Alberto Abrate

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.

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.

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.

Long-term oncologic outcomes of laparoscopic renal cryoablation as primary treatment for small renal masses

INTRODUCTION Data regarding long-term oncologic outcomes of laparoscopic renal cryoablation (LRC) as first treatment for small renal masses (SRMs) are lacking. We hypothesized that LRC might provide an effective long-term cancer control in patients with a single cT1a SRM without a previous history of renal cell carcinoma (RCC). MATERIALS AND METHODS The study design was a retrospective analysis of 174 consecutive patients who received LRC as first treatment for a single computed tomography or magnetic resonance imaging contrast-enhancing cT1a SRM between 2000 and 2013. Patients with a previous history of RCC were excluded. Treatment failure was evaluated 1 day after surgery. Local recurrence, metachronous SRM, systemic progression, disease relapse, cancer-specific mortality, and all-cause mortality were evaluated 10 years after surgery. Kaplan-Meier plots were used to depict outcome-free survival rate. RESULTS Median patient age was 66 years. Median tumor size was 20mm. Median follow-up was 48 months. Among patients with biopsy-proven RCC (63%, n = 109), the treatment failure-free rate was 98%. The 10-year recurrence-free survival rate was 95% and the 10-year metachronous SRM-free survival rate was 87%. The 10-year systemic progression-free survival rate was 100% and the 10-year disease relapse-free survival rate was 81%. The cancer-specific mortality-free survival rate was 100%, and the all-cause mortality-free survival rate was 61%. CONCLUSIONS LRC provides safe long-term cancer control in patients newly diagnosed with a single cT1a SRM. Treatment failure and local recurrence are uncommon. Systemic progression-free survival and cancer-specific-free survival are optimal.

Margin, Ischemia, and Complications System to Report Perioperative Outcomes of Robotic Partial Nephrectomy: A European Multicenter Observational Study (EMOS Project)

OBJECTIVE To explore the margin, ischemia, and complications (MIC) system achievement rate within a population of patients who were treated with robotic partial nephrectomy (RAPN), at 3 different tertiary care centers, and to determine the factors predicting MIC achievement. METHODS The study population consisted of 339 patients who underwent RAPN for cT1 renal tumors at 3 centers. Cancer control was defined as the absence of positive surgical margin. Ideal threshold of warm ischemia time (WIT) was considered ≤20 minutes. Safety was defined as the absence of major complications. The achievement of MIC was considered as the fulfillment of all these 3 outcomes. The primary endpoint was to determine the MIC rate in our study population; the secondary endpoint was to detect factors affecting its achievement. RESULTS The overall MIC rate was 67%. Median WIT was 17 minutes (range, 7-51 minutes). In 88 cases (26%), WIT was >20 minutes. Positive surgical margins were found in 22 patients (6.5%). Overall postoperative and major complication rates were 14.5% (n = 49) and 3.8% (n = 13). In multivariate logistic regression analysis, continuously coded and categorically coded preoperative aspects and dimensions used for an anatomical scores were an independent predictor of MIC achievement (odds ratio, 0.636; confidence interval, 0.436-0.928; P = .019 and odds ratio, 0.098; confidence interval, 0.030-0.326; P <.001). CONCLUSION The MIC binary system may represent a useful tool to summarize the achievement of optimal perioperative outcomes of RAPN. In the current population, tumor complexity was significantly associated with MIC achievement.

Robot-assisted, Single-site, Dismembered Pyeloplasty for Ureteropelvic Junction Obstruction with the New da Vinci Platform: A Stage 2a Study

BACKGROUND Laparoendoscopic single-site surgery (LESS) has gained popularity in urology over the last few years. OBJECTIVE To report a stage 2a study of robot-assisted single-site (R-LESS) pyeloplasty for ureteropelvic junction obstruction (UPJO). DESIGN, SETTING, AND PARTICIPANTS This study is an investigative pilot study of 30 consecutive cases of R-LESS pyeloplasty performed at two participating institutions between July 2011 and September 2013. SURGICAL PROCEDURE Dismembered R-LESS pyeloplasty was performed at two surgical centers. MEASUREMENTS Feasibility (conversion rate), safety (complication rate and Clavien-Dindo classification), efficacy (clinical outcome) of the procedure were assessed. RESULTS AND LIMITATIONS The median patient age was 37 yr (range: 19-65 yr) and median body mass index was 23 kg/m(2) (range: 19-29 kg/m(2)). The median operative time was 160 min (range: 101-300 min), the median postoperative stay was 5 d (range: 3-13 d), and the median time to catheter removal was 3 d (range: 2-10). Two cases required conversion, the first one to standard laparoscopic technique and the second one to standard robotic technique. No intraoperative complications were reported. In three cases, an additional 5-mm trocar was needed. The postoperative complications rate was 26% (n=8). Most of them were grade 1 complications (n=4; 13%), followed by grade 2 (n=3; 10%) and grade 3 (n=1; 3.3%) complications, according to the Clavien-Dindo classification. One patient needed a surgical reintervention with standard robotic technique 3 d after surgery for urinary leakage. The overall success rate, considered as the resolution of symptoms and the absence of functional impairment at postoperative imaging, was 93.3% (n=28) at a median follow-up of 13 mo (range: 3-21 mo). The main limitations of this study are the limited number of patients included and the short-term follow-up. CONCLUSIONS Single-site robotic pyeloplasty is a feasible technique in selected patients, with good cosmetic results and excellent short-term clinical outcomes. Prospective studies are needed to further assess its role for the treatment of UPJO. PATIENT SUMMARY Single-site robot-assisted pyeloplasty is a feasible technique with good cosmetic results and excellent short-term clinical outcomes.

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.

Radical prostatectomy represents an effective treatment in patients with specimen-confined high pathological Gleason score prostate cancer.

To date, only a few studies have addressed the long‐term oncological outcomes of radical prostatectomy (RP) in patients with pathological Gleason score ≥ 8 prostate cancer. According to these reports, some individuals with pathological Gleason score ≥ 8 may benefit from RP, with cancer‐control outcomes comparable with those of patients with low‐ and intermediate‐risk prostate cancer. The presence of pathological Gleason score 8–10 represents a poor prognostic factor in the outcome of men with prostate cancer. However, in patients with specimen‐confined disease, RP and bilateral PLND provided long‐term cancer‐control outcomes similar to those of patients with more favourable disease characteristics.

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.

Clinical Use of [-2]proPSA (p2PSA) and Its Derivatives (%p2PSA and Prostate Health Index) for the Detection of Prostate Cancer: A Review of the Literature

Prostate-specific antigen (PSA) is recognized as an organ-specific marker with low specificity and sensitivity in discriminating prostate cancer (PCa) from other benign conditions, such as prostatic hyperplasia or chronic prostatitis. Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as a new marker to accurately detect PCa. The aim of this systematic review was to discuss the available literature regarding the clinical validity and utility of p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index (PHI). A systematic search of the PubMed and Scopus electronic databases was performed in accordance with the PRISMA statement (http://www.prisma-statement.org), considering the time period from January 1990 to January 2014 and using the following search terms: proprostate specific antigen, proenzyme PSA, proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies have been published, but only 35 were considered for the qualitative analysis. These studies suggested that p2PSA is the most cancer-specific form of PSA, being preferentially expressed in PCa tissue and being significantly elevated in the serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements improve the specificity of the available tests (PSA and derivatives) in detecting PCa. Moreover, increasing PHI values seem to correlate with more aggressive disease. Some studies have compared p2PSA and its derivatives with other new biomarkers and found p2PSA to be significantly more accurate. Indeed, the implementation of these tests in clinical practice has the potential to significantly increase the physicians ability to detect PCa and avoid unnecessary biopsies, while also having an effective impact on costs. Further studies in large, multicenter, prospective trials are required to confirm these encouraging results on the clinical utility of these new biomarkers.