Gleason score of 4, ≥50% positive biopsy cores (PPBC), or more than one D'Amico intermediate-risk factor (i.e., cT2b, PSA 10-20, or Gleason score 7). Remaining PCa cases were classified as favorable. Main endpoints were pathologic results (pT stage, final Gleason score, surgical margin status), and oncologic outcomes were assessed according to PSA recurrence-free survival (PSA-RFS). Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. RESULTS: Median follow-up was 48 months (95% CI = [45-49]). Patients with UIR had worse PSA-RFS (68.17 vs. 81.98% at 4 years, HR = 1.97, 95% CI = [1.71; 2.27], p < 0.0001) compared to those with a favorable disease. The need for adjuvant therapy was significantly greater for UIR patients (43.5 vs. 29.2%, p < 0.0001). In multivariate analysis, primary Gleason score of 4 (HR = 1.81, 95% CI = [1.55; 2.12], p < 0.0001) and PPBC ≥ 50% (HR = 1.26, 95% CI = [1.02; 1.56], p = 0.0286) were significant preoperative predictors for worse PSA-RFS. CONCLUSIONS: This study highlights the heterogeneity of NCCN intermediate-risk patients and validates (in a large RP cohort) the previously proposed subclassification for this group. This classification can significantly predict both pathologic and oncologic outcomes. This easy-to-use stratification could help physicians' decision making. Prospective study and new tools as genomic tests and novel molecular-based approaches can improve this stratification in the future for patient counseling.

Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) is a high incidence form of bladder cancer (BCa), where genetic and epigenetic alterations occur frequently. We assessed the performance of associating a FGFR3 mutation assay and a DNA methylation analysis to improve bladder cancer detection and to predict disease recurrence of NMIBC patients. METHODS: We used allele specific PCR to determine the FGFR3 mutation status for R248C, S249C, G372C, and Y375C. We preselected 18 candidate genes reported in the literature as being hypermethylated in cancer and measured their methylation levels by quantitative multiplex-methylation specific PCR. We selected HS3ST2, SLIT2 and SEPTIN9 as the most discriminative between control and NMIBC patients and we assayed these markers on urine DNA from a diagnostic study consisting of 167 NMIBC and 105 controls and a follow-up study consisting of 158 NMIBC at diagnosis time's and 425 at follow-up time. ROC analysis was performed to evaluate the diagnostic accuracy of each assay alone and in combination. RESULTS: For Diagnosis: Using a logistic regression analysis with a model consisting of the 3 markers' methylation values, FGFR3 status, age and known smoker status at the diagnosis time we obtained sensitivity/specificity of 97.6 %/84.8 % and an optimism-corrected AUC of 0.96. With an estimated BCa prevalence of 12.1 % in a hematuria cohort, this corresponds to a negative predictive value (NPV) of 99.6 %. For Follow-up: Using a logistic regression with FGFR3 mutation and the CMI at two time points (beginning of the follow-up and current time point), we got sensitivity/specificity/NPV of 90.3 %/65.1 %/97.0 % and a corrected AUC of 0.84. We also tested a thresholding algorithm with FGFR3 mutation and the two time points as described above, obtaining sensitivity/specificity/NPV values of, respectively, 94.5 %/75.9 %/98.5 % and an AUC of 0.82. CONCLUSIONS: We showed that combined analysis of FGFR3 mutation and DNA methylation markers on urine can be a useful strategy in diagnosis, surveillance and for risk stratification of patients with NMIBC. These results provide the basis for a highly accurate noninvasive test for population screening and allowing to decrease the frequency of cystoscopy, an important feature for both patient quality of life improvement and care cost reduction.

[The level of evidence for the use of biomarkers in the early detection of prostate cancer]. / Les niveaux de preuve des biomarqueurs utilisés pour la détection précoce des cancers de la prostate.

To systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer, we searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects. The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system. A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review. We attributed a level of evidence (LoE) of IA to PSA for early PCa detection, but we do not recommend its use in mass screening. Emerging biomarkers were assessed in prospective case-control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA (n=5); fusion oncogenes (n=2). These studies used biopsy results for prostate cancer to determine specificity and sensitivity, but they did not assess the effect on PCa mortality. The LoE attributed was III-C. PSA can be used for early prostate cancer detection but mass screening is not recommended. Studies on other biomarkers suggest that they could be used, individually or in combination, to improve the selection of patients with elevated PSA levels for biopsy, but RCTs assessing their impact on prostate cancer management and mortality are needed. A better use of available tests is possible for men at risk in order to maximize the risk-benefit ratio.