Ahmed Elshafei

Urinary PCA3 as a Predictor of Prostate Cancer in a Cohort of 3,073 Men Undergoing Initial Prostate Biopsy

PURPOSE PCA3 is a urinary marker that has shown promise in predicting the presence of prostate cancer in men undergoing repeat prostate biopsy. We studied PCA3 before initial prostate biopsy. MATERIALS AND METHODS Records from a single organization were retrospectively reviewed. The predictive value of PCA3 was explored using nonparametric receiver operating characteristic curve analysis (ROC) and multivariable logistic regression analysis. RESULTS A total of 3,073 men underwent PCA3 analysis before initial prostate biopsy sampling of 12 to 14 areas. Mean PCA3 was 27.2 and 52.5 for patients without and with cancer, respectively. Prostate cancer was identified in 1,341 (43.6%) men. Overall 54.5% had Gleason 6 disease and 45.5% had Gleason 7 or greater (high grade prostate cancer). Mean PCA3 was 47.5 and 58.5 for the patients with Gleason 6 and 7 or greater disease, respectively. On multivariable logistic analysis PCA3 was statistically significantly associated with prostate cancer and high grade prostate cancer after adjusting for prostate specific antigen (p<0.001 for both), free prostate specific antigen (p=0.04 and p=0.01, respectively), age (p<0.001 for both), family history (p<0.001 and p=0.59, respectively), abnormal digital rectal examination (p=0.31 and p<0.001, respectively), prostate volume (p<0.001 for both) and body mass index (p<0.001 for both). Using ROC analysis PCA3 outperformed prostate specific antigen in the prediction of prostate cancer (AUC 0.697 vs 0.599, p<0.01) but not for high grade prostate cancer (AUC 0.682 vs 0.679, p=0.702). CONCLUSIONS PCA3 proved a useful tool in identifying patients at risk for prostate cancer before initial prostate biopsy. To our knowledge this is the largest PCA3 study in the initial biopsy population. These results suggest that further exploration of the value of PCA3 is warranted.

Salvage focal prostate cryoablation for locally recurrent prostate cancer after radiotherapy: Initial results from the cryo on-line data registry

Several investigators have tried to apply salvage focal prostate cryoablation to small numbers of patients with biopsy‐proven unilateral recurrent prostate cancer (PCa) after radiotherapy with the aim of decreasing complications of salvage cryoablation. We report contemporary outcomes of salvage focal cryoablation for locally recurrent PCa after radiotherapy within the Cryo On‐Line Data (COLD) Registry.

When serial prostate biopsy is recommended: most cancers detected are clinically insignificant

Study Type – Disagnostic (exploratory cohort)

Transrectal Saturation Technique May Improve Cancer Detection as an Initial Prostate Biopsy Strategy in Men with Prostate-specific Antigen <10 ng/ml

BACKGROUND Using transrectal saturation prostate biopsy (SPBx) as an initial strategy remains a controversial topic. OBJECTIVE To compare SPBx with extended prostate biopsy (EPBx) as an initial biopsy template in a large sequential cohort study. DESIGN, SETTING, AND PARTICIPANTS We reviewed 438 men with initial SPBx and 3338 men who underwent initial EPBx between January 2002 and October 2011. INTERVENTION Office-based SPBx under periprostatic local anesthesia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The yield of SPBx was compared with EPBx. Multivariable logistic regression models addressed cancer detection (CD) and cancer characteristics. RESULTS AND LIMITATIONS Overall CD was 51.6% and 42.6% in men who underwent initial SPBx and EPBx, respectively. Multivariate analysis confirmed that SPBx was an independent predictor factor correlated with the CD (odds ratio [OR]: 1.66; 95% confidence interval [CI], 1.30-1.92). Stratified by prostate-specific antigen (PSA) values, CD was higher in SPBx compared with EPBx, 47.1% versus 32.8% (OR: 2.00; 95% CI, 1.19-3.38) in patients with a PSA <4 ng/ml and 50.9% versus 42.9% in patients with a PSA from 4 ng/ml to 9.9 ng/ml (OR: 1.62; 95% CI, 1.20-2.20). By contrast, SPBx did not increase CD in men with a PSA >10 ng/ml (60.0% vs 61%; OR: 1.42; 95% CI, 0.70-2.89). There was no significant difference in the detection of insignificant cancer (p = 0.223) or low-risk cancer (p = 0.077) between the two biopsy schemes. The limitation of our study is its retrospective nature and inhomogeneity. CONCLUSIONS Compared with EPBx, SPBx significantly increases CD as an initial biopsy strategy in men with a PSA <10 ng/ml without a significant increase in the detection of insignificant cancer. These findings suggest that SPBx may merit further investigation as an initial biopsy strategy in men with a PSA <10 ng/ml in hopes of avoiding repeat biopsy for missed malignancy during the initial biopsy.

The utility of PSA velocity in prediction of prostate cancer and high grade cancer after an initially negative prostate biopsy

Prostate specific antigen kinetics (PSAK) including prostate specific antigen velocity (PSAV) and PSA doubling time (PSADT) are used as predictors of prostate cancer (PCa) therapeutic outcome, disease prognosis, and cancer‐specific mortality. However controversy persists regarding use of these parameters in cancer detection. Our aim is to evaluate PSAV as a predictor of PCa and intermediate/high grade PCa (HGPCa).

Primary Cryotherapy for High-Grade Clinically Localized Prostate Cancer: Oncologic and Functional Outcomes from the COLD Registry.

OBJECTIVE To evaluate the oncological and functional outcomes of primary cryotherapy in men with clinically localized, high-grade prostate cancer. SUBJECTS AND METHODS We included all men with biopsy Gleason score ≥8, localized (cT1-2) disease with a serum prostate-specific antigen (PSA) ≤50 ng/mL from the Cryo On-Line Data (COLD) registry. The primary outcome was biochemical progression free survival (BPFS) as defined by the Phoenix criteria (nadir PSA +2 ng/mL). Secondary outcomes of continence (defined as strictly no leak) and potency (able to have intercourse) were patient reported. Factors influencing BPFS were evaluated individually using Kaplan Meier and in a multivariate model using Cox regression. RESULTS Altogether, 300 men were included for analysis. The median follow-up was 18.2 months (mean 28.4) and median BPFS was 69.8 months. Based on Kaplan-Meier analysis, the estimated 2- and 5-year BPFS rate was 77.2% and 59.1%, respectively. Neoadjuvant hormonal therapy was administered to 41% of men and this tended to occur in men with larger prostates, likely as a technical consideration for downsizing before cryosurgery. At multivariate analysis, the presence of Gleason score 9 or 10 (Hazard Ratio [HR] 1.9) and a posttreatment PSA nadir of ≥0.4 ng/mL (HR 5.7) were the only significant variables associated with biochemical progression using Cox regression. Complete continence was noted in 90.5% of men and potency in 17% of men at the 12-month follow-up. The incidence of rectourethral fistulae and urinary retention requiring intervention beyond temporary catheterization was 1.3% and 3.3%, respectively. CONCLUSION Primary cryotherapy appears to be effective and safe in the community setting for high-grade, clinically localized prostate cancer in the short term.

PCA3-based nomogram for predicting prostate cancer and high grade cancer on initial transrectal guided biopsy

To develop a validated prostate cancer antigen 3 (PCA3) based nomogram that predicts likelihood of overall prostate cancer (PCa) and intermediate/high grade prostate cancer (HGPCa) in men pursuing initial transrectal prostate biopsy (TRUS‐PBx).

Intermediate-Term Outcomes for Men with Very Low/Low and Intermediate/High Risk Prostate Cancer Managed by Active Surveillance

Purpose: We compare intermediate term clinical outcomes among men with favorable risk and intermediate/high risk prostate cancer managed by active surveillance. Materials and Methods: A total of 635 men with localized prostate cancer have been on active surveillance since 2002 at a high volume academic hospital in the United States. Median followup is 50.5 months (IQR 31.1–80.3). Time to event analysis was performed for our clinical end points. Results: Of the cohort 117 men (18.4%) had intermediate/high risk disease. Overall 5 and 10‐year all cause survival was 98% and 94%, respectively. Cumulative metastasis‐free survival at 5 and 10 years was 99% and 98%, respectively. To date no cancer specific deaths had been observed. Overall freedom from intervention was 61% and 49% at 5 and 10 years, respectively. Overall cumulative freedom from failure of active surveillance, defined as metastasis or biochemical failure after local therapy with curative intent, was 97% and 91% at 5 and 10 years, respectively. Of the men 21 (9.9%) experienced biochemical failure after deferred treatment and the 5‐year progression‐free probability was 92%. Compared to men with favorable risk disease those with intermediate/high risk cancer experienced no difference in metastases, surveillance failure or curative intervention. However, patients at higher risk were at significantly increased risk for all cause mortality, likely reflecting patient selection factors. These conclusions may be limited by the small number of events and the duration of our study. Conclusions: Patients with localized prostate cancer who are on active surveillance demonstrated a low rate of active surveillance failure, prostate cancer specific mortality and metastases regardless of baseline risk.

External validation of a PCA-3-based nomogram for predicting prostate cancer and high-grade cancer on initial prostate biopsy

The aim of this study was to externally validate a previously developed PCA3‐based nomogram for the prediction of prostate cancer (PCa) and high‐grade (intermediate and/or high‐grade) prostate cancer (HGPCa) at the time of initial prostate biopsy.

For Single Dosing, Levofloxacin Is Superior to Ciprofloxacin When Combined With an Aminoglycoside in Preventing Severe Infections After Prostate Biopsy.

OBJECTIVE To investigate whether there is benefit with a longer acting oral fluoroquinolone, we compared the rate of infection after transrectal ultrasound-guided prostate biopsy between 2 prophylactic antibiotic regimens: ciprofloxacin vs levofloxacin, each combined with an aminoglycoside (AG). METHODS A retrospective review was performed of all transrectal ultrasound-guided prostate biopsies from September 2011 to January 2013. Initially our regimen entailed 1 dose of 500-mg ciprofloxacin and an AG. In June 2012, we switched to 1 dose of 750-mg levofloxacin and an AG. Infections were categorized as severe if requiring hospital admission, overnight observation, or emergency room treatment for fever or chills. Those treated as an outpatient were defined as mild. RESULTS Of 1189 total biopsies, the total infection rate was 3.18% (17 of 535) in the ciprofloxacin group and 2.14% (14 of 654) in the levofloxacin group (P = .26). The rate of mild infection was 0.75% (4 of 535) in the ciprofloxacin group and 1.22% (8 of 654) in the levofloxacin group (P = .56). The rate of severe infection was significantly higher in the ciprofloxacin group at 2.43% (13 of 535) compared with that of 0.92% (6 of 654) in the levofloxacin group (P = .04). On multivariate analysis, use of ciprofloxacin rather than levofloxacin was associated with an increased risk of severe infection (odds ratio, 4.59; P = .04). CONCLUSION Empiric prophylaxis for prostate biopsies with a single-dose fluoroquinolone augmented with an AG is optimal to reduce infectious complications. We found 750-mg levofloxacin resulted in significantly fewer severe infections compared with 500-mg ciprofloxacin potentially because of its longer half-life.