Giuliana Lista

Head-to-Head Comparison of Prostate Health Index and Urinary PCA3 for Predicting Cancer at Initial or Repeat Biopsy

PURPOSE We performed a head-to-head comparison of the PHI (Prostate Health Index) and PCA3. MATERIALS AND METHODS We evaluated PHI and PCA3 performance in 211 patients undergoing initial (116) or repeat (95) prostate biopsy. Multivariable logistic regression analysis was done using the AUC to test the accuracy of PHI and PCA3 for predicting prostate cancer in the overall population and in each setting. Decision curve analysis was used to compare the clinical benefit of different models. RESULTS Overall, the AUC of the PHI (0.70) was significantly higher than the AUC of PCA3 (0.59), total prostate specific antigen (0.56) and free-to-total prostate specific antigen (0.60) (p = 0.043, 0.002 and 0.037, respectively). PHI was more accurate than PCA3 for predicting prostate cancer in the initial setting (AUC 0.69 vs 0.57) and in the repeat setting (AUC 0.72 vs 0.63), although no statistically significant difference was observed. Including PCA3 in the base multivariable model (prostate specific antigen plus free-to-total prostate specific antigen plus prostate volume) did not increase predictive accuracy in either setting (AUC 0.79 vs 0.80 and 0.75 vs 0.76, respectively). Conversely, including PHI in the base multivariable model improved predictive accuracy by 5% (AUC 0.79 to 0.84) and 6% (AUC 0.75 to 0.81) in the initial and repeat prostate biopsy settings, respectively. On decision curve analysis the highest net benefit was observed when PHI was added to the base multivariable model. CONCLUSIONS PHI and PCA3 provide a significant increase in sensitivity and specificity compared to all other examined markers and they may help guide biopsy decisions. PCA3 does not increase the accuracy of predicting prostate cancer when PHI is assessed.

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.

Impact of Adjuvant Radiation Therapy on Urinary Continence Recovery After Radical Prostatectomy

BACKGROUND Little is known about the impact of adjuvant radiation therapy (aRT) after radical prostatectomy (RP) on urinary continence (UC). OBJECTIVE To evaluate the impact of aRT on UC recovery in patients with unfavourable pathologic characteristics. DESIGN, SETTING, AND PARTICIPANTS The study included 361 patients with either pT2 with positive surgical margin(s) or pT3a/pT3b node-negative disease treated with RP at a tertiary care referral centre. INTERVENTION Patients were stratified according to the administration of aRT into two groups: group 1 (no aRT; n=208; 57.8%) and group 2 (aRT; n=153; 42.2%). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Continence was defined as no use of protective pads. Log-rank test was used to compare the rate of UC recovery according to aRT status. The association between aRT and UC was also tested in Cox regression models after accounting for age, Cancer of the Prostate Risk Assessment (CAPRA) score, nerve-sparing (NS) status, Charlson Comorbidity Index, body mass index, and year of surgery. RESULTS AND LIMITATIONS At a mean follow-up of 30 mo, 254 patients (70.4%) recovered complete UC. The 1- and 3-yr UC recovery was 51% and 59% for patients submitted to aRT versus 81% and 87% for patients not receiving aRT, respectively (p<0.001). At univariable analysis, older age (p<0.001), presence of non-organ-confined disease (p<0.001), non-NS procedure (p<0.001), and delivery of aRT (p<0.001) were significantly associated with lower UC. At multivariable analysis, the delivery of aRT remained an independent predictor of worse UC recovery (hazard ratio: 0.57; p=0.001). Patients treated with aRT had a 1.6-fold higher risk of incontinence. Younger age (p=0.02), lower CAPRA score (p=0.03), and NS approach (p<0.001) also represented independent predictors of UC recovery. The main limitations of the study are related to the lack of validated questionnaires in the evaluation of UC and in the lack of information regarding UC status at aRT. CONCLUSIONS The delivery of aRT has a detrimental effect on UC. The oncologic benefits must be balanced with an impaired UC recovery. Patients should be informed of such impairment before adjuvant treatments are planned.

Feasibility and Preliminary Clinical Outcomes of Robotic Laparoendoscopic Single-Site (R-LESS) Pyeloplasty Using a New Single-Port Platform

This study tested the technical feasibility and short-term perioperative outcomes of the novel da Vinci Single-Site Instrumentation platform for the treatment of upper ureteropelvic junction obstruction (UPJO) in a selected group of patients. Nine patients underwent robotic laparoendoscopic single-site (R-LESS) pyeloplasty using a new single-site platform for UPJO at our department of urology. All the procedures were completed without the need for traditional robotic surgery or laparoscopic/open conversion, although in one patient with congenital hepatomegaly it was necessary to use an auxiliary 3-mm trocar to retract the liver properly and expose the surgical field. Mean operative time was 166 min, and no intraoperative complications were recorded. The indwelling catheter was removed on postoperative day 2 in five patients and on postoperative day 3 in four patients. Patients were discharged the day after drain removal. One patient experienced transient hyperpyrexia, treated with antibiotics. No other complications were observed. All patients had the DJ stent removed 4 wk after surgery, following a negative urine culture and abdominal ultrasound evaluation. The five patients who reached a 3-mo follow-up had a clinical resolution of preoperative symptoms and hydronephrosis at the abdominal ultrasound. The same results were maintained in the two patients with 6-mo follow-up evaluations. In selected patients, R-LESS pyeloplasty using the new single-port platform appears to be a technically feasible and reproducible surgical procedure for the minimally invasive treatment of UPJO. Prolonged follow-up and larger series are required to confirm its potential role as a valid alternative to standard robotic pyeloplasty.

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.

Development and Internal Validation of a Prostate Health Index Based Nomogram for Predicting Prostate Cancer at Extended Biopsy

PURPOSE We developed and validated a Prostate Health Index (Beckman Coulter, Brea, California) based nomogram to predict prostate cancer at extended prostate biopsy. MATERIALS AND METHODS The study population consisted of 729 patients who were scheduled for prostate biopsy following suspicious digital rectal examination and/or increased prostate specific antigen. Total and free prostate specific antigen, percent free-to-total prostate specific antigen, [-2]proPSA and the prostate health index [([-2]proPSA/free prostate specific antigen) × √total prostate specific antigen)] were determined. Logistic regression models were fitted to test prostate cancer predictors. Predictive accuracy estimates of biopsy outcome predictions were quantified. Regression coefficients were used to create a decision making tool to predict prostate cancer. A calibration plot was used to evaluate the extent of overestimating or underestimating the observed prostate cancer rate. Decision curve analysis provided an estimate of the net benefit obtained using the prostate health index based nomogram. RESULTS Overall 280 of 729 patients (38.4%) were diagnosed with prostate cancer at extended prostate biopsy. On accuracy analyses prostate health index emerged as the most informative predictor of prostate cancer (AUC 0.70) compared to established predictors, such as total prostate specific antigen (0.51) and percent free-to-total prostate specific antigen (0.62). Including the prostate health index in a multivariable logistic regression model based on patient age, prostate volume, digital rectal examination and biopsy history significantly increased predictive accuracy by 7% from 0.73 to 0.80 (p <0.001). Nomogram calibration was good. Decision curve analysis showed that using the prostate health index based nomogram resulted in the highest net benefit. CONCLUSIONS The prostate health index based nomogram can assist clinicians in the decision to perform biopsy by providing an accurate estimation of an individual risk of prostate cancer.

Serum index test %[-2]proPSA and Prostate Health Index are more accurate than prostate specific antigen and %fPSA in predicting a positive repeat prostate biopsy.

PURPOSE We tested the hypothesis that serum isoform [-2]proPSA derivatives %p2PSA and Prostate Health Index are accurate predictors of prostate cancer in men scheduled for repeat biopsy. MATERIALS AND METHODS The study was an observational prospective evaluation of a clinical cohort of men with 1 or 2 previous negative prostate biopsies, with persistent suspicion of prostate cancer. They were enrolled in the study to determine the diagnostic accuracy of %p2PSA using the formula, (p2PSA pg/ml)/(free prostate specific antigen ng/ml × 1,000)]× 100, and Beckman-Coulter Prostate Health Index using the formula, (p2PSA/free prostate specific antigen) × √total prostate specific antigen), and to compare it with the accuracy of established prostate cancer serum tests (total prostate specific antigen, free prostate specific antigen and percent free prostate specific antigen). Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. RESULTS Prostate cancer was found in 71 of 222 (31.9%) subjects. %p2PSA and Prostate Health Index were the most accurate predictors of disease. %p2PSA significantly outperformed total prostate specific antigen, free prostate specific antigen, percent free prostate specific antigen and p2PSA in the prediction of prostate cancer (p ≤0.01), but not Prostate Health Index (p = 0.094). Prostate Health Index significantly outperformed total prostate specific antigen and p2PSA (p ≤0.001) but not free prostate specific antigen (p = 0.109) and free/total prostate specific antigen (p = 0.136). In multivariable logistic regression models %p2PSA and Prostate Health Index achieved independent predictor status, and significantly increased the accuracy of multivariable models including prostate specific antigen and prostate volume with or without percent free prostate specific antigen and prostate specific antigen density by 8% to 11% (p ≤0.034). At a %p2PSA cutoff of 1.23, 153 (68.9%) biopsies could have been avoided, missing prostate cancer in 6 patients. At a Prostate Health Index cutoff of 28.8, 116 (52.25%) biopsies could have been avoided, missing prostate cancer in 6 patients. CONCLUSIONS Serum %p2PSA and Prostate Health Index are more accurate than standard reference tests in predicting repeat prostate biopsy outcome, and could avoid unnecessary repeat biopsies.

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.

Retroperitoneal and Transperitoneal Robot-Assisted Pyeloplasty in Adults: Techniques and Results

BACKGROUND The surgical management of ureteropelvic junction obstruction (UPJO) has dramatically evolved over the past 20 yr due to the development of new technology. OBJECTIVE Our aim was to report the feasibility and efficacy of robot-assisted pyeloplasty (RAP) performed by either the retroperitoneal or the transperitoneal approach. DESIGN, SETTING, AND PARTICIPANTS A stage 2 investigative study was conducted including development (stage 2a) and exploration (stage 2b) of transperitoneal and retroperitoneal RAP performed in 55 patients at an urban tertiary university department of urology. SURGICAL PROCEDURE Retroperitoneal RAP was performed with the patient in full flank position using a 12-mm Hasson-style optical port at the tip of the 12th rib, plus two operative 8-mm robotic trocars and an assistant 5-mm port. The stenotic ureteropelvic junction was excised, the ureter was spatulated, and a dismembered pyeloplasty was performed in all cases. Transperitoneal RAP was performed with the patients in the 60° flank position. The optical port is in the umbilical area, plus two 8-mm operative robotic ports and one 5-mm assistant port. The pyeloplasty technique is similar to the retroperitoneoscopic approach. In both groups, the stent can be positioned in an anterograde or retrograde fashion. MEASUREMENTS Success consisted of no evidence of obstruction on computed tomography urography or mercaptoacetyltriglycine-3 diuretic renal scan, no postoperative symptoms, and no further treatment. RESULTS AND LIMITATIONS Thirty-six patients underwent retroperitoneoscopic RAP and 19 transperitoneal RAP for UPJO. All the procedures were completed with robotic assistance. The overall objective success (measured by diuretic renal scan and/or imaging techniques) was 96% with two cases of recurrence (both in the retroperitoneal group). The main limitation was the short follow-up, although all patients reached at least a 6-mo follow-up. CONCLUSIONS RAP performed either retroperitoneally or transperitoneally was revealed as a feasible and reproducible surgical option for the treatment of UPJO, offering a subjective optimal plasty reconfiguration at short follow-up.

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.