Role of serum response factor expression in prostate cancer biochemical recurrence.

BACKGROUND: Up to a third of prostate cancer patients fail curative treatment strategies such as surgery and radiation therapy in the form of biochemical recurrence (BCR) which can be predictive of poor outcome. Recent clinical trials have shown that men experiencing BCR might benefit from earlier intervention post-radical prostatectomy (RP). Therefore, there is an urgent need to identify earlier prognostic biomarkers which will guide clinicians in making accurate diagnosis and timely decisions on the next appropriate treatment. The objective of this study was to evaluate Serum Response Factor (SRF) protein expression following RP and to investigate its association with BCR. MATERIALS AND METHODS: SRF nuclear expression was evaluated by immunohistochemistry (IHC) in TMAs across three international radical prostatectomy cohorts for a total of 615 patients. Log-rank test and Kaplan-Meier analyses were used for BCR comparisons. Stepwise backwards elimination proportional hazard regression analysis was used to explore the significance of SRF in predicting BCR in the context of other clinical pathological variables. Area under the curve (AUC) values were generated by simulating repeated random sub-samples. RESULTS: Analysis of the immunohistochemical staining of benign versus cancer cores showed higher expression of nuclear SRF protein expression in cancer cores compared with benign for all the three TMAs analysed (P < 0.001, n = 615). Kaplan-Meier curves of the three TMAs combined showed that patients with higher SRF nuclear expression had a shorter time to BCR compared with patients with lower SRF expression (P < 0.001, n = 215). Together with pathological T stage T3, SRF was identified as a predictor of BCR using stepwise backwards elimination proportional hazard regression analysis (P = 0.0521). Moreover ROC curves and AUC values showed that SRF was better than T stage in predicting BCR at year 3 and 5 following radical prostatectomy, the combination of SRF and T stage had a higher AUC value than the two taken separately. CONCLUSIONS: SRF assessment by IHC following RP could be useful in guiding clinicians to better identify patients for appropriate follow-up and timely treatment.

Ex vivo metabolic fingerprinting identifies biomarkers predictive of prostate cancer recurrence following radical prostatectomy.

This corrects the article DOI: 10.1038/bjc.2017.346.

Ex vivo metabolic fingerprinting identifies biomarkers predictive of prostate cancer recurrence following radical prostatectomy.

BACKGROUND: Robust biomarkers that identify prostate cancer patients with high risk of recurrence will improve personalised cancer care. In this study, we investigated whether tissue metabolites detectable by high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) were associated with recurrence following radical prostatectomy. METHODS: We performed a retrospective ex vivo study using HR-MAS MRS on tissue samples from 110 radical prostatectomy specimens obtained from three different Norwegian cohorts collected between 2002 and 2010. At the time of analysis, 50 patients had experienced prostate cancer recurrence. Associations between metabolites, clinicopathological variables, and recurrence-free survival were evaluated using Cox proportional hazards regression modelling, Kaplan-Meier survival analyses and concordance index (C-index). RESULTS: High intratumoural spermine and citrate concentrations were associated with longer recurrence-free survival, whereas high (total-choline+creatine)/spermine (tChoCre/Spm) and higher (total-choline+creatine)/citrate (tChoCre/Cit) ratios were associated with shorter time to recurrence. Spermine concentration and tChoCre/Spm were independently associated with recurrence in multivariate Cox proportional hazards modelling after adjusting for clinically relevant risk factors (C-index: 0.769; HR: 0.72; P=0.016 and C-index: 0.765; HR: 1.43; P=0.014, respectively). CONCLUSIONS: Spermine concentration and tChoCre/Spm ratio in prostatectomy specimens were independent prognostic markers of recurrence. These metabolites can be noninvasively measured in vivo and may thus offer predictive value to establish preoperative risk assessment nomograms.

Psychometric testing of the Norwegian version of the Expanded Prostate Cancer Index Composite 26-item version (EPIC-26).

OBJECTIVES: In patients with prostate cancer, evaluation of quality of care requires the inclusion of patient-reported outcomes measures assessed by validated and reliable instruments. Basic psychometric tests of the Norwegian version of the Expanded Prostate Cancer Index Composite with 26 items (EPIC-26) were performed in this study. MATERIAL AND METHODS: Translation of the original questionnaire (University of California, Los Angeles Prostate Cancer Index Composite), field testing and retranslation were done according to published guidelines. The final EPIC-26 items were subsequently selected from the Norwegian version of the EPIC-50 with slight verbal adjustments to comply with the English version of the EPIC-26. Reliability and validity were tested among 471 patients who, between 2009 and 2010, had been included in a prospective Norwegian multicenter study assessing adverse effects after radical prostatectomy or prostatic radiotherapy, usually combined with (neo)adjuvant hormone treatment. All patients completed the EPIC-26 before treatment and 3 and 12 months afterwards. RESULTS: Internal consistency was documented by Cronbach's alpha coefficients ranging from 0.64 to 0.91 for the five domains/subdomains. Item-to-scale correlation coefficients ranged from 0.20 to 0.88, with the lowest value (0.20) for overall sexual problem. Criterion validity was proven by significant correlations between individual responses to the International Prostate Symptom Score and sum scores of the irritative/obstructive subdomain score of the EPIC-26. Satisfactory sensitivity and responsiveness reflected clinical utility for assessing between-group differences and treatment-related changes. CONCLUSIONS: Based on basic psychometric tests, the Norwegian version of the EPIC-26 showed acceptable reliability and validity for assessment of adverse effects after treatment of non-metastatic prostate cancer.

Detection of the index tumour and tumour volume in prostate cancer using T2-weighted and diffusion-weighted magnetic resonance imaging (MRI) alone.

OBJECTIVE: To examine the performance of T2-weighted (T2W) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for detecting the index tumour in patients with prostate cancer and to examine the agreement between MRI and histology when assessing tumour volume (TV) and overall tumour burden. PATIENTS AND METHODS: The study included 199 consecutive patients with biopsy confirmed prostate cancer randomised to MRI before radical prostatectomy from December 2009 to July 2012. MRI-detected tumours (MRTs) were ranked from 1 to 3 according to decreasing volume and were compared with histologically detected tumours (HTs) ranked from 1 to 3, with HT 1 = index tumour. Whole-mount section histology was used as a reference standard. The TVs of true-positive MRTs (MRTVs 1-3) were compared with the TVs found by histology (HTVs 1-3). All tumours were registered on a 30-sector map and by classifying each sector as positive/negative, the rate of true-positive and -negative sectors was calculated. RESULTS: The detection rate for the HT 1 (index tumour) was 92%; HT 2, 45%; and HT 3, 37%. The MRTV 1-3 vs the HTV 1-3 were 2.8 mL vs 4.0 mL (index tumour, P < 0.001), 1.0 mL vs 0.9 mL (tumour 2, P = 0.413), and 0.6 mL vs 0.5 mL (tumour 3, P = 0.492). The rate of true-positive and -negative sectors was 50% and 88%, κ = 0.39. CONCLUSION: A combination of T2W and DW MRI detects the index tumour in 92% of cases, although MRI underestimates both TV and tumour burden compared with histology.

Pathogens in Urine from a Female Patient with Overactive Bladder Syndrome Detected by Culture-independent High Throughput Sequencing: A Case Report.

INTRODUCTION: Overactive bladder syndrome (OAB) is described as urgency, with or without urgency incontinence. A range of medical conditions shares the symptoms of OAB, however the diagnosis is contingent on the exclusion of urinary tract infection (UTI). Knowing that urine dipstick and routine culture of bacteria can miss UTI diagnosis caused by low-count bacteriuria or "difficult-to-culture" pathogens, we examined a case of OAB with a culture-independent approach. CASE PRESENTATION: A 61-year-old Norwegian female with a long history of urinary symptoms and a diagnosis of OAB was selected as a suitable subject for a culture-independent 16S rDNA analysis on the patient´s urine. The patient's medical records showed no history of recurrent UTI, however, when the urine specimen was sent to routine culture at the time of study it showed a significant bacteriuria caused by a single bacterium, and the patient was prescribed antibiotics. The 16S rDNA analysis revealed not one, but many different bacteria, including a considerable amount of fastidious bacteria, indicating a polymicrobial state. One year later, the subject was still experiencing severe symptoms, and a follow-up analysis was performed. This time the urine-culture was negative, however, the 16S rDNA profile was quite similar to that of the first sample, again displaying a complex bacterial profile. CONCLUSION: The use of 16S rDNA pyrosequencing and sequence analysis to uncover "difficult-to-culture" bacteria should be considered when examining patients with chronic urinary symptoms. These methods may contribute to further elucidation of the etiology of overactive bladder syndrome and other urinary syndromes.

A prospective study of transition from laparoscopic to robot-assisted radical prostatectomy: quality of life outcomes after 36-month follow-up.

OBJECTIVE: To compare quality of life (QOL) outcomes after conversion from laparoscopic radical prostatectomy (LRP) to robot-assisted radical prostatectomy (RALP) as the routine procedure for surgical treatment of localized cancer of the prostate (CaP). METHODS: In November 2007, we changed the routine operative technique for localized CaP from LRP to RALP. The last 210 consecutive patients operated with LRP were compared with the first 210 consecutive patients operated with RALP. The patients were mailed University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and Short Form Health Survey (SF)-12 questionnaires at baseline and at 3, 12, and 36-month follow-up. RESULTS: In the LRP group, 89.0%, 93.8%, 93.8%, and 88.1% of patients answered questionnaires at baseline and at 3, 12, and 36-month follow-up. The corresponding numbers in the RALP group were 92.4%, 94.3%, 85.7%, and 76.4%. At 36-month follow-up, 87.9% and 82.6% of LRP and RALP patients, respectively, had regained baseline urinary function score (ns). At 36-month follow-up, 57.3% and 61.3% of LRP and RALP patients, respectively, had regained baseline sexual function score (ns). Nerve-sparing surgical procedures mitigated the adverse effects on sexual function in both groups. Surgical method was not associated with urinary function and sexual function at 36 months. Better urinary function was associated with better general mental health. CONCLUSION: Introduction of RALP did not result in improvement of functional outcome. There was no difference regarding urologic function/bother score or sexual function/bother score at 36-month follow-up in patients treated with LRP or RALP.

Can sexual bother after radical prostatectomy be predicted preoperatively? Findings from a prospective national study of the relation between sexual function, activity and bother.

UNLABELLED: What's known on the subject? And what does the study add? Sexual function is often impaired after radical prostatectomy resulting in reduced sexual activity and sexual bother. The main focus in the literature concerning sexual adverse effects has been on erectile dysfunction and impairment of sexual function rather than the actual sexual bother it causes, although the sexual bother is most important to the individual patient's quality of life. The relation between these measures, and in particular preoperative prediction of postoperative sexual bother, has only been studied in a limited way and with varying results. Some studies have found good mental health, low levels of preoperative sexual bother, and higher education to be associated with absence of postoperative sexual bother, but another study could not identify any preoperative predictors of postoperative sexual bother. Severe sexual bother after radical prostatectomy was reported by 64% to 95% of patients 3 years after operation, and the prevalence was associated with the level of pretreatment sexual bother and peroperative nerve preservation. On the other hand, others have reported that only 43% of men have sexual bother 2 years after radical prostatectomy. However, none of these studies stratified patients according to their preoperative sexual activity and most of them were American. It has been shown that American findings concerning sexual bother may not always be valid for non-American patients due to differing sex role expectations, thus warranting the need for more non-American studies. This study has shown that two-thirds of patients experienced sexual bother 1 year after radical prostatectomy. We have identified patients with increased risk of experiencing overall sexual bother postoperatively: those who report preoperative sexual bother, those who are sexually active before radical prostatectomy, and those who display neurotic personality traits. Another important finding is that the proportion of patients who experienced bother relevant to having impaired postoperative sexual function was significantly higher among preoperatively sexually active patients than those who had been inactive. This study adds knowledge that patients' preoperative sexual activity, sexual bother and personality should be taken into account to be able to give individualized information about the risk of experiencing sexual bother after radical prostatectomy. Study Type--Therapy (outcomes research). Level of Evidence 2c. OBJECTIVE: • To explore the prevalence and prediction of overall sexual bother (SB) 1 year after radical prostatectomy (RP) in relation to preoperative sexual activity and postoperative sexual function. PATIENTS AND METHODS: • This prospective national study included 453 men who completed the sexual domain of the Expanded Prostate Cancer Index Composite before and 1 year after RP. • Preoperatively the patients were classified as sexually active or inactive based on frequency of intercourse during the previous 4 weeks. • The prevalence of 1-year SB and the proportion of bothered patients with impaired sexual function were calculated. • Preoperative factors significantly associated with postoperative SB on univariate analysis (P < 0.05) were included in multivariate regression analysis, post-prostatectomy SB being the dependent variable. RESULTS: • The prevalence of SB increased from 18% preoperatively to 66% at 1 year after RP with a larger proportion of change in the active than the inactive group (59% vs 25%). • The proportion of men reporting postoperative SB related to their impaired sexual function 1 year after RP was significantly higher in the preoperatively sexually active group (83%) compared with the inactive group (63%). • In multivariate analysis preoperative SB, sexual activity and nervousness (neuroticism) significantly predicted postoperative SB with odds ratios of 3.71, 2.11 and 1.57, respectively. CONCLUSION: • Sexual activity and SB the last month before prostatectomy and neuroticism identify men at risk of developing SB 1 year postoperatively. Assessment of preoperative sexual activity and SB should be a part of preoperative counselling.

Comparative study of pressure-flow parameters.

Methods for quantification of bladder outlet obstruction (BOO) are still controversial. Parameters such as detrusor opening pressure (p(det.open)), maximum detrusor pressure (p(det.max)), minimum voiding pressure (p(det.min.void)), and detrusor pressure at maximum flow rate (P(det.Qmax)) separate obstructed from nonobstructed patients to some extent, but two nomograms, the Abrams-Griffiths nomogram and the linearized passive urethral resistance relation (LinPURR), are more accepted for this purpose, along with the urethral resistance algorithm. In this retrospective, methodologic study, we evaluated the properties of these parameters with regard to test-retest reproducibility and ability to detect a moderate (pharmacologic) and a pronounced (surgical) relief of bladder outlet obstruction. We studied the pressure-flow charts of 42 patients who underwent 24 weeks of androgen suppressive therapy, 42 corresponding patients who received placebo, and 30 patients who had prostate surgery. The patients performed repeat void pressure-flow examinations before and after treatment or placebo. The various parameters were compared. Among the bladder pressure parameters, P(det.Qmax) seemed to have some advantages, supporting the belief that it is the most relevant detrusor pressure parameter to include in nomograms to quantify BOO. In assessment of a large decrease in urethral resistance, such as after TURp, resistance parameters that are based on maximum flow rate as well as detrusor pressure are preferable.