Cerebral revascularization surgery reduces cerebrovascular events in children with sickle cell disease and moyamoya syndrome: Results of the stroke in sickle cell revascularization surgery retrospective study.

BACKGROUND: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD-MMS). METHODS: We performed a multicenter, retrospective study of children with SCD-MMS treated with conservative management alone (conservative group)-chronic blood transfusion and/or hydroxyurea-versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates-a composite of strokes and transient ischemic attacks. Multivariable logistic regression was used to compare CVE occurrence and multivariable Poisson regression was used to compare incidence rates between groups. Covariates in multivariable models included age at treatment start, age at moyamoya diagnosis, antiplatelet use, CVE history, and the risk period length. RESULTS: We identified 141 patients with SCD-MMS, 78 (55.3%) in the surgery group and 63 (44.7%) in the conservative group. Compared with the conservative group, preoperatively the surgery group had a younger age at moyamoya diagnosis, worse baseline modified Rankin scale scores, and increased prevalence of CVEs. Despite more severe pretreatment disease, the surgery group had reduced odds of new CVEs after surgery (odds ratio = 0.27, 95% confidence interval [CI] = 0.08-0.94, p = .040). Furthermore, comparing surgery group patients during presurgical versus postsurgical periods, CVEs odds were significantly reduced after surgery (odds ratio = 0.22, 95% CI = 0.08-0.58, p = .002). CONCLUSIONS: When added to conservative management, cerebral revascularization surgery appears to reduce the risk of CVEs in patients with SCD-MMS. A prospective study will be needed to validate these findings.

Associations Between Prostate Volume and Oncologic Outcomes in Men Undergoing Focal Cryoablation of the Prostate.

INTRODUCTION: The purpose of this study was to assess the relationship of total prostate volume (TPV) and oncologic outcomes following focal prostate cryoablation. MATERIALS AND METHODS: A query of the Cryo On-Line Database (COLD) registry for men who underwent primary focal prostate cryoablation revealed 829 patients with complete data. The impact of TPV on oncologic outcomes including progression-free survival (PFS) and post-cryoablation biopsy outcome was assessed using Kaplan-Meier curves and Cox and logistic regression models. RESULTS: The median follow-up time was 25.2 months (interquartile range [IQR], 12.7-48.2 months). The median age at time of treatment was 68 years (IQR, 63-74 years) with median prostate-specific antigen (PSA) 5.6 ng/mL (IQR, 4.4-7.5 ng/mL), and median TPV 35 mL (IQR, 26.5-46 mL). PFS was achieved in 83.2%, with positive post-cryoablation biopsy detected in 81 (35.7%) of 228 patients. Higher TPV was associated with higher biochemical progression (BP) using the Phoenix definition (39 vs. 34.5 mL; P = .003) and was an independent predictor of BP (hazard ratio, 1.01; P = .02). Conversely, men who had a positive post-cryoablation biopsy had significantly smaller median TPV on univariate and multivariate analyses (31 vs. 39 mL; P < .001), (odds ratio, 0.97; P = .001), respectively. Higher median pretreatment PSA density was associated with higher BP (0.18 vs. 0.16; P = .005) and positive post-cryoablation biopsy rates (0.2 vs. 0.16; P = .003). CONCLUSION: Prostate volume has contradictory effects on BP and post-cryoablation biopsy outcome in men who underwent primary focal prostate cryoablation. Remnant viable tissue in larger prostates continues to produce more PSA over time, which may impact BP. This may raise the need to develop a new definition for oncologic success following focal gland therapy rather than the American Society for Radiation Oncology (ASTRO) and Phoenix definitions.

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

BACKGROUND: 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). METHODS: Data were collected on 3,675 men with serum prostate specific antigen level (PSA) ≤ 20 ng/ml who underwent initial prostate biopsy with at least 10 cores sampling at time of the biopsy. Two logistic regression models were constructed to predict overall PCa and HGPCa incorporating age, race, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and digital rectal exam (DRE). RESULTS: One thousand six hundred twenty (44%) patients had biopsy confirmed PCa with 701 men (19.1%) showing HGPCa. Statistically significant predictors of overall PCa were age (P < 0.0001, OR. 1.51), PSA at diagnosis (P < 0.0001, OR.1.95), PCA3 (P < 0.0001, OR.3.06), TPV (P < 0.0001, OR.0.47), FH (P = 0.003, OR.1.32), and abnormal DRE (P = 0.001, OR. 1.32). While for HGPCa, predictors were age (P < 0.0001, OR.1.77), PSA (P < 0.0001, OR.2.73), PCA3 (P < 0.0001, OR.2.26), TPV (P < 0.0001, OR.0.4), and DRE (P < 0.0001, OR.1.53). Two nomograms were reconstructed for predicted overall PCa probability at time of initial biopsy with a concordance index of 0.742 (Fig. 1), and HGPCa with a concordance index of 0.768 (Fig. 2). CONCLUSIONS: Our internally validated initial biopsy PCA3 based nomogram is reconstructed based on a large dataset. The c-index indicates high predictive accuracy, especially for high grade PCa and improves the ability to predict biopsy outcomes.

Transrectal Saturation Biopsy Improves Risk Stratification (Reclassification) of Patients with Prostate Cancer on Active Surveillance.

INTRODUCTION: We assessed the accuracy of transrectal saturation prostate biopsy compared to extended prostate biopsy in patients on active surveillance. Determining prostate cancer aggressiveness is mandatory to determine appropriate candidates for active surveillance and appropriateness to remain on active surveillance protocols. METHODS: From our institutional review board approved database we reviewed the biopsies of 277 patients diagnosed with prostate cancer on an active surveillance protocol. Eligibility criteria included clinical stage T1 to T2a, Gleason score 6 or less, prostate specific antigen 10 ng/ml or less and percent of positive cores 33% or less of the total cores taken on diagnostic biopsy. We defined recategorization or pathological progression on first confirmatory and surveillance biopsies as no longer meeting the standard definition of low risk by cancer volume or Gleason score criteria. RESULTS: Of 444 biopsies 279 were extended prostate biopsy (10 to 14 cores) and 165 were saturation prostate biopsy (20 cores or greater). The rate of cancer recategorization (reclassification) was highest on the first confirmatory biopsy at 25%. There was no significant difference between extended and saturation prostate biopsy for detecting recategorization on the first confirmatory biopsy (21.5% vs 29.4%, p = 0.13). Saturation prostate biopsy was significantly more likely to detect cancer progression on all subsequent surveillance biopsies. CONCLUSIONS: Disease progression or recategorization was more frequently identified on the first confirmatory biopsy than on subsequent surveillance biopsies. The incidence of disease recategorization was higher in the saturation biopsy group than in the extended biopsy group on the first confirmatory biopsy but the difference was not statistically significant. Disease progression was more likely to be identified by saturation prostate biopsy on subsequent surveillance biopsies.

Low risk patients benefit from extreme anterior apical sampling on initial biopsy for prostate cancer diagnosis.

BACKGROUND: To assess the effect of additional extreme apical sampling on prostate cancer (PCa) detection and aggressiveness in patients with standard risk versus high risk of a positive biopsy. METHODS: Three thousand fifty three men were reviewed from our institution review board approved prostate biopsy database. Two thousand five hundred and twenty one underwent biopsy with 12 cores while 532 underwent 14 core sampling (2 extra cores from the extreme anterior apex). Patients were stratified into one of two risk groups: (1) standard risk of PCa (elevated prostate specific antigen (PSA) < 10 ng/ml, normal digital rectal exam (DRE), and no lesions on transrectal ultrasound (TRUS)), and (2) higher risk of PCa (PSA > 10 ng/ml and/or abnormal DRE and/or lesion on TRUS). Prostate cancer detection and disease characteristics were compared between the biopsy schemes stratified by risk of a positive biopsy. RESULTS: PCa detection with 14 core sampling was more likely in all patients (OR 1.339, 95% CL 1.070-1.676) and in men with standard risk (OR 1.334, 95% CL 1.007-1.769). A greater median number of positive cores (3 vs. 2) and a higher maximum cancer % per core (40% vs. 25%) were seen in the 14 core cohort when stratified to standard risk. Gleason ≥7 was more likely detected with 14 cores in the standard risk group (55.6% vs. 45.2%). Differences in PCa detection and Gleason ≥7 between biopsy techniques were not noted in the higher risk group. CONCLUSION: Extreme apical sampling increases aggressive cancer detection on initial biopsy, especially in patients with standard risk of PCa.

Definition of biochemical success following primary whole gland prostate cryoablation.

PURPOSE: We identified an evidence-based definition of biochemical success following primary whole gland prostate cryoablation. MATERIALS AND METHODS: The COLD Registry was queried for a risk stratified cohort of otherwise treatment naïve patients who underwent primary whole gland prostate cryoablation, of whom none had received any type of adjuvant therapy. Minimum followup in all study patients was 5 years. Variables included patient age, prostate specific antigen at diagnosis, Gleason score, D'Amico risk category and followup prostate specific antigen. Biochemical progression-free survival was studied based on Kaplan-Meier results using the Phoenix definition. HRs were calculated using proc PHReg. RESULTS: Of 1,111 patients 891 achieved nadir prostate specific antigen less than 0.4 ng/ml, which correlated with a 5-year biochemical progression-free survival rate of 90.4% in those at low risk, 81.1% in those at intermediate risk and 73.6% in those at high risk. Nadir prostate specific antigen 0.4 ng/ml or greater was associated with 24-month biochemical failure of 29.2% in those at low risk, 46.4% in those at intermediate risk and 48.9% in those at high risk. Statistical analysis failed to reveal a superior prostate specific antigen end point compared to 0.4 ng/ml. HR findings supported the relevance of the end point of less than 0.4 ng/ml (p <0.0001). CONCLUSIONS: To our knowledge this study represents the first evidence-based definition of biochemical success after primary whole gland prostate cryoablation. Nadir prostate specific antigen less than 0.4 ng/ml was the best objective indicator of biochemical success. Nadir prostate specific antigen 0.4 ng/ml or greater was associated with less favorable biochemical progression, precluding the use of a higher nadir prostate specific antigen end point (HR 5.649, 95% CI 4.33-7.38, p <0.0001).

Potential benefit of transrectal saturation prostate biopsy as an initial biopsy strategy: decreased likelihood of finding significant cancer on future biopsy.

OBJECTIVE: To identify the ability of transrectal saturation prostate biopsy (SPBx) as the initial diagnostic approach to reduce the likelihood of finding previously unrecognized prostate cancer (PCa) during repeat prostate biopsy. MATERIALS AND METHODS: We reviewed PCa detection in 561 men who underwent first repeat SPBx after initial negative biopsy between March 2002 and April 2012. We divided the patients on the basis of the number of cores retrieved on initial biopsy (group 1, initial negative SPBx [n = 81] and group 2, initial negative extended prostate biopsy [n = 480]). The yield of repeat SPBx was compared between the 2 groups. Insignificant PCa and low-risk PCa were defined according to Epstein criteria and D'Amico risk criteria, respectively. RESULTS: PCa detection on first repeat SPBx was 43.1% lower in group 1 (19.8% vs 34.8%; P = .008). Moreover, lower rate of significant PCa (31.3% vs 74.3%; P <.001) and intermediate- and/or high-risk PCa (25.0% vs 50.9%; P = .048) in group 1. Multivariate analysis confirmed that initial negative SPBx decreased PCa detection on first repeat SPBx (odds ratio = 0.41, 95% confidence interval 0.22-0.78). CONCLUSION: Men whose initial biopsy was per transrectal saturation technique were less likely to have cancer identified during repeat biopsy. Furthermore, PCa diagnosed after negative initial SPBx was much more likely to be clinically insignificant. These findings suggest that SPBx may be less likely to miss clinically significant cancer during initial prostate biopsy. If confirmed in other studies, this suggests that initial biopsy by saturation technique may eliminate the need for most men to undergo repeat biopsy.

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

BACKGROUND: 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). METHODS: We included 682 patients that underwent repeat transrectal ultrasound guided biopsy after initial negative biopsy. Univariate and multivariate analyses as well as area under the receiver operating characteristic curve (ROC-AUC) were performed to assess predictive accuracy regarding detection of PCa and intermediate/HGPCa (Gleason score ≥ 7). RESULTS: PCa was detected in 179/682 (26.24%) patients. Our univariate analysis suggested that age, total prostate volume (TPV), atypical small acinar proliferation (ASAP) and PSA indices in the form of PSA at the time of repeat biopsy (PSA2), PSAV, PSA density (PSAD2) and percent free PSA at time of repeat biopsy (%FPSA2) were all predictors of overall PCa and intermediate/HGPCa. Meanwhile, our multivariate model showed that factors associated with overall PCa and intermediate/HGPCa were age, PSAV and TPV. CONCLUSIONS: In men pursuing a second biopsy after an initial negative biopsy, PSAV was an independent predictor of overall PCa, intermediate and high grade cancer.

Does positive family history of prostate cancer increase the risk of prostate cancer on initial prostate biopsy?

OBJECTIVE: To assess the role of family history (FH) in the risk of a positive prostate biopsy (PBx) in a large North American biopsy population as earlier reports showed increased risk of prostate cancer (PCa) in men with a FH, but the risk has been limited to low grade prostate cancer in smaller studies, and the REDUCE trial found no such risk in North American patients. METHODS: We evaluated 4360 men undergoing initial extended biopsy (8-14 cores). Indications were elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE). Variables including age, FH of PCa, race, PSA, and DRE results were included in our analysis to assess risk factors associated with PCa, high-grade prostate cancer (HGPCa), and low-grade prostate cancer (LGPCa). RESULTS: Two hundred sixty-eight patients had an FH of PCa whereas 4092 had negative FH. Positive biopsy was found in 1976 patients with HGPCa in 1149 and LGPCa in 827. Among 268 patients with an FH, overall PCa was found in 144 of 268 patients (54%); HGPCa in 79 of 144 patients (55%) and LGPCa in 65 of 144 patients (45%). FH was a significant risk factor for PCa, HGPCa, and LGPCa in univariate and multivariate analysis (P = .0001, .02, and .02, respectively). Also, FH was associated with high-risk benign pathology in the form of atypical small acinar cell proliferation (ASAP) or high-grade prostatic intraepithelial neoplasm (HGPIN) (P = .04). CONCLUSION: Men in North America with an FH of PCa who undergo prostate biopsy are more likely to be diagnosed with both HGPCa and LGPCa.