Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. METHODS: We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. RESULTS: The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. CONCLUSIONS: In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Systematic review of the safety and efficacy of osseointegration prosthesis after limb amputation.

BACKGROUND: Osseointegration, an approach for direct skeletal attachment of a prosthesis to an amputated limb, may address many of the problems associated with socket prostheses. The safety of osseointegration remains uncertain. The aim of this study was to summarize evidence on functional and clinical outcomes, as well as adverse effects of osseointegration for patients with a limb amputation. METHODS: MEDLINE, Embase, Web of Science and the Cochrane Library were searched to April 2018. Eligible studies were observational, case and qualitative studies, and RCTs conducted in patients with a limb amputation, who were managed with osseointegrated prostheses and had follow-up data. RESULTS: Twenty-two eligible articles comprising 13 unique studies were included. No RCT was identified. Apart from three case reports that comprised one to five patients, the sample size of studies ranged from 11 to 100 participants. All relevant studies reported improvement in functional outcomes (walking ability, prosthetic use and mobility), satisfaction and quality of life following osseointegration, compared with their preoperative status or when using a conventional socket prosthesis. Infection rates ranged from 1 (95 per cent c.i. 0 to 5) to 77 (59 to 88) per cent. The majority of infections were described as low-grade soft tissue or superficial infections related to the skin-implant interface, and were treated effectively with antibiotics. None of the studies reported additional amputation or death as a result of osseointegration. CONCLUSION: Osseointegration after limb amputation improves prosthetic use, comfort when sitting, walking ability, mobility, gait and quality of life. However, it is associated with an increased risk of soft tissue infection.

Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel.

BACKGROUND: The development of androgen independence, chemo-, and radioresistance are critical markers of prostate cancer progression and the predominant reasons for its high mortality. Understanding the resistance to therapy could aid the development of more effective treatments. AIM: The aim of this study is to investigate the effects of insulin-like growth factor-binding protein-2 (IGFBP-2) on prostate cancer cell proliferation and its effects on the response to docetaxel. METHODS: DU145 and PC3 cells were treated with IGFBP-2, insulin-like growth factor I (IGF-I) alone or in combination with blockade of the IGF-I receptor or integrin receptors. Cells were also treated with IGFBP-2 short interfering ribonucleic acid with or without a PTEN (phosphatase and tensin homologue deleted on chromosome 10) inhibitor or docetaxel. Tritiated thymidine incorporation was used to measure cell proliferation and Trypan blue cell counting for cell death. Levels of IGFBP-2 mRNA were measured using RT-PCR. Abundance and phosphorylation of proteins were assessed using western immunoblotting. RESULTS: The IGFBP-2 promoted cell growth in both cell lines but with PC3 cells this was in an IGF-dependent manner, whereas with DU145 cells the effect was independent of IGF receptor activation. This IGF-independent effect of IGFBP-2 was mediated by interaction with ß-1-containing integrins and a consequent increase in PTEN phosphorylation. We also determined that silencing IGFBP-2 in both cell lines increased the sensitivity of the cells to docetaxel. CONCLUSION: The IGFBP-2 has a key role in the growth of prostate cancer cells, and silencing IGFBP-2 expression reduced the resistance of these cells to docetaxel. Targeting IGFBP-2 may increase the efficacy of docetaxel.

Clinical presentation and initial management of black men and white men with prostate cancer in the United Kingdom: the PROCESS cohort study.

BACKGROUND: In the United States, Black men have a higher risk of prostate cancer and worse survival than do White men, but it is unclear whether this is because of differences in diagnosis and management. We re-examined these differences in the United Kingdom, where health care is free and unlikely to vary by socioeconomic status. METHODS: This study is a population-based retrospective cohort study of men diagnosed with prostate cancer with data on ethnicity, prognostic factors, and clinical care. A Delphi panel considered the appropriateness of investigations and treatments received. RESULTS: At diagnosis, Black men had similar clinical stage and Gleason scores but higher age-adjusted prostate-specific antigen levels (geometric mean ratio 1.41, 95% confidence interval (95% CI): 1.15-1.73). Black men underwent more investigations and were more likely to undergo radical treatment, although this was largely explained by their younger age. Even after age adjustment, Black men were more likely to undergo a bone scan (odds ratio 1.37, 95% CI: 1.05-1.80). The Delphi analysis did not suggest differential management by ethnicity. CONCLUSIONS: This UK-based study comparing Black men with White men found no evidence of differences in disease characteristics at the time of prostate cancer diagnosis, nor of under-investigation or under-treatment in Black men.

Ketamine-associated lower urinary tract destruction: a new radiological challenge.

AIM: Ketamine is a short-acting dissociative anaesthetic whose hallucinogenic side effects have led to an increase in its illicit use amongst club and party goers. There is a general misconception amongst users that it is a safe drug with few long term side effects, however ketamine abuse is associated with severe urinary tract dysfunction. Presenting symptoms include urinary frequency, nocturia, dysuria, haematuria and incontinence. MATERIALS AND METHODS: We describe the radiological findings found in a series of 23 patients, all with a history of ketamine abuse, who presented with severe lower urinary tract symptoms (LUTS). Imaging techniques used included ultrasonography (US), intravenous urography (IVU), and computed tomography (CT). These examinations were reviewed to identify common imaging findings. All patients with positive imaging findings had also undergone cystoscopy and bladder wall biopsies, which confirmed the diagnosis. The patients in this series have consented to the use of their data in the ongoing research into ketamine-induced bladder pathology. RESULTS: Ultrasound demonstrated small bladder volume and wall thickening. CT revealed marked, generalized bladder wall thickening, mucosal enhancement, and perivesical inflammation. Ureteric wall thickening and enhancement were also observed. In advanced cases ureteric narrowing and strictures were identified using both CT and IVU. Correlation of clinical history, radiological and pathological findings was performed to confirm the diagnosis. CONCLUSION: This case series illustrates the harmful effects of ketamine on the urinary tract and the associated radiological findings. Delayed diagnosis can result in irreversible renal tract damage requiring surgical intervention. It is important that radiologists are aware of this emerging clinical entity as early diagnosis and treatment are essential for successful management.

Pathways to diagnosis for Black men and White men found to have prostate cancer: the PROCESS cohort study.

Black men in England have three times the age-adjusted incidence of diagnosed prostate cancer as compared with their White counterparts. This population-based retrospective cohort study is the first UK-based investigation of whether access to diagnostic services underlies the association between race and prostate cancer. Prostate cancer was ascertained using multiple sources including hospital records. Race and factors that may influence prostate cancer diagnosis were assessed by questionnaire and hospital records review. We found that Black men were diagnosed an average of 5.1 years younger as compared with White men (P<0.001). Men of both races were comparable in their knowledge of prostate cancer, in the delays reported before presentation, and in their experience of co-morbidity and symptoms. Black men were more likely to be referred for diagnostic investigation by a hospital department (P=0.013), although general practitioners referred the large majority of men. Prostate-specific antigen levels were comparable at diagnosis, although Black men had higher levels when compared with same-age White men (P<0.001). In conclusion, we found no evidence of Black men having poorer access to diagnostic services. Differences in the run-up to diagnosis are modest and seem insufficient to explain the higher rate of prostate cancer diagnosis in Black men.

A systematic review of PFE pre-prostatectomy.

Male Stress Urinary Incontinence is a complication post robotic radical prostatectomy. This is a major problem that needs to be solved, since it has great impact on quality of life affecting the patient's physical activity and social well-being. A systematic review relating to literature on impact of preoperative PFE on continence outcomes for patients undergoing prostatectomy was conducted. The search strategy aimed to identify all references related to pelvic floor exercises and post-prostatectomy. Search terms used were as follows: (Pelvic floor exercises) AND (incontinence) AND (prostatectomy). The following databases were screened from 2000 to September 2017: CINAHL, MEDLINE (NHS Evidence), Cochrane, AMed, EMBASE, PsychINFO, SCOPUS, Web of Science. In addition, searches using Medical Subject Headings (MeSH) and keywords were conducted using Cochrane databases. Two UK-based experts in prostate cancer and robotic surgery were consulted to identify any additional studies. In the 6 months following surgery, the continence rates, as defined by the use of one pad or less per day, were 94% (44 of 47) and 96% (48 of 50) in the PFE and biofeedback groups and control groups (PFE alone), respectively (P = 0.596) (Bales et al. in Urology 56: 627-630, 2000). This demonstrates preoperative PFE may improve early continence after RP. Geraerts et al. (Eur Urol 64:766-772, 2013) demonstrated the "incontinence impact" was in favour of a group with PFE at 3 and 6 months after surgery. This demonstrates again the advantage of preoperative PFE. Cornel et al. [World J Urol 23:353-355, 2005] determined the benefit of starting pelvic floor muscle exercise (PFE) 30 days before RP and of continuing PFE postoperatively for early recovery of continence as part of a randomised, prospective study (Moher quality A). This demonstrated preoperative PFE may improve early continence and QoL outcomes after RP. Post-prostatectomy incontinence is a bothersome complication of radical prostatectomy [Chughtai et al. in Rev Urol 15:61-66, 2013]. Weak pelvic floor muscles compromised normal pelvic floor function and led to urinary incontinence and erectile dysfunction. Strengthening the pelvic floor muscles was shown to significantly improve post-prostatectomy urinary continence, post-micturition dribble and erectile function. It would be prudent for all men to exercise their pelvic floor muscles to maintain normal pelvic floor function and start prior to surgery.

Hyperglycaemia-induced resistance to Docetaxel is negated by metformin: a role for IGFBP-2.

The incidence of many common cancers varies between different populations and appears to be affected by a Western lifestyle. Highly proliferative malignant cells require sufficient levels of nutrients for their anabolic activity. Therefore, targeting genes and pathways involved in metabolic pathways could yield future therapeutics. A common pathway implicated in energetic and nutritional requirements of a cell is the LKB1/AMPK pathway. Metformin is a widely studied anti-diabetic drug, which improves glycaemia in patients with type 2 diabetes by targeting this pathway. We investigated the effect of metformin on prostate cancer cell lines and evaluated its mechanism of action using DU145, LNCaP, PC3 and VCaP prostate cancer cell lines. Trypan blue dye-exclusion assay was used to assess levels of cell death. Western immunoblotting was used to determine the abundance of proteins. Insulin-like growth factor-binding protein-2 (IGFBP-2) and AMPK genes were silenced using siRNA. Effects on cell morphology were visualised using microscopy. IGFBP-2 gene expression was assessed using real-time RT-PCR. With DU145 and LNCaP cells metformin alone induced cell death, but this was reduced in hyperglycaemic conditions. Hyperglycaemia also reduced the sensitivity to Docetaxel, but this was countered by co-treatment with metformin. LKB1 was required for the activation of AMPK but was not essential to mediate the induction of cell death. An alternative pathway by which metformin exerted its action was through downregulation of IGFBP-2 in DU145 and LNCaP cells, independently of AMPK. This finding could have important implications in relation to therapeutic strategies in prostate cancer patients presenting with diabetes.

Erectile function post robotic radical prostatectomy: technical tips to improve outcomes?

Robotic surgery is becoming more and more commonplace. At the same time, so are complications, especially related to erectile function. The population being diagnosed with cancer is younger, with more aggressive cancers and higher expectations for good erectile function postoperatively. We conduct a retrospective analysis of literature over 20 years for Embase and Medline. Search terms used include (Robotic) AND (prostatectomy) AND (erectile function). There are a variety of multifactorial causes, resulting in worsening ED post-robotic radical prostatectomy; however, there are a number of treatments that can support this. There is much we can do to help prevent patients getting postoperative erectile dysfunction post-radical surgery. However, part of this is management of realistic patient expectations.

Bicalutamide vs cyproterone acetate in preventing flare with LHRH analogue therapy for prostate cancer--a pilot study.

OBJECTIVE: To evaluate the efficacy of bicalutamide vs cyproterone acetate in preventing PSA flare (as a surrogate for tumour flare) for patients requiring luteinizing hormone-releasing hormone (LHRH) analogue therapy for prostate cancer. PATIENTS AND METHODS: In this pilot study, 40 men were randomized 1 : 1 to bicalutamide 50 mg o.d. or cyproterone acetate 100 mg t.i.d. 5 days prior to goserelin acetate and continued for 21 days thereafter. PSA, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were obtained before treatment and on days 6, 8, 10, 16, 21 and 28. Primary end point was PSA. Hormone profile and clinical features including urinary symptoms and bone pain were secondary end points. RESULTS: Both groups were equally matched apart from serum creatinine and ALP. The speed and magnitude of the percentage change in median PSA from baseline was increased for the CPA group but there was no statistically significant difference in the two groups. Although those receiving bicalutamide all showed a testosterone peak, this remained within the normal range. No difference in the frequency of drug-specific adverse events was found. None of the patients died or developed cord compression during the study period. CONCLUSION: Bicalutamide is able to suppress the initial PSA surge as effectively as cyproterone acetate albeit slightly delayed. A statement whether bicalutamide is equally good at preventing clinical flare cannot be made and should be assessed in an appropriately powered study.

PSA recurrence following radical prostatectomy is comparable for all age groups in the UK.

UNLABELLED: Increasing numbers of men are being diagnosed with prostate cancer and undergo operative curative treatment. It has been suggested that outcome after radical prostatectomy (RP) may vary for different age groups. OBJECTIVE: To investigate whether PSA recurrence-free survival after RP is related to age at operation for a cohort of English men. METHODS: A total of 854 patients notes from four Urology units were audited for preoperative staging parameters and follow-up data obtained. The relationship of PSA, age, biopsy Gleason grade, clinical stage, era and institution on PSA recurrence-free survival was competitively assessed with a multivariate model. RESULTS: Only preoperative PSA (P<0.0001) and biopsy Gleason grade (P < 0.0001) were found to be strongly associated with PSA recurrence-free survival on multivariate analysis. PSA recurrence-free survival probabilities at 5 y for patients aged 45-55 y, 55.1-60 y, 60.1-65 y, 65.1-70 y and 70.1-75 y were 0.59 (CI 0.47-0.71), 0.74 (CI 0.64-0.784), 0.56 (CI 0.44-0.68), 0.61 (CI 0.53-0.69) and 0.60 (CI 0.46-0.74), respectively. No significant difference of PSA recurrence-free survival between any of the age groups was found (Log-rank, P = 0.8567). CONCLUSION: No significant difference of pathological variables or biochemical recurrence across the age groups was found. The widely held belief of poorer outcome in younger men selected for RP does not seem to be borne out by this study.

Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer.

Angiogenesis is required for tumour growth and is induced principally by vascular endothelial growth factor A (VEGF-A). VEGF-A pre-mRNA is alternatively spliced at the terminal exon to produce two families of isoforms, pro- and anti-angiogenic, only the former of which is upregulated in prostate cancer (PCa). In renal epithelial cells and colon cancer cells, the choice of VEGF splice isoforms is controlled by the splicing factor SRSF1, phosphorylated by serine-arginine protein kinase 1 (SRPK1). Immunohistochemistry staining of human samples revealed a significant increase in SRPK1 expression both in prostate intra-epithelial neoplasia lesions as well as malignant adenocarcinoma compared with benign prostate tissue. We therefore tested the hypothesis that the selective upregulation of pro-angiogenic VEGF in PCa may be under the control of SRPK1 activity. A switch in the expression of VEGF165 towards the anti-angiogenic splice isoform, VEGF165b, was seen in PC-3 cells with SRPK1 knockdown (KD). PC-3 SRPK1-KD cells resulted in tumours that grew more slowly in xenografts, with decreased microvessel density. No effect was seen as a result of SRPK1-KD on growth, proliferation, migration and invasion capabilities of PC-3 cells in vitro. Small-molecule inhibitors of SRPK1 switched splicing towards the anti-angiogenic isoform VEGF165b in PC-3 cells and decreased tumour growth when administered intraperitoneally in an orthotopic mouse model of PCa. Our study suggests that modulation of SRPK1 and subsequent inhibition of tumour angiogenesis by regulation of VEGF splicing can alter prostate tumour growth and supports further studies for the use of SRPK1 inhibition as a potential anti-angiogenic therapy in PCa.

Do height-related variations in insulin-like growth factors underlie the associations of stature with adult chronic disease?

Tall people, particularly those with long legs, have an increased risk of developing cancer but a reduced risk of cardiovascular disease and type II diabetes. We examined associations of stature and body mass index with IGF-I, IGF-II, and IGF binding protein (IGFBP)-2 and IGFBP-3 in 274 men aged 50-70 yr to investigate whether variations in growth factor levels underlie associations of anthropometry with a number of adult diseases. Height and leg and trunk length were not strongly associated with circulating levels of IGF-I, IGF-II, or IGFBP-3. The molar ratio of IGF-I/IGFBP-3 increased with increases in the leg/trunk length ratio (P = 0.06). IGFBP-2 was positively associated with leg length and inversely associated with trunk length. Mean levels of IGFBP-2 (in nanograms per milliliter) across quartiles of increasing leg length were 504.4 493.6, 528.7, and 578.8 (P(trend) = 0.06), and for trunk length were 615.2, 507.2, 498.6, 488.5 (P(trend) < 0.01), suggesting that variations in IGFBP-2, or a factor influencing its levels in the circulation, may contribute to biological mechanisms underlying height-disease associations. We conclude that whereas growth-influencing exposures during childhood, which may operate through effects on IGF-I levels, have long-term influences on disease risk, they do not necessarily program IGF-I levels throughout life. The associations of anthropometry with IGFBP-2 merit additional investigation.

Her-2/neu oncogene amplification in clinically localised prostate cancer.

AIM: To examine the incidence of Her-2/neu oncogene amplification in clinically localised prostate cancer using in situ hybridisation. METHODS: One hundred and seventeen patients, who had undergone radical prostatectomy, were identified and in situ hybridisation was performed on formalin fixed, paraffin wax embedded tissue using the Quantum Appligene probe for Her-2/neu. The enzyme peroxidase was used to detect the probe because this enabled a permanent record to be kept. Tumours in which there were five or more signals in each nucleus in > 20% of the tumour cells were considered to have a significantly increased copy number. A serial section from these tumours was then hybridised with the chromosome 17 alpha satellite probe. The ratio of the percentage of cells showing an increase in Her-2/neu copy number to the number showing polysomy for chromosome 17 was calculated. A ratio above 2 was considered amplified. RESULTS: Biochemical recurrence occurred in 50 (43%) patients and 24 (21%) had clinical recurrence. In situ hybridisation for Her-2/neu was accessible in 114 (97%) patients. A significant increase in copy number was present in two patients (1.75 %), but chromosome 17 hybridisation showed that the increase was the result of polysomy rather than true amplification. Both these patients had a Gleason score of 7 and stage T3; they also had recurrent clinical disease with distal metastasis within two and 19 months. CONCLUSIONS: Increased Her-2/neu oncogene copy number appears to be rare in clinically localised prostatic adenocarcinoma and is related to chromosome 17 polysomy rather than true amplification. As a result, it would not be a useful biomarker for identifying those patients who will have recurrences after radical prostatectomy.

High-dose intravenous estrogen therapy in advanced prostatic carcinoma. Use of serum prostate-specific antigen to monitor response.

High-dose intravenous estrogen therapy was shown to be effective in relieving bone pain due to metastatic disease in 22 of 29 (75.9%) men with advanced hormone-resistant prostate cancer. This clinical response was accompanied by significant falls in serum prostate-specific antigen (PSA) levels in 13 (44.8%) patients. It is suggested that this clinical benefit is due to a direct inhibitory effect of estrogen on prostate cancer cells.

Initial human clinical experience with diode laser interstitial treatment of benign prostatic hyperplasia.

OBJECTIVES: To report the initial results of treatment of outlet obstruction induced by benign prostatic hyperplasia (BPH) using interstitial laser coagulation performed with the Indigo 830 nm diode laser system. METHODS: A group of 112 men with lower urinary tract symptoms caused by BPH underwent treatment with the Indigo 830 nm laser system between October 1994 and November 1995. Patients were assessed prior to treatment and at specified post-treatment intervals for symptom score, uroflow, postvoid residual, and prostate volume. Adverse events and changes in laboratory parameters were monitored at each post-treatment visit to investigate safety of the procedure. RESULTS: Symptom score decreased from 20.9 at initial measurement to 9.6 at 3 months after procedure and 7.9 at 6 months. Uroflow rate increased from 8.0 mL/s initially to 15.2 and 14.2 mL/s at 3 and 6 months, respectively. Residual bladder volumes decreased from 105 mL initially to 59 and 38 mL at 3 and 6 months, respectively. There were no major complications (impotence, sustained incontinence, significant blood loss). Minor complications occurred in a small number of patients but were generally associated with urinary tract infection in patients with catheters. Three patients (2.7%) required retreatment and underwent transurethral resection of the prostate. CONCLUSIONS: Interstitial laser coagulation using an 830-nm diode laser system appears to be a promising new treatment, with substantial improvements in objective and subjective parameters of obstruction and a favorable side-effect profile.

Diagnosis, management and screening of early localised prostate cancer.

The incidence of prostate cancer is rising worldwide, caused mainly by demographic factors, particularly the increasingly elderly population and, more importantly, the increasing number of cases identified following prostate specific antigen (PSA) testing. It is commonly quoted that many more men die with prostate cancer than of it. Autopsy/post-mortem studies show that while a very high proportion of elderly men have histological evidence of the disease, a much smaller proportion develop clinically apparent cancer. The natural history of prostate cancer is poorly understood, but progression appears to be related to stage and grade of tumour. Prostate cancer can be diagnosed by digital rectal examination (DRE), serum PSA test, and/or transrectal ultrasound (TRUS), with confirmation by biopsy. Each test identifies a proportion of cancers, with higher rates of detection when they are used in combination. The tests are also used to determine which tumours are localised within the prostate and are, thus, potentially treatable. Unfortunately, clinical staging is unreliable, with approximately one half of all tumours upstaged following surgery. Three major treatment options are available for localised prostate cancer: radical prostatectomy, radical radiotherapy and conservative management (involving monitoring and treatment of symptoms). Although radical treatment rates are rising, good quality evidence concerning their comparative effectiveness and cost-effectiveness is lacking. Observational studies of highly selected patient groups suggests that there may be a slightly lower mortality rate following radical treatments compared with conservative management, but there has been very little research into treatment complications and quality of life of men after any of the treatments. In the past, investigations of prostate cancer were reserved largely for patients exhibiting symptoms, but the introduction of the PSA test has opened up the possibility of screening healthy men for the disease. Observational studies suggest that DRE and PSA, combined with TRUS and biopsy, can identify localised prostate cancer in 3-5% of men, although the tests do result in a number of false positives and negatives. Major questions remain concerning the natural history of the disease, potential costs (financial, social and psychological) of a screening programme, and the effectiveness and cost-effectiveness of treatments for localised disease. The lack of good quality data and the strength of these concerns means that population screening for prostate cancer cannot be recommended.