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.

Research on texture images and radiomics in urology: a review of urological MR imaging applications.

PURPOSE OF REVIEW: Tumor volume and heterogenicity are associated with diagnosis and prognosis of urological cancers, and assessed by conventional imaging. Quantitative imaging, Radiomics, using advanced mathematical analysis may contain information imperceptible to the human eye, and may identify imaging-based biomarkers, a new field of research for individualized medicine. This review summarizes the recent literature on radiomics in kidney and prostate cancers and the future perspectives. RECENT FINDINGS: Radiomics studies have been developed and showed promising results in diagnosis, in characterization, prognosis, treatment planning and recurrence prediction in kidney tumors and prostate cancer, but its use in guiding clinical decision-making remains limited at present due to several limitations including lack of external validations in most studies, lack of prospective studies and technical standardization. SUMMARY: Future challenges, besides developing prospective and validated studies, include automated segmentation using artificial intelligence deep learning networks and hybrid radiomics integrating clinical data, combining imaging modalities and genomic features. It is anticipated that these improvements may allow identify these noninvasive, imaging-based biomarkers, to enhance precise diagnosis, improve decision-making and guide tailored treatment.

Dose to the penile bulb and individual patient anatomy are predictive of erectile dysfunction in men treated with 125I low dose rate brachytherapy for localized prostate cancer.

Background: To evaluate the occurrence of erectile dysfunction at 3 years (3yED) after prostate brachytherapy (BT) and to predict 3yED after treatment based on patients and treatments characteristics. Material and methods: From September 2007 to July 2015, 117 men with mild or no ED [International Index of Erectile Function (IIEF-5) > 16] underwent 125Iodine real-time ultrasound-guided low-dose rate BT to a total dose of 160 Gy for low-risk or favorable intermediate-risk prostate adenocarcinoma, and were followed prospectively during 3 years. Median age was 63 years (51-79). The post-implant dosimetric parameters on the postoperative computer tomography were derived from the dose-volume histogram of the prostate and the penile bulb (PB), crura, neurovascular bundles (NVBs) and internal pudendal arteries (IPAs). Potential clinical confounding factors were collected. Additionally, anatomical indexes reflecting the prostate anatomical location within the pelvis were studied. These variables were compared between patients with and without 3yED. 3yED was defined as an IIEF-5 score change to the lower category between baseline, with or without medication. Results: The 3yED rate was 59% (62% maintained an IIEF-5 > 16). On multivariate analysis, prostate D90% (p > .5) and pretreatment characteristics including age (p > .5), pre-implant potency (p > .5), diabetes (p = .08) and high cardiovascular risk rates (p = .1) did not influence the occurrence of 3yED. Only the PB dose especially the D10% > 51 Gy was associated with 3yED (p = .005). Conversely, dose to the crura, IPAs or NVBs did not seem to impact the erectile function. The prostate position, especially the apex location varied significantly between potent and impotent patients and 3yED was significantly associated with close position of the prostate apex to PB (p = .008). Conclusion: The most predictive factor of 3yED was the dose to the PB. This may be explained by variation in individual patients' anatomy and this could allow for the development of better strategies to prevent ED.

Target definition in salvage postoperative radiotherapy for prostate cancer: 18F-fluorocholine PET/CT assessment of local recurrence.

PURPOSE: Inadequate clinical target volume (CTV) definition is likely to be a major contributing factor to local recurrence (LR) rate after radiotherapy. Our aims were to identify sites of prostate cancer LR in biochemical recurrence post-prostatectomy using 18F-Fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) and to compare different CTV-delineation guidelines in a cohort of postoperative patients. MATERIAL AND METHODS: Thirty-six patients presenting with LR within the prostatic bed on 18F-FCH PET/CT between 10/2011 and 06/2016 were included in this retrospective study. Median PSA at the time of 18F-FCH PET/CT was 2.7 ng/mL (0.8-9.4) and median PSA doubling time was 11 months (3-28). For each patient, the CTVRTOG, CTVFROGG and CTVEORTC following the corresponding guidelines were outlined and compared. Forty-one LR were delineated using a gradient-based method and the percentage of FCH uptake included in each CTV was evaluated. RESULTS: The anastomosis was the most common recurrence site (52.8%), followed by the retrovesical region (31.7%) and the bladder neck (7%). The median SUV max value was 4.8 (2.3-16.1). The percentage of LR entirely included in the CTVRTOG was not significantly different from that included in the CTVFROGG (84% versus 83%, p = .5). Significantly more recurrences were included in the CTVRTOG volume compared to the CTVEORTC (84% versus 68%, p=.006), due to a better coverage of the bladder neck and retrovesical regions. Six out of 10 relapses occurring in the posterior region of the anastomosis were not covered by any of the CTVs. CONCLUSIONS: In our study, the CTVRTOG and CTVFROGG ensured the best coverage of LR seen on 18F-FCH PET/CT. When outlining the prostatic fossa, greater coverage of the posterior vesico-urethral region may allow better coverage of potential microscopic disease.

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.

Genome-wide association study of prostate cancer identifies a second risk locus at 8q24.

Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 x 10(-13); heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13-1.41; homozygote OR: 1.58, 95% c.i.: 1.40-1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 x 10(-11); rs6983267 P = 6.62 x 10(-10)). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%).

Anti-alpha-actinin antibodies are part of the anti-cell membrane antibody spectrum that characterize patients with lupus nephritis.

Anti-membrane autoantibodies (MbA) have been reported in sera from patients with lupus nephritis (LN) but the targets of the MbA remain to be explored, which is the aim of the current study. Sera were collected from 40 patients with LN determined by renal biopsy, and from 30 systemic lupus erythematosus (SLE) patients without clinical evidence of LN. Thirty autoimmune disease control patients (rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis), and 30 healthy controls were also included. Using flow cytometry, the presence of anti-MbA was explored revealing that IgG anti-MbA positivity was associated with LN (62.5% vs 13.3%) when compared to non-LN SLE patients, autoimmune disease patients (6.7%) and healthy controls (0%). Next, using purified plasma membrane fractions from human embryonic kidney (HEK) cells, the more prominent targets and their occurrence rates were located at 50 kDa, 60/65 kDa, 90 kDa, 110 kDa, 180 kDa and 220 kDa. Alpha-actinin (110 kDa) autoAb was characterized as a major target in LN patients positive for anti-MbA, and anti-MbA binding activity was reduced (36.9 ± 13.7%) in the presence of α-actinin. Laminin (200 kDa) was also characterized as a minor target, which was not the case for annexin A2 (36 kDa). Finally, anti-MbA IgG subclass analysis indicated a predominance of IgG2. In conclusion, IgG anti-MbA were detected at high levels in LN patients supporting a primary pathogenic role for anti-MbA and anti-MbA/α-actinin+ in LN that needs further research.

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.

Impact of micropapillary histological variant on survival after radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: To assess the impact of micropapillary histological variant on oncological outcome after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinomas (UTUCs). METHODS: A French multicenter retrospective study was performed on patients who underwent RNU between 1995 and 2010. Pathological reports were reviewed to identify patients with pure urothelial carcinomas (PUC) and those with micropapillary histological variant (MPC). Uni- and multivariate Cox regression analyses were performed to identify factors predictive of survival. RESULTS: Overall, 519 patients were included and divided into two groups: 480 PUC and 39 MPC. Median follow-up were 28 and 19 months, respectively (p = 0.63). There was no difference between the two groups for gender, age and tumor location (pelvicalyceal or ureteral). MPC was associated with high-stage and high-grade UTUC (p < 0.001 and 0.04). No difference was observed between the two groups for 5-year cancer-specific survival (76.1 vs. 88.2 %; p = 0.54). The 5-year metastasis-free survival was significantly lower in the MPC group (48.9 vs. 73.8 %; p = 0.037). In multivariate analysis, pT stage, lymphovascular invasion, margin status and adjuvant chemotherapy administration were independent predictors of specific survival (p = 0.002; 0.001; 0.02; 0.01), contrary to histological variant (p = 0.94). CONCLUSIONS: Micropapillary histological variant was associated with advanced UTUC and reduced metastasis-free survival after RNU. It should be considered as an aggressive tumor and thus be stated in any pathological report after radical surgery.

Risk stratification of metastatic recurrence in invasive upper urinary tract carcinoma after radical nephroureterectomy without lymphadenectomy.

PURPOSE: To assess the risk factors of metastasis relapse in pT2-3 upper tract urothelial carcinomas (UTUCs) treated by radical nephroureterectomy (RNU) without lymphadenectomy (LN). METHODS: A multicentric retrospective study was performed for pT2-3 pNx UTUCs treated by RNU between 1995 and 2010. The following criteria were retrieved: age, gender, American Society of Anaesthesiologists physical status, surgical approach, preoperative hydronephrosis, stage, grade, tumor location, surgical margin, lymphovascular invasion (LVI) status and outcomes. Metastasis-free survival (MFS) was measured by Kaplan-Meier method with the log-rank test. RESULTS: Overall, 151 patients were included. The median follow-up was 18.5 months (IQR 9.5-37.9). The 2- and 5-year MFS were 69 % ± 4.5 and 54.1 % ± 5.8, respectively. In univariate analysis, ureteral location, pT3 stage, positive LVI status and positive surgical margin were significantly associated with worse MFS (p = 0.03; 0.02; 0.01 and 0.006, respectively). In the multivariate analysis of ureteral location and pT3 stage were independent prognostic factors (p = 0.03 and 0.03, respectively). Based on the results of the univariate analysis, we proposed a risk model predicting MFS, which classifies patients into 3 categories with different overall survival (p < 0.001). CONCLUSION: In view of our data, tumor location, T stage, LVI and surgical margin status are mandatory to predict survival in case of RN without LN. Contingent upon external validation, our risk model based on these variables could be useful to provide relevant information concerning metastasis relapse probability and necessity of close follow-up for these patients.