Surgery Versus Radiation for High-risk Prostate Cancer: The Fight Continues. But Is It Time To Call a Draw and Reach Consensus?

N/

Making Sense of Your Medical Career Riaz Agha. Published by Hodder Arnold, ISBN 0340887370 (Price £15.99, 200 pp.)

Unknow

Effect of Comorbidity on Prostate Cancer-Specific Mortality: A Prospective Observational Study.

Purpose To determine the effect of comorbidity on prostate cancer (PCa)-specific mortality across treatment types. Patients and Methods These are the results of a population-based observational study in Sweden from 1998 to 2012 of 118,543 men who were diagnosed with PCa with a median follow-up of 8.3 years (interquartile range, 5.2 to 11.5 years) until death from PCa or other causes. Patients were categorized by patient characteristics (marital status, educational level) and tumor characteristics (serum prostate-specific antigen, tumor grade and clinical stage) and by treatment type (radical prostatectomy, radical radiotherapy, androgen deprivation therapy, and watchful waiting). Data were stratified by Charlson comorbidity index (0, 1, 2, or ≥ 3). Mortality from PCa and other causes and after stabilized inverse probability weighting adjustments for clinical patient and tumor characteristics and treatment type was determined. Kaplan-Meier estimates and Cox proportional hazards regression models were used to calculate hazard ratios. Results In the complete unadjusted data set, we observed an effect of increased comorbidity on PCa-specific and other-cause mortality. After adjustments for patient and tumor characteristics, the effect of comorbidity on PCa-specific mortality was lost but maintained for other-cause mortality. After additional adjustment for treatment type, we again failed to observe an effect for comorbidity on PCa-specific mortality, although it was maintained for other-cause mortality. Conclusion This large observational study suggests that comorbidity affects other cause-mortality but not PCa-specific- mortality after accounting for patient and tumor characteristics and treatment type. Regardless of radical treatment type (radical prostatectomy or radical radiotherapy), increasing comorbidity does not seem to significantly affect the risk of dying from PCa. Consequently, differences in oncologic outcomes that were observed in population-based comparative effectiveness studies of PCa treatments may not be a result of the varying distribution of comorbidity among treatment groups

Correlation of Urinary Engrailed-2 Levels to Tumour Volume and Pathological Stage in Men Undergoing Radical Prostatectomy

yesThe aim of this study was to assess the relationship between pre-prostatectomy urinary Engrailed-2 (EN2), a transcription factor secreted by prostate cancer cells, with tumour volume and pathological characteristics in resected prostate specimens. First pass urine samples (10 ml) without prior prostatic massage were collected and stored at –80°C. EN2 levels were measured using an enzyme-linked immunoabsorbent assay. Tumour volume in the prostatectomy specimens was determined histologically. 57 men undergoing RP in one urological cancer network were evaluated. EN2 was detected in 85% of RP patients. EN2 correlated with tumour volume (but not total prostatic volume) in a linear regression analysis, with increasing pathological T stage and margin positivity. Using three “cutoff levels” of tumour volume (0.5 ml, 1.3 ml and 2.5 ml) to define “significant disease”, men with “significant disease” had markedly higher levels of urinary EN2 (p < 0.001 for each cut off level). Levels of urinary EN2 may be useful in predicting tumour volume in men with prostate cancer by potentially identifying men with small volume “insignificant” disease. This study justifies a larger multicentre evaluation of urinary EN2 levels as a biomarker of PC significance using cancer volume, pathological and PSA criteria

Renal angiomyolipoma presenting with massive retroperitoneal haemorrhage due to deranged clotting factors: a case report

BACKGROUND: Angiomyolipomata of the kidney are unusual lesions composed of abnormal vasculature, smooth muscle, and adipose elements. They may be associated with tuberous sclerosis and occasionally present with flank pain, a palpable mass, and gross haematuria. As angiomyolipomata grow their risk of bleeding increases, with a greater than 50% chance of significant bleeding in lesions &gt; 4 cm; anticoagulant therapy accentuates this risk. CASE PRESENTATION: A case of massive retroperitoneal haemorrhage in a patient on warfarin is presented. The underlying diagnosis of renal angiomyolipoma was diagnosed based on CT findings. Emergency resuscitation and selective interpolar arterial embolization was performed which saved the patient's life as well as his kidney. CONCLUSION: This case illustrates the clinical scenario of massive retroperitoneal haemorrhage in an anticoagulated patient with renal angiomyolipomata. In the emergent situation, adequate resuscitation along ABC principles, as well as control of haemorrhage with either nephrectomy (partial or radical), non-selective renal arterial embolization, or selective embolization of the feeding vessel(s), is necessary. For this to occur, it is imperative to consider the diagnosis early in warfarinized patients (and others at risk of bleeding) who present with abdominal pain. The authors hope this case report highlights to readers the clinical scenario of massive retroperitoneal haemorrhage in anticoagulated patients with renal angiomyolipomata so that they can deal appropriately with such presentations

Comparing a new risk prediction model with prostate cancer risk calculator apps in a Taiwanese population

PURPOSE: To develop a novel Taiwanese prostate cancer (PCa) risk model for predicting PCa, comparing its predictive performance with that of two well-established PCa risk calculator apps. METHODS: 1545 men undergoing prostate biopsies in a Taiwanese tertiary medical center between 2012 and 2019 were identified retrospectively. A five-fold cross-validated logistic regression risk model was created to calculate the probabilities of PCa and high-grade PCa (Gleason score ≧ 7), to compare those of the Rotterdam and Coral apps. Discrimination was analyzed using the area under the receiver operator characteristic curve (AUC). Calibration was graphically evaluated with the goodness-of-fit test. Decision-curve analysis was performed for clinical utility. At different risk thresholds to biopsy, the proportion of biopsies saved versus low- and high-grade PCa missed were presented. RESULTS: Overall, 278/1309 (21.2%) patients were diagnosed with PCa, and 181 out of 278 (65.1%) patients had high-grade PCa. Both our model and the Rotterdam app demonstrated better discriminative ability than the Coral app for detection of PCa (AUC: 0.795 vs 0.792 vs 0.697, DeLong's method: P < 0.001) and high-grade PCa (AUC: 0.869 vs 0.873 vs 0.767, P < 0.001). Using a ≥ 10% risk threshold for high-grade PCa to biopsy, our model could save 67.2% of total biopsies; among these saved biopsies, only 3.4% high-grade PCa would be missed. CONCLUSION: Our new logistic regression model, similar to the Rotterdam app, outperformed the Coral app in the prediction of PCa and high-grade PCa. Additionally, our model could save unnecessary biopsies and avoid missing clinically significant PCa in the Taiwanese population

Ex-vivo Fluorescence Confocal Microscopy: The First Application For Real-Time Pathologic Examination of Prostatic Tissue

Prostate cancer "real time" intra-operative pathological examination currently utilizes frozen section, despite the many inherent limitations of this procedure. Ex vivo Fluorescence Confocal Microscopy (FCM) is a novel technology, which provides fast microscopic fluorescence and reflectance tissue imaging. FCM has been proven beneficial in colorectal, breast, thyroid and skin lesions. However, it was never applied in urology. The aim of our study is to report the first application of FCM in the urologic field assessing its diagnostic accuracy for non-neoplastic and cancerous prostate tissue (prostatic adenocarcinoma) compared to the gold standard histopathological diagnoses.Objective: To report the first application of ex vivo fluorescence confocal microscopy (FCM) - a novel optical technology that is capable of providing fast microscopic imaging of unfixed tissue specimens- in the urological field assessing its diagnostic accuracy for non neoplastic and cancerous prostate tissue (prostatic adenocarcinoma) compared to the 'gold standard' histopathological diagnoses. Patients and methods: In all, 89 specimens from 13 patients with clinically localised prostate cancer were enrolled into the study. All patients underwent robot-assisted laparoscopic radical prostatectomy with fresh prostatic tissue biopsies taken at the end of each intervention using an 18-G biopsy punch. Specimens were randomly assigned to the three collaborating pathologists for evaluation. Intra- and inter-observer agreement was tested by the means of Cohen's κ. The diagnostic performance was evaluated on receiver operating characteristic curve analysis. Results: The overall diagnostic agreement between FCM and histopathological diagnoses was substantial with a 91% correct diagnosis (κ&nbsp;=&nbsp;0.75) and an area under the curve of 0.884 (95% confidence interval 0.840–0.920), 83.33% sensitivity, and 93.53% specificity. Conclusion: FCM seems to be a promising tool for enhanced specimens' reporting performance, given its simple application and very rapid microscopic image generation (&lt;5&nbsp;min/specimen). This technique may potentially be used for intraoperative pathological specimens' analysis

Role of multiparametric magnetic resonance imaging in early detection of prostate cancer.

UNLABELLED: Most prostate cancers (PC) are currently found on the basis of an elevated PSA, although this biomarker has only moderate accuracy. Histological confirmation is traditionally obtained by random transrectal ultrasound guided biopsy, but this approach may underestimate PC. It is generally accepted that a clinically significant PC requires treatment, but in case of an non-significant PC, deferment of treatment and inclusion in an active surveillance program is a valid option. The implementation of multiparametric magnetic resonance imaging (mpMRI) into a screening program may reduce the risk of overdetection of non-significant PC and improve the early detection of clinically significant PC. A mpMRI consists of T2-weighted images supplemented with diffusion-weighted imaging, dynamic contrast enhanced imaging, and/or magnetic resonance spectroscopic imaging and is preferably performed and reported according to the uniform quality standards of the Prostate Imaging Reporting and Data System (PIRADS). International guidelines currently recommend mpMRI in patients with persistently rising PSA and previous negative biopsies, but mpMRI may also be used before first biopsy to improve the biopsy yield by targeting suspicious lesions or to assist in the selection of low-risk patients in whom consideration could be given for surveillance. TEACHING POINTS: ? MpMRI may be used to detect or exclude significant prostate cancer. ? MpMRI can guide targeted rebiopsy in patients with previous negative biopsies. ? In patients with negative mpMRI consideration could be given for surveillance. ? MpMRI may add valuable information for the optimal treatment selection

Outcomes of the RAFT Trial: Robotic surgery After Focal Therapy

OBJECTIVES: To report toxicity of treatment observed in men participating in the Robotic surgery After Focal Therapy (RAFT) clinical trial. SUBJECTS/PATIENTS AND METHODS: Men were eligible for this prospective single group interventional study if they had histologically confirmed recurrent/residual prostate adenocarcinoma following primary FT. The short-form Expanded Prostate Cancer Index Composite (EPIC-26) measured prior to salvage robotic prostatectomy (S-RARP) and 3-monthly post-operatively together with Clavien-Dindo complications (I-IV). Secondary outcomes included biochemical recurrence-free survival (BCFS) following surgery and need for salvage treatment after surgery. This study is registered with ClinicalTrials.gov NCT03011606. RESULTS: 24 men were recruited between February 2016 and September 2018. 1 patient withdrew from the trial after consenting and before S-RARP. 23 men completed 12-month post S-RARP follow-up. Median EPIC-26 urinary continence scores initially deteriorated after 3 months (82.4 versus 100) but there was no statistically significant difference from baseline at 12 months (100 versus 100, p=0.31). Median lower urinary tract symptom scores improved after 12 months compared to baseline (93.8 versus 87.5, p=0.01). At 12 months, 19/23 (83%) were pad-free and 22/23 (96%) required 0/1 pads. Median sexual function subscale scores deteriorated and remained low at 12 months (22.2 versus 58.3, p<0.001). Utilising a minimally important difference of 9 points, at 12 months after surgery 17/23 (74%) reported urinary continence to be "better" or "not different" to pre-operative baseline. The corresponding figure for sexual function (utilising a minimally important difference of 12 points) was 7/23 (30%). There was no statistically significant difference on median bowel/hormonal subscale scores. Only a single patient had a post-operative complication (Clavien-Dindo Grade I). BCFS at 12 months after surgery was 82.6% (95% confidence interval [CI]: 60.1% - 93.1%] while 4/23 (17%) received salvage radiation. CONCLUSIONS: The RAFT clinical trial suggests toxicity of surgery after FT is low, with good urinary function outcomes, albeit sexual function deteriorated overall. Oncological outcomes at 12 months appear acceptable

Best practice considerations on the assessment of robotic assisted surgical systems:results from an international consensus expert panel

Background Health technology assessments (HTAs) of robotic assisted surgery (RAS) face several challenges in assessing the value of robotic surgical platforms. As a result of using different assessment methods, previous HTAs have reached different conclusions when evaluating RAS. While the number of available systems and surgical procedures is rapidly growing, existing frameworks for assessing MedTech provide a starting point, but specific considerations are needed for HTAs of RAS to ensure consistent results. This work aimed to discuss different approaches and produce guidance on evaluating RAS. Methods A consensus conference research methodology was adopted. A panel of 14 experts was assembled with international experience and representing relevant stakeholders: clinicians, health economists, HTA practitioners, policy makers, and industry. A review of previous HTAs was performed and seven key themes were extracted from the literature for consideration. Over five meetings, the panel discussed the key themes and formulated consensus statements. Results A total of ninety-eight previous HTAs were identified from twenty-five total countries. The seven key themes were evidence inclusion and exclusion, patient- and clinician-reported outcomes, the learning curve, allocation of costs, appropriate time horizons, economic analysis methods, and robotic ecosystem/wider benefits. Conclusions Robotic surgical platforms are tools, not therapies. Their value varies according to context and should be considered across therapeutic areas and stakeholders. The principles set out in this paper should help HTA bodies at all levels to evaluate RAS. This work may serve as a case study for rapidly developing areas in MedTech that require particular consideration for HTAs.</p