Nathan Perlis

Limitations in Predicting Organ Confined Prostate Cancer in Patients with Gleason Pattern 4 on Biopsy: Implications for Active Surveillance

Purpose: In prostate cancer biopsy Gleason score predicts stage and helps determine active surveillance suitability. Evidence suggests that small incremental differences in the quantitative percent of Gleason pattern 4 on biopsy stratify disease extent, biochemical failure following surgery and eligibility for active surveillance. We explored the overall quantitative percent of Gleason pattern 4 levels and adverse outcomes in patients with low and intermediate risk prostate cancer to whom active surveillance may be offered under expanded criteria. Materials and Methods: We analyzed the records of patients with biopsy Gleason score 6 (3 + 3) or 7 (3 + 4) who underwent radical prostatectomy from January 2008 to August 2015. Age, prostate specific antigen, Gleason score, quantitative percent of Gleason pattern 4, overall percent positive cores (percent of prostate cancer) and clinical stage were explored as predictors of nonorgan confined disease and time to failure after radical prostatectomy. Results: In 1,255 patients biopsy Gleason score 7 (3 + 4) was associated with T3 or greater disease at radical prostatectomy in 35.0% compared with Gleason score 6 (3 + 3) in 19.0% (p <0.001). On multivariate analysis for each quantitative percent of Gleason pattern 4 increase there were 2% higher odds of T3 or greater disease (OR 1.02, 95% CI 1.01–1.04, p <0.001). When stratified, patients with Gleason score 7 (3 + 4) only approximated the pT3 rates of Gleason score 6 (3 + 3) when prostate specific antigen was less than 8 ng/ml and the percent of prostate cancer was less than 15%. In those cases the quantitative percent of Gleason pattern 4 had less effect. Time to failure after radical prostatectomy was worse in Gleason score 7 (3 + 4) than 6 (3 + 3) cases. Conclusions: The quantitative percent of Gleason pattern 4 helps predict advanced disease and Gleason score 7 (3 + 4) is associated with worse outcomes. However, the impact of the quantitative percent of Gleason pattern 4 on adverse pathological and clinical outcomes is best used in combination with prostate specific antigen, age and disease volume since each has a greater impact on predicting nonorgan confined disease. The calculated absolute risk of T3 or greater can be used in shared decision making on prostate cancer treatment by patients and clinicians.

Defining a Cohort that May Not Require Repeat Prostate Biopsy Based on PCA3 Score and Magnetic Resonance Imaging: The Dual Negative Effect

Purpose: Prostate cancer over diagnosis and overtreatment are concerns for clinicians and policy makers. Multiparametric magnetic resonance imaging and the PCA3 (prostate cancer antigen 3) urine test select for clinically significant cases. We explored how well the tests performed together with previous biopsies. Materials and Methods: In accordance with ethics committee approval we collected clinicopathological data on all patients in whom a PCA3 test was done from January 2011 to June 2016. This included patients on active surveillance for low risk prostate cancer and those without prostate cancer who had previous negative biopsies and suspicion of occult disease. We explored whether age, prostate specific antigen, PCA3 score, multiparametric magnetic resonance imaging, digital rectal examination, family history and prostate size would predict clinically significant prostate cancer on repeat biopsy. The negative predictive value of multiparametric magnetic resonance imaging and PCA3 score was calculated. Results: A total of 470 patients were included in study. The PCA3 score was abnormal at 35 or greater in 32.5% of cases. In the multivariate model including 154 men only age (OR 1.08, 95% CI 1.01–1.16), multiparametric magnetic resonance imaging PI‐RADS™ (Prostate Imaging‐Reporting and Data System) score 4 (OR 16.6, 95% CI 3.9–70.0) or 5 (OR 28.3, 95% CI 5.7–138) and PCA3 score (OR 2.9, 95% CI 1.0–8.8) predicted clinically significant cancer on biopsy. No patient with negative multiparametric magnetic resonance imaging and a normal PCA3 score had clinically significant prostate cancer on biopsy for a negative predictive value of 100% (p <0.0001). Conclusions: In patients with dual negative tests (multiparametric magnetic resonance imaging and PCA3 score) clinically significant prostate cancer was never found on biopsy, which may be unnecessary in this group. This study was limited by its retrospective design, selection bias and lack of cost‐effectiveness data.

Development and external validation of a biopsy-derived nomogram to predict risk of ipsilateral extraprostatic extension.

To develop and externally validate a nomogram that predicts risk of side‐specific extraprostatic extension (EPE) at time of surgery, using commonly available preoperative markers.

Systematic Review, Critical Appraisal, and Analysis of the Quality of Economic Evaluations in Stroke Imaging

Background and Purpose— This study reviews the quality of economic evaluations of imaging after acute stroke and identifies areas for improvement. Methods— We performed full-text searches of electronic databases that included Medline, Econlit, the National Health Service Economic Evaluation Database, and the Tufts Cost Effectiveness Analysis Registry through July 2012. Search strategy terms included the following: stroke*; cost*; or cost–benefit analysis*; and imag*. Inclusion criteria were empirical studies published in any language that reported the results of economic evaluations of imaging interventions for patients with stroke symptoms. Study quality was assessed by a commonly used checklist (with a score range of 0% to 100%). Results— Of 568 unique potential articles identified, 5 were included in the review. Four of 5 articles were explicit in their analysis perspectives, which included healthcare system payers, hospitals, and stroke services. Two studies reported results during a 5-year time horizon, and 3 studies reported lifetime results. All included the modified Rankin Scale score as an outcome measure. The median quality score was 84.4% (range=71.9%–93.5%). Most studies did not consider the possibility that patients could not tolerate contrast media or could incur contrast-induced nephropathy. Three studies compared perfusion computed tomography with unenhanced computed tomography but assumed that outcomes guided by the results of perfusion computed tomography were equivalent to outcomes guided by the results of magnetic resonance imaging or noncontrast computed tomography. Conclusions— Economic evaluations of imaging modalities after acute ischemic stroke were generally of high methodological quality. However, important radiology-specific clinical components were missing from all of these analyses.

Role of Magnetic Resonance Imaging Targeted Biopsy in Detection of Prostate Cancer Harboring Adverse Pathological Features of Intraductal Carcinoma and Invasive Cribriform Carcinoma

Purpose: The aim of this study was to compare biopsy detection of intraductal and cribriform pattern invasive prostate carcinoma in multiparametric magnetic resonance imaging positive and negative regions of the prostate. Materials and Methods: We queried a prospectively maintained, single institution database to identify patients who underwent multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and concurrent systematic sextant biopsy of magnetic resonance imaging negative regions between January 2013 and May 2016. All multiparametric magnetic resonance imaging targets were reviewed retrospectively by 2 readers for the PI‐RADS™ (Prostate Imaging‐Reporting and Data System), version 2 score, the maximum dimension, the apparent diffusion coefficient parameter and whether positive or negative on dynamic contrast enhancement sequence. Biopsy slides were reviewed by 2 urological pathologists for Gleason score/Grade Group and the presence or absence of an intraductal/cribriform pattern. Results: A total of 154 patients were included in study. Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and systematic sextant biopsy of magnetic resonance imaging negative regions were negative for prostate carcinoma in 51 patients, leaving 103 available for the correlation of multiparametric magnetic resonance imaging and the intraductal/cribriform pattern. Prostate carcinoma was identified by multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy in 93 cases and by systematic sextant biopsy of magnetic resonance imaging negative regions in 76 (p = 0.008). Intraductal/cribriform positive tumor was detected in 23 cases, including at the multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy site in 22 and at the systematic sextant biopsy of magnetic resonance imaging negative region site in 3 (p <0.001). The intraductal/cribriform pattern was significantly associated with a PI‐RADS score of 5 and a decreasing apparent diffusion coefficient value (p = 0.008 and 0.005, respectively). In 19 of the 23 cases with the intraductal/cribriform pattern prior 12‐core standard systematic biopsy was negative in 8 and showed Grade Group 1 disease in 11. Conclusions: Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy was associated with significantly increased detection of intraductal/cribriform positive prostate carcinoma compared to systematic sextant biopsy of multiparametric magnetic resonance imaging negative regions. This supports the role of magnetic resonance imaging to enhance the detection of clinically aggressive intraductal/cribriform positive prostate carcinoma.

The Bladder Utility Symptom Scale: A Novel Patient Reported Outcome Instrument for Bladder Cancer

Purpose: Health related quality of life is important in bladder cancer care and clinical decision making because patients must choose between diverse treatment modalities with unique morbidities. A patient reported outcome measure of overall health related quality of life for bladder cancer regardless of disease severity and treatment could benefit clinical care and research. Materials and Methods: Prospective questionnaire development was completed in 3 parts. In study 1 the BUSS (Bladder Utility Symptom Scale) questions were created by experts using a conceptual framework of bladder cancer health related quality of life generated through patient focus groups. In study 2 patients with bladder cancer, including those treated with surgery, radiation and chemotherapy, completed the BUSS and 5 health related quality of life instruments at baseline and 4 weeks to assess validity and test‐retest reliability. External validity was then explored in study 3 by administering the BUSS to 578 patients online and at clinics. Construct validity was assessed by whole and subscale Spearman rank correlations, and by comparisons of BUSS scores across known groups. Results: The BUSS had high whole scale correlation with the FACT‐Bl (Functional Assessment of Cancer Therapy‐Bladder) (rs = 0.82, p <0.0001) and substantial to high subscale correlations with the EQ‐5D™‐3L (EuroQol 5 Dimensions Questionnaire‐3 Levels) (eg emotional well‐being rs = 0.69, p <0.0001). BUSS scores were lower in patients with comorbidity and advanced disease. Cognitive debriefing and the 94% completion rate suggested good comprehensibility. There was excellent test‐retest reliability (ICC = 0.79). Limitations included an extended time from diagnosis in many patients. Conclusions: The BUSS is a reliable and valid patient reported outcome instrument for health related quality of life in all patients with bladder cancer regardless of the treatment received or the stage of disease.

Testosterone Responders to Continuous Androgen Deprivation Therapy Show Considerable Variations in Testosterone Levels on Followup: Implications for Clinical Practice

Purpose We determined whether men on continuous androgen deprivation therapy who achieve testosterone less than 0.7 nmol/l demonstrate subsequent testosterone elevations during followup and whether such events predict worse oncologic outcomes. Materials and Methods We evaluated a random, retrospective sample of 514 patients with prostate cancer treated with continuous androgen deprivation therapy in whom serum testosterone was less than 0.7 nmol/l at University Health Network between 2007 and 2016. Patients were followed from the date of the first testosterone measurement of less than 0.7 nmol/l to progression to castrate resistance, death or study period end. Study outcomes were the development of testosterone elevations greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, and progression to a castrate resistant state. Survival curves were constructed to determine the rate of testosterone elevations. Multivariate Cox regression analysis was done to assess whether elevations predicted progression to castrate resistance. Results Median patient age was 74 years and median followup was 20.3 months. Within 5 years of followup 82%, 45% and 18% of patients had subsequent testosterone levels greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, respectively. In 96% to 100% of these patients levels less than 0.7 nmol/l were subsequently reestablished within 5 years. No patient baseline characteristic was associated with elevations and elevations were not a significant predictor of progression to a castrate resistant state. Conclusions Men on continuous androgen deprivation therapy in whom initial testosterone is less than 0.7 nmol/l frequently show subsequent elevations in serum testosterone. Such a development should not trigger an immediate response from physicians as these events are prognostically insignificant with regard to oncologic outcomes. Levels are eventually reestablished at less than 0.7 nmol/l.

PD24-08 TESTOSTERONE RESPONDERS TO CONTINUOUS ANDROGEN DEPRIVATION THERAPY EXHIBIT CONSIDERABLE VARIATION IN TESTOSTERONE LEVELS ON FOLLOW UP

receiving ADT. We collected their clinical and demographic data, and whether BT was administered. Because our study period preceded the approval of novel agents for mCP and the shift to upfront chemotherapy, we defined castrate resistance as the initiation of chemotherapy. Statistical analysis was performed using SAS v9.3 (Cary, NC). RESULTS: A total of 2563 men were treated with ADT for mCP, and BT was administered to 431 (16.8%). Utilization of BT increased significantly during the study period, from 5.9% in 2004 to 35.2% in 2011 (p<0.01). On multivariate analysis, men had increased odds of receiving BT if year of diagnosis was later than 2008 or an oncologist was involved in their care, and decreased odds of BT if receiving care in a less urban area (p<0.05, Table 1). Among the subset of men with mCRCP (433, 16.9%), BT was administered to 136 (31.4%). On multivariate analysis, age 80-85 and diagnosis year later than 2010 were associated with increased odds of BT (OR 2.57 and 1.57, respectively; p1⁄40.01). Adverse events related to BT were rare, with osteonecrosis of the jaw occurring in 7 (1.6%) and hypocalcemia in 34 (8.0%). CONCLUSIONS: Utilization of BT among men with mCP is increasing, though the overall usage of these medications remains low. Among men with mCRCP, only 31.4% received bone health treatments in accordance with NCCN guidelines. As novel anti-androgens expand the role of urologists in management of mCRCP, careful consideration of appropriate management of bone health must not be overlooked.

Case ‒ Foamy high-grade prostatic intraepithelial neoplasia: A false positive for prostate cancer on multiparametric magnetic resonance imaging?

The introduction of multiparametric magnetic resonance imaging (mpMRI) of the prostate, and specifically the introduction of diffusion-weighted imaging (DWI), has significantly impacted the diagnosis of prostate cancer and the management of clinically localized prostate cancer. Indeed, its localizing ability has now opened up opportunities to target focal lesions in partial gland ablation therapy as a treatment option for localized prostate cancer. With negative predictive rates of mpMRI approaching 90% in certain series, 1 mpMRI has the ability to discriminate between clinically significant intermediate-to-high-risk prostate cancer and low-risk indolent disease. However, false positives can occur. In recent studies, lesions observed on MRI were classified as tumour on targeted biopsy in 47.6% to over 94% for tumours larger than 0.5 ml in volume. 2,3 Herein, we present a case of a rare non-cancer, but putatively pre-malignant prostatic histology that was found on biopsies directed at a category 5 Prostate Imaging Reporting and Data System (PIRADS) v2 lesion.

Replacing surveillance cystoscopy with urinary biomarkers in followup of patients with non-muscle-invasive bladder cancer: Patients’ and urologic oncologists’ perspectives

INTRODUCTION Urinary biomarkers are being developed to detect bladder cancer recurrence/progression in patients with non-muscle-invasive bladder cancer (NMIBC). We conducted a questionnaire-based study to determine what diagnostic accuracy and cost would such test(s) need for both patients and urologic oncologists to comfortably forgo surveillance cystoscopy in favour of these tests. METHODS Surveys were administered to NMIBC patients at followup cystoscopy visit and to physician members of the Society of Urologic Oncology. Participants were questioned about acceptable false-negative (FN) rates and costs for such alternatives, in addition to demographics that could influence chosen error rates and costs. RESULTS A total of 137 patient and 51 urologic oncologist responses were obtained. Seventy-seven percent of patients were not comfortable with urinary biomarker(s) alternatives to repeat cystoscopy, with a further 14% willing to accept such alternatives only if the FN rate were 0.5% or lower. Seventy-five percent of urologic oncologists were comfortable with an alternative urinary biomarker test(s), with 37% and 33% willing to accept FN rates of 5% and 1%, respectively. Forty-seven percent of patients were not willing to pay out-of-pocket for such tests, while 61% of urologic oncologists felt that a price range of