Eliciting men's preferences for decision-making relative to treatments of localized prostate cancer with a good or moderate prognosis.

PURPOSE: In diseases where there is no real consensus regarding treatment modalities, promoting shared decision-making can contribute to improving safety and quality of care. This is the case in low- or intermediate-risk localized prostate cancer (PC) treatment. The aim of this study was to investigate the preferences guiding men's decisions regarding the characteristics of the treatment strategies for PC to help physicians adopt a more patient-centered approach. METHODS: This prospective multicenter study used a discrete choice experiment (DCE). The attributes and the modalities were identified from a qualitative study and a literature review. Relative preferences were estimated using a logistic regression model. Interaction terms (demographic, clinical and socio-economic characteristics) were added to the model to assess heterogeneity in preferences. RESULTS: 652 men were enrolled in the study and completed a questionnaire with 12 pairs of hypothetical therapeutic alternatives between which they had to choose. Men's choices were significantly negatively influenced by the risk of impotence and urinary incontinence, death, and the length and frequency of care. They preferred treatments with a rescue possibility in case of deterioration or recurrence and the use of innovative technology. Surprisingly, the possibility of undergoing prostate ablation negatively influenced their choice. The results also highlighted differences in trade-offs according to socio-economic level. CONCLUSION: This study confirmed the importance of considering patients' preferences in the decision-making process. It appears essential to better understand these preferences to allow physicians to improve communication and promote case-by-case decision-making.

Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma.

BACKGROUND: Cytoreductive nephrectomy has been the standard of care in metastatic renal-cell carcinoma for 20 years, supported by randomized trials and large, retrospective studies. However, the efficacy of targeted therapies has challenged this standard. We assessed the role of nephrectomy in patients with metastatic renal-cell carcinoma who were receiving targeted therapies. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with confirmed metastatic clear-cell renal-cell carcinoma at presentation who were suitable candidates for nephrectomy to undergo nephrectomy and then receive sunitinib (standard therapy) or to receive sunitinib alone. Randomization was stratified according to prognostic risk (intermediate or poor) in the Memorial Sloan Kettering Cancer Center prognostic model. Patients received sunitinib at a dose of 50 mg daily in cycles of 28 days on and 14 days off every 6 weeks. The primary end point was overall survival. RESULTS: A total of 450 patients were enrolled from September 2009 to September 2017. At this planned interim analysis, the median follow-up was 50.9 months, with 326 deaths observed. The results in the sunitinib-alone group were noninferior to those in the nephrectomy-sunitinib group with regard to overall survival (stratified hazard ratio for death, 0.89; 95% confidence interval, 0.71 to 1.10; upper boundary of the 95% confidence interval for noninferiority, ≤1.20). The median overall survival was 18.4 months in the sunitinib-alone group and 13.9 months in the nephrectomy-sunitinib group. No significant differences in response rate or progression-free survival were observed. Adverse events were as anticipated in each group. CONCLUSIONS: Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic renal-cell carcinoma who were classified as having intermediate-risk or poor-risk disease. (Funded by Assistance Publique-Hôpitaux de Paris and others; CARMENA ClinicalTrials.gov number, NCT00930033 .).

Intraoperative Cyst Rupture during Partial Nephrectomy for Cystic Renal Masses-Does it Increase the Risk of Recurrence?

PURPOSE: Our objective was to assess the prevalence of intraoperative cyst rupture and its impact on oncologic outcomes. MATERIALS AND METHODS: All patients who underwent partial nephrectomy for a cystic renal mass via an open or robot-assisted approach at a total of 8 academic institutions were included in this retrospective study. All operative reports were carefully reviewed and any description of cyst rupture, cyst effraction or local spillage intraoperatively was recorded as cyst rupture. Multivariate logistic regression analysis was done to assess the variables associated with cyst rupture. Recurrence-free, cancer specific and overall survival was estimated by the Kaplan-Meier method and compared with the log rank test. RESULTS: Overall 268 patients were included in study. There were 50 intraoperative cyst ruptures (18.7%) in the whole cohort. No preoperative parameter was significantly associated with a risk of intraoperative cyst rupture on univariate or multivariate analysis. Of the cystic renal masses 75% were malignant on the final pathology report. At a median followup of 32 months 5 patients (2.5%) had local recurrence while progression to metastasis was observed in 2%. There were no peritoneal carcinomatosis nor port site metastasis. There was also no local or metastatic recurrence in the subgroup with intraoperative cyst rupture. Estimated recurrence-free survival did not differ significantly between patients with vs without intraoperative cyst rupture at 100% vs 92.7% at 5 years (p = 0.20). CONCLUSIONS: Intraoperative cyst rupture during partial nephrectomy is a relatively common occurrence but with few oncologic implications.

Testicle-sparing surgery versus radical orchiectomy in the management of Leydig cell tumors: results from a multicenter study.

OBJECTIVE: To compare the oncological outcomes of testicle-sparing surgery (TSS) and radical orchiectomy (RO) in patients with Leydig cell tumor (LCT) of the testis. PATIENTS AND METHODS: A multicenter retrospective clinical study was conducted in 12 centers in France. All the patients with histologically proven LCT were included and analyzed according to treatment (organ-sparing surgery or radical orchiectomy). Patients underwent preoperative clinical, biological and imaging assessment. Demographic, clinical, and pathological variables were collected at baseline and compared between groups according to surgical treatment. Follow-up was calculated using the reverse Kaplan-Meier estimation and was updated at the end of 2015. RESULTS: Between 1986 and 2014, 56 patients presented with LCT were identified and included in the study. Twenty-one patients (37.5%) underwent TSS and 35 (62.5%) RO. Demographics and tumor characteristics were not significantly different between the groups. Median follow-up was 62 months after TSS, but only 35 months after RO. Two patients (9.5%) developed local recurrence 15 and 34 months after TSS and underwent secondary RO. No local recurrence or metastasis was observed after complementary treatment. No recurrence was observed after RO. Disease-free survival did not differ between the groups (95.2% in TSS versus 77.1% in the RO group, p = 0.23). No patient died in the TSS group, but three patients (8.6%) in the RO group died from other diseases without evidence of relapse. One patient (4.8%) in the TSS group versus five (14.3%) in the RO group were lost to follow-up. CONCLUSION: Long-term follow-up suggests that testicle-sparing surgery does not compromise relapse-free survival in the treatment of Leydig cell tumor of the testis.

Correlation between prostate volume and single nucleotide polymorphisms implicated in the steroid pathway.

OBJECTIVES: A few preliminary studies have suggested a link between some genetics variants and benign prostatic hyperplasia (BPH). Our goal was to study the link between a set of single nucleotide polymorphisms (SNPs) implicated in the steroid pathway and accurate measurement of prostate volume in a cohort of men who underwent radical prostatectomy. METHODS: Clinical and pathological data including prostate weight were obtained from 611 Caucasian patients with small volume, localized prostate cancer treated by radical prostatectomy. Patients were genotyped for 90 SNPs located inside or nearby genes implicated in the steroid pathway (Sequenom iPLEX). Correlation between prostate weight and genotypes from each SNP was studied by analysis of covariance, adjusted on age and tumor stage. A Bonferroni correction was applied, and the SNPs implicated were then incorporated in a multivariable model. RESULTS AND LIMITATIONS: Seven SNPs located in or nearby genes implicated in steroid hormone metabolism were significantly associated with prostate volume: HSD17B2 (rs1119933), ESR2 (rs8006145), SULT2B1 (rs279451), NQO1 (rs2917670), ESR1 (rs1569788), GSTP1 (rs1138272), and CYP19A1 (rs17523880). Significant association was maintained after multivariate analysis for four SNPs, indicating their independent association with prostate volume. The power of the association of each SNP with prostate volume was comparable to the effect of age. The strongest associations were found with variants in ESR1, ESR2, HSD17B2, and CYP19A1 genes, indicating a potential role of the estrogen signaling pathway in genesis of BPH. CONCLUSIONS: Our results are in favor of an implication of estrogen biotransformation and signaling pathways in the pathophysiology of BPH.

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.

Capsular incision in normal prostatic tissue during robot-assisted radical prostatectomy: a new concept or a waste of time?

PURPOSE: Because radical prostatectomy with robot-assisted surgery can lead to unwanted prostatic capsular incisions, capsular incision in normal prostatic tissue (CINPT) is not rare. To study the relationship between positive surgical margins (PSM) and CINPT after robot-assisted radical prostatectomy. METHODS: From September 2009 to January 2013, 203 consecutive robot-assisted prostatectomies were carried out by the same surgeon. A transperitoneal Montsouris technique was used for all cases, but modified to suit the use of the four-arm DaVinci device. The data were recorded prospectively in our database. Preoperative data were patient's age, body mass index, prostate-specific antigen level, prostate weight, percentage of positive biopsy, clinical stage, and Gleason score. Postoperative data were preservation of the bladder neck and neurovascular bundles (NVB), the presence of extended pelvic lymph-node dissection (ePLND), pathological stage, Gleason score, margin status, blood loss, and operative room times. The CINPT and no-CINPT groups were analysed and compared retrospectively. RESULTS: The CINPT rates were 23.2 versus 18.2 % for PSM. CINPT contrary to PSM seemed to be more frequent in low-risk prostate cancer. NVB preservation led to more CINPT (p = 0.01). At the multivariate analysis, only the absence of ePLND significantly affected the CINPT status (p = 0.03) and the absence of CINPT positively affected the PSM rate (p = 0.03). CONCLUSIONS: Capsular incision in normal prostatic tissue is not a predictive factor of PSM but reflected risk-taking during surgery especially when NVB preservation is indicated in low-risk prostate cancer. It can therefore only be considered a means to evaluate a surgical technique, but not a real predictor of PSM.

Carboplatin and Etoposide for the Treatment of Metastatic Prostate Cancer with or without Neuroendocrine Features: A French Single-Center Experience.

BACKGROUND: Chemotherapy using carboplatin and etoposide (CE) is frequently pragmatically proposed to treat metastatic prostate cancer (mPC), both primary small-cell neuroendocrine (PSC-NE) carcinoma and adenocarcinoma with or without neuroendocrine (NE) marker elevation. However, the real benefit of CE is poorly reported in the recent therapeutic context. METHODS: We retrospectively analyzed the efficacy and tolerance of CE chemotherapy in these three different groups of mPC patients. Efficacy endpoints included radiological response, progression-free survival (PFS), and overall survival (OS), as well as PSA response and PFS2/PFS1 ratio in patients with adenocarcinoma. RESULTS: Sixty-nine patients were included in this single-center study (N = 18 with PSC-NE carcinoma and 51 with adenocarcinoma with (N = 18) or without (N = 33) NE marker elevation). Patients with adenocarcinoma were highly pretreated with next-generation hormonal agents (NHAs) and taxanes. In patients with adenocarcinoma, a PSA response ≥50% was observed in six patients (15.8%), four of whom had NE marker elevation. The radiological response was higher in PSC-NE and tended to be higher in adenocarcinoma when NE marker elevation was present. Comparing patients with adenocarcinoma with vs. without NE marker elevation, the median PFS was 3.7 and 2.1 months and the median OS was 7.7 and 4.7 months, respectively. Overall, 62.3% of patients experienced grade 3-4 adverse events (mainly hematological), and three treatment-related deaths were recorded. CONCLUSION: Reports of the clinical results of CE suggest that we should not mix PSC-NE and castration-resistant adenocarcinoma of the prostate. In patients with heavily pretreated adenocarcinoma, the benefit/risk ratio of CE chemotherapy seems unfavorable due to poor response and high toxicity.

Intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinomas: predictors and impact on subsequent oncological outcomes from a national multicenter study.

OBJECTIVES: To identify predictive factors and assess the impact on oncological outcomes of intravesical recurrence after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). METHODS: Using a national multicentric retrospective dataset, we identified all patients with UTUC who underwent a RNU between 1995 and 2010 (n = 482). Intravesical recurrence was tested as a prognostic factor for survival through univariable and multivariable Cox regression analysis. RESULTS: Overall, intravesical recurrence occurred in 169 patients (35 %) with a median age of 69.2 years (IQR: 60-76) and after a median follow-up of 39.5 months (IQR: 25-60). Actuarial intravesical recurrence-free survival estimates at 2 and 5 years after RNU were 72 and 45 %, respectively. On univariable analyses, previous history of bladder tumor, tumor multifocality, laparoscopic approach, pathological T-stage, presence of concomitant CIS and lymphovascular invasion were all associated with intravesical recurrence. On multivariable analysis, previous history of bladder cancer, tumor multifocality and laparoscopic approach remained independent predictors of intravesical recurrence. Existence of intravesical recurrence was not correlated with worst oncological outcomes in terms of disease recurrence (p = 0.075) and cancer-specific mortality (p = 0.06). CONCLUSIONS: In the current study, intravesical recurrence occurred in 35 % of patients with UTUC after RNU. Previous history of bladder cancer, tumor multifocality, concomitant CIS and laparoscopic approach were independent predictors of intravesical recurrence. These findings are in line with recent published data and should be considered carefully to provide a definitive surveillance protocol regarding management of urothelial carcinomas regardless of the location of urothelial carcinomas in the whole urinary tract.

The impact of lymph node status and features on oncological outcomes in urothelial carcinoma of the upper urinary tract (UTUC) treated by nephroureterectomy.

PURPOSE: Prognostic impact of lymphadenectomy during radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UTUC) is controversial. Our aim was to assess the impact of lymph node status (LNS) on survival in patients treated by RNU. METHODS: In our multi-institutional, retrospective database, 714 patients with non-metastatic UTUC had undergone RNU between 1995 and 2010. LNS was tested as prognostic factor for survivals through univariate and multivariable Cox regression analysis. RESULTS: Median age was 70 years [interquartile range (IQR), 60-75] with median follow-up of 27 months (IQR, 10-50). Overall, lymphadenectomy was performed in 254 patients (35.5 %). Among these patients, 204 (80 %) had negative lymph nodes (pN0) and 50 (20 %) had positive lymph nodes (pN1/2). The 5-year cancer-specific survival (CSS) was 81 % [95 % confidence interval (CI), 73-88 %] for pN0 patients, 85 % (95 % CI, 80-90 %) for pNx patients and 47 % (95 % CI, 24-69 %) for pN1/2 patients (p < 0.001). Metastasis-free survival (MFS) and overall survival (OS) rates were significantly lower in pN1/2 patients than in pN0 and pNx patients (p < 0.05). On multivariable analysis, LNS did not appear as an independent prognostic factor for CSS, OS or MFS (p > 0.05). In case of lymph node involvement, extra-nodal extension was marginally associated with worse CSS (log rank p = 0.07). The retrospective design was the main limitation. CONCLUSION: LNS is helpful for survival stratification in patients treated with RNU for UTUC. However, LNS did not appear as an independent predictor of survival in this retrospective series and needs to be investigated in a large multicentre, prospective evaluation.

Role of magnetic resonance imaging for preoperative prediction of early biochemical failure in localized prostate cancer.

Background: The purpose of our study was to assess preoperative clinical biological and Magnetic Resonance Imaging (MRI) predictive factors of early biochemical failure (BF), defined as persistence of significant post-operative plasmatic prostate specific antigen (PSA) level after radical prostatectomy (RP) in patients with localized prostate cancer (PCa). Methods: In a retrospective cohort study we included 142 patients from our university hospital with newly diagnosed PCa, who underwent 3T multiparametric MRI prior to RP. Only the MRI target lesions [Prostate Imaging Reporting and Data System (PIRADS) ≥3] with histological correspondence were considered significant. Clinical, biological, MRI and pathological preoperative data were studied. We performed univariate and multivariate logistic regression analysis to identify significant parameters associated with early BF. Results: Early BF occurred in 14% of patients (20/142). Patients with BF had higher PSA level at diagnosis, Gleason score, number of positive biopsies, size of the largest positive biopsy and higher National Comprehensive Cancer Network (NCCN) risk score (P<0.001 for all). According to MRI, they also had higher T stage and a higher size of capsular contact (P<0.001 for all). In contrast, there was no difference concerning neither ADC value, perfusion profile and zonal location of the index lesion. In multivariate analysis, the best combination of predictive factors of early BF was the association of preoperative Gleason score ≥4+3 [odds ratio (OR) =6.8 (1.4-32.5); P=0.002] and T stage ≥3 on preoperative MRI [OR =17.4 (3.2-94.9); P<0.001] with an area under the curve (AUC) of 0.89 [99% confidence interval (CI): 0.77-1], a negative predictive value of 94% and a positive predictive value of 75%. Conclusions: Combination of simple preoperative biomarkers as Gleason score and T stage according to MRI accurately stratify the risk of early BF following RP. These results emphasize the pivotal role of preoperative MRI for the management of localized PCa.

The Safety and Efficacy of Salvage Stereotactic Radiation Therapy in Patients with Intraprostatic Tumor Recurrence After Previous External Radiation Therapy: Phase 1 Results from the GETUG-AFU 31 Study.

BACKGROUND: There is no consensus on the best local salvage treatment for prostate cancer recurrence after primary external beam radiotherapy. Prospective data on stereotactic body radiation therapy (SBRT) are very scarce. OBJECTIVE: To determine the optimal dose regimen for salvage SBRT. DESIGN, SETTING, AND PARTICIPANTS: The present report concerns the phase 1 part of the GETUG-AFU 31 multicenter open-label study. The main inclusion criteria were histologically proven biochemical recurrence, clinical stage T1-T2 upon relapse, multiparametric magnetic resonance imaging data, prostate-specific antigen (PSA) level ≤10 ng/ml prior to salvage SBRT, PSA doubling time >10 mo, and an International Prostate Symptom Score of ≤12. INTERVENTION: Five or six fractions of 6 Gy were delivered using focal SBRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Dose-limiting toxicity (DLT) was defined as grade ≥3 gastrointestinal or genitourinary tract toxicity, or any grade 4 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03) occurring in the first 18 wk following treatment initiation. A time-to-event continual reassessment method was used to select the dose regimen. RESULTS AND LIMITATIONS: Twenty-one patients were treated (median [interquartile range] age: 76.8 yr [72.2-80.8]), including 12 at 6 × 6 dose level. No DLT was observed. The acute grade 2 genitourinary tract toxicity rate was 19%. With a median follow-up of 12.3 mo, the estimated cumulative incidence of late grade 2 genitourinary toxicity was 41.2% (95% confidence interval: 18.1-63.1%). No grade >2 genitourinary toxicity and no grade ≥2 gastrointestinal toxicity were reported. All treated patients were alive and relapse free at the last follow-up. CONCLUSIONS: A 6 × 6 Gy dose regimen was selected for our phase 2 study of salvage SBRT. With a short follow-up period, the level of toxicity appears to be acceptable. PATIENT SUMMARY: There is no consensus on the best local treatment for patients with local relapse after radiotherapy for prostate cancer. Prospective data are very scarce. Our early phase trial allowed us to recommend six fractions of 6 Gy using high-precision radiotherapy for further studies.

Anterior suspension combined with posterior reconstruction during robot-assisted laparoscopic prostatectomy improves early return of urinary continence: a prospective randomized multicentre trial.

UNLABELLED: What's known on the subject? and What does the study add? Urinary incontinence is one of the major drawbacks of radical prostatectomy, regardless of the procedure used (i.e. open, laparoscopic or robotic-assisted). Several technical modifications have been described to improve postoperative continence, highlighting the role of puboprostatic ligaments and posterior reconstruction of the rhabdomyosphincter. The results obtained are inconsistent when applied to robotic surgery. The present multicentre randomized study shows that anterior suspension combined with posterior reconstruction is a safe and easy-to-perform technique for improving early continence after robotic-assisted laparoscopic prostatectomy. OBJECTIVE: To assess the impact on urinary continence of anterior retropubic suspension with posterior reconstruction during robot-assisted laparoscopic prostatectomy (RALP). PATIENTS AND METHODS: In total, 72 patients who were due to undergo prostatectomy between July 2009 and July 2010 were prospectively randomized into two groups: group A underwent a standard RALP procedure and group B had anterior suspension and posterior reconstruction during RALP. The primary outcome measure was urinary continence, assessed using the University of California Los Angeles Prostate Cancer Index questionnaire at 15 days, and at 1, 3 and 6 months, after surgery. Other data recorded were operation duration, blood loss, length of hospital stay, duration of bladder catheterization, complications and positive margin rate. RESULTS: The continence rates at 15 days, and at 1, 3 and 6 months, after surgery were 3.6%, 7.1%, 15.4% and 57.9%, respectively, in group A, and 5.9%, 26.5%, 45.2% and 65.4%, respectively, in group B. The continence rates differed statistically between groups at 1 and 3 months (P = 0.047 and P = 0.016, respectively). There was no significant difference between groups regarding complications (P = 0.8) or positive margin rate (P = 0.46). CONCLUSION: Anterior suspension associated with posterior reconstruction during RALP improved the early return of continence, without increasing complications.

A proportion of hereditary upper urinary tract urothelial carcinomas are misclassified as sporadic according to a multi-institutional database analysis: proposal of patient-specific risk identification tool.

UNLABELLED: What's known on the subject? and What does the study add? Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant multi-organ cancer syndrome. Upper urinary tract urothelial carcinomas belong to HNPCC-related tumours and rank third within this group after colorectal and endometrial cancer. However, many urologists are not aware of this association and it is presumed that some hereditary cancers are misclassified as sporadic and that their incidence is underestimated. Consequently, family members of patients with upper urinary tract urothelial carcinomas secondary to HNPCC may be denied appropriate surveillance and early detection. A significant proportion of patients (21.3%) with newly diagnosed upper urinary tract urothelial carcinomas may have underlying HNPCC. Demographic and epidemiological characteristics suggest different mechanisms of carcinogenesis among this population. Recognition of such potential is essential for appropriate clinical and genetic management of patients and family. In order to help to identify these patients, we propose a patient-specific checklist. OBJECTIVE: • To identify, based on previously described clinical criteria, hereditary upper urinary tract urothelial carcinomas (UUT-UCs) that are likely to be misclassified as sporadic although they may belong to the spectrum of hereditary non-polyposis colorectal cancer (HNPCC) associated cancers. PATIENTS AND METHODS: • We identified, using established clinical criteria, suspected hereditary UUT-UC among 1122 patients included in the French national database for UUT-UC. • Patients were considered at risk for hereditary status in the following situations: age at diagnosis <60 years with no previous history of bladder cancer; previous history of HNPCC-related cancer regardless of age; one first-degree relative with HNPCC-related cancer diagnosed before 50 years of age or two first-degree relatives diagnosed regardless of age. RESULTS: • Overall, 239 patients (21.3%) were considered to be at risk of hereditary UUT-UC. • Compared with sporadic cases, hereditary cases are more likely to be female (P= 0.047) with less exposure to tobacco (P= 0.012) and occupational carcinogens (P= 0.037). A greater proportion of tumours were located in the renal pelvis (54.5% vs 48.4%; P= 0.026) and were lower grade (40% vs 30.1%; P= 0.015) in the hereditary cohort. • The overall, cancer-specific and recurrence-free survival rates were similar in both cohorts. • We propose a patient-specific risk identification tool. CONCLUSIONS: • A significant proportion (21.3%) of patients with newly diagnosed UUT-UC may have underlying HNPCC as a cause. • Recognition of such potential and application of a patient-specific checklist upon diagnosis will allow identification and appropriate clinical and genetic management for patient and family.

Robot-assisted or pure laparoscopic nerve-sparing radical prostatectomy: what is the optimal procedure for the surgical margins? A single center experience.

OBJECTIVES: To compare positive surgical margin rates after robot-assisted and pure laparoscopic radical prostatectomy when neurovascular bundles are preserved, and to identify parameters affecting surgical margin status. METHODS: From March 2004 to January 2009, 279 consecutive prostatectomies with preservation of neurovascular bundles were carried out by the same surgeon: 175 robot-assisted radical prostatectomies and 104 laparoscopic radical prostatectomies. An intraperitoneal Montsouris's technique was used for all cases. Patient's age, body mass index, prostate weight, prostate-specific antigen level, clinical stage, preoperative and postoperative Gleason score, percentage of positive biopsies, pathological stage, and positive surgical margin status were prospectively recorded in an institutional database. The two groups were retrospectively analyzed and compared. RESULTS: Positive surgical margin rates were 17% and 13% for the robot-assisted radical prostatectomy and laparoscopic radical prostatectomy group (P = 0.4), respectively. At multivariable analysis, only prostate-specific antigen level and prostate weight significantly affected the surgical margin status, where the type of procedure (robotic vs laparoscopic) did not have any effect. CONCLUSION: In our single-surgeon experience, prostate-specific antigen levels and prostate weight are predictive of positive surgical margin in patients undergoing nerve-sparing radical prostatectomy, whereas there seems to be no difference between the robot-assisted radical prostatectomy and the laparoscopic radical prostatectomy techniques.

Prediction of prostate cancer recurrence after radiation therapy using multiparametric magnetic resonance imaging and spectroscopy: assessment of prognostic factors on pretreatment imaging.

Background: To assess whether data from pre-therapeutic multiparametric magnetic resonance imaging (mpMRI) combined with three-dimensional magnetic resonance spectroscopy (3D MRS) provide prognostic factors of biochemical relapse in patients with localized prostate cancer treated by external radiotherapy or brachytherapy. Methods: In our single institution observational retrospective study we included a cohort of 230 patients treated by external radiotherapy or brachytherapy who had an initial mpMRI with 3D MRS from January 2008 to December 2015 for newly diagnosed localized prostatic cancer, proven histologically. Three trained radiologists recorded tumor characteristics, MRI T-stage and metabolic abnormalities from 3D MRS data. Univariate and multivariate Cox analyzes explored the relationship between clinical and imaging variables to highlight prognostic factors for recurrence, using biochemical relapse as the primary endpoint. Results: mpMRI data analysis allowed to reclassify 21.7% of the patients in a MRI National Comprehensive Cancer Network (NCCN) group higher than their initial clinical T-stage, but also to detect a lesion in 78% of the patients considered as clinically T1c. After a median of follow-up of 8.7 years (IQR, 6.6-10.1) following cancer diagnosis, 36 (16%) patients developed a biochemical relapse. The multivariate Cox analysis demonstrated the existence of 3 independent factors for prediction of biochemical recurrence: extracapsular extension (ECE) (HR =3.33; 95% CI: 1.93-5.73; P<0.01), choline/citrate ratio in healthy tissue in the transition zone (TZ) (HR =2.96; 95% CI: 1.06-8.28; P=0.04) and the NCCN Magnetic Resonance Imaging classification (intermediate versus low-risk, HR =3.06; 95% CI: 1.13-8.30; P<0.01). Conclusions: Combination of mpMRI and 3DMRS could aid in the prognostic stratification of localized prostate cancer treated by radiotherapy or brachytherapy, by combining accurate evaluation of tumor extension, and quantification of prostate metabolism.

Automatic Evaluation of Histological Prognostic Factors Using Two Consecutive Convolutional Neural Networks on Kidney Samples.

BACKGROUND AND OBJECTIVES: The prognosis of patients undergoing kidney tumor resection or kidney donation is linked to many histologic criteria. These criteria notably include glomerular density, glomerular volume, vascular luminal stenosis, and severity of interstitial fibrosis/tubular atrophy. Automated measurements through a deep-learning approach could save time and provide more precise data. This work aimed to develop a free tool to automatically obtain kidney histologic prognostic features. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 241 samples of healthy kidney tissue were split into three independent cohorts. The "Training" cohort (n=65) was used to train two convolutional neural networks: one to detect the cortex and a second to segment the kidney structures. The "Test" cohort (n=50) assessed their performance by comparing manually outlined regions of interest to predicted ones. The "Application" cohort (n=126) compared prognostic histologic data obtained manually or through the algorithm on the basis of the combination of the two convolutional neural networks. RESULTS: In the Test cohort, the networks isolated the cortex and segmented the elements of interest with good performances (>90% of the cortex, healthy tubules, glomeruli, and even globally sclerotic glomeruli were detected). In the Application cohort, the expected and predicted prognostic data were significantly correlated. The correlation coefficients r were 0.85 for glomerular volume, 0.51 for glomerular density, 0.75 for interstitial fibrosis, 0.71 for tubular atrophy, and 0.73 for vascular intimal thickness, respectively. The algorithm had a good ability to predict significant (>25%) tubular atrophy and interstitial fibrosis level (receiver operator characteristic curve with an area under the curve, 0.92 and 0.91, respectively) or a significant vascular luminal stenosis (>50%) (area under the curve, 0.85). CONCLUSION: This freely available tool enables the automated segmentation of kidney tissue to obtain prognostic histologic data in a fast, objective, reliable, and reproducible way.

Impact of genotyping on outcome of prostatic biopsies: a multicenter prospective study.

Single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk and tumor aggressiveness in retrospective studies. To assess the value of genotyping in a clinical setting, we evaluated the correlation between three genotypes (rs1447295 and rs6983267[8q24] and rs4054823[17p12]) and prostatic biopsy outcome prospectively in a French population of Caucasian men. Five hundred ninety-eight patients with prostatic-specific antigen (PSA) >4 ng/mL or abnormal digital rectal examination (DRE) participated in this prospective, multicenter study. Age, familial history of PCa, body mass index (BMI), data of DRE, International Prostate Symptom Score (I-PSS) score, PSA value and prostatic volume were collected prospectively before prostatic biopsy. Correlation between genotypes and biopsy outcome (positive or negative) and Gleason score (≤6 or >6) were studied by univariate and multivariable analysis. rs1447295 and rs6983267 risk variants were found to be associated with the presence of PCa in univariate analysis. rs6983267 genotype remained significantly linked to a positive biopsy (odds ratio [OR] = 1.66, 95% confidence interval [CI]: 1.06-2.59, P = 0.026) in multivariable analysis, but rs1447295 genotype did not (OR = 1.47, 95% CI: 0.89-2.43, P = 0.13).When biopsy outcome was stratified according to Gleason score, risk variants of rs1447295 were associated with aggressive disease (Gleason score ≥7) in univariate and multivariable analysis (OR = 2.05 95% CI: 1.10-3.79, P = 0.023). rs6983267 GG genotype was not related to aggressiveness. The results did not reach significance concerning rs4054823 for any analysis. This inaugural prospective evaluation thus confirmed potential usefulness of genotyping PCa assessment. Ongoing clinical evaluation of larger panels of SNPs will detail the actual impact of genetic markers on clinical practice.

Visceral fat area as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with antiangiogenic agents.

Purpose. A better identification of patients who are more likely to benefit from vascular endothelial growth factor-targeted therapy is warranted in metastatic renal cell carcinoma (mRCC). As adipose tissue releases angiogenic factors, we determined whether parameters such as visceral fat area (VFA) were associated with outcome in these patients. Experimental Design. In 113 patients with mRCC who received antiangiogenic agents (bevacizumab, sunitinib, or sorafenib) (n = 64) or cytokines (n = 49) as first-line treatment, we used computed tomography to measure VFA and subcutaneous fat area (SFA). We evaluated associations linking body mass index (BMI), SFA, and VFA to time to progression (TTP) and overall survival (OS). Results. High SFA and VFA values were significantly associated with shorter TTP and OS. By multivariate analysis, high VFA was independently associated with shorter TTP and OS. These results were internally validated using bootstrap analysis. By contrast, VFA was not associated with survival in the cytokine group. In the whole population, interaction between VFA and treatment group was significant for TTP and OS, thereby confirming the results. Conclusion. Our study provides the first evidence that high VFA could be a predictive biomarker from shorter survival in patients given first-line antiangiogenic agents for mRCC.

Oncologic outcomes and survival in pT0 tumors after radical cystectomy in patients without neoadjuvant chemotherapy: results from a large multicentre collaborative study.

PURPOSE: To assess the postsurgical survival of patients with urothelial carcinoma of the bladder with pT0 tumor at pathologic examination of cystectomy specimens. METHODS: A multi-institutional, retrospective database was analyzed with data from 4758 radical cystectomy (RC) patients who underwent RC without neoadjuvant chemotherapy and who were diagnosed with pT0 on the basis of the pathologic specimen. Survival curves were estimated. A multivariate Cox model was used to evaluate the association between prognosis factors and disease recurrence or survival. RESULTS: Overall, 258 patients (5.4%) were included in the study. The median age was 64 years. At last resection, 171 tumors were invasive (at least pT2), and 87 were not. Median follow-up was 51 months. At multivariate analysis, initial location of the tumor and absence of lymphadenectomy were associated with tumor recurrence (P = 0.03 and P = 0.005, respectively) and specific mortality (P = 0.005 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of this situation. Cancer-specific and recurrence-free survival rates were 89 and 85%, respectively, at 5 years and 82 and 80%, respectively, at 10 years. CONCLUSIONS: Despite acceptable oncological outcomes, patients with a pT0 tumor at the time of RC are still at risk of recurrence and progression and should not be considered to be entirely cured. In this population, stringent follow-up according to current recommendations should be effective.