Risk Stratification Management Research Articles

Abstract 14602: Vascular Calcification is Associated With Major Adverse Cardiovascular Events and Mortality in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging

Background: Hormone therapy is a front-line therapy for men with prostate cancer and is associated with adverse cardiovascular events. The utility of vascular calcification for cardiovascular risk stratification in men with prostate cancer is unknown. Methods: 211 consecutive patients who underwent 18F-fluciclovine positron emission tomography (PET)/computed tomography (CT) at a single institution for recurrent prostate cancer were retrospectively identified. Clinical and demographic data were obtained from the medical record. Coronary and aortic calcification were qualitatively assessed on non-gated CT scans using standardized scoring systems. The primary outcome was a composite of subsequent major adverse cardiovascular event (MACE; myocardial infarction, stroke, coronary or peripheral revascularization, heart failure hospitalization) or all-cause mortality. Results: Median age was 69 (IQR 64, 75) years and cardiovascular comorbidities were common (70% hypertension, 65% hyperlipidemia, 47% current or former smoking, 20% diabetes mellitus). Over a median of 16.5 months, 8 patients (4%) met the primary outcome. Patients with MACE or death were older and had higher prevalence of traditional cardiovascular comorbidities (risk ratio [RR] 1.3 for hypertension, 1.4 for hyperlipidemia, 1.3 for diabetes mellitus; p>0.05 for all). Coronary and aortic calcification were more common in patients with MACE or death. Severe coronary calcification (RR=6.1, 95% CI 1.6-23.2, p=0.008) and severe thoracic aortic calcification (RR=9.9, 95% CI 2.0-47.6, p=0.004) were associated with significantly increased risk of MACE or death. Conclusions: Coronary and aortic calcification on PET/CT imaging are associated with significantly increased risk of MACE or death in men with recurrent prostate cancer. Vascular calcification may have utility for cardiovascular risk stratification in men receiving hormone therapy for prostate cancer.

Changing the Prostate Cancer Detection Paradigm: Clinical Application of European Association of Urology Guideline–recommended Magnetic Resonance Imaging–based Risk Stratification in Men with Suspected Prostate Cancer

BackgroundMultiparametric magnetic resonance imaging using the Prostate Imaging Reporting and Data System version 2.1 allows for a personalized, risk-stratified approach to indicating prostate biopsies (PBx) in order to reduce PBx and concomitant complications in men with suspected prostate cancer (PCa). One way to achieve this goal is to implement the risk-stratified pathway (RSP) using the Rotterdam Prostate Cancer Risk Calculator. ObjectiveTo describe the clinical implementation of the RSP and to examine its impact on the number of PBx and the resulting changes in the PCa detection pattern compared with men undergoing PBx in a detection-focused pathway (DFP) without prior risk assessment. Design, setting, and participantsAn institutional dataset of 505 consecutive patients with suspected PCa between July 2019 and February 2020 was used. Outcome measurements and statistical analysisChi-square test and Mann-Whitney U test were employed to examine differences in the number of PBx and the PCa detection pattern between the DFP (n = 195, 38.6%) and the RSP (n = 310, 61.4%). To minimize differences in risk stratification, inverse probability of treatment weighting was used. Results and limitationsAfter implementing the RSP, the overall biopsy rate could be reduced by 11.2% (100% vs 88.8%, p < 0.001. Additionally, compared with the DFP, the number of biopsy cores per patient was reduced in the RSP (14 [interquartile range {IQR} 14–15] vs 14 [IQR 6–14], p < 0.001) and the detection of clinically significant PCa was increased (44.3% vs 57.7%, p = 0.038). Overdiagnosis of clinically insignificant disease was decreased in the RSP (22.8% vs 12.6%, p = 0.039). ConclusionsImplementation of the RSP in clinical practice reduced the number of PBx and brought forth a shift in the PCa detection pattern toward clinically significant disease, while reducing overdiagnosis of clinically insignificant disease. Patient summaryIn this study, we examined the impact of risk stratification on the number of prostate biopsies (PBx) and the consecutive detection pattern in men with suspected prostate cancer (PCa). We found that the risk-stratified pathway reduced the number of PBx while simultaneously shifting the PCa detection pattern toward clinically significant PCa.

Identification of a novel gene expression signature associated with overall survival in patients with lung adenocarcinoma: A comprehensive analysis based on TCGA and GEO databases

ObjectivesLung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Understanding the molecular mechanisms underlying tumor progression is of clinical significance. This study aimed to identify novel molecular markers associated with LUAD prognosis. Materials and MethodsRNA sequencing data from the Cancer Genome Atlas (TCGA) database of LUAD tumors and paired normal tissues, and microarray data from the Gene Expression Omnibus (GEO) database were obtained. In the TCGA dataset, differentially expressed (DE) genes were identified by comparing gene expression between early-stage tumors and normal tissue, as well as between advanced-stage and early-stage tumors. A risk score was developed using a weighted linear combination of individual dysregulated protein-coding genes that was associated with overall survival (OS). The prognostic value of the risk score was evaluated using Kaplan-Meier and multivariate Cox analysis. The gene signature was further validated using independent datasets from GEO. ResultsAmong the 68 identified DE genes, 19 were individually associated with OS in univariate analyses. A risk score was constructed for each patient based on the coefficients in multivariate Cox model and normalized expression levels of these 19 genes. LUAD patients with a low risk score had a significantly better survival than those with a high risk score (log-rank P < 0.0001). After adjusting for age, sex, clinical stage, smoking history, and treatments, the patients with a low risk score had a 81 % decreased risk for death, compared to those with a high risk score (hazard ratio 0.19, 95 % confidence interval 0.097−0.36). The significant association of the risk score with OS in LUAD patients was further validated in three independent GEO datasets. ConclusionA novel 19-gene prognostic signature based on gene expression was identified in LUAD patients. The findings further improve the understanding of LUAD prognostication and have the potential to facilitate risk-stratified disease management.

SIOP PODC-adapted treatment guidelines for craniopharyngioma in low- and middle-income settings.

Pediatric craniopharyngioma is a rare tumor with excellent survival but significant long-term morbidities due to the loco-regional tumor growth or secondary to its treatment. Visual impairment, panhypopituitarism, hypothalamic damage, and behavioral changes are among the main challenges. This tumor should be managed under the care of a multidisciplinary team to determine the optimum treatment within the available resources. This is particularly important for low middle-income countries where resources are variable. This report provides risk-stratified management guidelines for children diagnosed with craniopharyngioma in a resource-limited setting.

PT160 - Trends and variations in risk stratified prostate cancer management: A cross-sectional study of the National Prostate Cancer Audit database using the Cambridge Prognostic Group criteria

PT160 - Trends and variations in risk stratified prostate cancer management: A cross-sectional study of the National Prostate Cancer Audit database using the Cambridge Prognostic Group criteria

The Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension

To describe the prevalence of pulmonary arterial hypertension (PAH)-associated gene mutations, and other genetic characteristics in a national cohort of children with PAH from the Dutch National registry and to explore genotype-phenotype associations and outcomes. Children (n=70) diagnosed with idiopathic PAH, heritable PAH, PAH associated with congenital heart disease with coincidental shunt (PAH-congenital heart disease group 3), PAH after closure of a cardiac shunt (PAH-congenital heart disease group 4), or PAH associated with other noncardiac conditions were enrolled. Targeted next-generation sequencing was performed on PAH-associated genes (BMPR2, ACVRL1, EIF2AK4, CAV1, ENG, KCNK3, SMAD9, and TBX4). Also, children were tested for specific genetic disorders in case of clinical suspicion. Additionally, children were tested for copy number variations. Nineteen children (27%) had a PAH-associated gene mutation/variant: BMPR2 n=7, TBX4 n=8, ACVRL1 n=1, KCNK3 n=1, and EIF2AK4 n=2. Twelve children (17%) had a genetic disorder with an established association with PAH (including trisomy 21 and cobalamin C deficiency). In another 16 children (23%), genetic disorders without an established association with PAH were identified (including Noonan syndrome, Beals syndrome, and various copy number variations). Survival rates differed between groups and was most favorable in TBX4 variant carriers. Children with PAH show a high prevalence of genetic disorders, not restricted to established PAH-associated genes. Genetic architecture could play a role in risk-stratified care management in pediatric PAH.

Risk stratified multidisciplinary ambulatory management of malignant bowel obstruction (MAMBO) program for women with gynecological cancers: Preliminary results from a prospective single-center study.

6062 Background: Malignant Bowel Obstruction (MBO) is one of the most common and devastating complications in women with gynecological cancer (GC). There is currently no consensus guideline to improve patient (pt) care in this setting. MAMBO (NCT03260647) is an ongoing prospective study evaluating the clinical implementation of a novel management algorithm for multidisciplinary management of MBO in GC pts. We report preliminary patient outcomes. Methods: All GC pts at Princess Margaret Cancer Centre with a confirmed diagnosis of or are at risk of MBO are eligible for enrollment. Participants follow a low fiber diet titrated by severity of symptom and their monthly weight and albumin levels are recorded, along with standardized patient-reported outcome measures (PROMs) at different time points. For pts who develop MBO, inpatient and ambulatory management algorithms are applied using a multidisciplinary and interprofessional care model consisting of nurses, surgeons, oncologists, radiologists, nutritionists, total parenteral nutrition team, social work, and palliative care. Decisions regarding most optimal management strategies are made by this team with regular MAMBO rounds. A retrospective analysis of pts hospitalized with MBO between 2012 and 2017 was performed in order to have a historical comparison for outcome and survival analysis using Kaplan Meier methods. Results: Since August 2017, 70 pts have been enrolled in MAMBO. Most had high-grade serous ovarian carcinoma (75%), of whom 68% are platinum-resistant. So far, 36 (51%) developed MBO, 6 of whom had multiple sequential episodes. Mean number of days in hospital with MBO was 10 days (median 7, range 0-45), compared to 18 days (median 9, range 0-134) for historical control (p = 0.009). There was no significant loss in weight 6 months from MBO diagnosis but a significant reduction in albumin level by 2.75 g/L after 3 months (p = 0.005). PROMs suggest fatigue and general lack of wellbeing were the symptoms with highest distress. Most patients (78%) received chemotherapy following MBO and most received weekly paclitaxel (36%). Median time from first MBO to death was 219 days (95% CI: 101-not reached) for all-comers in MAMBO and 174 days (95% CI: 98-363) for MBO requiring hospitalization, compared to 108 days (95% CI: 79-160) for historical controls (p = 0.007 and p = 0.062, respectively). Conclusions: Patient care and outcomes from MBO seem to be improved in GC pts enrolled in MAMBO compared to historical controls. Clinical trial information: NCT03260647.

Omics-derived hepatocellular carcinoma risk biomarkers for precision care of chronic liver diseases.

Precise hepatocellular carcinoma (HCC) risk prediction will play increasingly important roles with the contemporary HCC etiologies, that is, non-alcoholic fatty liver disease and resolved hepatitis C virus infection. Because the HCC incidence rate in this emerging patient population is relatively low (~1% per year), identification of a subset of patients at the highest risk is critical to concentrate the effort and resources of regular HCC screening to those who most need it. Omics profiling has been derived using several candidate HCC risk biomarkers, which could refine HCC screening by enabling individual risk-based personalized or risk-stratified patient management. Various types of biomolecules have been explored as sources of information to predict HCC risk at various time horizons. Germline DNA polymorphisms likely reflect race/ethnicity- and/or etiology-specific susceptibility to HCC development or chronic liver disease progression toward carcinogenesis. Transcriptomic dysregulations in the diseased liver capture functional molecular status supporting oncogenesis such as inflammatory pathway and myofibroblast activation. Circulating nucleic acids, proteins, and metabolites could serve as less-invasive measures of molecular HCC risk. Characterization of gut microbiota could also inform HCC risk estimation. Each biomarker could have its niche of clinical application depending on logistics of use, performance, and costs with a goal to eventually improve patient prognosis as a part of the whole algorithm of chronic liver disease management.

Re: Utility of Multiparametric Magnetic Resonance Imaging in the Risk Stratification of Men with Grade Group 1 Prostate Cancer on Active Surveillance.

Re: Utility of Multiparametric Magnetic Resonance Imaging in the Risk Stratification of Men with Grade Group 1 Prostate Cancer on Active Surveillance.

Correction: Cost-effectiveness of risk stratified medication management for reducing premature cardiovascular mortality in Kenya.

[This corrects the article DOI: 10.1371/journal.pone.0218256.].

Management of systemic sclerosis: the first five years.

This review provides a risk-stratified and evidence-based management for subsets of systemic sclerosis (SSc) patients in the first five years from disease onset. Cardiopulmonary disease remains the primary cause of mortality in SSc patients. Morbidity and mortality in SSc-associated pulmonary arterial hypertension have improved with combination treatment, in either an upfront or sequential treatment pattern. Traditional therapies for interstitial lung disease (SSc-ILD) have targeted those with clinically significant and progressive ILD with immunosuppression. New data suggest a possible paradigm shift, introducing immunosuppressive therapy to patients before they develop clinically significant or progressive ILD. The year 2019 saw the approval of the first FDA-approved therapy for SSc-associated interstitial lung disease, using an antifibrotic agent previously approved for idiopathic pulmonary fibrosis. To date, only autologous hematopoietic stem cell transplant has demonstrated a mortality benefit for SSc-ILD, albeit in a narrow spectrum of SSc-ILD patients. SSc is a highly heterogeneous autoimmune disease typified by varying clinical trajectories. Its management may be stratified within the first five years by subclassifying patients based on factors that have important prognostic significance: skin distribution and autoantibody status.

PD03-07 A MULTI-INSTITUTIONAL EVALUATION OF RESCUE THERAPY WITH INTRAVESICAL GEMCITABINE AND DOCETAXOL FOR NON-MUSCLE INVASIVE BLADDER CANCER AFTER BCG FAILURE

INTRODUCTION AND OBJECTIVE:After the recurrence of NMIBC following BCG therapy, risk stratified management directs patients toward radical cystectomy, clinical trial enrollment, and off-label use o...

MRI-targeted biopsies in prostate cancer screening and the value of its combination with blood-based risk-prediction: The randomized, diagnostic study STHLM3MRI.

TPS378 Background: Blood-based biomarkers and magnetic resonance imaging followed by targeted biopsies have been suggested to improve detection of prostate cancer by increasing sensitivity to detect significant disease, decrease over-detection of low-risk cancers and avoid benign biopsies. The STHLM3-MRI projects aims to assess the value of combining blood-based risk prediction with bi-parametric MRI (bpMRI) in the prostate cancer diagnostic chain. Methods: The STHLM3MRI Main Study is a randomized, diagnostic study recruiting ≈10,000 Swedish men aged 50-74 for prostate cancer testing in a screen-by-invitation setting. The study design includes a first paired step (blood-test) followed by a randomized step (biopsy technique). Participants with elevated blood-test levels (PSA≥3ng/ml or Stockholm3 test≥11% risk of GG≥2 cancer) are recommended further work-up and randomized 2:3 to 12-core systematic biopsies (standard arm) or to bpMRI followed by MRI-targeted biopsies and systematic biopsies in men with PI-RADSv2 ≥3 lesions (experimental arm). Endpoints include number of detected prostate cancers, number of performed biopsy procedures and number of performed MRIs. The study is centralized to three biopsy sites, one radiology department and one pathology department. A data safety and monitoring board monitors study progress and participant safety. There are two pre-planned main analyses. First, we will report the first large randomized evidence comparing MRI-targeted biopsies and systematic biopsies for prostate cancer detection in a screen-by-invitation setting. Second, we will report a comparison of a diagnostic strategy including the Stockholm3 blood-test and MRI-targeted biopsies with standard practice using PSA and systematic biopsies. A third analysis will compare the use of the bloodtests PSA and Stockholm3 for risk-stratification of men undergoing MRI-targeted biopsy. 9 Oct 2019 the study had included 47% of planned participants (n = 4,701), aiming to close inclusion by March 2020 with first report during 2020. The study is registered at ClinicalTrials.gov: NCT03377881 and has regional ethical approval (2017-1280/31). Clinical trial information: NCT03377881.

Risk-Stratified Management Offers a Safe Approach to Removing Low-Risk Penicillin Allergy Labels in the Intensive Care Unit

Risk-Stratified Management Offers a Safe Approach to Removing Low-Risk Penicillin Allergy Labels in the Intensive Care Unit

PI-RADS score is associated with biochemical control and distant metastasis in men with intermediate-risk and high-risk prostate cancer treated with radiation therapy

BackgroundNovel methods of risk stratification are needed for men with prostate cancer. The Prostate Imaging Reporting and Data System (PI-RADS) uses multiparametric MRI (mpMRI) to assign a score indicating the likelihood of clinically significant prostate cancer. We evaluated pretreatment mpMRI findings, including PI-RADS score, as a marker for outcome in patients treated with primary radiation therapy (RT). MethodsOne hundred and twenty-three men, 64% and 36% of whom had National Comprehensive Cancer Network (NCCN) intermediate-risk and high-risk disease, respectively, underwent mpMRI prior to RT. PI-RADS score and size of the largest nodule were analyzed with respect to freedom from biochemical failure (FFBF) and freedom from distant metastasis. ResultsA PI-RADS score of ≤3, 4, or 5 was defined in 7%, 49%, and 44%; with a median nodule size of 0, 8, and 18 mm, respectively (P < 0.001). Median follow-up was 67 months. Men with PI-RADS ≤ 3, 4, or 5 disease had 7-year FFBF of 100%, 92%, and 65% (P = 0.002), and a 7-year freedom from distant metastasis of 100%, 100%, and 82%, respectively (P = 0.014). PI-RADS (Hazard Ratio 5.4 for PI-RADS 5 vs. 4, P = 0.006) remained associated with FFBF when controlling for NCCN risk category (P = 0.063) and receipt of androgen deprivation therapy (P = 0.535). Nodule size was also associated with FFBF (Hazard Ratio 1.08 per mm, P < 0.001) after controlling for NCCN risk category (P = 0.156) and receipt of androgen deprivation therapy (P = 0.776). ConclusionmpMRI findings, including PI-RADS score and nodule size, may improve risk stratification in men treated with primary RT

Immunosuppression, BK polyomavirus infections, and BK polyomavirus-specific T cells after pediatric kidney transplantation.

After kidney transplantation, immunosuppressive therapy increases risk of BK polyomavirus-associated nephropathy (BKPyVAN). Outcomes of BKPyV viremia are various and prognostic markers are missing. The impact of different immunosuppressive regimens on BKPyV infections is currently under discussion. We analyzed immunosuppressive therapy and BKPyV-specific cellular immunity to distinguish patients at risk of BKPyVAN from those with self-limiting viremia for purposes of risk-stratified BKPyV management. In a retrospective analysis, 46 pediatric kidney recipients with BKPyV viremia were analyzed with regard to duration of BKPyV viremia and immunosuppressive therapy; in addition, in 37/46 patients, BKPyV-specific CD4 and CD8 T cells were measured. Nine patients showed persistent BKPyV viremia and BKPyVAN, and required therapeutic intervention, while 37 patients had asymptomatic, self-limiting viremia. At onset of viremia, 78% of patients with persistent viremia and BKPyVAN were treated with tacrolimus, whereas tacrolimus therapy was significantly less frequent in patients with self-limiting viremia (14%). The majority of patients with transient, self-limiting viremia received cyclosporine A (81%) and/or mTOR inhibitors (81%). Patients with persistent BKPyV viremia and BKPyVAN showed lack of BKPyV-specific CD4 and CD8 T cells (6/6), whereas the majority of patients with self-limiting viremia (27/31) had detectable BKPyV-specific CD4 and/or CD8 T cells ≥ 0.5 cells/μl (p < 0.001). These results indicate that tacrolimus enhances risk of BKPyVAN with need of therapeutic intervention, whereas under cyclosporine A and mTOR inhibitors, the majority of pediatric kidney recipients showed self-limiting viremia. In patients at risk of BKPyV infections, combination of cyclosporine A and mTOR inhibitor may be advantageous.

Universal hepatitis B screening and management in patients with cancer who received immunosuppressive chemotherapy.

Clinical data to guide management of patients with cancer and hepatitis B virus (HBV) infection who are treated with immunosuppressive chemotherapy are lacking. The purpose of this study was to describe HBV+ rates in a population of patients with cancer and evaluate a risk-stratified management protocol for the prevention of HBV reactivation (HBVr). This was a descriptive study conducted in an integrated healthcare delivery system. Patients with cancer and hepatitis B virus infection who received immunosuppressive chemotherapy between 1 January 2014 and 31 January 2016 were included. A risk-stratified management protocol that continued for six months after chemotherapy completion or 12 months after completion of B-cell targeted chemotherapy was assessed. Outcomes included the proportion of patients who were HBV+ and amongst patients who initiated immunosuppressive therapy, proportions who received hepatitis B virus monitoring or anti-hepatitis B virus prophylaxis, or experienced HBVr or hepatitis B virus-related complications. There were 2463 patients with cancer screened for hepatitis B virus with 114 (4.6%) HBV+ of whom 59 (51.8%) initiated chemotherapy. Included patients were primarily older, male, and white with gastrointestinal or hematologic cancers and initiated intermediate/low-risk cytotoxic chemotherapy. During follow-up, 41 (69.5%) received hepatitis B virus DNA monitoring and 17 (28.8%) initiated anti-hepatitis B virus prophylaxis. No HBVr was observed. ALT and AST abnormalities were common but mostly Grade 1 and primarily related to the patient's malignancy or medications. Universal hepatitis B virus screening coupled with a risk-stratified management strategy utilizing HBVr monitoring and anti-hepatitis B virus prophylaxis in HBV+ patients receiving immunosuppressive chemotherapy for cancer may prevent HBVr.

Individual participant data validation of the PICNICC prediction model for febrile neutropenia

BackgroundRisk-stratified approaches to managing cancer therapies and their consequent complications rely on accurate predictions to work effectively. The risk-stratified management of fever with neutropenia is one such very common area...

Persistent Discordance in Grade, Stage, and NCCN Risk Stratification in Men Undergoing Targeted Biopsy and Radical Prostatectomy

To elucidate the accuracy of MRI and MRI-ultrasound fusion guided targeted biopsy (TBx) on risk stratification in men who underwent subsequent radical prostatectomy (RP). A single-center, retrospective study was performed in men at risk for prostate cancer who (n = 140) underwent TBx and RP between November 2012 and August 2018. Comparisons were made between patients clinically staged by preoperative MRI and TBx Gleason grade group (GGG) and stage after RP. Multivariable regression was performed to identify factors associated with MRI and TBx compared to RP grading, staging, and consistency with National Comprehensive Cancer Network (NCCN) risk stratification. There was an increase in NCCN risk stratification in 47 men (33.6%) and a decrease in 17 men (12.1%) compared to the resected prostate. GGG upgrading and downgrading occurred in 35 (25.0%) and 31 men (22.1%), respectively. Upstaging occurred in 41 men (29.3%). In adjusted analysis for age, BMI, PSA Density (PSAD), median maximal diameter of the regions of interest, and PIRADS, men with PIRADS 4 were less likely to be upgraded (OR 0.26, 95% CI 0.08-0.81, P = .020) than PIRADS 3. PSAD ≥ 0.15 ng/mL/cc was associated with upstaging (OR 3.92, 95% CI 1.60-9.62, P = .003). Accurate risk stratification is critical for disease management, mandated by the increasing use of active surveillance, partial gland ablation, and androgen deprivation therapy with radiation therapy for men with unfavorable intermediate and high-risk prostate cancer. This study confirms the need for advances in imaging and biomarker to increase the accuracy of pretreatment staging.

Stability of a 17-Gene Genomic Prostate Score in Serial Testing of Men on Active Surveillance for Early Stage Prostate Cancer.

Genomic testing may improve risk stratification in men with prostate cancer managed by active surveillance. We aimed to characterize the stability and usefulness of serial genomic test scores in men undergoing serial biopsies during active surveillance. We compiled clinical and disease characteristics of men on active surveillance using an institutional Urologic Outcomes Database. We included patients initially diagnosed with Gleason 3 + 3 prostate cancer who elected active surveillance and received 2, 17-gene GPS (Genomic Prostate Score) results. We examined the association of GPS results and Gleason grade reclassification (Gleason 3 + 4 or greater) with definitive treatment using multivariable Cox proportional hazards regression models. We identified 111 men who underwent serial genomic testing. There were 49 grade reclassification events (44%) at a median followup of 64 months. The mean ± SD GPS change between the first and second biopsies was 2.1 ± 10.3. The GPS at first biopsy (per 5 units HR 1.04, 95% CI 1.00-1.07, p=0.03) was associated with an upgrade at second biopsy, although the second GPS was not (HR 1.02, 95% CI 0.99-1.05, p=0.13). The first and second GPSs (HR 1.09, 95% CI 1.04-1.14 and HR 1.09, 95% CI 1.04-1.14, each p <0.01) were associated with active treatment. The GPS undergoes small changes with time. Absolute GPS results at the first and second biopsies were associated with Gleason upgrading and transition from active surveillance to active treatment.