Local anaesthetic transperineal (LATP) prostate biopsy using a probe-mounted transperineal access system: a multicentre prospective outcome analysis.

OBJECTIVES: To assess the feasibility of local anaesthetic transperineal (LATP) technique using a single-freehand transperineal (TP) access device, and report initial prostate cancer (PCa) detection, infection rates, and tolerability. PATIENTS AND METHODS: Observational study of a multicentre prospective cohort, including all consecutive cases. LATP was performed in three settings: (i) first biopsy in suspected PCa, (ii) confirmatory biopsies for active surveillance, and (iii) repeat biopsy in suspected PCa. All patients received pre-procedure antibiotics according to local hospital guidelines. Local anaesthesia was achieved by perineal skin infiltration and periprostatic nerve block without sedation. Ginsburg protocol principles were followed for systematic biopsies including cognitive magnetic resonance imaging-targeted biopsies when needed using the PrecisionPoint™ TP access device. Procedure-related complications and oncological outcomes were prospectively and consecutively collected. A validated questionnaire was used in a subset of centres to collect data on patient-reported outcome measures (PROMs). RESULTS: Some 1218 patients underwent LATP biopsies at 10 centres: 55%, 24%, and 21% for each of the three settings, respectively. Any grade PCa was diagnosed in 816 patients (67%), of which 634 (52% of total) had clinically significant disease. Two cases of sepsis were documented (0.16%) and urinary retention was observed in 19 patients (1.6%). PROMs were distributed to 419 patients, with a 56% response rate (n = 234). In these men, pain during the biopsy was described as either 'not at all' or 'a little' painful by 64% of patients. Haematuria was the most common reported symptom (77%). When exploring attitude to re-biopsy, 48% said it would be 'not a problem' and in contrast 8.1% would consider it a 'major problem'. Most of the patients (81%) described the biopsy as a 'minor or moderate procedure tolerable under local anaesthesia', while 5.6% perceived it as a 'major procedure that requires general anaesthesia'. CONCLUSION: Our data suggest that LATP biopsy using a TP access system mounted to the ultrasound probe achieves excellent PCa detection, with a very low sepsis rate, and is safe and well tolerated. We believe a randomised controlled trial comparing LATP with transrectal ultrasound-guided biopsy (TRUS) to investigate the relative trade-offs between each biopsy technique would be helpful.

Comparison of Prostate Biopsy with or without Prebiopsy Multiparametric Magnetic Resonance Imaging for Prostate Cancer Detection: An Observational Cohort Study.

PURPOSE: We hypothesized that 1) introducing prebiopsy multiparametric magnetic resonance imaging would increase the diagnostic yield of transrectal prostate biopsy and 2) this would inform recommendations regarding systematic transrectal prostate biopsy in the setting of negative prebiopsy multiparametric magnetic resonance imaging. MATERIALS AND METHODS: A total of 997 biopsy naïve patients underwent transrectal prostate biopsy alone to June 2016 (cohort 1) and thereafter 792 underwent transrectal prostate biopsy following prebiopsy multiparametric magnetic resonance imaging (cohort 2). Patients with lesions on prebiopsy multiparametric magnetic resonance imaging underwent cognitive targeted plus systematic transrectal prostate biopsy. Patients without lesions underwent systematic transrectal prostate biopsy. RESULTS: Cohort 2 comprised younger men (age 68 vs 69 years, p = 0.01) with lower prostate specific antigen (7.6 vs 7.9 ng/ml, p = 0.024) and smaller prostate volume (56.1 vs 62 cc, p = 0.006). In cohort 2 vs cohort 1 there was no increase in overall prostate cancer detection (57.6% vs 56.7%, p = 0.701), the Gleason Grade Group or the number of positive cores (each p >0.05). Increased multifocal prostatic intraepithelial neoplasia, maximum prostate cancer core length (5 mm or greater vs less than 5 mm) and radical surgery/high intensity focused ultrasound (each p <0.05) were observed in cohort 2. For Gleason Grade Group 2-5 prostate cancer negative prebiopsy multiparametric magnetic resonance imaging had 88.1% sensitivity, 59.8% specificity, 67.8% positive predictive value and 84% negative predictive value. For negative prebiopsy multiparametric magnetic resonance images a prostate specific antigen density cutoff of 0.15 ng/ml2 or greater increased clinically significant prostate cancer detection only if the latter was defined as Gleason Grade Group 3-5 disease and/or tumor length 6 mm or greater. CONCLUSIONS: Introducing prebiopsy multiparametric magnetic resonance imaging in our clinical setting increased the diagnostic yield of prostate cancer per biopsy core. Not performing a systematic transrectal prostate biopsy when prebiopsy multiparametric magnetic resonance imaging was negative would have led to under detection of 15.1% of Gleason Grade Group 2 or greater prostate cancer cases (approximately 1 in 6).

Partial ablation versus radical prostatectomy in intermediate-risk prostate cancer: the PART feasibility RCT.

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men in the UK. Patients with intermediate-risk, clinically localised disease are offered radical treatments such as surgery or radiotherapy, which can result in severe side effects. A number of alternative partial ablation (PA) technologies that may reduce treatment burden are available; however the comparative effectiveness of these techniques has never been evaluated in a randomised controlled trial (RCT). OBJECTIVES: To assess the feasibility of a RCT of PA using high-intensity focused ultrasound (HIFU) versus radical prostatectomy (RP) for intermediate-risk PCa and to test and optimise methods of data capture. DESIGN: We carried out a prospective, multicentre, open-label feasibility study to inform the design and conduct of a future RCT, involving a QuinteT Recruitment Intervention (QRI) to understand barriers to participation. SETTING: Five NHS hospitals in England. PARTICIPANTS: Men with unilateral, intermediate-risk, clinically localised PCa. INTERVENTIONS: Radical prostatectomy compared with HIFU. PRIMARY OUTCOME MEASURE: The randomisation of 80 men. SECONDARY OUTCOME MEASURES: Findings of the QRI and assessment of data capture methods. RESULTS: Eighty-seven patients consented to participate by 31 March 2017 and 82 men were randomised by 4 May 2017 (41 men to the RP arm and 41 to the HIFU arm). The QRI was conducted in two iterative phases: phase I identified a number of barriers to recruitment, including organisational challenges, lack of recruiter equipoise and difficulties communicating with patients about the study, and phase II comprised the development and delivery of tailored strategies to optimise recruitment, including group training, individual feedback and 'tips' documents. At the time of data extraction, on 10 October 2017, treatment data were available for 71 patients. Patient characteristics were similar at baseline and the rate of return of all clinical case report forms (CRFs) was 95%; the return rate of the patient-reported outcome measures (PROMs) questionnaire pack was 90.5%. Centres with specific long-standing expertise in offering HIFU as a routine NHS treatment option had lower recruitment rates (Basingstoke and Southampton) - with University College Hospital failing to enrol any participants - than centres offering HIFU in the trial context only. CONCLUSIONS: Randomisation of men to a RCT comparing PA with radical treatments of the prostate is feasible. The QRI provided insights into the complexities of recruiting to this surgical trial and has highlighted a number of key lessons that are likely to be important if the study progresses to a main trial. A full RCT comparing clinical effectiveness, cost-effectiveness and quality-of-life outcomes between radical treatments and PA is now warranted. FUTURE WORK: Men recruited to the feasibility study will be followed up for 36 months in accordance with the protocol. We will design a full RCT, taking into account the lessons learnt from this study. CRFs will be streamlined, and the length and frequency of PROMs and resource use diaries will be reviewed to reduce the burden on patients and research nurses and to optimise data completeness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN99760303. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 52. See the NIHR Journals Library website for further project information.

Overcoming difficulties with equipoise to enable recruitment to a randomised controlled trial of partial ablation vs radical prostatectomy for unilateral localised prostate cancer.

OBJECTIVE: To describe how clinicians conceptualised equipoise in the PART (Partial prostate Ablation vs Radical prosTatectomy in intermediate-risk unilateral clinically localised prostate cancer) feasibility study and how this affected recruitment. SUBJECTS AND METHODS: PART included a QuinteT Recruitment Intervention (QRI) to optimise recruitment. Phase I aimed to understand recruitment, and included: scrutinising recruitment data, interviewing the trial management group and recruiters (n = 13), and audio-recording recruitment consultations (n = 64). Data were analysed using qualitative content and thematic analysis methods. In Phase II, strategies to improve recruitment were developed and delivered. RESULTS: Initially many recruiters found it difficult to maintain a position of equipoise and held preconceptions about which treatment was best for particular patients. They did not feel comfortable about approaching all eligible patients, and when the study was discussed, biases were conveyed through the use of terminology, poorly balanced information, and direct treatment recommendations. Individual and group feedback led to presentations to patients becoming clearer and enabled recruiters to reconsider their sense of equipoise. Although the precise impact of the QRI alone cannot be determined, recruitment increased (from a mean [range] of 1.4 [0-4] to 4.5 [0-12] patients/month) and the feasibility study reached its recruitment target. CONCLUSION: Although clinicians find it challenging to recruit patients to a trial comparing different contemporary treatments for prostate cancer, training and support can enable recruiters to become more comfortable with conveying equipoise and providing clearer information to patients.

Does the introduction of prostate multiparametric magnetic resonance imaging into the active surveillance protocol for localized prostate cancer improve patient re-classification?

OBJECTIVES: To determine whether replacement of protocol-driven repeat prostate biopsy (PB) with multiparametric magnetic resonance imaging (mpMRI) ± repeat targeted prostate biopsy (TB) when evaluating men on active surveillance (AS) for low-volume, low- to intermediate-risk prostate cancer (PCa) altered the likelihood of or time to treatment, or reduced the number of repeat biopsies required to trigger treatment. PATIENTS AND METHODS: A total of 445 patients underwent AS in the period 2010-2016 at our institution, with a median (interquartile range [IQR]) follow-up of 2.4 (1.2-3.7) years. Up to 2014, patients followed a 'pre-2014' AS protocol, which incorporated PB, and subsequently, according to the 2014 National Institute for Health and Care Excellence (NICE) guidelines, patients followed a '2014-present' AS protocol that included mpMRI. We identified four groups of patients within the cohort: 'no mpMRI and no PB'; 'PB alone'; 'mpMRI ± TB'; and 'PB and mpMRI ± TB'. Kaplan-Meier plots and log-rank tests were used to compare groups. RESULTS: Of 445 patients, 132 (30%) discontinued AS and underwent treatment intervention, with a median (IQR) time to treatment of 1.55 (0.71-2.4) years. The commonest trigger for treatment was PCa upgrading after mpMRI and TB (43/132 patients, 29%). No significant difference was observed in the time at which patients receiving a PB alone or receiving mpMRI ± TB discontinued AS to undergo treatment (median 1.9 vs 1.33 years; P = 0.747). Considering only those patients who underwent repeat biopsy, a greater proportion of patients receiving TB after mpMRI discontinued AS compared with those receiving PB alone (29/66 [44%] vs 32/87 [37%]; P = 0.003). On average, a single set of repeat biopsies was needed to trigger treatment regardless of whether this was a PB or TB. CONCLUSIONS: Replacing a systematic PB with mpMRI ±TB as part of an AS protocol increased the likelihood of re-classifying patients on AS and identifying men with clinically significant disease requiring treatment. mpMRI ±TB as part of AS thereby represents a significant advance in the oncological safety of the AS protocol.

Reducing Mortality in the Ageing Patient: Treatment of the Primary Tumour Is Not Necessary.

Robot-assisted radical prostatectomy for older men remains an unproven intervention in terms of both cancer control and functional and voiding outcomes. We highlight some of the evidence against radical surgery for older men while acknowledging that this is the direction of travel.

Altered expression of epithelial-to-mesenchymal transition proteins in extraprostatic prostate cancer.

Epithelial to mesenchymal transition (EMT) of cancer cells involves loss of epithelial polarity and adhesiveness, and gain of invasive and migratory mesenchymal behaviours. EMT occurs in prostate cancer (PCa) but it is unknown whether this is in specific areas of primary tumours. We examined whether any of eleven EMT-related proteins have altered expression or subcellular localisation within the extraprostatic extension component of locally advanced PCa compared with other localisations, and whether similar changes may occur in in vitro organotypic PCa cell cultures and in vivo PCa models. Expression profiles of three proteins (E-cadherin, Snail, and α-smooth muscle actin) were significantly different in extraprostatic extension PCa compared with intra-prostatic tumour, and 18/27 cases had an expression change of at least one of these three proteins. Of the three significantly altered EMT proteins in pT3 samples, one showed similar significantly altered expression patterns in in vitro organotypic culture models, and two in in vivo Pten-/- model samples. These results suggest that changes in EMT protein expression can be observed in the extraprostatic extension component of locally invasive PCa. The biology of some of these changes in protein expression may be studied in certain in vitro and in vivo PCa models.

Establishing nurse-led active surveillance for men with localised prostate cancer: development and formative evaluation of a model of care in the ProtecT trial.

OBJECTIVES: To develop a nurse-led, urologist-supported model of care for men managed by active surveillance or active monitoring (AS/AM) for localised prostate cancer and provide a formative evaluation of its acceptability to patients, clinicians and nurses. Nurse-led care, comprising an explicit nurse-led protocol with support from urologists, was developed as part of the AM arm of the Prostate testing for cancer and Treatment (ProtecT) trial. DESIGN: Interviews and questionnaire surveys of clinicians, nurses and patients assessed acceptability. SETTING: Nurse-led clinics were established in 9 centres in the ProtecT trial and compared with 3 non-ProtecT urology centres elsewhere in UK. PARTICIPANTS: Within ProtecT, 22 men receiving AM nurse-led care were interviewed about experiences of care; 11 urologists and 23 research nurses delivering ProtecT trial care completed a questionnaire about its acceptability; 20 men managed in urology clinics elsewhere in the UK were interviewed about models of AS/AM care; 12 urologists and three specialist nurses working in these clinics were also interviewed about management of AS/AM. RESULTS: Nurse-led care was commended by ProtecT trial participants, who valued the flexibility, accessibility and continuity of the service and felt confident about the quality of care. ProtecT consultant urologists and nurses also rated it highly, identifying continuity of care and resource savings as key attributes. Clinicians and patients outside the ProtecT trial believed that nurse-led care could relieve pressure on urology clinics without compromising patient care. CONCLUSIONS: The ProtecT AM nurse-led model of care was acceptable to men with localised prostate cancer and clinical specialists in urology. The protocol is available for implementation; we aim to evaluate its impact on routine clinical practice. TRIAL REGISTRATION NUMBERS: NCT02044172; ISRCTN20141297.

Variation between specialist uropatholgists in reporting extraprostatic extension after radical prostatectomy.

AIMS: Extraprostatic extension of prostate cancer in radical prostatectomy specimens significantly affects patient management. We evaluated the degree of interobserver variation between uropathologists at a tertiary referral teaching hospital in assessing the extraprostatic extension of prostate cancer in radical prostatectomy specimens. METHODS: Histopathological data from a consecutive series of 293 radical prostatectomy specimens (January 2007-December 2012) were reviewed. A subset of 50 consecutive radical prostatectomy cases originally staged as tumours confined to the prostate (pT2) or tumours extending into periprostatic tissue (pT3a) during this period were reviewed by four specialist uropathologists. RESULTS: Five consultant histopathologists reported these specimens with significant differences in the reported stage (p=0.0164) between pathologists. Double-blind review by 4 uropathologists of 50 consecutive radical prostatectomy cases showed a lack of consensus in 16/50 (32%) cases (κ score 0.58, moderate agreement). A consensus meeting was held, but consensus could still not be reached in 9/16 cases. CONCLUSIONS: Our findings highlight variability in the reporting of pT stage in radical prostatectomy specimens even by specialist uropathologists. Assessment of extraprostatic extension has important implications for patient management and there is a need for more precise guidance.

Contemporary practice and technique-related outcomes for radical prostatectomy in the UK: a report of national outcomes.

OBJECTIVE: To determine current radical prostatectomy (RP) practice in the UK and compare surgical outcomes between techniques. PATIENTS AND METHODS: All RPs performed between 1 January 2011 and 31 December 2011 in the UK with data entered into the British Association of Urological Surgeons (BAUS) database, were identified for analysis. Overall surgical outcomes were assessed and subgroup analyses of these outcomes, based on operative technique [open RP (ORP), laparoscopic RP (LRP) and robot-assisted laparoscopic RP (RALP)], were made. Continuous variables were compared using the Mann-Whitney U-test and categorical variables using the Pearson chi-squared test. Univariate and multivariate binary regression analyses were performed to assess the effect of patient, surgeon and technique-related variables on surgical outcomes. RESULTS: During the study period 2163 RPs were performed by 115 consultants with a median (range) of 11 (1-154) cases/consultant. Most RPs were performed laparoscopically (ORP 25.8%, LRP 54.6%, RALP 19.6%) and those performing minimally invasive techniques are more likely to have a higher annual case volume with <1% ORP, 39% LRP and 62% RALP being performed by consultants with an annual caseload of >50 cases/year. Most patients were classified as having intermediate- or high-risk disease preoperatively (1596 patients, 82.5%) and this increased to 97.2% (1649) on postoperative risk stratification. The overall intraoperative complication rate was 14.2% and was significantly greater for LRP (17.8%) vs ORP (8.2%) and RALP (12.4%), (P < 0.001). In all, 71% of patients had an estimated blood loss (EBL) of <500 mL, although there were significantly more patients undergoing ORP with >500, > 1000 and >2000 mL EBL compared with the other techniques (P < 0.001). The postoperative complication rate was 10.7% overall, with a significantly greater postoperative complication rate in the LRP group (LRP 14.6%, ORP 8.8% and RALP 10.3% respectively, P = 0.007). Positive surgical margin (PSM) rates were 17.5% for pT2 disease and 42.3% for pT3 disease. The PSM rate was significantly lower in the RALP patients compared with the ORP patients for those with pT2 disease (P = 0.025), while there was no difference between ORP and LRP (ORP 21.7%, LRP 18.1% and RALP 13.0%). There was no significant difference in the PSM rate in pT3 disease between surgical techniques. CONCLUSION: Most RPs in the UK are performed using minimally invasive techniques, which offer reduced blood loss and transfusion rates compared with ORP. The operation time, complication rate, PSM rates, and association with higher volume practice support RALP as the minimally invasive technique of choice, which could have implications for regions without access to such services. The disparity in outcomes between this national study and high-volume single centres, most probably reflects the low median national case volume, and combined with the positive effect of high case volume on multivariate analysis of surgical outcomes and PSM rates, strengthens the argument for centralisation of services.

Mullerianosis: a rare cause of acute renal colic.

A 50-year-old woman presented to the urology department with an acute history suggestive of left-sided renal colic. There were no other associated symptoms, but urine dipstick revealed non-visible haematuria. CT-KUB revealed a soft tissue mass at the left vesico-ureteric junction. Flexible cystoscopy demonstrated a mass intruding into the posterior bladder. A transurethral resection of the bladder 'tumour' was undertaken, and it was noted that the mass was not macroscopically consistent with transitional cell carcinoma. Histology demonstrated Müllerianosis, a rare lesion characterised by locally invasive growth of tissue originating from the Müllerian (paramesonephric) duct. The patient was seen by gynaecologist who initiated hormone treatment with an lutenising hormone--releasing hormone (LH-RH) analogue. Urological follow-up 3 months later highlighted ongoing pelvic pain but no further colicky loin pain. Repeat cystoscopy showed the mass had become smaller and the left ureter was laterally displaced. Further gynaecological input is planned if symptoms are ongoing.

PSA Velocity and Doubling Time in Diagnosis and Prognosis of Prostate Cancer.

Cancer is a growth process and it is natural that we should be concerned with how the routinely used marker of prostate cancer tumour burden - PSA - changes over time. Such change is measured by PSA velocity or PSA doubling time, described in general as "PSA kinetics". However, it turns out that calculation of PSA velocity and doubling time is far from straightforward. More than 20 different methods have been proposed, and many of these give quite divergent results. There is clear evidence that PSA kinetics are critical for understanding prognosis in advanced or relapsed prostate cancer. However, PSA kinetics have no value for men with an untreated prostate: neither PSA velocity nor doubling time have any role in diagnosing prostate cancer or providing a prognosis for men before treatment.

Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks.

BACKGROUND AND PURPOSE: IGF-1R depletion sensitizes prostate cancer cells to ionizing radiation and DNA-damaging cytotoxic drugs. This study investigated the hypothesis that IGF-1R regulates DNA double strand break (DSB) repair. METHODS: We tested effects of IGF-1R siRNA transfection on the repair of radiation-induced DSBs by immunoblotting and immunofluorescence for γH2AX, and pulsed-field gel electrophoresis. Homologous recombination (HR) was quantified by reporter assays, and cell cycle distribution by flow cytometry. RESULTS: We confirmed that IGF-1R depletion sensitized DU145 and PC3 prostate cancer cells to ionizing radiation. DU145 control transfectants resolved radiation-induced DSBs within 24 h, while IGF-1R depleted cells contained 30-40% unrepaired breaks at 24 h. IGF-1R depletion induced significant reduction in DSB repair by HR, although the magnitude of the repair defect suggests additional contributory factors. Radiation-induced G2-M arrest was attenuated by IGF-1R depletion, potentially suppressing cell cycle-dependent processes required for HR. In contrast, IGF-1R depletion induced only minor radiosensitization in LNCaP cells, and did not influence repair. Cell cycle profiles were similar to DU145, so were unlikely to account for differences in repair responses. CONCLUSIONS: These data indicate a role for IGF-1R in DSB repair, at least in part via HR, and support use of IGF-1R inhibitors with DNA damaging cancer treatments.

Prostate cancer: to screen or not to screen.

This paper evaluates the use of prostate-specific antigen (PSA) as a screening tool for prostate cancer. A current and contentious issue in both public and medical spheres, we are still lacking clear evidence and guidelines. Here, the Wilson and Jungner screening criteria are used as a framework to suggest that PSA-testing is not yet a proven tool for population screening. Additionally, the conflicting results of two recent randomised controlled trials are compared. The European Randomised trial of Screening for Prostate Cancer (ERSPC) found that PSA screening reduced prostate cancer-related deaths by 20% (adjusted p=0.04). Meanwhile the North American Prostate, Lung, Colon and Ovarian cancer trial (PLCO) found no significant impact of screening on mortality. The reasons for these differing outcomes are discussed in greater detail under the categories of methodology, study size, screening interval, cause of death and tumour demographics. The authors of this article conclude that PSA screening, at best, has a moderate impact on prostate cancer mortality. PSA-screening does, however, pose a high risk of over-diagnosis and over-treatment with its associated morbidity. Furthermore, economic and quality of life evaluations are lacking at present. Data are awaited from the UK Department of Health - funded ProtecT study,as well as longer-term outcomes of the ERSPC.

Cáncer de próstata: ¿hacer o no hacer cribado? / Prostate cancer: to screen or not to screen

Este artículo valora el uso del PSA (Antígeno prostático específico) como instrumento de cribado en cáncer de próstata. Siendo un tema de actualidad y polémico, tanto en la esfera médica como en la pública, todavía carecemos de evidencia clara y guías de actuación. Aquí, los criterios de cribado de Wilson y Jungner se utilizan como marco para sugerir que la prueba de PSA no es todavía un instrumento probado de cribado poblacional.Además, se comparan los resultados en conflicto de dos estudios aleatorizados controlados. El ERSPC (European Randomised trial of Screening for Prostate Cancer) encontró que el cribado con PSA reducía un 20% la mortalidad relacionada con cáncer de próstata (ajustada, p=0,04). Mientras que el ensayo PLCO (North American Prostate, Lung, Colon and Ovarian cancer Trial) no encuentra impacto significativo del cribado en la mortalidad. Las razones de estas diferencias de resultados se discuten en gran detalle bajo las categorías de metodología, tamaño del estudio, intervalo de cribado, causa de la muerte y datos demográficos del tumor. Los autores de este artículo concluyen que el cribado con PSA tiene, como mucho, un impacto moderado en la mortalidad por cáncer de próstata. Sin embargo, el cribado con PSA representa un problema de sobrediagnóstico y sobretratamiento con su morbilidad asociada. Más aun, faltan evaluaciones económicas y de calidad de vida en el presente. Se esperan los datos del estudio Protect –T financiado por el Departamento de Salud del Reino Unido, así como los resultados a más largo plazo del ERSPC(AU)

This paper evaluates the use of prostate-specific antigen (PSA) as a screening tool for prostate cancer. A current and contentious issue in both public and medical spheres, we are still lacking clear evidence and guidelines. Here, the Wilson and Jungner screening criteria are used as a framework to suggest that PSA-testing is not yet a proven tool for population screening. Additionally, the conflicting results of two recent randomised controlled trials are compared. The European Randomised trial of Screening for Prostate Cancer (ERSPC) found that PSA screening reduced prostate cancer-related deaths by 20% (adjusted p=0.04). Meanwhile the North American Prostate, Lung, Colon and Ovarian cancer trial (PLCO) found no significant impact of screening on mortality. The reasons for these differing outcomes are discussed in greater detail under the categories of methodology, study size, screening interval, cause of death and tumour demographics. The authors of this article conclude that PSA screening, at best, has a moderate impact on prostate cancer mortality. PSA-screening does, however, pose a high risk of over-diagnosis and over-treatment with its associated morbidity. Furthermore, economic and quality of life evaluations are lacking at present. Data are awaited from the UK Department of Health- funded ProtecT study,as well as longer-term outcomes of the ERSPC(AU)

Serial analysis of resected prostate cancer suggests up-regulation of type 1 IGF receptor with disease progression.

OBJECTIVE: • To compare immunostaining protocols using different antibodies for the type 1 insulin-like growth factor receptor (IGF-1R) in channel transurethal resection of the prostate (chTURP) chips, and to investigate how IGF-1R expression varies with time in serial prostate cancer specimens from individual patients. METHODS: • We studied IGF-1R expression in 44 prostate cancer specimens from 18 patients who had undergone serial chTURP at least 3 months apart. • Retrospective analysis of the hospital notes was undertaken to obtain clinical information, including age, Gleason score, prostate-specific antigen (PSA) level, hormone treatment and metastatic disease status at the time of each operation. • After an optimization process using three commercially-available IGF-1R antibodies, we used two antibodies for semiquantititve immunostaining of serial chTURP chips. RESULTS: • Santa Cruz antibody sc713 gave positive staining in IGF-1R null R- cells, and was not used further. Antibodies from Cell Signaling Technology (Beverly, MA, USA) (CS) and NeoMarkers Inc. (Fremont, CA, USA) (NM) did not stain R- cells and, in prostate tissue, showed staining of the glandular epithelium, with negligible stromal staining. All 44 chTURP samples contained identifiable malignant tissue and, of these, 73% and 64% scored moderately or strongly (score 3 or 4) with the CS and NM antibodies respectively. • There was significant correlation of IGF-1R scores of malignant tissue between the two antibodies (P < 0.001). By contrast, staining of benign glands showed poor correlation between antibodies: CS gave significantly weaker staining than malignant epithelium in the same sections (P < 0.001), whereas NM showed poor discrimination between malignant and benign glands. IGF-1R staining scores generated by the CS antibody were used to analyze the clinical data. • Most patients (six of seven) with falling IGF-1R staining scores were responding to androgen deprivation therapy (confirmed by PSA response) between operations. Conversely, in seven of eight patients who had progression to androgen-independence between procedures, IGF-1R levels increased or remained high. Finally, seven of 11 patients who developed radiologically confirmed metastases between procedures showed stable or increasing IGF-1R staining scores. CONCLUSION: • The present study is the first to assess changes in IGF-1R expression in serial prostate cancer samples. The results obtained indicate that IGF-1R expression usually remains high throughout the course of histologically-proven disease progression in serial specimens, suggesting that the IGF-1R remains a valid treatment target for advanced prostate cancer.

5A prospective survey of current prostate biopsy practices among oncological urologists.

BACKGROUND: Needle biopsy of the prostate is a common outpatient procedure. In March 2009, the European Association of Urology (EAU) published an updated, evidence-based "Guidelines on Prostate Cancer," including recommendations for this procedure. OBJECTIVE: To survey onco-urology specialists attending the 6th European Section of Oncological Urology (ESOU) meeting in Istanbul, Turkey in January 2009, to assess their biopsy practices and compare them with March 2009 EAU guidelines. DESIGN, SETTING AND PARTICIPANTS: The authors designed a questionnaire and distributed it to 606 conference delegates. It was completed by 298 delegates, of whom 156 were experienced onco-urological specialists. MEASUREMENTS: The survey results from the 156 experienced onco-urologist specialists were analyzed. RESULTS AND LIMITATIONS: Most (59%) of the 156 respondents worked in large (> 20 bed) units, and 76% said urologists always performed the biopsies. Transrectal ultrasound (TRUS)-guided biopsy was the preferred procedure for 78% of respondents. Prostate-specific antigen (PSA) cut-off points of 4 ng/mL, 3.5 ng/mL, 3 ng/mL, and 2.5 ng/ml were used by 42%, 18%, 23%, and 8% of respondents, respectively, to determine whether a biopsy was indicated. A total of 95% of respondents gave patients prophylactic antibiotics. Another of 15% and 17% of respondents did not advise patients to stop taking warfarin or clopidogrel, respectively. A total of 23% of respondents did not give patients pre-procedure anesthesia, while others gave patients periprostatic lidocaine (31% of respondents), topical lidocaine jelly (35%), or general or spinal anesthesia (5.7%). High grade prostatic intraepithelial neoplasia (HGPIN) was considered by 71% of respondents as being a pre-malignant condition requiring a repeat biopsy. If atypical small acinar proliferation (ASAP) was reported, 62% of respondents recommended a repeat biopsy. Magnetic resonance imaging (MRI) was used to help diagnose cancer (53% of respondents), help stage cancer (83%), or help diagnose cancer recurrence (62%). Study limitations include possible difficulties with the English questionnaire. CONCLUSIONS: Many surveyed specialists were not performing prostate biopsies according to March 2009 evidence-based EAU practice guidelines, which could have adverse consequences for patients.