Hanan Goldberg

Defining high-risk prostate cancer.

Purpose of review High-risk prostate cancer often represents a lethal disease requiring timely diagnosis and effective therapy. Standardized criteria that define high-risk prostate cancer have yet to be established, rendering the discrimination of high-risk from nonhigh-risk patients a challenge. This review summarizes the contemporary definitions of high-risk prostate cancer and their clinical utility. Recent findings As currently defined, high-risk prostate cancer constitutes a heterogeneous group of tumors with varying pathological features and inconsistent outcomes. Some high-risk patients may harbor systemic disease and relapse after local definitive therapy, whereas a substantial proportion have localized cancers and may be cured by surgery alone. If properly identified, these high-risk patients should be deemed candidates for curative treatment and spared the morbidity of systemic therapy. Additional information derived from systematic prostate biopsy, magnetic resonance findings, and, possibly, pretreatment prostate-specific antigen kinetics may be incorporated into the currently available models to yield a better prediction and to allow more informed decision-making. Summary The quandary of how to define high-risk prostate cancer is pertinent. Various contemporary definitions of high-risk prostate cancer are available, most of which lack adequate sensitivity and specificity. Patients with high-risk clinically localized prostate cancer, by any of the current definitions, should not be uniformly disqualified from local definitive therapy with curative intent.

Metastatic renal cell carcinoma: Patterns and predictors of metastases—A contemporary population-based series

OBJECTIVE To assess the patterns and predictors of metastatic disease in renal cell carcinoma (RCC) at the time of diagnosis in a contemporary series. METHODS The Surveillance, Epidemiology, and End Results database was queried for all patients with kidney RCC from 2010 to 2013 (N = 50,815). Distribution and predictors of distant metastases at diagnosis were assessed. Multivariate logistic regression hazard analyses were performed to determine covariates associated with the likelihood of having metastases at diagnosis, whereas competing risks regression analysis was used to assess predictors of cancer-specific mortality (CSM) in patients with metastatic disease. RESULTS Lung (7.73%) and bone (5.17%) metastases were the most common. The strongest predictors of metastatic disease were disease-specific factors, such as clinical T-stage (cT4 vs. cT1; odds ratio = 43.08; P<0.01) and higher Fuhrman grade (FG4 vs. FG1; odds ratio = 5.09; P<0.01). Papillary RCC and chromophobe RCC were associated with localized disease at the time of diagnosis. For CSM, the presence of brain and liver metastases were associated with worse CSM than lung or bone metastases. Although patient factors did not contribute to the presence of metastases at diagnosis, lower socioeconomic status and being widowed/divorced predicted worse CSM. CONCLUSION Understanding the distribution of distant metastases and associated CSM is important to counseling patients with newly diagnosed metastatic RCC. Although pathologic factors drive the presence of metastases at diagnosis, health care deficits in treatment remain.

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.

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.

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.

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