Thomas McNicholas

Serum Isoform [−2]proPSA Derivatives Significantly Improve Prediction of Prostate Cancer at Initial Biopsy in a Total PSA Range of 2–10 ng/ml: A Multicentric European Study

BACKGROUND Strategies to reduce prostate-specific antigen (PSA)-driven prostate cancer (PCa) overdiagnosis and overtreatment seem to be necessary. OBJECTIVE To test the accuracy of serum isoform [-2]proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (fPSA; %p2PSA) and the Prostate Health Index (PHI)-called index tests-in discriminating between patients with and without PCa. DESIGN, SETTING, AND PARTICIPANTS This was an observational, prospective cohort study of patients from five European urologic centers with a total PSA (tPSA) range of 2-10 ng/ml who were subjected to initial prostate biopsy for suspected PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary end point was to evaluate the specificity, sensitivity, and diagnostic accuracy of index tests in determining the presence of PCa at prostate biopsy in comparison to tPSA, fPSA, and percentage of fPSA to tPSA (%fPSA) (standard tests) and the number of prostate biopsies that could be spared using these tests. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. RESULTS AND LIMITATIONS Of >646 patients, PCa was diagnosed in 264 (40.1%). Median tPSA (5.7 vs 5.8 ng/ml; p=0.942) and p2PSA (15.0 vs 14.7 pg/ml) did not differ between groups; conversely, median fPSA (0.7 vs 1 ng/ml; p<0.001), %fPSA (0.14 vs 0.17; p<0.001), %p2PSA (2.1 vs 1.6; p<0.001), and PHI (48.2 vs 38; p<0.001) did differ significantly between men with and without PCa. In multivariable logistic regression models, p2PSA, %p2PSA, and PHI significantly increased the accuracy of the base multivariable model by 6.4%, 5.6%, and 6.4%, respectively (all p<0.001). At a PHI cut-off of 27.6, a total of 100 (15.5%) biopsies could have been avoided. The main limitation is that cases were selected on the basis of their initial tPSA values. CONCLUSIONS In patients with a tPSA range of 2-10 ng/ml, %p2PSA and PHI are the strongest predictors of PCa at initial biopsy and are significantly more accurate than tPSA and %fPSA.

Clinical performance of serum prostate-specific antigen isoform (-2)proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project

To test the sensitivity, specificity and accuracy of serum prostate‐specific antigen isoform [‐2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI.

Complications of vasectomy.

INTRODUCTION Vasectomy is a common method of sterilisation. However, it is less popular than tubal ligation world-wide. It is also a frequent cause of litigation relating to its complications. This article reviews the early and late risks associated with the procedure. PATIENTS AND METHODS Data collection was done using the internet to search Medline for obtaining evidence-based medicine reviews. Cross-references were obtained from key articles. Websites of government bodies and medical associations were searched for guidelines relating to vasectomy. DISCUSSION Early complications include haematoma, wound and genito-urinary infections, and traumatic fistulae. Vasectomy failure occurs in 0-2% of patients. Late recanalisation causes failure in 0.2% of vasectomies. Significant chronic orchalgia may occur in up to 15% of men after vasectomy, and may require epididyectomy or vasectomy reversal. Antisperm antibodies develop in a significant proportion of men post-vasectomy, but do not increase the risk of immune-complex or atherosclerotic heart disease. Similarly, vasectomy does not enhance risk of testicular or prostate cancer. Vasectomy has a lower mortality as compared to tubal occlusion, but is still significantly high in non-industrialised countries because of infections. CONCLUSIONS Vasectomy, though safe and relatively simple, requires a high level of expertise to minimise complications. Adequate pre-operative counselling is essential to increase patient acceptability of this method of permanent contraception.

Multicenter European External Validation of a Prostate Health Index–based Nomogram for Predicting Prostate Cancer at Extended Biopsy

BACKGROUND External validation of a prediction tool is mandatory to assess the tools accuracy and generalizability within different patient cohorts. OBJECTIVE To externally validate a previously developed Prostate Health Index (PHI)-based nomogram for predicting the presence of prostate cancer (PCa) at biopsy. DESIGN, SETTING, AND PARTICIPANTS The study population consisted of 883 patients who were scheduled for a prostate biopsy at one of five European tertiary care centers. Total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and [-2]pro-prostate-specific antigen (p2PSA) levels were determined. The fPSA-to-tPSA ratio (%fPSA), p2PSA, and PHI ([p2PSA / fPSA] × √tPSA) were calculated. INTERVENTION Extended initial and repeat prostate biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Logistic regression models were fitted to test the predictors of PCa and to determine their predictive accuracy. A calibration plot was used to evaluate the extent of overestimation or underestimation between nomogram predictions and observed PCa rate. Decision curve analysis (DCA) provided an estimate of the net benefit obtained by using the PHI-based nomogram. RESULTS AND LIMITATIONS Of 833 patients, 365 (41.3%) were diagnosed with PCa at extended prostate biopsy. In accuracy analyses, PHI was the most informative predictor of PCa (0.68), outperforming tPSA (0.51) and %fPSA (0.64). The predictive accuracy of the previously developed nomogram was 75.2% (95% confidence interval, 71.4-78.1). Calibration of the nomogram was good in patients at a low to intermediate predicted probability of PCa, while calibration was suboptimal, with a tendency to overestimate the presence of PCa, in high-risk patients. Finally, DCA demonstrated that the use of the PHI-based nomogram resulted in the highest net benefit. The main limitation of the study is the fact that only Caucasian patients were included. CONCLUSIONS At external validation, the previously developed PHI-based nomogram confirmed its ability to determine the presence of PCa at biopsy. These findings provide further evidence supporting the potential role of the nomogram in the biopsy decision pathway for European men with suspected PCa. PATIENT SUMMARY In the current study, we externally validated a Prostate Health Index-based nomogram to predict the presence of prostate cancer (PCa) at biopsy. This tool may help clinicians determine the need for a prostate biopsy in European patients with suspected PCa.

Successful Use of Steroids and Ureteric Stents in 24 Patients with Idiopathic Retroperitoneal Fibrosis: A Retrospective Study

Background/Aims: Retroperitoneal fibrosis (RPF) is a chronic inflammatory disorder causing obstructive nephropathy and renal failure. We reviewed our management of this condition. Method: All patients with RPF treated at a single center over a 15-year period were identified. A full review of notes and computer records was undertaken. Results: Data was available on 27 patients, 3 of which were excluded from later analysis. Diagnosis was based on clinical history and cross-sectional imaging. Retroperitoneal biopsy was undertaken in 3 patients. 96% had significant renal impairment at presentation with a mean serum creatinine of 688 µmol/l. 46% required emergency hemodialysis. All patients were treated with a combination of ureteric stents and/or steroids with an excellent clinical response. The mean best creatinine reached by the cohort was 136 µmol/l, and renal function remained stable in the long term. No patients required chronic dialysis. Ureteric stents were removed within 12 months and low-dose steroids were continued for a mean of 34 months. Recurrent disease was observed in 25% of patients, who all responded well to further steroid therapy. Mean duration of follow-up was 76 months. Conclusions: RPF is very effectively treated by a combination of ureteric stents and steroids, with excellent long-term results using this approach. Continued follow-up is advised because of the possibility of recurrent disease.

Preoperative Prostate-specific Antigen Isoform p2PSA and Its Derivatives, %p2PSA and Prostate Health Index, Predict Pathologic Outcomes in Patients Undergoing Radical Prostatectomy for Prostate Cancer: Results from a Multicentric European Prospective Study.

BACKGROUND Currently available predictive models fail to assist clinical decision making in prostate cancer (PCa) patients who are potential candidates for radical prostatectomy (RP). New biomarkers would be welcome. OBJECTIVE To test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its derivatives, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI), predict PCa characteristics at final pathology. DESIGN, SETTING, AND PARTICIPANTS An observational prospective multicentre European study was performed in 489 consecutive PCa patients treated with RP. Total PSA (tPSA), free PSA (fPSA), and p2PSA levels were determined. The %fPSA [(fPSA / tPSA) × 100], %p2PSA [(p2PSA pg/ml) / (fPSA ng/ml × 1000) × 100], and PHI [(p2PSA / fPSA) × √tPSA] were calculated. INTERVENTION Open or robot-assisted RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Logistic regression models were fitted to test the predictors of pT3 stage and/or pathologic Gleason score (GS) ≥7 and to determine their predictive accuracy. The base multivariable model included tPSA, digital rectal examination, biopsy GS, and percentage of positive biopsy cores. Decision curve analysis provided an estimate of the net benefit obtained using p2PSA, %p2PSA, or PHI. RESULTS AND LIMITATIONS Overall, 344 patients (70%) were affected by pT3 disease or pathologic GS ≥7; pT3 disease and pathologic GS ≥7 were present in 126 patients (26%). At univariable analysis, p2PSA, %p2PSA, and PHI were significant predictors of pT3 disease and/or pathologic GS ≥7 (all p ≤ 0.001). The inclusion of PHI significantly increased the accuracy of the base multivariable model by 2.3% (p=0.003) and 2.4% (p=0.01) for the prediction of pT3 disease and/or pathologic GS ≥7, respectively. However, at decision curve analysis, models including PHI did not show evidence of a greater clinical net benefit. CONCLUSIONS Both %p2PSA and PHI are significant predictors of unfavourable PCa characteristics at final pathology; however, %p2PSA and PHI did not provide a greater net benefit for clinical decision making. PATIENT SUMMARY Prostate-specific antigen (PSA) isoform p2PSA and its derivatives, percentage of p2PSA to free PSA and the Prostate Health Index, are associated with adverse characteristics of prostate cancer; however, these biomarkers provided only a slight net benefit for clinical decision making.

Clinical performance of serum isoform [‐2]proPSA (p2PSA), and its derivatives %p2PSA and the Prostate Health Index, in men aged <60 years: results from a multicentric European study

To test the hypothesis that [‐2]proPSA (p2PSA) and its derivatives are more accurate than total prostate‐specific antigen (tPSA), free prostate‐specific antigen (fPSA) and fPSA as percentage of tPSA (%fPSA) in detecting prostate cancer (PCa) in men aged <60 years.

Drug treatments for lower urinary tract symptoms secondary to bladder outflow obstruction: focus on quality of life.

Benign prostatic hyperplasia (BPH), now referred to as lower urinary tract symptoms suggestive of bladder outflow obstruction (LUTS/BOO), is a significant cause of morbidity in ageing men. Surgery has virtually eliminated BPH-related mortality, and so the focus for men and their urologist is improvement in urinary symptoms and quality of life. Numerous tools have been developed to quantify symptoms and impact on quality of life — the most commonly used is the International Prostate Symptom Score. Sexual function and the avoidance of BPH-related complications such as acute urinary retention and surgery are also important to men — tools are available to assess sexual function but the benefits of complication avoidance are difficult to quantify. Approximately one million men in the UK have brought their symptoms to the attention of their doctor and been given a diagnosis of BPH, but extrapolation from community based studies suggests that many more (up to 2.5 million men) may have significant symptoms without seeking attention. Histopathological BPH, diminishing peak urinary flow rate, worsening lower urinary tract symptoms and increasing impact on quality of life all become more common as men age. Two groups of drugs are commonly used to treat LUTS/BOO — α-adrenoreceptor antagonists and 5α-reductase inhibitors. Both groups have been shown to improve quality of life measures in randomised, placebo-controlled trials — usually by approximately twice as much as placebo.

Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: Data from the PROMEtheuS project, a multicentre European prospective study

To test serum prostate‐specific antigen (PSA) isoform [‐2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients.

Interstitial laser coagulation therapy for benign prostatic hyperplasia

Alternatives to the side-firing laser method include controlled destruction of prostatic adenoma by an atraumatic saline cooled laser fiber introduced endoscopically into the prostate under visual and transrectal ultrasound (TRUS) control. Laser light produces intense heating and interstitial laser coagulation (ILC) occurs with characteristic TRUS changes which are used to control the volume of tissue destruction. The prostatic urethral lining is preserved which may reduce laser side effects). Thirty-six men with symptomatic BPH were treated by ILC between April 1994 and September 1995. All were discharged home on the first post-operative day and reviewed periodically to 12 months post-treatment with measurement of IPSS, flow rate (FR), residual volume, complications, potency and TRUS. Seventeen men (47%) voided immediately, 15 (42%) performed intermittent self-catheterization (ISC) for 3.5 days (2 - 5). Four men (11%) required catheterization for 1/52. Thirty-five men tolerated the treatment well, requiring only mild oral analgesia. One man developed dysuria and required early transurethral resection revealing a large volume of coagulative necrosis. Improvement in symptoms and flow rate developed from 1 - 30 days later. There were no significant complications. Hyperechoic and cystic zones developed at the ILC site which persisted to 12 months. This clinical study indicates the feasibility and safety of intense heating by ILC with visible and ultrasound control to coagulate the adenoma while preserving the urethra. Changes are easily seen on TRUS, symptomatic improvement is good and there have been minimal urethral symptoms or complications.