Issues

Management Options for Nocturia

Herbert LeporRoger R Dmochowski

[Rev Urol. 2018;20(2):53–55 doi: 10.3909/riu0811] © 2018 MedReviews®, LLC

Nocturia: Evaluation and Current Management Strategies

Management Update

Roger R DmochowskiW Stuart ReynoldsAlan J WeinCasey G KowalikJoshua A CohnSophia DelpeMelissa R KaufmanDoug F Milam

Nocturia is a complex condition that not only significantly affects quality of life, but may be an indicator of systemic disease. Initial assessment includes a detailed history and physical examination and completion of a frequency volume chart to help identify underlying causes, such as sleep disorders, bladder storage disorders, and polyuria. Treatment with alpha-blockers or antimuscarinic medications may help if the underlying cause is determined to be benign prostatic hyperplasia or overactive bladder, respectively. Treatment options for nocturnal polyuria have been limited to behavioral therapy and off-label use of timed diuretics and desmopressin. Desmopressin acetate nasal spray (Noctiva™, Avadel Pharmaceuticals, Chesterfield, MO) was approved by the US Food and Drug Administration in 2017 for the treatment of nocturia due to nocturnal polyuria in adults who awaken at least twice nightly and has shown efficacy in reducing nocturnal voids by $50% in up to 49% of patients in clinical trials. [Rev Urol. 2018;20(1):1–6 doi: 10.3909/riu0797] © 2018 MedReviews®, LLC

Active Surveillance Use Among a Low-risk Prostate Cancer Population in a Large US Payer System: 17-Gene Genomic Prostate Score Versus Other Risk Stratification Methods

Original Research

Michael J KemeterPhillip G FebboSteven CanfieldJohn Hornberger

Many men with low-risk prostate cancer (PCa) receive definitive treatment despite recommendations that have been informed by two large, randomized trials encouraging active surveillance (AS). We conducted a retrospective cohort study using the Optum™ Research Database (Eden Prairie, MN) of electronic health records and administrative claims data to assess AS use for patients tested with a 17-gene Genomic Prostate Score™ (GPS; Genomic Health, Redwood City, CA) assay and/or prostate magnetic resonance imaging (MRI). De-identified records were extracted on health plan members enrolled from June 2013 to June 2016 who had ≥1 record of PCa (n = 291,876). Inclusion criteria included age ≥18 years, new diagnosis, American Urological Association low-risk PCa (stage T1-T2a, prostate-specific antigen ≥10 ng/mL, Gleason score = 6), and clinical activity for at least 12 months before and after diagnosis. Data included baseline characteristics, use of GPS testing and/or MRI, and definitive procedures. GPS or MRI testing was performed in 17% of men (GPS, n = 375, 4%; MRI, n = 1174, 13%). AS use varied from a low of 43% for men who only underwent MRI to 89% for GPS-tested men who did not undergo MRI (P<001). At 6-month follow-up, AS use was 31.0% higher (95% CI, 27.6%-34.5%; P<001) for men receiving the GPS test only versus men who did not undergo GPS testing or MRI; the difference was 30.5% at 12-month follow-up. In a large US payer system, the GPS assay was associated with significantly higher AS use at 6 and 12 months compared with men who had MRI only, or no GPS or MRI testing. [Rev Urol. 2017;19(4):203–212 doi: 10.3909/riu0786] © 2018 MedReviews®, LLC

Clinical Performance of the 4Kscore Test to Predict High-grade Prostate Cancer at Biopsy: A Meta-analysis of US and European Clinical Validation Study Results

Predictive Performance Evaluation

Stephen M ZappalaPeter T ScardinoYan DongVincent LinderDavid Okrongly

The 4Kscore® Test (OPKO Diagnostics, Woburn, MA) is a blood test utilized prior to a prostate biopsy to determine a patient’s risk of high-grade prostate cancer (PCa) should the biopsy be performed, thus providing critical information in the clinical management of men with a suspicious prostate-specific antigen value or digital rectal examination result. Multiple US and European clinical studies confirmed that a prebiopsy 4Kscore Test has a high degree of discrimination for a subsequent discovery of high-grade (Gleason score ≥7) PCa. The aim of this study was to evaluate the predictive accuracy of the 4Kscore Test to discriminate between patients with and without high-grade PCa based on published clinical validation studies. A systematic review and meta-analysis of the eligible 4Kscore Test clinical validation studies was conducted. The pooled area under the curve (AUC) of the 4Kscore Test as reported from all the studies, and the heterogeneity among these studies were analyzed and repeated for subgroups of the studies. Twelve clinical validation studies were included in the meta-analysis, comprising a total of 11,134 patients. The pooled AUC to discriminate for high-grade PCa for all 12 studies was 0.81 (fixed effects 95% CI, 0.80-0.83). Restricting the analysis to the six publications that used the contemporary 4Kscore Test algorithm led to very similar results (AUC 0.81; 95% CI, 0.79-0.83). Heterogeneity was high among all of the 12 studies, as well as among the six publications that used the contemporary 4Kscore Test (Cochrane’s Q test, p = 0.001 for both); however, in both cases, after exclusion of a single outlying study with a much lower AUC, heterogeneity was no longer significant (p = 0.08 and p = 0.21). The pooled estimate of 4Kscore Test discrimination (AUC) for high-grade PCa is .0.80, and is consistent across multiple US and European clinical validation studies. [Rev Urol. 2017;19(3):149–155 doi: 10.3909/riu0776] © 2017 MedReviews®, LLC

Active Surveillance of Prostate Cancer: Current State of Practice and Utility of Multiparametric Magnetic Resonance Imaging

Practice Update

H Ballentine CarterJonathan I EpsteinRidwan AlamJeffrey J Tosoian

Active surveillance (AS) is an alternative to immediate intervention in patients with very low- and low-risk prostate cancer. Ongoing reports from multiple AS programs have consistently demonstrated a very low rate of metastasis and prostate cancer-specific mortality in appropriately selected patients. Accordingly, AS has been adopted by major clinical organizations as a safe and effective management strategy. Clinical focus has now shifted to identifying the optimal approach to selecting and monitoring patients. Multiparametric magnetic resonance imaging (mpMRI) has emerged as one potentially helpful tool in the AS setting. The utility of mpMRI has been well demonstrated in the setting of screening and diagnosis, but its role in AS remains unclear. We summarize the published experience with AS and review pertinent, contemporary data on the use of mpMRI in the setting of AS. [Rev Urol. 2017;19(2):77–88 doi: 10.3909/riu0757] © 2017 MedReviews®, LLC

Use of the 4Kscore Test to Predict the Risk of Aggressive Prostate Cancer Prior to Prostate Biopsy: Overall Cost Savings and Improved Quality of Care to the US Healthcare System

Health Economics

Yan DongVincent LinderJeffrey D VoigtStephen Zappala

The 4Kscore® Test (BioReference Laboratories, Elmwood Park, NJ) is a blood test that accurately determines the risk of aggressive prostate cancer and significantly reduces prostate biopsies and associated overdiagnosis and overtreatment of indolent cancer. A budget impact model was developed to test the hypothesis that the 4Kscore Test can improve quality of care and deliver cost savings for patients who are suspected of having prostate cancer and would otherwise undergo prostate biopsy under the current standard of care (SOC) in the United States. The direct costs (diagnosis plus treatment) utilized in the model are based on Medicare payment data and were calculated over a 1-year time horizon. The model compares SOC, in which all patients have prostate biopsy, to a “4Kscore strategy,” in which the 4Kscore Test is used to guide the decision to biopsy the prostate. A set of one-way sensitivity analyses was conducted to examine the robustness of the findings. Savings of more than $169 million (15.6% of total SOC costs) were realized in the 4Kscore strategy versus SOC ($917 M versus $1,086 M, respectively) in a cohort of 100,000 patients. Sensitivity analyses demonstrated that the findings are robust. Most cost savings for the 4Kscore strategy were realized in patients who, when managed by SOC, are found to have no prostate cancer or Gleason score 6 pathology. The patients with Gleason score 6 exhibited the greatest benefits from the 4Kscore strategy, avoiding both an unnecessary prostate biopsy and subsequent overtreatment. The 4Kscore Test was shown to significantly reduce costs to the healthcare system while improving patients’ quality of care. Providers and their patients suspected of having prostate cancer should consider using the 4Kscore Test prior to proceeding with prostate biopsy. [Rev Urol. 2017;19(1):1-10 doi: 10.3909/riu0753] © 2017 MedReviews®, LLC

Frequency of Gleason Score 7 to 10 in 5100 Elderly Prostate Cancer Patients

Cancer Screening Update

Navin ShahVladimir Ioffe

Men 70 to 80 years of age are known to have an increased incidence of high-grade (Gleason sum score [GSS] 7-10) prostate cancer. We determined the frequency of high-grade prostate cancer among men 70 to 80 years old in our practice. We retrospectively reviewed our 5100 prostate cancer patients who are 70 to 80 years old and who opted for radiation therapy (external radiation, brachytherapy, or combination). Data were gathered on race, prostate-specific antigen value, digital rectal examination (DRE) results, and GSS. Patients were further subdivided by age in two categories, those 70 to 75 years and 76 to 80 years, and also by time period: 2006-2010 and 2011-2015. In patients 70 to 75 years, 1426 patients had a GSS of 6 (41%) and 2042 patients had a GSS of 7 to 10 (59%). In patients 76 to 80 years old, 553 had a GSS of 6 (34%) and 1079 had a GSS of 7 to 10 (66%). In 1432 patients with an abnormal DRE result, the GSS was 6 in 376 (26%) and GSS was 7 to 10 in 1059 (74%). Based on analysis of 5100 prostate cancer patients in our practice, we determined that 61% of patients age 70 to 80 have a high-grade prostate cancer, as do 59% of patients age 70 to 75 years, and 66% of patients between age 76 and 80 years. Because biopsy underestimates the grade in GSS 6 patients by 50%, the actual frequency is approximately 80%. In patients with prostate cancer who had an abnormal DRE result, 74% had a GSS of 7 to 10—approximately 85% when accounting for biopsy under-grading. [Rev Urol. 2016;18(4):181-187 doi: 10.3909/riu0732] © 2016 MedReviews®, LLC

Health Economic Impact and Prospective Clinical Utility of Oncotype DX® Genomic Prostate Score

Michael J KemeterPhillip G FebboDavid AlbalaRuixiao LuVincy JohnDylan StoyBela DenesMarybeth McCallAlan W ShindelFrank Dubeck

Prostate cancer (CaP) will be diagnosed in approximately 181,000 American men in 2016. Despite the high number of deaths from CaP in the United States, the disease has a protracted natural history and many men diagnosed with CaP will not die of the disease regardless of treatment. Unfortunately, identification of men with truly indolent/nonaggressive CaP is challenging; limitations of conventional diagnostic modalities diminish the ability of physicians to accurately stage every case of CaP based on biopsy results alone. The resulting uncertainty in prognosis may prompt men with low-risk CaP to proceed to morbid and expensive treatments for an unclear survival benefit. Incorporation of the Genomic Prostate Score (GPS) as part of the decision algorithm for patients with National Comprehensive Cancer Network very low-risk and low-risk cancer led to a substantial increase in uptake of active surveillance and substantial cost savings. GPS provides physicians and patients with an additional tool in assessing personalized risk and helps guide individual decision making. [Rev Urol. 2016;18(3):123-132 doi: 10.3909/riu0725] © 2016 MedReviews®, LLC

Challenges and Opportunities in Radiation-induced Hemorrhagic Cystitis

Therapeutic Strategy Update

Michael B ChancellorBernadette MM ZwaansHeinz G NicolaiLaura E Lamb

As diagnosis and treatment of cancer is improving, medical and social issues related to cancer survivorship are becoming more prevalent. Hemorrhagic cystitis (HC), a rare but serious disease that may affect patients after pelvic radiation or systemic chemotherapy, has significant unmet medical needs. Although no definitive treatment is currently available, various interventions are employed for HC. Effects of nonsurgical treatments for HC are of modest success and studies aiming to control radiation-induced bladder symptoms are lacking. In this review, we present current and advanced therapeutic strategies for HC to help cancer survivors deal with long-term urologic health issues. [Rev Urol. 2016;18(2):57-65 doi: 10.3909/riu0700] © 2016 MedReviews®, LLC

Contemporary Role of the Decipher® Test in Prostate Cancer Management: Current Practice and Future Perspectives

Management Update

Deepansh DalelaBjörn LöppenbergAkshay SoodJesse SammonFiras Abdollah

We performed a systematic literature search to identify original articles and editorials about the Decipher® Prostate Cancer Test (GenomeDx Biosciences, San Diego, CA) to provide an overview of the current literature and its present role in urologic clinical practice. The Decipher test, which uses the expression of 22 selected RNA markers (from a total of over 1.4 million), showed a very high discrimination in predicting clinical metastasis (0.75-0.83) and cancer-specific mortality (0.78) in external validation studies, outperforming all routinely available clinicopathologic characteristics. Further, the timing of postoperative radiotherapy (adjuvant vs salvage) may be guided based on Decipher scores. The Decipher test was also the only independent predictor of clinical metastasis in patients with biochemical recurrence after surgery. The Decipher Genomic Resource Information Database (GRID) is a novel research tool that captures 1.4 million marker expressions per patient and may facilitate precision-guided, individualized care to patients with prostate cancer. In this era of precision medicine, Decipher, along with the Decipher GRID platform, is a promising genomic tool that may aid in managing prostate cancer patients throughout the continuum of care and delivering appropriate treatment at an individualized level. [Rev Urol. 2016;18(1):1-9 doi: 10.3909/riu0706] © 2016 MedReviews®, LLC