Rashid Sayyid

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.

Extended Venous Thromboembolism Prophylaxis after Radical Cystectomy: A Call for Adherence to Current Guidelines

Purpose: Radical cystectomy is inherently associated with morbidity. We assess the timing and incidence of venous thromboembolism, review current guideline recommendations and provide evidence for considering extended venous thromboembolism prophylaxis in all patients undergoing radical cystectomy. Materials and Methods: We searched PubMed® for available literature on radical cystectomy and venous thromboembolism, focusing on incidence and timing, evidence supporting extended venous thromboembolism prophylaxis in patients undergoing radical cystectomy or abdominal oncologic surgery, current guideline recommendations, safety considerations and direct oral anticoagulants. Search terms included “radical cystectomy,” “venous thromboembolism,” “prophylaxis,” and “extended oral anticoagulants” and “direct oral anticoagulants” alone and in combination. Relevant articles were reviewed, including original research, reviews and clinical guidelines. References from review articles and guidelines were also assessed to develop a narrative review. Results: The incidence of symptomatic venous thromboembolism in short‐term followup after radical cystectomy is 3% to 11.6%, of which more than 50% of cases will occur after hospital discharge. Meta‐analyses of clinical trials in patients undergoing major abdominal oncologic operations suggest a decreased risk of venous thromboembolisms for patients receiving extended (4 weeks) venous thromboembolism prophylaxis. Extended prophylaxis should be considered in all radical cystectomy cases. Although the relative risk of bleeding also increases, the overall net benefit of extended prophylaxis clearly favors use for at least 28 days postoperatively. Extrarenal eliminated prophylaxis agents are preferred given the risk of renal insufficiency in radical cystectomy cases, with newer oral anticoagulants providing an alternative route of administration. Conclusions: Patients undergoing radical cystectomy are at high risk for venous thromboembolism after hospital discharge. There is strong evidence that extended prophylaxis significantly decreases the risk of venous thromboembolism in oncologic surgery cases. Use of extended prophylaxis after radical cystectomy has been poorly adopted, emphasizing the need for better adherence to current urology procedure specific guidelines as extended prophylaxis for radical cystectomy is the standard of care. Specific and rare circumstances may require case by case assessment.

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.

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.

Lymphadenectomy in Gleason 7 prostate cancer: Adherence to guidelines and effect on clinical outcomes

BACKGROUND To examine usage trends, guideline adherence, and survival data for patients undergoing lymphadenectomy (LND) at the time of radical prostatectomy (RP) for Gleason 7 prostate cancer (PCa). METHODS The SEER database was queried for all patients with nonmetastatic biopsy Gleason 7 PCa from 2004 to 2013. Distribution and trends of LND were analyzed. The Memorial-Sloan Kettering Cancer Center nomogram was applied to stratify patients based on risk of nodal disease at time of RP (<5% risk or ≥5% risk). Analyses were performed to determine covariates associated with LND receipt at time of RP and cancer-specific mortality (CSM). RESULTS A total of 78,641 patients with either G34 or G43 PCa underwent RP (59,194 and 19,447, respectively). Of these patients, 61.2% of G34 and 73.5% of G43 patients underwent LND. During this 10-year period, the proportion of G43 patients undergoing LND remained relatively stable, whereas the proportion of G34 patients undergoing LND ranged between 55.9% and 67.9%. Regional differences were a predictor of LND receipt regardless of risk stratification, but did not translate to higher risk of CSM. Receipt of LND was not predictive of improved CSM in any of the cohorts analyzed. CONCLUSIONS The role of LND for Gleason 7 prostate adenocarcinoma is not yet standardized, as indicated by the variability of LND dissection rates. Receipt of LND did not improve CSM, and in G43 patients, it predicted higher CSM. As the effect of LND on CSM is uncertain, further evaluation of oncologic benefit in this patient population is warranted.

Does perioperative chemotherapy improve survival in upper tract urothelial carcinoma? A population based analysis

Objectives To evaluate the utilization and outcomes of perioperative chemotherapy in non-metastatic UTUC patients over the past decade using a large national database. Methods All patients aged 18 and older diagnosed with non-metastatic UTUC between 2004 and 2013 were identified within the Surveillance, Epidemiology and End Results (SEER) database. Relevant clinical data was collected and predictors of cancer specific mortality (CSM) and other cause mortality (OCM) were analyzed. Results The total cohort included 8,762 patients. Of these, 1,402 (16%) patients received chemotherapy, including only 35% of high-risk patients (>pT2 or N1). Treated patients had higher CSM (21.3% vs. 13.1%, p<0.001). Predictors of chemotherapy utilization included residence in Midwest states, tumor located in the ureter, higher stage and grade. Predictors of CSM included older age, residence in southern states, receipt of chemotherapy (HR = 1.151, 95% CI: 1.003-1.32, p=0.044), higher stage and grade. OCM was predicted by male gender, older age, ureteral tumor, and higher stage. A subset analysis of patients younger than 65 showed similar predictors, while an analysis of high risk patients demonstrated that chemotherapy receipt did not predict CSM or OCM. Conclusions In this large contemporary non-metastatic UTUC cohort, chemotherapy utilization was found to be quite infrequent, but increasing steadily. Perioperative chemotherapy had no effect on CSM in high-risk patients, while correlated to higher CSM in the younger patients.

High competing risks minimize real-world utility of adjuvant targeted therapy in renal cell carcinoma: a population-based analysis

Objective To utilize a population-based approach to address the role of adjuvant TT in the management of RCC. Methods Patients with RCC (2006-2013) in the SEER database were stratified by metastatic disease at the time of diagnosis (cM0/cM1). cM0 patients following surgical excision were stratified into low and high-risk (ASSURE and S-TRAC criteria). Multivariable analyses performed to identify predictors of TT receipt; Fine and Gray competing risks analyses used to identify predictors of cancer-specific mortality (CSM). Subset analyses included patients with clear cell histology and high-risk cM0. Survival analyses were used to evaluate overall survival (OS) and cancer-specific survival (CSS) for all cohorts, stratified on TT receipt. Results 79,926 patients included (71,682 cM0, 8,244 cM1); median follow-up for the entire cohort was 40.1 months. Of 31,453 patients with histologic grade data, 18,328 and 13,125 were low- and high-risk cM0, respectively. TT utilization in cM1 patients peaked at 50.6% and was associated with reduced CSM (HR 0.73, p<0.01). In contrast, TT utilization (presumed salvage therapy) never exceeded 2.2% in the entire cM0 cohort and 3.5% in the high-risk cM0 cohort. On competing risks analysis, TT receipt was associated with increased CSM in all cohorts. Conclusion When compared to the cM1 patients, TT receipt in cM0 patients does not provide any cancer-specific survival benefit, even in the small percentage of patients that eventually progress to metastatic disease. Competing risks mortality further limit any potential benefit in this population. Based on current evidence, adjuvant TT cannot be recommended for RCC patients.

Lessons Learned from the Global Epidemiology of Kidney Cancer: A Refresher in Epidemiology 101

In first world countries, clinicians treating kidney cancer, much like prostate cancer, have had to address the potential for overdiagnosis and overtreatment of incidentally detected small renal masses. This has led to an effort advocating for active surveillance of small renal masses, particularly among the elderly and those with medical comorbidities [1]. However, even in economically advantaged countries, nearly one in five patients diagnosed with kidney cancer will present with de novo metastatic disease [2], contributing to 14 970 kidney and renal pelvic cancer– specific mortalities in the USA in 2018 [3]. In this issue of European Urology, Capitanio and colleagues [4] provide a global perspective on the epidemiology of renal cell carcinoma, with a specific focus on risk factors for nonhereditary, sporadic disease. Not surprisingly, kidney cancer incidence and mortality rates differ significantly across individual countries and regions of the world, ranging from an age-standardized rate (ASR) incidence per 100 000 people exceeding 12.0 in the Czech Republic, Lithuania, Slovakia, and USA to an ASR of 0–0.6 per 100 000 people in many African and Asian countries [4]. In addition, the authors highlight several risk factors for kidney cancer, including obesity/physical activity, fruit and vegetable intake, smoking, alcohol intake, and medical comorbidities such as hypertension, urinary stones, diabetes, and chronic kidney disease. This article offers several important lessons in our understanding of both kidney cancer and epidemiology. The authors present a descriptive, narrative summary of geographic differences in the incidence and mortality of kidney cancer and summarize common risk factors. In

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

MP38-05 DEFINING A COHORT OF MEN WHO MAY NOT REQUIRE REPEAT PROSTATE BIOPSY BASED ON PCA3 AND MRI: THE DOUBLE NEGATIVE EFFECT.

100-500 would be reasonable. CONCLUSIONS This is the first survey evaluating patient and urologic oncologist perspectives on acceptable error rates and costs for urinary biomarker alternatives to surveillance cystoscopy for patients with NMIBC. Despite potential responder bias, this study suggests that urinary biomarker(s) will require sensitivity equivalent to that of cystoscopy in order to completely replace it in surveillance of patients with NMIBC.