Neutralizing Monoclonal Antibody Treatment Reduces Hospitalization for Mild and Moderate Coronavirus Disease 2019 (COVID-19): A Real-World Experience.

BACKGROUND: Neutralizing monoclonal antibody (NmAb) treatments have received Emergency Use Authorization to treat patients with mild or moderate COVID-19 infection. To date, no real- world data on the efficacy of NmAbs have been reported from clinical practice. We assessed the impact of NmAb treatment given in the outpatient clinical practice setting on hospital utilization. METHODS: Electronic medical records were used to identify adult COVID-19 patients who received NmAbs (bamlanivimab [BAM] or casirivimab and imdevimab [REGN-COV2]) and historic COVID-19 controls. Post-index hospitalization rates were compared. RESULTS: 707 confirmed COVID-19 patients received NmAbs and 1709 historic COVID-19 controls were included; 553 (78%) received BAM, 154 (22%) received REGN-COV2. Patients receiving NmAb infusion had significantly lower hospitalization rates (5.8% vs 11.4%, P < .0001), shorter length of stay if hospitalized (mean, 5.2 vs 7.4 days; P = .02), and fewer ED visits within 30 days post-index (8.1% vs 12.3%, P = .003) than controls. Hospitalization-free survival was significantly longer in NmAb patients compared with controls (P < .0001). There was a trend towards a lower hospitalization rate among patients who received NmAbs within 2-4 days after symptom onset. In multivariate analysis, having received an NmAb transfusion was independently associated with a lower risk of hospitalization after adjustment for age, sex, race, BMI, and referral source (adjusted HR [95% CI], .54 [0.38-0.79]; P = .0012). Overall mortality was not different between the 2 groups. CONCLUSIONS: NmAb treatment reduced hospital utilization, especially when received within a few days of symptom onset. Further study is needed to validate these findings.

Patient-reported outcomes of blue-light flexible cystoscopy with hexaminolevulinate in the surveillance of bladder cancer: results from a prospective multicentre study.

OBJECTIVE: To evaluate blue-light flexible cystoscopy (BLFC) with hexaminolevulinate in the office surveillance of patients with non-muscle-invasive bladder cancer with a high risk of recurrence by assessing its impact on pain, anxiety, subjective value of the test and patient willingness to pay. MATERIALS AND METHODS: A prospective, multicentre, phase III study was conducted during which the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, Pain and 'Was It Worth It' questionnaires were administered at baseline, after surveillance with BLFC and after resection for those referred to the operating room. Comparisons of scores were performed between groups. RESULTS: A total of 304 patients were enrolled, of whom 103 were referred for surgical examination. Of these, 63 were found to have histologically confirmed malignancy. Pain levels were low throughout the study. Anxiety levels decreased after BLFC (∆ = -2.6), with a greater decrease among those with negative pathology results (P = 0.051). No differences in anxiety were noted based on gender, BLFC results, or test performance (true-positive/false-positive). Most patients found BLFC 'worthwhile' (94%), would 'do it again' (94%) and 'would recommend it to others' (91%), with no differences based on BLFC results or test performance. Most patients undergoing BLFC (76%) were willing to pay out of pocket. CONCLUSIONS: Anxiety decreased after BLFC in patients with negative pathology, including patients with false-positive results. Most of the patients undergoing BLFC were willing to pay out of pocket, found the procedure worthwhile and would recommend it to others, irrespective of whether they had a positive BLFC result or whether this was false-positive after surgery.

Efficacy and Safety of Blue Light Flexible Cystoscopy with Hexaminolevulinate in the Surveillance of Bladder Cancer: A Phase III, Comparative, Multicenter Study.

PURPOSE: We compared blue light flexible cystoscopy with white light flexible cystoscopy for the detection of bladder cancer during surveillance. MATERIALS AND METHODS: Patients at high risk for recurrence received hexaminolevulinate intravesically before white light flexible cystoscopy and randomization to blue light flexible cystoscopy. All suspicious lesions were documented. Patients with suspicious lesions were referred to the operating room for repeat white and blue light cystoscopy. All suspected lesions were biopsied or resected and specimens were examined by an independent pathology consensus panel. The primary study end point was the proportion of patients with histologically confirmed malignancy detected only with blue light flexible cystoscopy. Additional end points were the false-positive rate, carcinoma in situ detection and additional tumors detected only with blue light cystoscopy. RESULTS: Following surveillance 103 of the 304 patients were referred, including 63 with confirmed malignancy, of whom 26 had carcinoma in situ. In 13 of the 63 patients (20.6%, 95% CI 11.5-32.7) recurrence was seen only with blue light flexible cystoscopy (p <0.0001). Five of these cases were confirmed as carcinoma in situ. Operating room examination confirmed carcinoma in situ in 26 of 63 patients (41%), which was detected only with blue light cystoscopy in 9 of the 26 (34.6%, 95% CI 17.2-55.7, p <0.0001). Blue light cystoscopy identified additional malignant lesions in 29 of the 63 patients (46%). The false-positive rate was 9.1% for white and blue light cystoscopy. None of the 12 adverse events during surveillance were serious. CONCLUSIONS: Office based blue light flexible cystoscopy significantly improves the detection of patients with recurrent bladder cancer and it is safe when used for surveillance. Blue light cystoscopy in the operating room significantly improves the detection of carcinoma in situ and detects lesions that are missed with white light cystoscopy.

Impact of 5α-Reductase Inhibitors on Disease Reclassification among Men on Active Surveillance for Localized Prostate Cancer with Favorable Features.

PURPOSE: We determined the effect of 5α-reductase inhibitors on disease reclassification in men with prostate cancer optimally selected for active surveillance. MATERIALS AND METHODS: In this retrospective review we identified 635 patients on active surveillance between 2002 and 2015. Patients with favorable cancer features on repeat biopsy, defined as absent Gleason upgrading, were included in the cohort. Patients were stratified by those who did or did not receive finasteride or dutasteride within 1 year of diagnosis. The primary end point was grade reclassification, defined as any increase in Gleason score or predominant Gleason pattern on subsequent biopsy. This was assessed by multivariable Cox proportional hazards regression analysis. RESULTS: At diagnosis 371 patients met study inclusion criteria, of whom 70 (19%) were started on 5α-reductase inhibitors within 12 months. Median time on active surveillance was 53 vs 35 months in men on vs not on 5α-reductase inhibitors (p <0.01). Men on 5α-reductase inhibitors received them for a median of 23 months (IQR 6-37). On actuarial analysis there was no significant difference in grade reclassification for 5α-reductase inhibitor use in patients overall or in the very low/low risk subset. The overall percent of patients who experienced grade reclassification was similar at 13% vs 14% (p = 0.75). After adjusting for baseline clinicopathological features 5α-reductase inhibitors were not significantly associated with grade reclassification (HR 0.80, 95% CI 0.31-1.80, p = 0.62). Furthermore, no difference in adverse features on radical prostatectomy specimens was observed in treated patients (p = 0.36). CONCLUSIONS: Among our cohort of men on active surveillance 5α-reductase inhibitor use was not associated with a significant difference in grade reclassification with time.

Avoidance of androgen deprivation therapy in radiorecurrent prostate cancer as a clinically meaningful endpoint for salvage cryoablation.

BACKGROUND: To investigate the ability of salvage cryoablation of the prostate (SCAP) to delay the need for androgen deprivation therapy (ADT) in local recurrence after radiation therapy to the prostate using the Cryo-On-Line Database (COLD) registry. METHODS: The COLD registry is comprised of a combination of retrospectively and prospectively collected data on patients undergoing primary and SCAP. Patients with local recurrence after radiation therapy were identified. Kaplan-Meier analysis was used to calculate ADT-free survival. RESULTS: We identified 898 patients that have undergone SCAP in the COLD registry. Overall, the calculated 5-year ADT-free survival probability was 0.713. When stratified by D'Amico risk group, 264 high-risk patients (71.9%), 234 intermediate-risk (86.7%),and 228 low-risk (87.7%) were free of ADT post-SCAP. This correlates with a 5-year ADT-free survival of 60.7, 73.9, and 82.4%, respectively. Patients with post-SCAP PSA nadir of <0.2 ng/mL had a 5 year ADT-free survival of 87.1% compared to 48.7% with a PSA nadir ≥0.2 ng/mL. Pre-operative ADT use or full versus partial gland SCAP did not have an effect on ADT use post-operatively. In 118 (55.4%) of patients with post-operative biochemical recurrence, ADT was not used. CONCLUSION: For patients with local recurrence after radiation, SCAP is an option that provides a high chance of avoiding or delaying ADT. The potential to delay ADT and its associated side effects should be a part of counseling sessions with the patient when discussing treatment options for locally recurrent prostate cancer after radiation. Avoidance of ADT is more clinically relevant than PSA elevation.

Outcomes of Active Surveillance after Initial Surveillance Prostate Biopsy.

PURPOSE: We analyzed the rates of disease reclassification at initial and subsequent surveillance prostate biopsy as well as the treatment outcomes of deferred therapy among men on active surveillance for prostate cancer. MATERIALS AND METHODS: From a prospective database we identified 300 men on active surveillance who had undergone initial surveillance prostate biopsy, with or without confirmatory biopsy, within 1 year of diagnosis. Of these men 261 (87%) were classified as having NCCN very low or low risk disease at diagnosis. Disease reclassification on active surveillance was defined as the presence of 50% or more positive cores and/or surveillance prostate biopsy Gleason score upgrading. Patients with type I disease reclassification included those with any surveillance prostate biopsy Gleason score upgrading, while patients with type II reclassification had to have primary Gleason pattern 4-5 disease on surveillance prostate biopsy. Outcomes after initial surveillance prostate biopsy were evaluated using actuarial analyses. RESULTS: At the time of initial surveillance prostate biopsy 49 (16%) and 19 (6%) patients had type I and type II disease reclassification, respectively. Those who underwent confirmatory biopsy had significantly reduced rates of type I (9% vs 23%, p=0.001) and type II (3% vs 9%, p=0.01) reclassification at initial surveillance prostate biopsy. For the 251 patients without disease reclassification at initial surveillance prostate biopsy the 2-year rates of subsequent type I and II reclassification were 17% (95% CI 0-24) and 3% (95% CI 0.1-7), respectively. For the 93 patients who received deferred therapy the 5-year biochemical progression-free probability was 89% (95% CI 79-98), including 95%, 82% and 70% among those without, and those with type I and type II disease reclassification, respectively. CONCLUSIONS: Patients on active surveillance with stable disease at the time of initial surveillance prostate biopsy may be appropriate candidates for less intensive surveillance prostate biopsy schedules.

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.

INTRODUCTION: 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. METHODS: A retrospective review was performed on a cohort of 336 men from a large urban academic medical center. All men had serum PSA <20 ng/ml and underwent initial transrectal ultrasound-guided prostate biopsy with at least 10 cores sampling for suspicious exam and/or elevated PSA. Covariates were collected for the nomogram and included age, ethnicity, family history (FH) of PCa, PSA at diagnosis, PCA3, total prostate volume (TPV), and abnormal finding on digital rectal exam (DRE). These variables were used to test the accuracy (concordance index) and calibration of a previously published PCA3 nomogram. RESULTS: Biopsy confirms PCa and HGPCa in 51.0% and 30.4% of validation patients, respectively. This differed from the original cohort in that it had significantly more PCa and HGPCA (51% vs. 44%, P = 0.019; and 30.4% vs. 19.1%, P < 0.001). Despite the differences in PCa detection the concordance index was 75% and 77% for overall PCa and HGPCa, respectively. Calibration for overall PCa was good. CONCLUSIONS: This represents the first external validation of a PCA3-based prostate cancer predictive nomogram in a North American population. Prostate 76:1019-1023, 2016. © 2016 Wiley Periodicals, Inc.

More Favorable Pathological Outcomes in Men with Low Risk Prostate Cancer Diagnosed on Repeat versus Initial Transrectal Ultrasound Guided Prostate Biopsy.

PURPOSE: We assessed the pathological outcomes after radical prostatectomy in men with favorable risk prostate cancer diagnosed on first/initial biopsy compared to those of men who were diagnosed on a subsequent/repeat prostate biopsy. MATERIALS AND METHODS: We identified 422 patients who met National Comprehensive Cancer Network® very low (199) and low risk (223) prostate cancer definitions who instead underwent radical prostatectomy. In each risk category we compared adverse pathological outcomes, defined as Gleason score upgrading, extraprostatic extension, seminal vesicle invasion and positive surgical margins, between men diagnosed on initial prostate biopsy vs repeat/subsequent prostate biopsy after a negative biopsy(-ies). RESULTS: There were no significant differences in the baseline clinical and demographic characteristics between the groups. However, men who were diagnosed on initial prostate biopsy demonstrated a higher median maximum cancer percent per single core (p <0.001) and higher median percent of positive cores (p <0.001). Compared to repeat/subsequent prostate biopsy, men diagnosed on initial prostate biopsy had a higher Gleason score upgrade (7 or greater) (57.7% vs 42.1%, p=0.005) and extraprostatic extension (14.1% vs 5.4%, p=0.01). On stratified analysis comparing initial prostate biopsy to repeat/subsequent prostate biopsy, very low risk disease was associated with Gleason score upgrade (49.3% vs 31.8%, p=0.02) and low risk disease demonstrated higher rates of extraprostatic extension (19.9% vs 6.0%, p=0.02). CONCLUSIONS: The likelihood of adverse pathological outcomes at radical prostatectomy is lower in men diagnosed with favorable risk prostate cancer on repeat/subsequent prostate biopsy than in men diagnosed on initial prostate biopsy, and may represent an important consideration in risk stratifying cases of favorable risk prostate cancer.

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

BACKGROUND: 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. METHODS: We queried the COLD Registry to identify patients diagnosed as locally recurrent PCa after radiotherapy and treated with salvage focal cryoablation. Patients with hormone ablation after cryotherapy were excluded. The biochemical disease-free survival and morbidities were analyzed. Biochemical failure was defined using the Phoenix definition. RESULTS: From 2002 to 2012, 91 patients with biopsy-proven radio-recurrent PCa underwent salvage focal cryoablation with curative intent. The biochemical disease-free survival rates were 95.3%, 72.4%, and 46.5% at 1, 3, and 5 years, respectively. Positive biopsies after salvage focal cryoablation were observed in four of 14 patients who underwent biopsy (28.6%). Rectourethral fistula was observed in three cases (3.3%). Urinary retention was observed in six cases (6.6%). Incontinence (requiring pad use) was reported in five cases (5.5%). Intercourse was reported in 10 of 20 patients (50%) who reported potency before salvage focal cryoablation. CONCLUSIONS: The outcomes from this observational study indicate that salvage focal cryoablation can be an effective treatment with encouraging potency preservation for patients with locally recurrent PCa after radiotherapy. However, other morbidity including rectourethral fistula and incontinence are not clearly lower than for patients treated with salvage whole gland cryoablation. Studies with longer follow-up, more patients, and direct comparison to salvage whole gland cryoablation are needed before recommending salvage focal cryoablation as a standard treatment option for these patients.

A pretreatment nomogram for prediction of biochemical failure after primary cryoablation of the prostate.

BACKGROUND: To create a predictive nomogram for biochemical failure following primary whole-gland cryoablation of the prostate for localized prostate cancer (LPCa). METHODS: We retrospectively analyzed 2,242 patients from the Cryo On-Line Database (COLD) who were treatment naive and had undergone primary whole gland cryoablation of the prostate for biopsy-confirmed LPCa. Kaplan-Meier (KM) curves estimating 5 year biochemical progression-free survival (bPFS) were generated. Multivariable Cox proportional hazards analysis (CoxPH) was performed in order to construct the nomogram. The nomogram was internally validated using the bootstrap technique. RESULTS: Overall, the KM estimated 5 year bPFS was 72.8%. Stratified by D'Amico risk, The KM estimated 5 year bPFS was 82.6%, 71.1%, and 57.8% for low-, intermediate-, and high-risk groups, respectively. Statistically significant predictors of biochemical outcomes from CoxPH analysis were pre-treatment prostate specific antigen (PTPSA) (P < 0.001), total prostate volume (P = 0.004), clinical stage (P = 0.034), and Gleason score (0.004). A nomogram for predicted 5 year biochemical progression free probability was constructed with a concordance index of 0.652. An online risk calculator was also generated. CONCLUSIONS: To the best of our knowledge, this is the first predictive nomogram for biochemical outcomes after primary whole gland cryoablation of the prostate using socio-demographic, pretreatment, clinical, and prostate biopsy data. Our nomogram and online risk calculator can guide both patients and urologists for shared decision making regarding definitive treatment options.

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.

Does cumulative prostate cancer length (CCL) in prostate biopsies improve prediction of clinically insignificant cancer at radical prostatectomy in patients eligible for active surveillance?

OBJECTIVES: To evaluate if cumulative prostate cancer length (CCL) on prostate needle biopsy divided by the number of biopsy cores (CCL/core) could improve prediction of insignificant cancer on radical prostatectomy (RP) in patients with prostate cancer eligible for active surveillance (AS). PATIENTS AND METHODS: Patients diagnosed with prostate cancer on extended (≥10 cores) biopsy with an initial prostate-specific antigen (iPSA) level of <15 ng/mL, clinical stage (cT) ≤ 2a, and highest biopsy Gleason score 3 + 3 = 6 or 3 + 4 = 7 with <3 positive cores who underwent RP were included in the study. The CCL/core and presence of insignificant cancer (organ-confined, volume <0.5 mL, Gleason score at RP ≤6) were recorded. pT2 prostate cancer with RP Gleason score ≤3 + 4 = 7 and volume <0.5 mL were categorised as low-tumour-volume organ-confined disease (LV-OCD). RESULTS: In all, 221 patients met the inclusion criteria: the mean age was 59 years and the median iPSA level was 4.5 ng/mL. The clinical stage was cT1 in 86% of patients; biopsy Gleason score was 3 + 3 = 6 in 67% (group 1) and 3 + 4 = 7 in 33% of patients (group 2). The maximum percentage of biopsy core involvement was <50 in 85%; the median CCL/core was 0.15 mm. Insignificant cancer was found in 27% and LV-OCD in 44% of patients. Group 2 was associated with higher number of positive cores, maximum percentage core involvement, total prostate cancer length, and CCL/core. Group 1 was more likely to have insignificant cancer (39%) or LV-OCD (54%) than group 2 (3% and 23%, respectively). Group 2 had significantly higher RP Gleason score and pathological stage. Univariate analysis of group 1 showed that the iPSA level, maximum percentage core involvement, prostate cancer length, and CCL/core were all significantly associated with insignificant cancer and LV-OCD. For group 2, the number of positive cores (1 vs 2) was also significantly associated with LV-OCD. On multivariate logistic regression analysis, maximum percentage core involvement of <50, and number of positive cores (1 vs 2) were independent predictors of insignificant cancer in group 1; biopsy Gleason score, maximum percentage core involvement of <50 and prostate cancer length of <3 mm or CCL/core of <0.2 mm were all independent predictors of LV-OCD in the whole population. The maximum percentage of core involvement of <50 and prostate cancer length of <3 mm or CCL/core of <0.2 mm were also independent predictors of LV-OCD in group 1 patients. CONCLUSION: In patients eligible for AS, a CCL/core of <0.20 mm was significantly associated with insignificant cancer and LV-OCD. However, when parameters of cancer burden were considered, CCL/core did not independently add any additional value for predicting insignificant cancer in patients with biopsy Gleason score 6. The CCL/core was an independent predictor of LV-OCD in the whole population and in group 1 patients, although the model including prostate cancer length showed slightly higher area under the receiver operating characteristic curve.

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).

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.

Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies.

PURPOSE: The DOCUMENT multicenter trial in the United States validated the performance of an epigenetic test as an independent predictor of prostate cancer risk to guide decision making for repeat biopsy. Confirming an increased negative predictive value could help avoid unnecessary repeat biopsies. MATERIALS AND METHODS: We evaluated the archived, cancer negative prostate biopsy core tissue samples of 350 subjects from a total of 5 urological centers in the United States. All subjects underwent repeat biopsy within 24 months with a negative (controls) or positive (cases) histopathological result. Centralized blinded pathology evaluation of the 2 biopsy series was performed in all available subjects from each site. Biopsies were epigenetically profiled for GSTP1, APC and RASSF1 relative to the ACTB reference gene using quantitative methylation specific polymerase chain reaction. Predetermined analytical marker cutoffs were used to determine assay performance. Multivariate logistic regression was used to evaluate all risk factors. RESULTS: The epigenetic assay resulted in a negative predictive value of 88% (95% CI 85-91). In multivariate models correcting for age, prostate specific antigen, digital rectal examination, first biopsy histopathological characteristics and race the test proved to be the most significant independent predictor of patient outcome (OR 2.69, 95% CI 1.60-4.51). CONCLUSIONS: The DOCUMENT study validated that the epigenetic assay was a significant, independent predictor of prostate cancer detection in a repeat biopsy collected an average of 13 months after an initial negative result. Due to its 88% negative predictive value adding this epigenetic assay to other known risk factors may help decrease unnecessary repeat prostate biopsies.