Baseline prostate health index risk category and risk category changes during active surveillance predict grade reclassification.

BACKGROUND: It is not known whether baseline prostate health index (PHI) at the initiation of active surveillance (AS) or repeated PHI testing during AS is of clinical value after confirmatory biopsy in AS men followed with multiparametric magnetic resonance imaging (mpMRI). METHODS: We identified 382 AS patients with no greater than Grade Group 1 (GG1) prostate cancer on diagnostic and confirmatory biopsy, at least one mpMRI and PHI test, of which 241 had at least 2 PHI tests. Grade reclassification (GR) was defined as ≥GG2 on surveillance biopsy. PHI risk categories 1 to 4 were as defined by the manufacturer. Associations between baseline PHI risk category or baseline PSA density (PSAD), change in PHI risk categories over time or PSAD changes over time and GR were evaluated with multivariable Cox proportional hazard regression models adjusted for age, Prostate Imaging-Reporting and Data System score and number of positive cores. RESULTS: Men with baseline PHI scores in the highest risk categories had lower rates of GR-free survival (log-rank P < 0.001), as did those who increased in PHI risk category or remained in a high PHI risk category during surveillance (log-rank P = 0.032). On multivariable regression, baseline PHI risk category was a predictor of GR (risk category 4 [vs. 1] hazard ratio [HR] 2.74, 95% confidence interval [CI] 1.32-5.66, P = 0.002, model C-index 0.764, Akaike Information Criterion [AIC] 797), as were PHI risk category changes over time (risk category 4 [vs. 1] HR 4.20, 95% CI 1.76-10.05, P = 0.002, C-index 0.759, AIC 489). Separate models with baseline PSAD and PSAD changes over time yielded C-indices of 0.709 (AIC 809) and 0.733 (AIC 495) respectively. CONCLUSIONS: Baseline PHI risk category and PHI changes over time were both independent predictors of GR after confirmatory biopsy, but the added benefit over PSAD seemed modest. However, baseline PHI and PHI risk category changes provided clinically useful risk stratification for time to GR, so further evaluation of PHI's ability to help reduce the frequency of mpMRI and/or surveillance biopsies with more PHI data points over time may be warranted.

Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) Magnetic Resonance Imaging Scoring to Predict Clinical Outcomes in Active Surveillance for Grade Group 1 Prostate Cancer.

OBJECTIVE: To determine whether radiological change on serial multiparametric magnetic resonance imaging scored using the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) Scoring system predicts grade reclassification (GR) at surveillance biopsy in men on active surveillance (AS) with Grade Group 1 (GG1) prostate cancer (PCa). METHODS: We retrospectively reviewed records of 255 men with low-risk PCa on AS with magnetic resonance imaging (MRI)-informed diagnostic and confirmatory biopsies and studied the subset who had surveillance biopsies (n = 163) within 6months of an interval MRI. RESULTS: We studied 309 PRECISE scores in 255 men. 14% demonstrated radiological progression (PRECISE 4-5) on interval MRI performed within 24months, compared to 34% of those whose interval MRI was performed at a >3-year interval (P = .002). 28% (46/163) of men undergoing surveillance biopsy experienced GR to ≥ GG2 PCa. There was no significant increase in the rate of GR with increasing PRECISE score (PRECISE 1-2: 24%, PRECISE 3: 23%, PRECISE 4-5: 38%; P = .11). There was a significant increase in the rate of GR with increasing PI-RADS score (P < .05). On multivariable analysis, a PI-RADS score of 4-5 was significantly associated with GR compared to men who had a highest PI-RADS ≤3 (OR=1.98 [95% CI: 1.45-3.09, P = .01]). CONCLUSION: In a low-risk AS cohort with limited follow-up, a patient's highest PI-RADS rather than their PRECISE score on interval MRI was predictive of GR on surveillance biopsy.

Identifying Men Who Can Remain on Active Surveillance Despite Biopsy Reclassification to Grade Group 2 Prostate Cancer.

PURPOSE: Men on active surveillance with Grade Group 1 prostate cancer who reclassify to Grade Group 2 on surveillance biopsy often leave active surveillance. We aimed to identify subgroups of men who can safely remain on active surveillance despite preoperative reclassification to Grade Group 2. MATERIALS AND METHODS: We studied 249 active surveillance patients with surveillance biopsies classified as Grade Group 1 or Grade Group 2 who underwent radical prostatectomy. Perineural invasion, cancer volume, linear length and maximum percentage of Gleason pattern 4, and prostate-specific antigen density were evaluated. Radical prostatectomy adverse pathology was defined by any of: pN1; ≥pT3; ≥Grade Group 2 with ≥20% Gleason pattern 4; intraductal carcinoma; large cribriform glands. RESULTS: A multivariable logistic regression model incorporating prostate-specific antigen density and perineural invasion stratified radical prostatectomy adverse pathology risk among Grade Group 1 and Grade Group 2 active surveillance patients. 57% (39/68) of Grade Group 1 men reclassified to Grade Group 2 while on active surveillance had favorable radical prostatectomy pathology. Those without biopsy perineural invasion and with low prostate-specific antigen density were more likely to have favorable radical prostatectomy pathology. CONCLUSIONS: Most Grade Group 1 men who enter active surveillance and subsequently reclassify to Grade Group 2 have favorable findings at radical prostatectomy and can remain on active surveillance. Among patients reclassified to Grade Group 2, those with low prostate-specific antigen density and without perineural invasion had the lowest risk of radical prostatectomy adverse pathology, comparable to (or below) that of Grade Group 1 patients who were not reclassified to Grade Group 2 preoperatively. Prostate-specific antigen density and perineural invasion stratify risk in active surveillance patients reclassified to Grade Group 2 and, if concordant with other clinicopathological and radiographic findings, can enable more patients to remain on active surveillance. Reclassification to Grade Group 2 alone should not disqualify men from remaining on active surveillance.

Clinical Significance of Perineural Invasion in Men With Grade Group 1 Prostate Cancer on Active Surveillance.

PURPOSE: We aimed to evaluate the clinical significance of perineural invasion in men on active surveillance for Grade Group 1 prostate cancer. MATERIALS AND METHODS: We identified 1,969 men with Grade Group 1 prostate cancer and at least 1 follow-up biopsy. A time-dependent Cox model and a logistic regression model were used to assess the association between biopsy-detected perineural invasion and grade reclassification (defined as the detection of Grade Group ≥2 prostate cancer on a surveillance biopsy), and adverse pathology (defined as Grade Group ≥3 ± seminal vesicle invasion ± lymph node involvement) at radical prostatectomy, respectively. RESULTS: The 198 men with perineural invasion detected during active surveillance had lower rates of grade reclassification-free survival than those without perineural invasion (P < .001). On multivariable analysis perineural invasion was significantly associated with grade reclassification (HR 3.25, 95% CI 2.54-4.16, P < .001); an association that persisted in the multiparametric magnetic resonance imaging subset. At radical prostatectomy, men with biopsy-detected perineural invasion had more extraprostatic extension than men without perineural invasion (Relative Risk 1.71, 95% CI 1.15-2.56). However, on multivariable analysis biopsy-detected perineural invasion was not associated with adverse pathology (OR 0.68, 95% CI 0.27-1.68, P = .40) and these patients did not exhibit more biochemical recurrence at 5 years (P > .05). CONCLUSIONS: Perineural invasion during active surveillance was associated with grade reclassification. At radical prostatectomy biopsy-detected perineural invasion patients exhibited more extraprostatic extension but biopsy-detected perineural invasion was not independently associated with more adverse pathology. In addition, these patients did not have more biochemical recurrence during follow-up. Perineural invasion should not preclude Grade Group 1 patients from active surveillance but they may warrant more stringent monitoring.

Association of prostate cancer polygenic risk score with number and laterality of tumor cores in active surveillance patients.

BACKGROUND: Prostate cancer (PCa) is characterized by its tendency to be multifocal. However, few studies have investigated the endogenous factors that explain the multifocal disease. The primary objective of the current study is to test whether inherited PCa risk is associated with multifocal tumors in PCa patients. METHODS: Subjects in this study were PCa patients of European ancestry undergoing active surveillance at Johns Hopkins Hospital (N = 805) and NorthShore University HealthSystem (N = 432). The inherited risk was measured by genetic risk score (GRS), an odds ratio-weighted and population-standardized polygenic risk score based on known risk-associated single nucleotide polymorphisms. PCa multifocality was indirectly measured by the number and laterality of positive tumor cores from a 12-core systematic biopsy. RESULTS: In the combined cohort, 35.7% and 66.3% of patients had ≥2 tumor cores at the initial diagnostic biopsy and on at least one subsequent surveillance biopsy, respectively. For tumor laterality, 7.8% and 47.8% of patients had bilateral tumor cores at diagnostic and surveillance biopsies, respectively. We found, for the first time, that patients with higher numbers of positive cores at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values; p = .01 and p = 5.94E-04. Additionally, patients with bilateral tumors at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values than those with unilateral tumors; p = .04 and p = .01. In contrast, no association was found between GRS and maximum core length of tumor or tumor grade at diagnostic/surveillance biopsies (all p > .05). Finally, we observed a modest trend that patients with higher GRS quartiles had a higher risk for tumor upgrading on surveillance biopsies. The trend, however, was not statistically significant (p > .05). CONCLUSIONS: The associations of GRS with two measurements of PCa multifocality (core numbers and laterality) provide novel and consistent evidence for the link between inherited PCa risk and multifocal tumors.

Transperineal Prostate Biopsy Improves the Detection of Clinically Significant Prostate Cancer among Men on Active Surveillance.

PURPOSE: Transperineal prostate biopsy offers improved sampling of the anterior prostate compared to the transrectal approach. The objective of this study was to determine if transperineal prostate biopsy is associated with an increased incidence of cancer upgrading among men on active surveillance for very low or low risk prostate cancer. MATERIALS AND METHODS: Our active surveillance registry was queried to identify patients who underwent a surveillance biopsy following the introduction of transperineal prostate biopsy at our institution. Patients were dichotomized by the type of biopsy performed. The baseline characteristics and rates of cancer upgrading were compared between groups. RESULTS: Between November 2017 and June 2020, 790 men with very low or low risk prostate cancer underwent a surveillance biopsy. In total, 59 of 279 men (21.2%) in the transperineal prostate biopsy group were upgraded to grade group ≥2 as compared to 75 of 511 (14.7%) in the transrectal biopsy group (p=0.01). Among patients who were upgraded to grade group ≥2, 26 of 59 (44%) had grade group ≥2 detected in the anterior/transition zone with transperineal prostate biopsy compared to 14 of 75 (18.7%) with transrectal biopsy (p=0.01). Additionally, 17 of 279 men (6.1%) who underwent transperineal prostate biopsy were upgraded to grade group ≥3 vs 17 of 511 (3.3%) who underwent transrectal biopsy (p=0.05). After adjusting for age, prostate specific antigen density, use of magnetic resonance imaging, and number of prior transrectal biopsies, transperineal prostate biopsy was significantly associated with upgrading to grade group ≥2 (OR 1.49, 95% CI 1.11-2.19, p=0.01). CONCLUSIONS: Among men on active surveillance for very low or low risk prostate cancer, transperineal prostate biopsy was associated with an increased likelihood of upgrading to clinically significant prostate cancer. This is likely due to improved sampling of the anterior prostate with the transperineal approach.

Utility of multiparametric magnetic resonance imaging in the risk stratification of men with Grade Group 1 prostate cancer on active surveillance.

OBJECTIVE: To assess if the adoption of multiparametric magnetic resonance imaging (mpMRI) in active surveillance (AS) has improved the identification of occult higher-grade prostate cancer (PCa). PATIENTS AND METHODS: We retrospectively identified men from the Johns Hopkins AS registry enrolled since 2013 (year of mpMRI adoption) with Grade Group (GG) 1 PCa and who underwent a single mpMRI. Men in this group were dichotomised by the presence (n = 207) or absence (negative mpMRI, n = 225) of one or more lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of ≥ 3. Both groups were compared to a third cohort of men with GG1 PCa enrolled in AS prior to 2013 (pre-mpMRI era, n = 669). The risk of upgrading to GG ≥ 2 PCa on follow-up biopsies (performed with or without MRI targeting) was evaluated among the groups using survival analysis. RESULTS: Men in both mpMRI groups underwent a median (interquartile range [IQR]) of 2 (2-3) biopsies separated by a median (IQR) interval of 13 (12-16) months, whereas men in the pre-MRI era underwent a median (IQR) of 3 (2-5) biopsies, separated by a median (IQR) interval of 12 (12-14) months. The 2- and 4-year upgrade-free survival rates were 93% and 83%, 74% and 59%; and, 87% and 76% for the negative mpMRI, PI-RADS ≥ 3, and pre-mpMRI-era groups, respectively (P < 0.001). On multivariable analysis, both mpMRI groups had significantly different risk of upgrading compared to pre-mpMRI-era group (negative mpMRI group: hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.39-0.95, P = 0.03; PI-RADS ≥ 3 group: HR 1.96, 95% CI 1.36-2.82, P < 0.001). CONCLUSIONS: mpMRI improves the risk stratification of men on AS and should be used to aid enrolment and monitoring decisions.

Active Surveillance of Grade Group 1 Prostate Cancer: Long-term Outcomes from a Large Prospective Cohort.

BACKGROUND: Active surveillance (AS) is the preferred management option for most men with grade group (GG) 1 prostate cancer (PCa). Questions persist regarding long-term outcomes and the optimal approach to AS. OBJECTIVE: To determine survival and metastatic outcomes in AS patients. Secondary objectives were to measure the cumulative incidence and association of patient-level factors on biopsy grade reclassification. DESIGN, SETTING, AND PARTICIPANTS: A prospective, active, open-enrollment cohort study was conducted from 1995 through July 2018 at a tertiary-care academic institution. Patients with very-low-risk or low-risk PCa were enrolled. INTERVENTION: AS with semiannual prostate-specific antigen (PSA) and digital rectal examination, serial prostate biopsy, and multiparametric magnetic resonance imaging (mpMRI). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The 10- and 15-yr cumulative incidences of primary and secondary outcomes were determined. RESULTS AND LIMITATIONS: Overall, 1818 men were monitored on AS for a median of 5.0yr (interquartile range 2.0-9.0). There were 88 non-PCa deaths, four PCa deaths, and one additional case of metastasis. The cumulative incidence of PCa-specific mortality or metastasis was 0.1% (95% confidence interval, 0.04-0.6%) at both 10 and 15yr. The 5-, 10-, and 15-yr cumulative incidences of biopsy grade reclassification were 21%, 30%, and 32%, respectively. On multivariable analysis, biopsy grade reclassification was associated with older age, African-American race, PSA density, and increased cancer volume on biopsy, and men who underwent mpMRI prior to enrollment were less likely to undergo grade reclassification. Our selection and monitoring are more stringent than many other contemporary AS programs. CONCLUSIONS: In a large, single-institution, prospective AS cohort, the risk of cancer death or metastasis was <1% over long-term follow-up. Consistent with clinical guidelines, these data support the use of AS for the management of most men diagnosed with GG1 PCa. PATIENT SUMMARY: This study investigated long-term outcomes in patients with grade group 1 prostate cancer managed with active surveillance (AS). Ten years after enrolling in AS, the risk of metastasis or death from prostate cancer was <1%, while 48% of men switched to treatment. Patients who underwent multiparametric magnetic resonance imaging (mpMRI)/ultrasound-fusion targeted biopsy prior to enrollment were less likely to experience biopsy grade reclassification during follow-up, suggesting a role for mpMRI as part of a comprehensive risk assessment to confirm AS eligibility. These findings support the safety of AS in most men with grade group 1 prostate cancer, but specific outcomes may differ in programs with less intensive monitoring.

Evaluation of Apparent Diffusion Coefficient as a Predictor of Grade Reclassification in Men on Active Surveillance for Prostate Cancer.

OBJECTIVE: To evaluate the association between apparent diffusion coefficient (ADC) on initial multiparametric MRI (mpMRI) and biopsy grade reclassification (GR) to grade group (GG) ≥2 prostate cancer (CaP) in men on active surveillance (AS) with GG 1 CaP. METHODS: We retrospectively identified 242 AS patients with reported ADC values on their initial mpMRI. ADC value from the index lesion was assessed as an independent predictor of GR using a Cox model. To ease clinical interpretation, we used a log-rank test to establish an ADC cutoff of 1128 × 10-6 mm2/s for Kaplan-Meier analysis. RESULTS: Of the 242 men, 70 underwent GR following initial mpMRI, of which 26 (37%) had GR at the index lesion. There was no significant difference in the median interval between biopsies for men with and without GR (P >.9). Men with GR had significantly lower median ADC than those without GR (P = .01). In multivariable analysis adjusting for age, prostate-specific antigen density, and National Comprehensive Cancer Network risk group, a 100-unit decrease in ADC was associated with a 12% increase in the risk of GR (HR = 1.12, 95% CI: 1.01-1.22, P = .03). Two- and 4-year rates of freedom from GR were significantly lower for men with ADC <1128 × 10-6 mm2/s vs ADC ≥1128 × 10-6 mm2/s (62% and 42% vs 78% and 68%, respectively; P <.001). CONCLUSION: For AS patients, lower ADC on initial mpMRI index lesion is associated with increased risk of GR to GG ≥2 CaP and would be a useful component of multivariable risk prediction tools.

Development and Validation of the False Disorder Score: The Focal Scale of the Inventory of Problems.

This article introduces the Inventory of Problems (IOP)-a new, computerized, 181-item tool designed to discriminate bona fide from feigned mental illness and cognitive impairment-and presents the development and validation of its focal, feigning scale, the False Disorder Score (IOP-FDS). The initial sample included (a) 211 patients and 64 offenders who took the IOP under standard conditions, and (b) 210 community volunteers and 64 offenders who feigned mental illness. We split this sample into three subsamples. The first (n = 301) was used to select the variables to generate the IOP-FDS; the second (n = 148) scaled the IOP-FDS into a probability score; and the third (n = 100) tested its validity with an independent data set. In this third subsample, the IOP-FDS had sensitivity = .90, specificity = .80, and a greater area under the curve (AUC = .95) than the IOP-29 (.91). For 40 participants, the Personality Assessment Inventory (PAI) was available, too. Within this subgroup, the IOP-FDS outperformed the selected PAI validity scales (AUC = .99 vs. AUC ≤ .85).

Germline Mutations in ATM and BRCA1/2 Are Associated with Grade Reclassification in Men on Active Surveillance for Prostate Cancer.

BACKGROUND: Mutations in DNA repair genes are associated with aggressive prostate cancer (PCa). OBJECTIVE: To assess whether germline mutations are associated with grade reclassification (GR) in patients undergoing active surveillance (AS). DESIGN, SETTING, AND PARTICIPANTS: Two independent cohorts of PCa patients undergoing AS; 882 and 329 patients from Johns Hopkins and North Shore, respectively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Germline DNA was sequenced for DNA repair genes, including BRCA1/2 and ATM (three-gene panel). Pathogenicity of mutations was defined according to the American College of Medical Genetics guidelines. Association of mutation carrier status and GR was evaluated by a competing risk analysis. RESULTS AND LIMITATIONS: Of 1211, 289 patients experienced GR; 11 of 26 with mutations in a three-gene panel and 278 of 1185 noncarriers; adjusted hazard ratio (HR)=1.96 (95% confidence interval [CI]=1.004-3.84, p=0.04). Reclassification occurred in six of 11 carriers of BRCA2 mutations and 283 of 1200 noncarriers; adjusted HR=2.74 (95% CI=1.26-5.96, p=0.01). The carrier rates of pathogenic mutations in the three-gene panel, and BRCA2 alone, were significantly higher in those reclassified (3.8% and 2.1%, respectively) than in those not reclassified (1.6% and 0.5%, respectively; p=0.04 and 0.03, respectively). Carrier rates for BRCA2 were greater for those reclassified from Gleason score (GS) 3+3 at diagnosis to GS ≥4+3 (4.1% vs 0.7%, p=0.01) versus GS 3+4 (2.1% vs 0.6%; p=0.03). Results are limited by the small number of mutation carriers and an intermediate end point. CONCLUSIONS: Mutation status of BRCA1/2 and ATM is associated with GR among men undergoing AS. PATIENT SUMMARY: Men on active surveillance with inherited mutations in BRCA1/2 and ATM are more likely to harbor aggressive prostate cancer.

Targeted antimicrobial prophylaxis for transrectal ultrasound-guided prostate biopsy during active surveillance: Effect on hospitalization.

OBJECTIVES: We investigated the effect of targeted antibiotic prophylaxis using rectal swab cultures on hospitalization for infectious complications after transrectal ultrasound-guided prostate biopsy (TRUSP). MATERIALS AND METHODS: A cohort of men (1995-2016) with prostate cancer on active surveillance receiving annual TRUSP biopsies was surveyed to determine the incidence of hospitalization for suspected postbiopsy sepsis. We compared biopsy events (i.e., unique biopsies) in the era of empiric prophylaxis to those in the era of targeted prophylaxis based on culture. The effect of fluoroquinolone resistant organisms (FQ-R), and other demographic and clinical factors, on hospitalization was assessed using logistic regression. RESULTS: Of 1,167 men on active surveillance, 825 responded for a total of 3,361 biopsy events; 7 (0.79%) of 886 biopsies preceded by rectal swab culture resulted in hospitalization compared to 24 (0.97%) of 2,475 biopsies without culture (OR = 0.81, 95% CI: 0.35-1.89, P = 0.63). Among 886 cultures performed, FQ-R organisms were identified in 194 (21.9%); 6 out of 194 (3.1%) biopsies with swabs positive for FQ-R resulted in admission compared to 1 out of 692 (0.14%) biopsies with fluoroquinolone sensitive swabs (OR = 22.1, 95% CI: 2.6-184.3, P<0.01). Smaller prostate volume at diagnosis was significantly associated with hospitalization (OR = 2.57, 95% CI: 1.04-6.31) for<45 g vs. ≥45 g, P = 0.039). CONCLUSION: Targeted antibiotic prophylaxis is not associated with a significant reduction in hospitalization for suspected post-TRUSP biopsy sepsis. FQ-R and prostate volume exhibited strong associations with risk of hospitalization and could be included in a risk-adapted approach to prophylaxis, but better prophylactic strategies are needed for patients identified to be at high risk of subsequent hospitalization.

Comparison of Biochemical Recurrence-Free Survival after Radical Prostatectomy Triggered by Grade Reclassification during Active Surveillance and in Men Newly Diagnosed with Similar Grade Disease.

PURPOSE: We compared biochemical recurrence between men on active surveillance who underwent radical prostatectomy triggered by grade reclassification and men diagnosed with similar grade disease treated with immediate radical prostatectomy. MATERIALS AND METHODS: We retrospectively analyzed the records of men who underwent surgery from 1995 to 2015 at our institution. We identified 4 groups, including 94 and 56 men on active surveillance who underwent radical prostatectomy following reclassification to Gleason 7 (3 + 4) or greater (grade groups 2 or greater) and Gleason 7 (3 + 4) (grade group 2), and 3,504 and 1,979 in the immediate prostatectomy group diagnosed with grade group 2 or greater and 2, respectively. Biochemical recurrence was assessed by Kaplan-Meir analysis and a multivariable Cox model. RESULTS: Men on active surveillance had a lower incidence of biochemical recurrence than men in the immediate radical prostatectomy groups for biopsy grade groups 2 or greater and 2 (each p <0.05). One, 5 and 10-year biochemical recurrence-free survival for men in the active surveillance group vs the immediate radical prostatectomy group was 97.9% vs 85.5%, 76.6% vs 65.1% and 69.0% vs 54.2% in biopsy grade groups 2 or greater (p = 0.009) and 96.4% vs 91.2%, 89.6% vs 74.0% and 89.6% vs 63.9%, respectively, in biopsy grade group 2 (p = 0.071). For biopsy grade groups 2 or greater there was no significant difference in the risk of biochemical recurrence between the groups after adjusting for age, biopsy extent of cancer and prostate specific antigen density. CONCLUSIONS: Patients on active surveillance reclassified to grade groups 2 or greater are at no greater risk for treatment failure than men newly diagnosed with similar grades.

The Role of Multiparametric Magnetic Resonance Imaging/Ultrasound Fusion Biopsy in Active Surveillance.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI)/ultrasound fusion biopsy (targeted biopsy or TB) may improve detection of high-grade cancers when compared to systematic biopsy (SB). OBJECTIVE: To assess TB in active surveillance (AS). DESIGN, SETTING, AND PARTICIPANTS: We retrospectively evaluated SB (12-core sector) and TB among 103 AS men undergoing surveillance biopsy, 54 men undergoing confirmatory biopsy (CB), and 73 men referred for diagnostic biopsy (DB; comparison group). Regions of interest (ROIs) on mpMRI were assigned a PI-RADS score and targeted if the score was ≥3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Detection of Gleason score (GS) ≥7 by TB and SB was the outcome of interest, except in a multivariable model, for which any cancer was the outcome. RESULTS AND LIMITATIONS: GS ≥7was detected by either biopsy method in 25 men (24.3%) in the AS group, 12 men (22.2%) in the CB group, and 55 men (75.3%) in the DB group.GS ≥7 was found in 24.3% by SB + TB versus 20.4% by SB in the AS group (p=0.13); in 22.2% by SB + TB versus 16.7% by SB in the CB group (p=0.25); and in 75.3% by SB + TB versus 58.9% by SB in the DB group (p=0.002). The sensitivity for GS ≥7 detection was lower for TB than for SB (p=0.006) in the AS cohort (relative sensitivity ratio 0.33, 95% confidence interval 0.16-0.71). Higher PI-RADS score (4 vs 3, odds ratio [OR] 2.00, p=0.04; 5 vs 3, OR 4.74, p=0.02), lower MRI-estimated prostate volume (OR 1.20 per 10-cm3 lower volume, p=0.01), larger ROI (OR 1.04 per mm, p=0.02), and right-sided ROI (OR 2.27, p=0.01) were associated with finding cancer on TB. A potential limitation is that not all men who presented for biopsy underwent TB and the urologist was not blinded to MRI results before SB. CONCLUSIONS: Owing to the low relative sensitivity of mpMRI for detection of GS ≥7 disease, SB still needs to be performed for men on AS. PATIENT SUMMARY: This study suggests that image-guided prostate biopsy alone may not be informative for men enrolled in an active surveillance program for prostate cancer.

Risk prediction tool for grade re-classification in men with favourable-risk prostate cancer on active surveillance.

OBJECTIVE: To create a nomogram for men on active surveillance (AS) for prediction of grade re-classification (GR) above Gleason score 6 (Grade group >2) at surveillance biopsy. PATIENTS AND METHODS: From a cohort of men enrolled in an AS programme, a multivariable model was used to identify clinical and pathological parameters predictive of GR. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision curve analysis. RESULTS: Of 1 374 men, 254 (18.50%) were re-classified to Gleason ≥7 on surveillance prostate biopsy. Variables predictive of GR were earlier year of diagnosis [≤2004 vs ≥2005; odds ratio (OR) 2.16, P < 0.001], older age (OR 1.05, P < 0.001), higher prostate-specific antigen density [OR 1.19 (per 0.1 unit increase), P = 0.04], bilateral disease (OR 2.86, P < 0.001), risk strata (low-risk vs very-low-risk, OR 1.79, P < 0.001), and total number of biopsies without GR (OR 0.68, P < 0.001). On internal validation, a nomogram created using the multivariable model had an area under the curve of 0.757 (95% confidence interval 0.730-0.797) for predicting GR at the time of next surveillance biopsy. CONCLUSION: The nomogram described is currently being used at each return visit to assess the need for a surveillance biopsy, and could increase retention in AS.

The Development of the Inventory of Problems-29: A Brief Self-Administered Measure for Discriminating Bona Fide From Feigned Psychiatric and Cognitive Complaints.

This article describes the development of the Inventory of Problems-29 (IOP-29), a new, short, paper-and-pencil, self-administered measure of feigned mental and cognitive disorders. Four clinical comparison simulation studies were conducted. Study 1 (n = 451) selected the items and produced an index of potential feigning. Study 2 (n = 331) scaled this index to produce a probability score, and examined its psychometric properties. Study 3 tested the generalizability of Study 2's findings with 2 additional samples (ns = 128 and 90). Results supported the utility of the IOP-29 for discriminating bona fide from feigned psychiatric and cognitive complaints. Validity was demonstrated in feigning mild traumatic brain injury, psychosis, posttraumatic stress disorder, and depression. Within the independent samples of Studies 2 and 3, the brief IOP-29 performed similarly to the MMPI-2 and Personality Assessment Inventory, and perhaps better than the Test of Memory Malingering. Classifications within these samples with base rates of .5 produced sensitivity, specificity, positive predictive power, and negative predictive power statistics of about .80. Further research is needed testing the IOP-29 in ecologically valid field studies.

Elevated Prostate Health Index (phi) and Biopsy Reclassification During Active Surveillance of Prostate Cancer.

The Prostate Health Index (phi) has been FDA approved for decision-making regarding prostate biopsy. Phi has additionally been shown to positively correlate with tumor volume, extraprostatic disease and higher Gleason grade tumors. Here we describe a case in which an elevated phi encouraged biopsy of a gentleman undergoing active surveillance leading to reclassification of his disease as high risk prostate cancer.

Pathologic Outcomes in Favorable-risk Prostate Cancer: Comparative Analysis of Men Electing Active Surveillance and Immediate Surgery.

BACKGROUND: It remains unclear whether men selecting active surveillance (AS) are at increased risk of unfavorable longer term outcomes as compared with men who undergo immediate treatment. OBJECTIVE: To compare adverse pathologic outcomes in men with favorable-risk prostate cancer who underwent delayed prostatectomy after surveillance (DPAS) to those who elected immediate prostatectomy (IRP). DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective analysis of a prospective AS registry from 2004 to 2014. From the Johns Hopkins AS program (n = 1298), we identified a subset of men who underwent DPAS (n = 89) and was representative of the entire cohort, not just those that were reclassified to higher risk. These men were compared with men who underwent IRP (n = 3788). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured adverse pathologic features (primary Gleason pattern ≥ 4, seminal vesicle invasion [SVI], or lymph node [LN] positivity). Multivariable models were adjusted for age, prostate-specific antigen density, and baseline risk classification. RESULTS AND LIMITATIONS: Delayed prostatectomy occurred at a median of 2.0 yr (range: 0.6-9.0) after diagnosis. The DPAS and IRP cohorts demonstrated similar proportions of men with primary Gleason pattern ≥ 4 (17% vs 20%; p = 0.11), SVI (3.3% vs 3.2%; p = 0.53), LN positivity (2.3% vs 1.2%; p = 0.37), and overall adverse pathologic features (21.3% vs 17.0%; p = 0.32). The adjusted odds ratio of adverse pathology was 1.33 (95% confidence interval, 0.82-2.79; p = 0.13) for DPAS as compared with IRP. Limitations include a modest cohort size and a limited number of events. CONCLUSIONS: In men with favorable-risk cancer, the decision to undergo AS is not independently associated with adverse pathologic outcomes. PATIENT SUMMARY: This report compares men with favorable-risk prostate cancer who elected active surveillance with those who underwent immediate surgery accounting for evidence that approximately one-third of men who choose surveillance will eventually undergo treatment. Our findings suggest that men who are closely followed with surveillance may have similar outcomes to men who elect immediate surgery, but additional research is needed.

Predictors of Adverse Pathology in Men Undergoing Radical Prostatectomy Following Initial Active Surveillance.

OBJECTIVE: To report pathologic outcomes and predictors of adverse pathology in men undergoing radical prostatectomy (RP) after an initial period of active surveillance (AS). METHODS: We studied pathologic outcomes in men who underwent RP after some time on AS. Pathologic outcomes were compared between men with and without evidence of disease reclassification on AS. Rates of adverse pathology (defined as pathologic stage ≥ pT3a, RP Gleason ≥ 4+3, or lymph node involvement) were determined and were compared depending on the variable that defined disease reclassification. RESULTS: Of 1086 men enrolled in AS, 130 (12.0%) underwent RP after a median time of 1.96 years (range, 0.55-12.26 years) on AS. Ninety-seven (74.6%) of these men had evidence of disease reclassification on AS. Rates of adverse pathology were greater in men with evidence of reclassification compared to those without (P = .05). Among men with disease reclassification, rates of adverse pathology ranged from 23.8% to 44.7% depending on the variable used to define reclassification. Longer time on AS was not associated with adverse pathology (P = .68). CONCLUSION: Adverse pathology after RP is more common in men with evidence of disease reclassification on AS compared to those undergoing RP for other reasons. However, we identified varying outcomes among these patients depending on the criterion that defined reclassification. These data may enable identification of men who can safely continue on AS despite evidence of disease reclassification.

Intermediate and Longer-Term Outcomes From a Prospective Active-Surveillance Program for Favorable-Risk Prostate Cancer.

PURPOSE: To assess long-term outcomes of men with favorable-risk prostate cancer in a prospective, active-surveillance program. METHODS: Curative intervention was recommended for disease reclassification to higher cancer grade or volume on prostate biopsy. Primary outcomes were overall, cancer-specific, and metastasis-free survival. Secondary outcomes were the cumulative incidence of reclassification and curative intervention. Factors associated with grade reclassification and curative intervention were evaluated in a Cox proportional hazards model. RESULTS: A total of 1,298 men (median age, 66 years) with a median follow-up of 5 years (range, 0.01 to 18.00 years) contributed 6,766 person-years of follow-up since 1995. Overall, cancer-specific, and metastasis-free survival rates were 93%, 99.9%, and 99.4%, respectively, at 10 years and 69%, 99.9%, and 99.4%, respectively, at 15 years. The cumulative incidence of grade reclassification was 26% at 10 years and was 31% at 15 years; cumulative incidence of curative intervention was 50% at 10 years and was 57% at 15 years. The median treatment-free survival was 8.5 years (range, 0.01 to 18 years). Factors associated with grade reclassification were older age (hazard ratio [HR], 1.03 for each additional year; 95% CI, 1.01 to 1.06), prostate-specific antigen density (HR, 1.21 per 0.1 unit increase; 95% CI, 1.12 to 1.46), and greater number of positive biopsy cores (HR, 1.47 for each additional positive core; 95% CI, 1.26 to 1.69). Factors associated with intervention were prostate-specific antigen density (HR, 1.38 per 0.1 unit increase; 95% CI, 1.22 to 1.56) and a greater number of positive biopsy cores (HR, 1.35 for one additional positive core; 95% CI, 1.19 to 1.53). CONCLUSION: Men with favorable-risk prostate cancer should be informed of the low likelihood of harm from their diagnosis and should be encouraged to consider surveillance rather than curative intervention.