Risk stratification for prostate cancer management: value of the Cambridge Prognostic Group classification for assessing treatment allocation.

BACKGROUND: The five-tiered Cambridge Prognostic Group (CPG) classification is a better predictor of prostate cancer-specific mortality than the traditional three-tiered classification (low, intermediate, and high risk). We investigated radical treatment rates according to CPG in men diagnosed with non-metastatic prostate cancer in England between 2014 and 2017. METHODS: Patients diagnosed with non-metastatic prostate cancer were identified from the National Prostate Cancer Audit database. Men were risk stratified according to the CPG classification. Risk ratios (RR) were estimated for undergoing radical treatment according to CPG and for receiving radiotherapy for those treated radically. Funnel plots were used to display variation in radical treatment rates across hospitals. RESULTS: A total of 61,999 men were included with 10,963 (17.7%) in CPG1 (lowest risk group), 13,588 (21.9%) in CPG2, 9452 (15.2%) in CPG3, 12,831 (20.7%) in CPG4, and 15,165 (24.5%) in CPG5 (highest risk group). The proportion of men receiving radical treatment increased from 11.3% in CPG1 to 78.8% in CGP4, and 73.3% in CPG5. Men in CPG3 were more likely to receive radical treatment than men in CPG2 (66.3% versus 48.4%; adjusted RR 1.44; 95% CI 1.36-1.53; P < 0.001). Radically treated men in CPG3 were also more likely to receive radiotherapy than men in CPG2 (59.2% versus 43.9%; adjusted RR, 1.18; 95% CI 1.10-1.26). Although radical treatment rates were similar in CPG4 and CPG5 (78.8% versus 73.3%; adjusted RR 1.01; 95% CI 0.98-1.04), more men in CPG5 had radiotherapy than men in CPG4 (79.9% versus 59.1%, adjusted RR 1.26; 95% CI 1.12-1.40). CONCLUSIONS: The CPG classification distributes men in five risk groups that are about equal in size. It reveals differences in treatment practices in men with intermediate-risk disease (CPG2 and CPG3) and in men with high-risk disease (CPG4 and CPGP5) that are not visible when using the traditional three-tiered risk classification.

Three-year experience of a dedicated prostate mpMRI pre-biopsy programme and effect on timed cancer diagnostic pathways.

AIM: To evaluate the effect of pre-biopsy magnetic resonance imaging (MRI) on cancer diagnostic times, and to report MRI-directed pathology outcomes. MATERIALS AND METHODS: In total, 1483 patients were referred with prostate cancer suspicion during a 30-month period. Upfront MRI was performed in 745 patients: 332 MRIs in the 15 months prior to dedicated scanning slots (group 1), and 413 in the 15 months post-introduction (group 2). A further 88 patients had initial MRI following clinical assessment. Biopsy via the transrectal (TR) or transperineal (TP) approach was performed, with MRI/ultrasound fusion for MRI targets. Clinically significant cancer (csPCa) was defined as Gleason ≥3+4. Negative MRIs were defined as Likert 1-2. Per-case clinical decisions were taken to biopsy or not. RESULTS: 44.4% of patients avoided biopsy. 484/833 (58.1%) MRIs were negative; 37.4% of these patients had biopsy with a negative predictive value (NPV) of 92.8% for Gleason ≥3+4 and 98.3% for ≥4+3. Overall prostate cancer prevalence was 34.3% (24.6% csPCa). In 323 MRI-positive cases, any cancer was present in 78.9% (csPCa 60.4%). Of the 1483 patients, 1232 (83.1%) completed all diagnostic tests within 28 days. Upfront MRI patients met this standard in 621/833 (74.5%), improving from 66.9% to 81.1% with reserved slots (group 2) with a reduced diagnostic time from median 25.5 to 20.9 days. Biopsy scheduling delayed the pathway in 69.7%, with MRI responsible in 22.3%, reducing to 10.3% in group 2. TP biopsies met the 28-day standard in significantly less cases (29.7%), compared to TR (67.4%, p<0.0001). CONCLUSION: Reserved MRI slots reduces time-to-diagnosis, and upfront MRI safely avoids biopsy in a significant proportion of men, whilst maintaining expected csPCa detection rates.

Improving the safety and tolerability of local anaesthetic outpatient transperineal prostate biopsies: A pilot study of the CAMbridge PROstate Biopsy (CAMPROBE) method.

OBJECTIVES: The aim of this study was to pilot the use of a bespoke device (CAMPROBE, the CAMbridge PROstate Biopsy) to enable routine outpatient free-hand local anaesthetic (LA) transperineal prostate biopsies. MATERIALS AND METHODS: The CAMPROBE prototype was designed and built in our institution. Men on active surveillance due prostate resampling were invited to have a CAMPROBE biopsy as an alternative to repeat transrectal ultrasound-guided prostate biopsies (TRUSBx) as part of an approved trial (NCT02375035). Biopsies were performed using LA infiltration only, without sedation or additional analgesia. Patient-reported outcomes were recorded at day 0 and 7 using validated questionnaires and visual analogue scales (VAS). Complications were recorded prospectively. RESULTS: Thirty men underwent biopsies with a median of 11 cores taken per procedure (interquartile range 10-12). There were no infections, sepsis or retention episodes. Haematuria and haematospermia occurred in 67% and 62% of patients, which are similar to rates reported for TRUSBx. Mean VAS for pain (0-10 scale) was less than 3 for every part of the procedure. All 30 men described the procedure as tolerable under LA. In total, 26/30 (86.7%) men expressed a preference for a CAMPROBE procedure over TRUSBx and a further 3 (10.0%) would have either. CONCLUSIONS: In this small pilot study, the CAMPROBE device and method appears to be a safe, simple and well-tolerated out-patient transperineal replacement for TRUSBx. A major new National Institute for Health Research grant will allow its further development from a prototype to a single use, low-cost disposable device ready for multi-centre testing. LEVEL OF EVIDENCE: 1b: individual cohort study.

The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study.

BACKGROUND: The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer. METHODS: We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality. RESULTS: The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n = 20,586), C-index 0.77 vs. 074; radiotherapy (n = 11,872), C-index 0.73 vs. 0.69; and conservative management (n = 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001). CONCLUSIONS: This validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

A comparison of operative and margin outcomes from surgeon learning curves in robot assisted radical prostatectomy in a changing referral practice.

Introduction The aim of this study was to explore the impact of increasing proportions of high risk referrals on surgical margin outcomes of a surgeon's learning curve in robotic prostatectomy. Methods All patients in this study underwent robot assisted radical prostatectomy (RARP) performed by three different consultant urological surgeons. Data collected included preoperative clinical stage, Gleason score and prostate specific antigen levels, which were used to risk stratify patients according to National Institute for Health and Care Excellence criteria. Oncological clearance was assessed by overall and stage specific positive margin status. Comparisons were made between each surgeon for the first and second 50 consecutive cases. Results For the three surgeons, there was a progressive increase in the proportion of high risk cases referred accompanied by a corresponding decline in low risk disease (p<0.001). Postoperative pathology also showed an upward trend in pT3 cases across the three eras. There was no statistical difference in overall positive margin rates between the surgeons. The overall rates were 12%, 20% and 23% for the first 50 cases, and 32%, 36% and 21% for the second 50 cases for the three surgeons respectively. Conclusions Our series demonstrates an upward trend in the risk profile of men referred for robotic prostatectomy over a nine-year period. Despite this, there was minimal impact on pathological and surgical outcomes among our surgeons, who were at the initial stages of their RARP learning curve. Our results suggest that there is no requirement for an active case selection bias against patients with high risk disease for surgeons newly embarking on their RARP learning experience.

Novel three-dimensional bone 'mapping' software can help assess progression of osseous metastases from routine CT.

Imaging of bone metastasis response to therapy is a research priority. Stradwin is a new software-tool, with demonstrated sub-voxel accuracy in assessing cortical bone properties from routine CT. We applied this technology to the context of osseous metastases, with particular focus on disease progression using prostate cancer as a model. 3D-rendered 'bone-maps' were produced for 20 men with advanced prostate cancer, including a sub-cohort of 9 who had undergone serial scans. Correlation between baseline interpretation and assessments of progression between modalities was assessed. Bone-maps took significantly less time to interpret than CT bone windows (P < 0.001). Initial bone-mapping, without adjustment, demonstrated sensitivity and specificity for suspicious areas on CT of 70.7% and 73.1% respectively. Evaluating disease over time, concordance between bone-maps and current practice using RECIST outcomes was 100%.This study demonstrates the feasibility and potential use of this free post-processing software in the serial assessment of osseous metastases.

Association Of Plasma And Urinary Mutant DNA With Clinical Outcomes In Muscle Invasive Bladder Cancer.

Muscle Invasive Bladder Cancer (MIBC) has a poor prognosis. Whilst patients can achieve a 6% improvement in overall survival with Neo-Adjuvant Chemotherapy (NAC), many do not respond. Body fluid mutant DNA (mutDNA) may allow non-invasive identification of treatment failure. We collected 248 liquid biopsy samples including plasma, cell pellet (UCP) and supernatant (USN) from spun urine, from 17 patients undergoing NAC. We assessed single nucleotide variants and copy number alterations in mutDNA using Tagged-Amplicon- and shallow Whole Genome- Sequencing. MutDNA was detected in 35.3%, 47.1% and 52.9% of pre-NAC plasma, UCP and USN samples respectively, and urine samples contained higher levels of mutDNA (p = <0.001). Longitudinal mutDNA demonstrated tumour evolution under the selective pressure of NAC e.g. in one case, urine analysis tracked two distinct clones with contrasting treatment sensitivity. Of note, persistence of mutDNA detection during NAC predicted disease recurrence (p = 0.003), emphasising its potential as an early biomarker for chemotherapy response.

The Prostate Health Index adds predictive value to multi-parametric MRI in detecting significant prostate cancers in a repeat biopsy population.

Both multi-parametric MRI (mpMRI) and the Prostate Health Index (PHI) have shown promise in predicting a positive biopsy in men with suspected prostate cancer. Here we investigated the value of combining both tests in men requiring a repeat biopsy. PHI scores were measured in men undergoing re-biopsy with an mpMRI image-guided transperineal approach (n = 279, 94 with negative mpMRIs). The PHI was assessed for ability to add value to mpMRI in predicting all or only significant cancers (Gleason ≥7). In this study adding PHI to mpMRI improved overall and significant cancer prediction (AUC 0.71 and 0.75) compared to mpMRI + PSA alone (AUC 0.64 and 0.69 respectively). At a threshold of ≥35, PHI + mpMRI demonstrated a NPV of 0.97 for excluding significant tumours. In mpMRI negative men, the PHI again improved prediction of significant cancers; AUC 0.76 vs 0.63 (mpMRI + PSA). Using a PHI≥35, only 1/21 significant cancers was missed and 31/73 (42%) men potentially spared a re-biopsy (NPV of 0.97, sensitivity 0.95). Decision curve analysis demonstrated clinically relevant utility of the PHI across threshold probabilities of 5-30%. In summary, the PHI adds predictive performance to image-guided detection of clinically significant cancers and has particular value in determining re-biopsy need in men with a negative mpMRI.

Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study.

BACKGROUND: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. METHODS: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. FINDINGS: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. INTERPRETATION: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

Primary radical therapy selection in high-risk non-metastatic prostate cancer.

As the incidence of prostate cancer rises, the detection and management of men with high-risk non-metastatic prostate cancer is becoming increasingly important. The benefits of radical treatment have been clearly shown in this group from a number of publications. The current mainstays of treatment are radical prostatectomy (with selective use of adjuvant radiation) and radical radiotherapy with concurrent androgen deprivation. The outcomes from these two approaches seem to be remarkably similar and are considered equally valid options for primary treatment. The choice of therapy is critically dependent on a number of factors, but ultimately left to the decision of the patients with advice from clinicians. Clinicians themselves, however, are known to be biased towards their particular skill set and experiences. Attempts at randomised comparisons between these two modalities have so far failed and are confounded by patient-clinician bias, the continual advances in therapy as well as the long natural history of the disease. In the lack of level 1 comparable evidence, this article explores the existing literature as to the key factors that should be considered in radical treatment selection for high-risk prostate cancer. These factors include disease aggressiveness, comorbidity and life expectancy, functional outcomes and the consequences of therapy failure with regards to salvage treatment. We propose that these factors may be useful in developing a decision guide for rationale radical therapy selection in the light of two apparently equally effective treatments. Ultimately, however, there is an urgent need for added clinical and biological markers that can provide a more precise approach to therapy selection.

Identification of pathologically insignificant prostate cancer is not accurate in unscreened men.

BACKGROUND: Identification of men harbouring insignificant prostate cancer (PC) is important in selecting patients for active surveillance. Tools have been developed in PSA-screened populations to identify such men based on clinical and biopsy parameters. METHODS: Prospectively collected case series of 848 patients was treated with radical prostatectomy between July 2007 and October 2011 at an English tertiary care centre. Tumour volume was assessed by pathological examination. For each tool, receiver operator characteristics were calculated for predicting insignificant disease by three different criteria and the area under each curve compared. Comparison of accuracy in screened and unscreened populations was performed. RESULTS: Of 848 patients, 415 had Gleason 3+3 disease on biopsy. Of these, 32.0% had extra-prostatic extension and 50.2% were upgraded. One had positive lymph nodes. Two hundred and six (24% of cohort) were D'Amico low risk. Of these, 143 had more than two biopsy cores involved. None of the tools evaluated has adequate discriminative power in predicting insignificant tumour burden. Accuracy is low in PSA-screened and -unscreened populations. CONCLUSIONS: In our unscreened population, tools designed to identify insignificant PC are inaccurate. Detection of a wider size range of prostate tumours in the unscreened may contribute to relative inaccuracy.

Changing presentation of prostate cancer in a UK population--10 year trends in prostate cancer risk profiles in the East of England.

BACKGROUND: Prostate cancer incidence is rising in the United Kingdom but there is little data on whether the disease profile is changing. To address this, we interrogated a regional cancer registry for temporal changes in presenting disease characteristics. METHODS: Prostate cancers diagnosed from 2000 to 2010 in the Anglian Cancer Network (n=21,044) were analysed. Risk groups (localised disease) were assigned based on NICE criteria. Age standardised incidence rates (IRs) were compared between 2000-2005 and 2006-2010 and plotted for yearly trends. RESULTS: Over the decade, overall IR increased significantly (P<0.00001), whereas metastasis rates fell (P<0.0007). For localised disease, IR across all risk groups also increased but at different rates (P<0.00001). The most striking change was a three-fold increase in intermediate-risk cancers. Increased IR was evident across all PSA and stage ranges but with no upward PSA or stage shift. In contrast, IR of histological diagnosis of low-grade cancers fell over the decade, whereas intermediate and high-grade diagnosis increased significantly (P<0.00001). CONCLUSION: This study suggests evidence of a significant upward migration in intermediate and high-grade histological diagnosis over the decade. This is most likely to be due to a change in histological reporting of diagnostic prostate biopsies. On the basis of this data, increasing proportions of newly diagnosed cancers will be considered eligible for radical treatment, which will have an impact on health resource planning and provision.

Evidence for downregulation of the negative regulator SPRED2 in clinical prostate cancer.

BACKGROUND: SPRED1 and 2 are key negative regulators of MAPK signalling in mammalian cells. Here, we investigate the expression and functional role of SPREDs in prostate cancer. METHODS: A transcriptome bank of microdissected grade-specific primary cancers was constructed and interrogated for transcript expression of prostate cancer genes, known negative signalling regulators as well as SPRED1 and 2. The effect of SPRED2 manipulation was tested in in vitro assays. RESULTS: In a panel of 5 benign glands and 15 tumours, we observed concomitant downregulation of the negative regulators SEF and DUSP1 in tumours with increasing Gleason grade. Profiling in the same cohorts revealed downregulation of SPRED2 mRNA in tumours compared with benign glands (P<0.05). By contrast, SPRED1 expression remained unchanged. This observation was further validated in two additional separate cohorts of microdissected tumours (total of n=10 benign and n=58 tumours) with specific downregulation of SPRED2 particularly in higher grade tumours. In functional assays, SPRED2 overexpression reduced ERK phosphorylation and inhibited prostate cancer cell proliferation and migration in response to different growth factors and full-media stimulation (P<0.001). Conversely, SPRED2 suppression by siRNA enhanced the mitogenic response to growth factors and full media (P<0.001). CONCLUSION: These data suggest first evidence that SPRED2 is downregulated in prostate cancer and warrants further investigation as a potential tumour-suppressor gene.

Polymyalgia rheumatica following robotic radical prostatectomy.

INTRODUCTION: Polymyalgia rheumatica (PMR) is an inflammatory syndrome of unknown etiology has also been associated with concurrent malignancy. Here we report PMR occurring de novo in a man following successful robotic radical prostatectomy. PRESENTATION OF CASE: A 67-year-old gentleman underwent uneventful robotic assisted radical prostatectomy with complete excision of a T2(C) Gleason 7 tumour and a post-operative undetectable PSA. Three weeks after surgery he developed pain and weakness of the upper arms requiring increasing doses of opioids. Assessment identified a grossly elevated ESR and CRP consistent with a clinical diagnosis of PMR. Treatment with oral steroids led to a rapid resolution of symptoms. DISCUSSION: There have been reported cases of polymyalgia rheumatica occurring following surgical procedures but not with robotic prostate surgery. It has been proposed that surgical tissue injury can cause a release of inflammatory markers. Surgical stress-related sympathetic activation can also stimulate lymphocyte dependent inflammatory reactions by modulation of cytokine production and lymphocyte expressed adrenergic receptors. CONCLUSION: We present here the first reported case of PMR developing acutely after radical robotic prostatectomy. It is possible that the surgical procedure in this case had triggered polymyalgia rheumatica possibly through activation of immune-mediated systemic inflammatory responses.

Risk profiles of prostate cancers identified from UK primary care using national referral guidelines.

OBJECTIVE: Prostate cancer in the United Kingdom is mainly diagnosed from primary care referrals based on national guidelines published by the Department of Health. Here we investigated the characteristics of cancers detected through the use of these guidelines. METHODS: A prospective two-centre study was established to assess men referred from the primary care based on the UK national guidelines. RESULTS: The overall cancer detection rate was 43% (169 out of 397) with 15% (26 out of 169) of all cancers metastatic at presentation. Amongst 50-69-year-old men these rates were 34% (68 out of 200) and 15% (10 out of 68). Only 21% (25 out of 123) of men with local cancers had low-risk disease. In comparison to a historical cohort from 2001 (n=137) we found no overall differences in rates of metastatic disease, locally advanced tumours, or risk categories. Amongst 50-69-year-old men with local disease, however, we observed an increase in detection of low-risk cancers in a contemporary cohort (P=0.04). This was primarily because of the increased detection of low-stage organ-confined tumours in this group (P=0.02). CONCLUSION: Use of the UK prostate cancer guidelines detects a high proportion of clinically significant cancers. Use of the guidelines does not seem to have led to an overall change in the clinical characteristics of presenting cancers. There may, however, be a specific benefit in detecting more low-risk disease in younger men.

DCE and DW MRI in monitoring response to androgen deprivation therapy in patients with prostate cancer: a feasibility study.

Androgen deprivation therapy (ADT) is a key primary treatment for advanced and metastatic prostate cancer and is an important neoadjuvant before radiotherapy. We evaluated 3.0 T dynamic contrast-enhanced MRI and diffusion-weighted (DW) MRI in monitoring ADT response. Twenty-three consecutive patients with prostate cancer treated by primary ADT were included. Imaging was performed at baseline and 3 months posttreatment with ADT. After 3 months therapy there was a significant reduction in all dynamic contrast-enhanced MRI parameters measured in tumor regions of interest (K(trans), k(ep), v(p), IAUGC-90); P < 0.001. Areas of normal-appearing peripheral zone showed no significant change; P = 0.285-0.879. Post-ADT, there was no significant change in apparent diffusion coefficient values in tumors, whilst apparent diffusion coefficient values significantly decreased in areas of normal-appearing peripheral zone, from 1.786 × 10(-3) mm(2) /s to 1.561 × 10(-3) mm(2) /s; P = 0.007. As expected the median Prostate-Specific Antigen (PSA) significantly reduced from 30 ng/mL to 1.5 ng/mL posttreatment, and median prostate volume dropped from 47.6 cm(3) to 24.9 cm(3) ; P < 0.001. These results suggest that dynamic contrast-enhanced MRI and diffusion-weighted MRI offer different information but that both could prove useful adjuncts to the anatomical information provided by T2-weighted imaging. dynamic contrast-enhanced as a marker of angiogenesis may help demonstrate ADT resistance and diffusion-weighted imaging may be more accurate in determining presence of tumor cell death versus residual tumor.

Outcomes and predictive factors for biochemical relapse following primary androgen deprivation therapy in men with bone scan negative prostate cancer.

PURPOSE: Primary androgen deprivation therapy (PADT) is an important treatment modality for men with localized or locally advanced prostate cancer and without bone metastasis. There is, however, a lack of data on the biochemical relapse (BR) outcomes in these patients. Here, we studied the outcome of a contemporary series of men treated by PADT and investigated predictive risk factors for BR. METHODS: One hundred and fifty-five patients treated by PADT formed the initial study cohort, and BR outcomes in this group were reviewed. The outcomes of men with bone scan negative disease were specifically analysed. The predictive value of a panel of clinical risk factors for BR was evaluated using univariate and multivariate analysis. The results were further validated in a separate cohort of patients without bone metastasis from a second institution (n = 84). RESULTS: Median follow-up was 70 months. In the first study cohort, 109/155 men (70%) had bone scan negative disease. In these patients, only 45% developed BR during the follow-up period with only 28% relapsing within 5 years of initiating PADT. Key-independent factors predicting BR were a high PSA nadir (p = 0.001) and a shorter time to nadir (p < 0.001). A nadir of ≤0.1 ng/ml and time to nadir of >24 months specifically identified men with a very good outcome from PADT. In a second-independent cohort, very similar overall and 5-year BR rates were observed in men without bone metastasis (39 and 35%, respectively). PSA nadir thresholds identified in the first cohort were again able to define a good prognostic group in this re-test cohort (p = 0.005 and p = 0.01, respectively). CONCLUSION: Men treated by PADT and without bone metastasis can have very durable responses to PADT with the majority remaining BR free at 5 years. PSA nadir and time to nadir are key predictors of a good outcome in this group.

Does a pre-operative urodynamic diagnosis of bladder outflow obstruction improve outcomes from palliative transurethral prostatectomy?

OBJECTIVE: Palliative transurethral prostatectomy (TURP) is the mainstay of treatment for lower urinary tract symptoms, (LUTS) in men with prostate cancer. Functional outcomes, however, can often be unsatisfactory. Here the value of preoperative urodynamics was investigated in these men. METHODS: A retrospective review was conducted of 41 men with prostate cancer and LUTS who were investigated by urodynamics prior to TURP. All were treated solely by primary androgen deprivation. 19 men with urodynamic proven bladder outflow obstruction (BOO) proceeded to palliative TURP. RESULTS: Of the 41 men investigated by cystometry, the urodynamic diagnosis was BOO in 12 (29%) men, detrusor overactivity in 12 (29%) men with 7 (17%) having both diagnoses. 6 (15%) men were found to have underactive or acontractile detrusors while 4 (10%) had normal studies. In men who proceeded to TURP, all demonstrated improved flow rates (p = 0.003). At 12 months, 95% were voiding spontaneously with only 1 man requiring permanent re-catheterisation. These results compared very favourably to published outcomes which have not used urodynamics to select men for surgery. CONCLUSIONS: Urodynamics may help identify objective BOO prior to palliative TURP. Further prospective trials are justified to assess the role of urodynamics in this context.