Ethnic differences in prostate cancer presentation: a time for testing advocacy.

PURPOSE: It is recognised that there are ethnic variations in prostate cancer (PCa) epidemiology, affecting outcomes. South Asians (SA) are less likely to be diagnosed with PCa than others, although recent evidence shows PCa is rising amongst SA. This study examines the differences between ethnicities in PCa presentation, progression risk and prostate-specific antigen (PSA) testing use. METHODS: This retrospective study is on biopsy-diagnosed PCa patients from a multi-ethnic area in London. We grouped ethnicities as SA, White, Black and others, compared presenting symptoms, PSA, Gleason score (GS), and clinical stage, and estimated the D'Amico risk across ethnicities. We also evaluated if the presentation was due to symptoms or an elevated PSA. RESULTS: We studied 1176 patients with biopsy-proven PCa. Black patients were diagnosed about 3 years before others (65 ± 8.8 years, p = < 0.001). There was no significant difference between ethnicities in presenting PSAs. At presentation, 65-71% were in the high-risk D'Amico category across all ethnicities. SA were least likely to have PSA test-detected cancers (38%, p = 0.001) and had the highest proportion with advanced GS (30.6%). There was no significant difference in the risk of disease progression between groups. CONCLUSION: Black men were diagnosed youngest. SA had the highest proportion with advanced GS. Most ethnicities had a high risk of progression. SA had the least PSA test-detected cases. The significance of the study lies in understanding ethnic variations in PCa, which could direct targeted prevention and management. We recommend further ethnicity studies and interventions encouraging SA men to embrace PSA testing.

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. METHODS: In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. RESULTS: A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). CONCLUSIONS: The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .).

Does urinary cytology have a role in haematuria investigations?

OBJECTIVES: To determine the diagnostic accuracy of urinary cytology to diagnose bladder cancer and upper tract urothelial cancer (UTUC) as well as the outcome of patients with a positive urine cytology and normal haematuria investigations in patients in a multicentre prospective observational study of patients investigated for haematuria. PATIENT AND METHODS: The DETECT I study (clinicaltrials.gov NCT02676180) recruited patients presenting with haematuria following referral to secondary case at 40 hospitals. All patients had a cystoscopy and upper tract imaging (renal bladder ultrasound [RBUS] and/ or CT urogram [CTU]). Patients, where urine cytology were performed, were sub-analysed. The reference standard for the diagnosis of bladder cancer and UTUC was histological confirmation of cancer. A positive urine cytology was defined as a urine cytology suspicious for neoplastic cells or atypical cells. RESULTS: Of the 3 556 patients recruited, urine cytology was performed in 567 (15.9%) patients from nine hospitals. Median time between positive urine cytology and endoscopic tumour resection was 27 (IQR: 21.3-33.8) days. Bladder cancer was diagnosed in 39 (6.9%) patients and UTUC in 8 (1.4%) patients. The accuracy of urinary cytology for the diagnosis of bladder cancer and UTUC was: sensitivity 43.5%, specificity 95.7%, positive predictive value (PPV) 47.6% and negative predictive value (NPV) 94.9%. A total of 21 bladder cancers and 5 UTUC were missed. Bladder cancers missed according to grade and stage were as follows: 4 (19%) were ≥ pT2, 2 (9.5%) were G3 pT1, 10 (47.6%) were G3/2 pTa and 5 (23.8%) were G1 pTa. High-risk cancer was confirmed in 8 (38%) patients. There was a marginal improvement in sensitivity (57.7%) for high-risk cancers. When urine cytology was combined with imaging, the diagnostic performance improved with CTU (sensitivity 90.2%, specificity 94.9%) superior to RBUS (sensitivity 66.7%, specificity 96.7%). False positive cytology results were confirmed in 22 patients, of which 12 (54.5%) had further invasive tests and 5 (22.7%) had a repeat cytology. No cancer was identified in these patients during follow-up. CONCLUSIONS: Urine cytology will miss a significant number of muscle-invasive bladder cancer and high-risk disease. Our results suggest that urine cytology should not be routinely performed as part of haematuria investigations. The role of urine cytology in select cases should be considered in the context of the impact of a false positive result leading to further potentially invasive tests conducted under general anaesthesia.

Performance Improvement (Pi) score: an algorithm to score Pi objectively during E-BLUS hands-on training sessions. A European Association of Urology, Section of Uro-Technology (ESUT) project.

OBJECTIVE: To evaluate the variability of subjective tutor performance improvement (Pi) assessment and to compare it with a novel measurement algorithm: the Pi score. MATERIALS AND METHODS: The Pi-score algorithm considers time measurement and number of errors from two different repetitions (first and fifth) of the same training task and compares them to the relative task goals, to produce an objective score. We collected data during eight courses on the four European Association of Urology training in Basic Laparoscopic Urological Skills (E-BLUS) tasks. The same tutor instructed on all courses. Collected data were independently analysed by 14 hands-on training experts for Pi assessment. Their subjective Pi assessments were compared for inter-rater reliability. The average per-participant subjective scores from all 14 proctors were then compared with the objective Pi-score algorithm results. Cohen's κ statistic was used for comparison analysis. RESULTS: A total of 50 participants were enrolled. Concordance found between the 14 proctors' scores was the following: Task 1, κ = 0.42 (moderate); Task 2, κ = 0.27 (fair); Task 3, κ = 0.32 (fair); and Task 4, κ = 0.55 (moderate). Concordance between Pi-score results and proctor average scores per participant was the following: Task 1, κ = 0.85 (almost perfect); Task 2, κ = 0.46 (moderate); Task 3, κ = 0.92 (almost perfect); Task 4 = 0.65 (substantial). CONCLUSION: The present study shows that evaluation of Pi is highly variable, even when formulated by a cohort of experts. Our algorithm successfully provided an objective score that was equal to the average Pi assessment of a cohort of experts, in relation to a small amount of training attempts.

The management of concomitant renal oncocytoma and giant coronary and bilateral common iliac artery aneurysms.

We present the rare case of a 66-year-old Caucasian male patient presenting with intermittent left-side abdominal pain. He underwent a kidneys, ureters, and bladder computed tomography scan on which an incidental 45-mm giant aneurysm of the left anterior descending coronary artery was discovered along with 55-mm right-sided and 62-mm left-sided common iliac artery aneurysms and a 100-mm benign renal oncocytoma. He underwent on-pump coronary artery bypass grafting of the left anterior descending, left circumflex and right coronary arteries using internal mammary artery and saphenous vein grafts. He subsequently underwent simultaneous open left nephrectomy and bilateral common iliac aneurysm repair using a bifurcated tube graft. He made a full recovery postoperatively. Giant coronary artery aneurysms are rare. In the pediatric population, they are predominantly secondary to Kawasaki disease. In adults, atheromatous disease is the leading cause. The coexistence of giant coronary artery aneurysms with extracoronary artery aneurysms is extremely unusual. We propose that the identification of giant coronary artery aneurysms necessitates further imaging investigations to identify the presence of extracoronary aneurysms. To our knowledge, this is the first description of such a case in the literature.

Probiotics, dendritic cells and bladder cancer.

What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette-Guérin).

Defining Factors Associated with High-quality Surgery Following Radical Cystectomy: Analysis of the British Association of Urological Surgeons Cystectomy Audit.

BACKGROUND: Radical cystectomy (RC) is associated with high morbidity. OBJECTIVE: To evaluate healthcare and surgical factors associated with high-quality RC surgery. DESIGN SETTING AND PARTICIPANTS: Patients within the prospective British Association of Urological Surgeons (BAUS) registry between 2014 and 2017 were included in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: High-quality surgery was defined using pathological (absence of positive surgical margins and a minimum of a level I lymph node dissection template with a minimum yield of ten or more lymph nodes), recovery (length of stay ≤10 d), and technical (intraoperative blood loss <500 ml for open and <300 ml for minimally invasive RC) variables. A multilevel hierarchical mixed-effect logistic regression model was utilised to determine the factors associated with the receipt of high-quality surgery and index admission mortality. RESULTS AND LIMITATIONS: A total of 4654 patients with a median age of 70.0 yr underwent RC by 152 surgeons at 78 UK hospitals. The median surgeon and hospital operating volumes were 23.0 and 47.0 cases, respectively. A total of 914 patients (19.6%) received high-quality surgery. The minimum annual surgeon volume and hospital volume of ≥20 RCs/surgeon/yr and ≥68 RCs/hospital/yr, respectively, were the thresholds determined to achieve better rates of high-quality RC. The mixed-effect logistic regression model found that recent surgery (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.11-1.34, p < 0.001), laparoscopic/robotic RC (OR: 1.85, 95% CI: 1.45-2.37, p < 0.001), and higher annual surgeon operating volume (23.1-33.0 cases [OR: 1.54, 95% CI: 1.16-2.05, p = 0.003]; ≥33.1 cases [OR: 1.64, 95% CI: 1.18-2.29, p = 0.003]) were independently associated with high-quality surgery. High-quality surgery was an independent predictor of lower index admission mortality (OR: 0.38, 95% CI: 0.16-0.87, p = 0.021). CONCLUSIONS: We report that annual surgeon operating volume and use of minimally invasive RC were predictors of high-quality surgery. Patients receiving high-quality surgery were independently associated with lower index admission mortality. Our results support the role of centralisation of complex oncology and implementation of a quality assurance programme to improve the delivery of care. PATIENT SUMMARY: In this registry study of patients treated with surgical excision of the urinary bladder for bladder cancer, we report that patients treated by a surgeon with a higher annual operative volume and a minimally invasive approach were associated with the receipt of high-quality surgery. Patients treated with high-quality surgery were more likely to be discharged alive following surgery.

Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial.

INTRODUCTION: Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone. METHODS: A phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. PRIMARY OUTCOME: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024. ETHICS AND DISSEMINATION: Approved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03763253; ISCRTN58401737.

Prostatic biopsy undergrading: the feasibility of secondary laparoscopic pelvic lymphadenectomy.

OBJECTIVES: Prostate biopsy grade is a key factor when deciding whether to perform pelvic lymph node dissection (PLND) at laparoscopic radical prostatectomy. In common with many laparoscopic radical prostatectomy centers, we perform PLND in patients found to have intermediate and high-risk prostate cancer based upon preoperative PSA, prostate biopsy and imaging. We assessed the feasibility of performing a secondary laparoscopic PLND 6 weeks postoperatively in the presence of postoperative upgrading in patients who did not have PLND. METHODS: A prospective study recording the pathological results and operative outcomes prospectively over a 10-month period during which 24 patients underwent a secondary PLND. All patients had a preoperative PSA level <10 ng/ml and biopsy Gleason score of ≤6 (3 + 3) and the prostatectomy specimen was subsequently found to have a Gleason score of ≥7 (4 + 3) or increased stage. RESULTS: During the 10-month period, 377 prostatectomies were carried out in our department in which 54 (18.3%) had an upgrading in the prostatectomy specimen. 24 patients (mean age 60 and mean PSA 6.7 ng/ml) agreed to a secondary PLND. No lymph nodes metastases were observed. One patient who was sexually potent following a nerve-sparing prostatectomy was impotent after the secondary PLND. CONCLUSIONS: Upgrading of prostate Gleason score is seen in up to a third of cases in many large published series that is reflected in our experience. A laparoscopic secondary lymphadenectomy is feasible with low morbidity and yields valuable pathological clinical staging for subsequent surveillance and therapy for these high-risk patients.

Teaching laparoscopy to residents: how can we select good candidates?

Modern medicine incorporates minimally invasive approaches in virtually all areas of surgery, and its application will continue to expand. The laparoscopic approach to many complex procedures is accompanied by a long learning curve that is not easily overcome or bypassed. Current training methods involve box trainers, virtual reality simulators, and live animal models that all attempt to replicate laparoscopic scenarios with varying degrees of success. The emphasis in training is now on intensive fellowship courses in high-volume centers that may overcome the learning curves associated with de novo development of laparoscopy. The many attempts to devise tools to assess laparoscopic skills have at best served as tests to discriminate between existing skill levels but do not provide a reliable tool to predict eventual laparoscopic ability. The traditional attributes of sound knowledge and clinical judgement that make a good surgeon are true of a good laparoscopist with perhaps the added requirement of stamina and motivation to complete the arduous training programs that are now needed to become competent in laparoscopy.

Correction to: The clinical utility of prostate cancer heterogeneity using texture analysis of multiparametric MRI.

Unfortunately, in the original article one co-author's name is missing. The co-author name and affiliation is given as follows.

The European Urology Residents Education Programme Hands-on Training Format: 4 Years of Hands-on Training Improvements from the European School of Urology.

BACKGROUND: The European School of Urology (ESU) started the European Urology Residents Education Programme (EUREP) in 2003 for final year urology residents, with hands-on training (HOT) added later in 2007. OBJECTIVE: To assess the geographical reach of EUREP, trainee demographics, and individual quality feedback in relation to annual methodology improvements in HOT. DESIGN, SETTING, AND PARTICIPANTS: From September 2014 to October 2017 (four EUREP courses) several new features have been applied to the HOT format of the EUREP course: 1:1 training sessions (2015), fixed 60-min time slots (2016), and standardised teaching methodology (2017). The resulting EUREP HOT format was verified by collecting and prospectively analysing the following data: total number of participants attending different HOT courses; participants' age; country of origin; and feedback obtained annually. RESULTS AND LIMITATIONS: A total of 796 participants from 54 countries participated in 1450 HOT sessions over the last 4 yr. This included 294 (20%) ureteroscopy (URS) sessions, 237 (16.5%) transurethral resection (TUR) sessions, 840 (58%) basic laparoscopic sessions, and 79 (5.5%) intermediate laparoscopic sessions. While 712 residents (89%) were from Europe, 84 (11%) were from non-European nations. Of the European residents, most came from Italy (16%), Germany (15%), Spain (15%), and Romania (8%). Feedback for the basic laparoscopic session showed a constant improvement in scores over the last 4 yr, with the highest scores achieved last year. This included feedback on improvements in tutor rating (p=0.017), organisation (p<0.001), and personal experience with EUREP (p<0.001). Limitations lie in the difficulties associated with the use of an advanced training curriculum with wet laboratory or cadaveric courses in this format, although these could be performed in other training centres in conjunction with EUREP. CONCLUSIONS: The EUREP trainee demographics show that the purpose of the course is being achieved, with excellent feedback reported. While European trainees dominate the demographics, participation from a number of non-European countries suggests continued ESU collaboration with other national societies and wider dissemination of simulation training worldwide. PATIENT SUMMARY: In this paper we look at methodological improvements and feedback for the European Urology Residents Education Programme hands-on-training over the last 4 yr.

Baseline Multiparametric MRI for Selection of Prostate Cancer Patients Suitable for Active Surveillance: Which Features Matter?

INTRODUCTION: Increasing evidence has supported the use of multiparametric magnetic resonance imaging (mpMRI) for the detection of prostate cancer. However, its role in selecting patients clinically suitable for active surveillance (AS) is still in development. We aimed to find relevant mpMRI features that might be helpful for refinement of the selection of low-risk prostate cancer patients for AS. We also evaluated the interobserver variability in reporting prostate mpMRI features. PATIENTS AND METHODS: From 2008 to 2012, 135 patients were selected for AS using Epstein criteria. Baseline mpMRI studies were performed within 3 months of recruitment and reviewed by 2 radiologists who were unaware of the patients' outcomes. The radiologists recorded the mpMRI features using the Prostate Imaging Reporting and Data System (PI-RADS) guidelines. The overall likelihood of the presence of significant prostate cancer was also determined using the Likert and PI-RADS, version 2 (v2), scores. Univariate and multivariate analyses, receiver operating characteristic curves, and Kaplan-Meier survival curves were calculated for the mpMRI features with respect to patient withdrawal from the AS program and failure-free survival (FFS). The interobserver agreement was also evaluated. RESULTS: At a median follow-up time of 31 months (range, 6-80 months), 84 patients (62.2%) were participating in the AS program. In 2 multivariate models, the variables significantly associated with outcomes for both readers were the index lesion size (hazard ratio [HR], 2.34 and 3.13, respectively) and overall PI-RADS, v2, score (HR, 2.51 and 3.21, respectively). The interobserver agreement was higher for the overall Likert and PI-RADS, v2, scores. CONCLUSION: Overall, the PI-RADS, v2, score and index lesion size were strongly associated with FFS. Overall, the Likert and PI-RADS, v2, scoring systems have been confirmed to be useful, although further improvements are needed.

Minimally invasive treatment of ureteropelvic junction obstruction: optimizing outcomes with concomitant cost reduction.

With the seemingly exponential increase in the use of minimally invasive techniques in urology, cost-benefit comparisons will continue to play a major part in establishing services and in improving those that already exist. The management of ureteropelvic junction obstruction is a focus of significant attention. An effective way of optimizing the economy of management is to understand the implications in terms of the success of each mode of treatment. Subsequently, costing models should be developed and applied in large-scale multicenter studies with the aid of health economists. The long-term benefits can then be assessed by also including patient's perceived quality of life. Economic assessment will not be enough to promote cost-effective practices. The take-up of any techniques will always be influenced not only by patient preference and surgeon expertise but also, perhaps ironically, by the way hospitals and surgeons are remunerated. In addition, the impact of the time taken to train a surgeon to carry out laparoscopic dismembered pyeloplasty competently may play a significant role. Until these issues are resolved, definitive recommendation for the treatment of ureteropelvic junction obstruction will continue to be made on an individual basis.

Expression of the type 1 insulin-like growth factor receptor is up-regulated in primary prostate cancer and commonly persists in metastatic disease.

The type 1 insulin-like growth factor receptor (IGF1R) mediates tumor cell growth, adhesion, and protection from apoptosis. High plasma IGF-I levels predispose to prostate cancer, but there is no consensus regarding IGF1R expression in primary and metastatic prostate cancer. Recent studies in a human cell line and a mouse model suggest that metastatic prostate cancer cell detachment may be favored by impairing cadherin function via loss of expression of insulin receptor substrate-1 (IRS-1), the principal IGF1R docking molecule. This may be accompanied by PTEN mutation, reactivating a key antiapoptotic pathway, and by IGF1R down-regulation to prevent Shc-mediated differentiation. We studied IGF1R expression in 54 samples of primary prostate tissue including 44 archival and 10 prospectively collected biopsies. We performed semiquantitative immunostaining for the IGF1R, IRS-1, and PTEN, and in situ hybridization for IGF1R. The IGF1R was significantly up-regulated at the protein and mRNA level in primary prostate cancer compared with benign prostatic epithelium. There was a trend toward increased expression of IRS-1 in the malignant biopsies. We also measured IGF1R, IRS-1, and PTEN expression in 12 paired biopsies of primary prostate cancer and subsequent bone metastases. In four cases, IGF1R and IRS-1 levels were lower in the metastases than in the primary tumors. Three of these metastases also lacked significant PTEN staining, compatible with findings in the model systems described above. However, this pattern was relatively uncommon, and 8 of 12 cases expressed detectable IGF1R and IRS-1 in both primary and metastatic biopsies. These findings challenge earlier reports of IGF1R down-regulation in metastatic disease and reinforce the importance of the IGF1R in prostate cancer biology.

Validating multiparametric MRI for diagnosis and monitoring of prostate cancer in patients for active surveillance.

PURPOSE: To compare multiparametric magnetic resonance imaging (mpMRI) with transrectal ultrasound-guided prostate biopsy (TRUS-bx) for the diagnosis and monitoring of small-volume prostate cancer (PCa) in patients on active surveillance (AS). METHODS: In a retrospective cross-sectional validation study, 100 patients on AS for PCa underwent a systematic 12-core TRUS-bx (the gold standard) as well as mpMRI, on either a 1.5 or 3 Tesla scanner (32 and 68 patients, respectively). Three pathologists reported biopsy histology separately. A single, experienced radiologist scored mpMRI scans using the PI-RADS system. We compared left- and right-sided PI-RADS scores of the peripheral zone with TRUS-bx results of the relevant prostate lobe. We then estimated the specificity and sensitivity of mpMRI in diagnosing low-grade low-risk PCa in our AS cohort. RESULTS: The sensitivity of mpMRI was 37% (95% CI 28-47%) and specificity was 85% (CI 76-92%) for cancer. The negative predictive value was 51% (CI 44-60%), and the positive predictive value was 76% (CI 62-87%). The positive and negative likelihood ratios were 2.5 and 0.7, respectively. CONCLUSION: Because of its low specificity and low negative predictive value, mpMRI is not suitable for diagnosing low-grade small-volume PCa. However, because of a specificity of 85% and a negative likelihood ratio of 0.7, mpMRI may be useful for follow-up of previously TRUS-bx diagnosed patients who are on AS.

Silencing of the IGF1R gene enhances sensitivity to DNA-damaging agents in both PTEN wild-type and mutant human prostate cancer.

The type 1 insulin-like growth factor receptor (IGF1R) is overexpressed in prostate cancer, and mediates proliferation, motility, and survival. Many prostate cancers harbor inactivating PTEN mutations, enhancing Akt phosphorylation. This activates the principal antiapoptotic pathway downstream of the IGF1R, calling into question the value of IGF1R targeting in this tumor. The aim of the current study was to assess the effect of IGF1R gene silencing in prostate cancer cells that lack functional PTEN protein. In human DU145, LNCaP and PC3 prostate cancer cells, transfection with IGF1R small interfering RNA induced significant enhancement of apoptosis and inhibition of survival, not only in PTEN wild-type DU145 but also in PTEN mutant LNCaP and PC3. This was attributed to attenuation of IGF signaling via Akt, ERKs and p38. In both DU145 and PC3, IGF1R knockdown led to enhancement of sensitivity to mitoxantrone, etoposide, nitrogen mustard and ionizing radiation. There was no sensitization to paclitaxel or 5-fluorouracil, which do not damage DNA, suggesting that chemosensitization results from impairment of the DNA damage response, in addition to removal of apoptosis protection. These results support the concept of IGF1R targeting in prostate cancer, and indicate that PTEN loss does not render tumor cells refractory to this strategy.

Predictive value of pretreatment inflammation-based prognostic scores (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio) for invasive bladder carcinoma.

PURPOSE: Inflammation-based prognostic scores including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are associated with oncologic outcomes in diverse malignancies. We evaluated the predictive value of pretreatment prognostic scores in differentiating nonmuscle invasive (NMIBC) and muscle invasive bladder cancer (MIBC). MATERIALS AND METHODS: Consecutive transurethral resection of bladder tumour (TURBT) cases from January 2011 to December 2013 were analysed retrospectively. Patient demographics, tumour characteristics and prognostic scores results were recorded. Receiver operating characteristics curves were used to determine prognostic score cutoffs. Univariate and multivariate binomial logistic regression analysis was performed to evaluate the association between variables and MIBC. RESULTS: A total of 226 patients were included, with 175 and 51 having NMIBC (stages Ta and T1) and MIBC (stage T2+) groups, respectively. Median age was 75 years and 174 patients were male. The NLR cutoff was 3.89 and had the greatest area under the curve (AUC) of 0.710, followed by LMR (cutoff<1.7; AUC, 0.650) and PLR (cutoff>218; AUC, 0.642). Full blood count samples were taken a median of 12 days prior to TURBT surgery. Multivariate logistic regression analysis identified tumour grade G3 (odds ration [OR], 32.848; 95% confidence interval [CI], 9.818-109.902; p=0.000), tumour size≥3 cm (OR, 3.353; 95% CI, 1.347-8.345; p=0.009) and NLR≥3.89 (OR, 8.244; 95% CI, 2.488-27.316; p=0.001) as independent predictors of MIBC. CONCLUSIONS: NLR may provide a simple, cost-effective and easily measured marker for MIBC. It can be performed at the time of diagnostic flexible cystoscopy, thereby assisting in the planning of further treatment.