Active Surveillance Cohort Research Articles

Active surveillance for cardiac complications after major noncardiac surgery: implications on resource utilization and safety in high-risk patients

Abstract Background The 2022 ESC guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery recommend that high-risk patients should undergo active surveillance for cardiac complications, including perioperative myocardial infarction/injury (PMI), following major noncardiac surgery. Unfortunately, little is known about the resource use and safety of active surveillance compared to a control cohort (i.e. without active surveillance). Objective To quantify the impact of active surveillance for cardiac complications, by perioperative cardiac troponin (cTn) measurements and a systematic PMI work-up on working days, on resource usage and safety. Methods We did a retrospective comparison of non-randomised pre- vs post-implementation of an active surveillance program for cardiac complications in patients at elevated cardiovascular risk undergoing noncardiac surgery at two hospitals in Switzerland. The two cohorts' resource use and safety were compared. Resource use encompassed perioperative cTn measurements, ECGs, cardiac imaging, cardiology consultations as well as coronary angiography (CAG) and revascularisation procedures. Safety was assessed based on the number of "seemingly normal CAG" and complications arising from CAG and revascularisation procedures. Results A total of 13’147 patients, 10’346 in the active surveillance cohort and 2’805 in the standard-of-care (SOC) cohort, were eligible for this analysis. Patient characteristics between both cohorts were comparable (e.g. median age of 74 vs 73 and 44.8% vs 43% female, respectively). Patients in the active surveillance cohort underwent significantly more perioperative cTn measurements (86.4% vs 3.5%, respectively), postoperative ECGs (13.5% vs 5.7%), postoperative cardiac consultations (5.9% vs 2.4%), postoperative transthoracic echocardiogram (TTE) (7.5% vs 6.1%), postoperative myocardial perfusion imaging (MPI) (1.2% vs 0.6%), and postoperative CAG (0.8% vs 0.4%, all p <0.05). The increased resource use led to a substantial increase in detected cardiac complications within the first 48h after surgery: active surveillance 1’207 (12%) (95%CI 11%-12%) vs SOC 68 (2.4%) (95%CI 1.9%-3.1%). The active surveillance cohort generated an overall cardiac management cost of 236 Euros (95%CI 223–250) per patient vs 133 Euros (95%CI 110–160) per patient in the SOC cohort, resulting in an incremental cost for the active surveillance of 103 Euros (95%CI 110–160) per patient. Thereby the cost of detecting one additional cardiac complication within 48h was 989 Euros. Concerning safety, no significant differences in the number of "seemingly normal CAG" (6.4% vs 15%, p=0.1) and complications due to CAG and revascularisation (0.6% vs 5.1%, p=0.08) were observed. Conclusion The active surveillance for cardiac complications is safe when compared to a standard-of-care cohort while 989 Euros per additional detected cardiac complication seems reasonably priced.Resource-utilization tableOverview

Artificial intelligence for detection of prostate cancer in biopsies during active surveillance.

To evaluate a cancer detecting artificial intelligence (AI) algorithm on serial biopsies in patients with prostate cancer on active surveillance (AS). A total of 180 patients in the Prostate Cancer Research International Active Surveillance (PRIAS) cohort were prospectively monitored using pre-defined criteria. Diagnostic and re-biopsy slides from 2011 to 2020 (n = 4744) were scanned and analysed by an in-house AI-based cancer detection algorithm. The algorithm was analysed for sensitivity, specificity, and for accuracy to predict need for active treatment. Prognostic properties of cancer size, prostate-specific antigen (PSA) level and PSA density at diagnosis were evaluated. The sensitivity and specificity of the AI algorithm was 0.96 and 0.73, respectively, for correct detection of cancer areas. Original pathology report diagnosis was used as the reference method. The area of cancer estimated by the pathologists correlated highly with the AI detected cancer size (r = 0.83). By using the AI algorithm, 63% of the slides would not need to be read by a pathologist as they were classed as benign, at the risk of missing 0.55% slides containing cancer. Biopsy cancer content and PSA density at diagnosis were found to be prognostic of whether the patient stayed on AS or was discontinued for active treatment. The AI-based biopsy cancer detection algorithm could be used to reduce the pathologists' workload in an AS cohort. The detected cancer amount correlated well with the cancer length measured by the pathologist and the algorithm performed well in finding even small areas of cancer. To our knowledge, this is the first report on an AI-based algorithm in digital pathology used to detect cancer in a cohort of patients on AS.

Association of Baseline Magnetic Resonance Imaging Prostate Imaging Reporting and Data System Score With Prostate Cancer Active Surveillance Early Biopsy Reclassification: Data From the Michigan Urological Surgery Improvement Collaborative (MUSIC).

The purpose of our study was to evaluate the association of baseline MRI Prostate Imaging Reporting and Data System (PI-RADS) score with biopsy reclassification in a multicenter active surveillance (AS) cohort. We identified men in the Michigan Urological Surgery Improvement Collaborative registry (46 hospital-based/academic/private practice urology groups) with National Comprehensive Cancer Network (NCCN) low-risk and favorable intermediate-risk prostate cancer who underwent MRI within 6 months before or after initial biopsy and enrolled in AS from June 2016 to January 2021. The primary objective was to determine the association of baseline MRI PI-RADS score (≥4 lesion) with reclassification to high-grade prostate cancer (≥grade group 3) on surveillance biopsy. Multivariable Cox proportional hazards regression models were constructed and adjusted for pathologic, MRI, and clinical/biopsy factors, with landmark time of 6 months from diagnostic biopsy. We included an interaction term between PI-RADS score and NCCN group in the Cox model. A total of 1491 men were included with median age 64 years (IQR: 59-69) with median follow-up 11.0 months (IQR: 6.0-23.0) after landmark. Baseline PI-RADS ≥ 4 lesion was associated with an increased hazard of biopsy reclassification (HR: 2.3 [95% CI: 1.6-3.2], P < .001), along with grade group 2 vs 1 (HR: 2.5 [95% CI: 1.7-3.7], P < .001), and increasing age (per 10 years; HR: 1.8 [95% CI: 1.4-2.4], P < .001). The interaction between NCCN risk group with MRI findings was not significant (P = .7). In this multicenter cohort study of real-world data, baseline MRI PI-RADS score was significantly associated with early biopsy reclassification in men undergoing AS with NCCN low- or favorable intermediate-risk prostate cancer.

Predicting prostate cancer grade reclassification on active surveillance using a deep learning-based grading algorithm.

Deep learning (DL)-based algorithms to determine prostate cancer (PCa) Grade Group (GG) on biopsy slides have not been validated by comparison to clinical outcomes. We used a DL-based algorithm, AIRAProstate, to regrade initial prostate biopsies in 2 independent PCa active surveillance (AS) cohorts. In a cohort initially diagnosed with GG1 PCa using only systematic biopsies (n = 138), upgrading of the initial biopsy to ≥GG2 by AIRAProstate was associated with rapid or extreme grade reclassification on AS (odds ratio = 3.3, P = .04), whereas upgrading of the initial biopsy by contemporary uropathologist reviews was not associated with this outcome. In a contemporary validation cohort that underwent prostate magnetic resonance imaging before initial biopsy (n = 169), upgrading of the initial biopsy (all contemporary GG1 by uropathologist grading) by AIRAProstate was associated with grade reclassification on AS (hazard ratio = 1.7, P = .03). These results demonstrate the utility of a DL-based grading algorithm in PCa risk stratification for AS.

The impact of pneumococcal serotype replacement on the effectiveness of a national immunization program: a population-based active surveillance cohort study in New Zealand

In Aotearoa New Zealand (NZ) PCV7 was introduced in 2008, then PCV10 in 2011 and PCV13 in 2014. In 2017 PCV10 was re-introduced, replacing PCV13. In the present study, we investigate the resultant rapidly changing invasive pneumococcal disease (IPD) epidemiology. We compare the IPD incidence rate ratio (IRR) in NZ (2022 versus 2020) with other countries, and describe the IPD epidemiology (including trends in overall IPD and serotype 19A, and antimicrobial resistance) within NZ. Additionally, we performed a genomic-epidemiology investigation identifying the most common 19A sequence types and associated risk factors. Though IPD incidence rates have increased in the US and Australia (2021-22) after declines in 2020, in NZ the incidence rate is the highest since 2011 with a significantly higher IRR than US (p<0.01). Incidence rates among children <2 and adults 65 or over in 2022 are the highest since 2009, driven by significant increases of serotype 19A (p=0.01). Māori and Pacific peoples are experiencing the highest rates since 2009. Further, penicillin resistance among 19A isolates has increased from 39% (2012) to 84% (2021) (p=0.02). Genomic sequencing identified the more virulent ST-2062 as most common among 19A isolates sequenced, increasing from 5% (2010) to 55% (2022). With very high incidence rates of IPD in NZ, inadequate protection against 19A, increasing resistance, and a more virulent 19A clade, targeted public health campaigns and increased PCV13 availability are needed. The NZ Ministry of Health funds IPD surveillance and typing in NZ.

Modeling Thyroid Cancer Epidemiology in the United States Using Papillary Thyroid Carcinoma Microsimulation Model

ObjectivesThyroid cancer incidence increased over 200% from 1992 to 2018, whereas mortality rates had not increased proportionately. The increased incidence has been attributed primarily to the detection of subclinical disease, raising important questions related to thyroid cancer control. We developed the Papillary Thyroid Carcinoma Microsimulation model (PATCAM) to answer them, including the impact of overdiagnosis on thyroid cancer incidence. MethodsPATCAM simulates individuals from age 15 until death in birth cohorts starting from 1975 using 4 inter-related components, including natural history, detection, post-diagnosis, and other-cause mortality. PATCAM was built using high-quality data and calibrated against observed age-, sex-, and stage-specific incidence in the United States as reported by the Surveillance, Epidemiology, and End Results database. PATCAM was validated against US thyroid cancer mortality and 3 active surveillance studies, including the largest and longest running thyroid cancer active surveillance cohort in the world (from Japan) and 2 from the United States. ResultsPATCAM successfully replicated age- and stage-specific papillary thyroid cancers (PTC) incidence and mean tumor size at diagnosis and PTC mortality in the United States between 1975 and 2015. PATCAM accurately predicted the proportion of tumors that grew more than 3 mm and 5 mm in 5 years and 10 years, aligning with the 95% confidence intervals of the reported rates from active surveillance studies in most cases. ConclusionsPATCAM successfully reproduced observed US thyroid cancer incidence and mortality over time and was externally validated. PATCAM can be used to identify factors that influence the detection of subclinical PTCs.

Real-world practice patterns and outcomes for RAI-refractory differentiated thyroid cancer.

The optimal timing for initiating multi-kinase inhibitors (MKIs) in patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC) remains unclear. Thus, we evaluated the real-world practice patterns and outcomes in asymptomatic patients with progressive RAI-R DTC (≥1 lesion ≥1 cm in diameter) in the USA (US population) and outside the USA (non-US population). In this prospective, non-interventional, open-label study, eligible patients were chosen by treating physicians to receive MKI therapy (cohort 1) or undergo active surveillance (cohort 2) at study entry. Cohort 2 patients were allowed to transition to MKI therapy later. The primary endpoint was time to symptomatic progression (TTSP) from study entry. Data were compared descriptively. When endpoints were inestimable, 36-month rates were calculated. Of the 647 patients, 478 underwent active surveillance (cohort 2) and 169 received MKI treatment (cohort 1). Patients underwent surveillance at a higher rate in the US (92.6%) vs the non-US (66.9%) populations. Half of US and non-US patients who qualified for MKI treatment had initial American Thyroid Association (ATA) low-to-intermediate-risk disease. In cohort 2, the 36-month TTSP rates from study entry were 65.6% and 66.5% in the US and non-US populations, respectively. Cohort 2 patients treated later demonstrated 36-month TTSP rates of 30.8% and 55.8% in the US and non-US populations, respectively. Active surveillance is a viable option for asymptomatic patients with progressive RAI-R DTC. However, early intervention with MKI therapy may be more suitable for others. Further research is needed to identify patients who are optimal for active surveillance. NCT02303444.

The Brazilian national prospective active surveillance (AS) cohort of patients with low-risk prostate cancer in the public health system: vigiaSUS study protocol

BackgroundProstate cancer exhibits a very diverse behaviour, with some patients dying from the disease and others never needing treatment. Active surveillance (AS) consists of periodic PSA assessment (prostate-specific antigen), DRE (digital rectal examination) and periodic prostate biopsies. According to the main guidelines, AS is the preferred strategy for low-risk patients, to avoid or delay definitive treatment. However, concerns remain regarding its applicability in certain patient subgroups, such as African American men, who were underrepresented in the main cohorts. Brazil has a very racially diverse population, with 56.1% self-reporting as brown or black. The aim of this study is to evaluate and validate the AS strategy in low-risk prostate cancer patients following an AS protocol in the Brazilian public health system.MethodsThis is a multicentre AS prospective cohort study that will include 200 patients from all regions of Brazil in the public health system. Patients with prostate adenocarcinoma and low-risk criteria, defined as clinical staging T1–T2a, Gleason score ≤ 6, and PSA < 10 ng/ml, will be enrolled. Archival prostate cancer tissue will be centrally reviewed. Patients enrolled in the study will follow the AS strategy, which involves PSA and physical examination every 6 months as well as multiparametric MRI (mpMRI) every two years and prostate biopsy at month 12 and then every two years. The primary objective is to evaluate the reclassification rate at 12 months, and secondary objectives include determining the treatment-free survival rate, metastasis-free survival, and specific and overall survival. Exploratory objectives include the evaluation of quality of life and anxiety, the impact of PTEN loss and the economic impact of AS on the Brazilian public health system.DiscussionThis is the first Brazilian prospective study of patients with low-risk prostate cancer under AS. To our knowledge, this is one of the largest AS study cohort with a majority of nonwhite patients. We believe that this study is an opportunity to better understand the outcomes of AS in populations underrepresented in studies. Based on these data, an AS national clinical guideline will be developed, which may have a beneficial impact on the quality of life of patients and on public health.Trial registrationClinicaltrials registration is NCT05343936.

Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer

Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited. To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis. This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023. At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months. Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters. A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months. In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.

Retrospective T2 quantification from conventional weighted MRI of the prostate based on deep learning.

To develop a deep learning-based method to retrospectively quantify T2 from conventional T1- and T2-weighted images. Twenty-five subjects were imaged using a multi-echo spin-echo sequence to estimate reference prostate T2 maps. Conventional T1- and T2-weighted images were acquired as the input images. A U-Net based neural network was developed to directly estimate T2 maps from the weighted images using a four-fold cross-validation training strategy. The structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), mean percentage error (MPE), and Pearson correlation coefficient were calculated to evaluate the quality of network-estimated T2 maps. To explore the potential of this approach in clinical practice, a retrospective T2 quantification was performed on a high-risk prostate cancer cohort (Group 1) and a low-risk active surveillance cohort (Group 2). Tumor and non-tumor T2 values were evaluated by an experienced radiologist based on region of interest (ROI) analysis. The T2 maps generated by the trained network were consistent with the corresponding reference. Prostate tissue structures and contrast were well preserved, with a PSNR of 26.41 ± 1.17 dB, an SSIM of 0.85 ± 0.02, and a Pearson correlation coefficient of 0.86. Quantitative ROI analyses performed on 38 prostate cancer patients revealed estimated T2 values of 80.4 ± 14.4 ms and 106.8 ± 16.3 ms for tumor and non-tumor regions, respectively. ROI measurements showed a significant difference between tumor and non-tumor regions of the estimated T2 maps (P < 0.001). In the two-timepoints active surveillance cohort, patients defined as progressors exhibited lower estimated T2 values of the tumor ROIs at the second time point compared to the first time point. Additionally, the T2 difference between two time points for progressors was significantly greater than that for non-progressors (P = 0.010). A deep learning method was developed to estimate prostate T2 maps retrospectively from clinically acquired T1- and T2-weighted images, which has the potential to improve prostate cancer diagnosis and characterization without requiring extra scans.

A urine extracellular vesicle lncRNA classifier for high-grade prostate cancer and increased risk of progression: A multi-center study

To construct a urine extracellular vesicle long non-coding RNA (lncRNA) classifier that can detect high-grade prostate cancer (PCa) of grade group 2 or greater and estimate the risk of progression during active surveillance, we identify high-grade PCa-specific lncRNAs by combined analyses of cohorts from TAHSY, TCGA, and the GEO database. We develop and validate a 3-lncRNA diagnostic model (Clnc, being made of AC015987.1, CTD-2589M5.4, RP11-363E6.3) that can detect high-grade PCa. Clnc shows higher accuracy than prostate cancer antigen 3 (PCA3), multiparametric magnetic resonance imaging (mpMRI), and two risk calculators (Prostate Cancer Prevention Trial [PCPT]-RC 2.0 and European Randomized Study of Screening for Prostate Cancer [ERSPC]-RC) in the training cohort (n= 350), two independent cohorts (n=232; n= 251), and TCGA cohort (n=499). In the prospective active surveillance cohort (n= 182), Clnc at diagnosis remains a powerful independent predictor for overall active surveillance progression. Thus, Clnc is a potential biomarker for high-grade PCa and can also serve as a biomarker for improved selection of candidates for active surveillance.

Aggressive Prostate Cancer in Patients Treated with Active Surveillance.

Active surveillance has emerged as a promising approach for managing low-risk and favorable intermediate-risk prostate cancer (PC), with the aim of minimizing overtreatment and maintaining the quality of life. However, concerns remain about identifying "aggressive prostate cancer" within the active surveillance cohort, which refers to cancers with a higher potential for progression. Previous studies are predictors of aggressive PC during active surveillance. To address this, a personalized risk-based follow-up approach that integrates clinical data, biomarkers, and genetic factors using risk calculators was proposed. This approach enables an efficient risk assessment and the early detection of disease progression, minimizes unnecessary interventions, and improves patient management and outcomes. As active surveillance indications expand, the importance of identifying aggressive PC through a personalized risk-based follow-up is expected to increase.

Editorial Comment.

No AccessJournal of UrologyAdult Urology27 Apr 2023Editorial CommentThis article comments on the following:Identifying Men Who Can Remain on Active Surveillance Despite Biopsy Reclassification to Grade Group 2 Prostate Cancer Sandip M. Prasad and Evan Kovac Sandip M. PrasadSandip M. Prasad Garden State Urology, Morristown Medical Center/Atlantic Health System, Morristown, New Jersey More articles by this author and Evan KovacEvan Kovac Rutgers New Jersey Medical School, Cancer Institute of New Jersey, Newark, New Jersey More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003461.01AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookLinked InTwitterEmail "Editorial Comment." The Journal of Urology, Publish Ahead of Print, pp. – REFERENCES 1. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol. 2015; 33(3):272-277. Crossref, Medline, Google Scholar 2. Identifying men who can remain on active surveillance despite biopsy reclassification to Grade Group 2 prostate cancer. J Urol. 2023; 210(1):000-000. Google Scholar 3. Risk of adverse pathology at prostatectomy in the era of MRI and targeted biopsies; rethinking active surveillance for intermediate risk prostate cancer patients. Urol Oncol. 2021; 39(10):729.e1-729.e6. Crossref, Medline, Google Scholar 4. . Optimal use of tumor-based molecular assays for localized prostate cancer. Curr Oncol Rep. 2022; 24(2):249-256. Crossref, Medline, Google Scholar © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology12 Apr 2023Identifying Men Who Can Remain on Active Surveillance Despite Biopsy Reclassification to Grade Group 2 Prostate Cancer Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sandip M. Prasad Garden State Urology, Morristown Medical Center/Atlantic Health System, Morristown, New Jersey More articles by this author Evan Kovac Rutgers New Jersey Medical School, Cancer Institute of New Jersey, Newark, New Jersey More articles by this author Expand All Advertisement PDF downloadLoading ...

The burden of respiratory syncytial virus in healthy term-born infants in Europe: a prospective birth cohort study.

Respiratory syncytial virus (RSV) is a major cause of hospitalisation in infants. The burden of RSV infection in healthy term infants has not yet been established. Accurate health-care burden data in healthy infants are necessary to determine RSV immunisation policy when RSV immunisation becomes available. We performed a multicentre, prospective, observational birth cohort study in healthy term-born infants (≥37 weeks of gestation) in five sites located in different European countries to determine the health-care burden of RSV. The incidence of RSV-associated hospitalisations in the first year of life was determined by parental questionnaires and hospital chart reviews. We performed active RSV surveillance in a nested cohort to determine the incidence of medically attended RSV infections. The study is registered with ClinicalTrials.gov, NCT03627572. In total, 9154 infants born between July 1, 2017, and April 1, 2020, were followed up during the first year of life and 993 participated in the nested active surveillance cohort. The incidence of RSV-associated hospitalisations in the total cohort was 1·8% (95% CI 1·6-2·1). There were eight paediatric intensive care unit admissions, corresponding to 5·5% of 145 RSV-associated hospitalisations and 0·09% of the total cohort. Incidence of RSV infection in the active surveillance cohort confirmed by any diagnostic assay was 26·2% (24·0-28·6) and that of medically attended RSV infection was 14·1% (12·3-16·0). RSV-associated acute respiratory infection causes substantial morbidity, leading to the hospitalisation of one in every 56 healthy term-born infants in high-income settings. Immunisation of pregnant women or healthy term-born infants during their first winter season could have a major effect on the health-care burden caused by RSV infections. Innovative Medicines Initiative 2 Joint Undertaking, with support from the EU's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations.

MP38-19 FOCAL THERAPY CANDIDACY: AN EVALUATION OF INITIAL AND CONTINUED ELIGIBILITY FOR FOCAL THERAPY IN AN ACTIVE SURVEILLANCE COHORT

You have accessJournal of UrologyCME1 Apr 2023MP38-19 FOCAL THERAPY CANDIDACY: AN EVALUATION OF INITIAL AND CONTINUED ELIGIBILITY FOR FOCAL THERAPY IN AN ACTIVE SURVEILLANCE COHORT Alexander P. Kenigsberg, Daniel Nemirovsky, Neil Mendhiratta, Zoe Blake, Jacob J. Enders, Samuel A. Gold, Michael B. Rothberg, Daniel Nethala, Brad Wood, Baris Turkbey, Sandeep Gurram, and Peter A. Pinto Alexander P. KenigsbergAlexander P. Kenigsberg More articles by this author , Daniel NemirovskyDaniel Nemirovsky More articles by this author , Neil MendhirattaNeil Mendhiratta More articles by this author , Zoe BlakeZoe Blake More articles by this author , Jacob J. EndersJacob J. Enders More articles by this author , Samuel A. GoldSamuel A. Gold More articles by this author , Michael B. RothbergMichael B. Rothberg More articles by this author , Daniel NethalaDaniel Nethala More articles by this author , Brad WoodBrad Wood More articles by this author , Baris TurkbeyBaris Turkbey More articles by this author , Sandeep GurramSandeep Gurram More articles by this author , and Peter A. PintoPeter A. Pinto More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003276.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Focal Therapy (FT) for Gleason grade group (GG) 1 prostate cancer (PCa) is controversial, given almost all of these patients are suitable active surveillance (AS) candidates. Little is known about how many AS GG 1 patients retain focal therapy eligibility (FTE) over time. The objective of this study is to evaluate initial and long-term FTE for patients with GG1 disease. METHODS: A prospectively maintained AS cohort was retrospectively queried for patients initiated on AS between 2009 and 2020 with GG1 PCa. Patients with a unilateral, biopsy-concordant, MRI-visible PIRADS or PIRADS-equivalent 2-5 lesions amenable to hemiablation who had a PSA<20, <4 positive systematic biopsy cores were considered FTE. Patients who remained GG1 were considered to have maintained FTE. Those who progressed were reassessed at time of progression for FTE. Patients with ≥GG4 disease, bilateral GG≥2, or MRI-invisible GG≥2 lost FTE. Univariate and multivariate analyses were conducted to evaluate factors associated with FTE. RESULTS: 282 GG1 PCa patients were identified, 164 of whom (58%) were FT candidates, with a mean follow-up of 4.9 years (range 1.0-13.4 years). 81/164 (49%) progressed to GG≥2 or higher on a subsequent biopsy. At the time of PCa upgrading, 36/164 (22%) of the FT candidate cohort lost FTE. Baseline characteristics are shown in Table 1. Patients who lost FTE trended toward increased PSA (6.3 vs 5.3, p=0.062 and MRI lesions (2.6 vs 2.0, p=0.007), and were more likely to have transitional or central zone (TZ/CZ) lesions (30.6% vs 14.1%, p=0.022) relative to those who maintained FTE. On logistic regression (Table 2), the number of MRI lesions and TZ/CZ lesions were associated with FTE loss (p=0.033 and 0.047, respectively). CONCLUSIONS: While approximately half of GG1 FT candidates demonstrate disease progression, almost 80% maintain FTE. Given the demonstrated safety of AS and relatively small number of patients who lose FTE while on surveillance, routine FT for GG1 disease would result in a large number of unnecessary procedures. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e532 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander P. Kenigsberg More articles by this author Daniel Nemirovsky More articles by this author Neil Mendhiratta More articles by this author Zoe Blake More articles by this author Jacob J. Enders More articles by this author Samuel A. Gold More articles by this author Michael B. Rothberg More articles by this author Daniel Nethala More articles by this author Brad Wood More articles by this author Baris Turkbey More articles by this author Sandeep Gurram More articles by this author Peter A. Pinto More articles by this author Expand All Advertisement PDF downloadLoading ...

Impact of an Expanded Definition of Family History on Outcomes of Active Surveillance for Prostate Cancer.

Despite family history being an established risk factor for prostate cancer, the role of a broader definition of family history inclusive of not just prostate cancer but other genetically related malignancies has not been investigated in the active surveillance population. Here, we evaluate the impact of an expanded definition of family history on active surveillance outcomes. Patients undergoing active surveillance for prostate cancer at Massachusetts General Hospital from 1997-2019 with detailed data available on family cancer history were identified. Primary outcome was biopsy progression-free survival, and secondary outcomes were treatment-free survival, adverse pathological features at prostatectomy, and biochemical recurrence after treatment. Statistical analyses were conducted using the Kaplan-Meier method and Cox regression. Among 855 evaluable patients, 300 (35.1%) patients had any family history of prostate cancer, and 95 (11.1%) had a family history of related malignancies suggestive of a hereditary cancer syndrome. Family history of prostate cancer alone was not associated with biopsy progression, whereas family history suggestive of a hereditary cancer syndrome was associated with a significantly increased risk of biopsy progression (HR 1.43, 95%CI 1.01-2.02), independent of other known clinicopathological risk factors in multivariable analysis. Similarly, family history suggestive of a hereditary cancer syndrome was associated with significantly lower treatment-free survival (HR 1.58, 95%CI 1.14-2.18) in multivariable analysis. No significant association was found between family history and adverse features on surgical pathology or biochemical recurrence. An expanded family history suggestive of a hereditary cancer syndrome is an independent predictor of biopsy progression during active surveillance. Men with such a family history may still be offered active surveillance but should be counseled regarding the higher risk of disease progression.

Limited Relevance of the Very Low Risk Prostate Cancer Classification in the Modern Era: Results from a Large Institutional Active Surveillance Cohort

Although the American Urological Association recently dropped the very low-risk (VLR) subcategory for low-risk prostate cancer (PCa) and the European Association of Urology does not substratify low-risk PCa, the National Comprehensive Cancer Network (NCCN) guidelines still maintain this stratum, which is based on the number of positive biopsy cores, tumor extent in each core, and prostate-specific antigen density. This subdivision may be less applicable in the modern era in which imaging-targeted prostate biopsies are common practice. In our large institutional active surveillance cohort of patients diagnosed from 2000 to 2020 (n = 1276), the number of patients meeting NCCN VLR criteria decreased significantly in recent years, with no patient meeting VLR criteria after 2018. By contrast, the multivariable Cancer of the Prostate Risk Assessment (CAPRA) score effectively substratified patients over the same period and was predictive of upgrading on repeat biopsy to Gleason grade group ≥2 on multivariable Cox proportional-hazards regression modeling (hazard ratio 1.21, 95% confidence interval 1.05–1.39; p < 0.01), independent of age, genomic test results, and magnetic resonance imaging findings. These findings suggest that the NCCN VLR criteria are less applicable in the targeted biopsy era, and that the CAPRA score or similar instruments are better contemporary risk stratification tools for men on active surveillance. Patient summaryWe investigated whether the National Comprehensive Cancer Network classification of very low risk (VLR) for prostate cancer is relevant in the modern era. We found that in a large group of patients on active surveillance, no man diagnosed after 2018 satisfied the VLR criteria. However, the Cancer of the Prostate Risk Assessment (CAPRA) score discriminated patients by cancer risk at diagnosis and was predictive of outcomes on active surveillance, and thus may be a more relevant classification scheme in the modern era.

Limited relevance of the “very low risk” prostate cancer classification in the modern era: Results from a large institutional active surveillance cohort.

381 Background: Although the American Urological Association recently dropped the “very low risk” (VLR) category for prostate cancer (PCa), the National Comprehensive Cancer Network (NCCN) guidelines still maintain this stratum based on number of positive biopsy cores, tumor extent in each core, and PSA density. This subdivision may be outdated in the modern era in which targeted prostate biopsies are common practice. We identified the proportion of VLR patients at our institution to determine whether an alternative classification may be more appropriate for risk-stratification in the modern era. Methods: Participants were diagnosed from 2000-2019 with cT1-2N0/xM0/x PCa, PSA &lt;20ng/ml, biopsy Gleason grade group (GG) 1-2, and initially managed with AS. VLR PCa was defined as &lt;3 positive cores, ≤50% cancer per core, and PSA density &lt;0.15. UCSF-CAPRA score was calculated for each patient. The primary outcome was major upgrade (≥GG3) on subsequent biopsy. Multivariable Cox proportional hazards regression models were used to calculate associations between CAPRA score and risk of major upgrade, adjusting for age, genomic testing, and prostate MRI finding. Results: Of 1554 patients initially managed with AS, 364 (23%) met NCCN VLR criteria. 49 (3%), 781 (50%), 505 (33%), and 219 (14%) patients had CAPRA scores of 0, 1, 2, and 3, respectively. Proportion of patients deemed VLR decreased over time; among 84 patients initially managed with AS during or after 2018, only one patient (1%) met VLR criteria in 2018, while the stratification by CAPRA demonstrated that 21 (25%), 25 (30%), and 38 (45%) patients had CAPRA scores of 1, 2, and 3, respectively, over the same period. CAPRA score was significantly associated with major upgrade on biopsy on multivariable Cox proportional hazards regression modeling independent of age, genomic testing, and MRI finding (HR 1.46, 95%CI 1.22-1.74, p&lt;0.01). Conclusions: The relevance of VLR PCa in the modern targeted biopsy era has diminished, with no cases meeting VLR criteria in a large AS cohort after 2018. CAPRA score is an option for a more contemporary risk stratification tool for men on AS.

Characterizing human movement patterns using GPS data loggers in an area of persistent malaria in Zimbabwe along the Mozambique border

BackgroundHuman mobility is a driver for the reemergence or resurgence of malaria and has been identified as a source of cross-border transmission. However, movement patterns are difficult to measure in rural areas where malaria risk is high. In countries with malaria elimination goals, it is essential to determine the role of mobility on malaria transmission to implement appropriate interventions.MethodsA study was conducted in Mutasa District, Zimbabwe, to investigate human movement patterns in an area of persistent transmission along the Mozambique border. Over 1 year, a convenience sample of 20 participants/month was recruited from active malaria surveillance cohorts to carry an IgotU® GT-600 global positioning system (GPS) data logger during all daily activities. Consenting participants were tested for malaria at data logger distribution using rapid antigen diagnostic tests and completed a survey questionnaire. GPS data were analyzed using a trajectory analysis tool, and participant movement patterns were characterized throughout the study area and across the border into Mozambique using movement intensity maps, activity space plots, and statistical analyses.ResultsFrom June 2016–May 2017, 184 participants provided movement tracks encompassing > 350,000 data points and nearly 8000 person-days. Malaria prevalence at logger distribution was 3.7%. Participants traveled a median of 2.8 km/day and spent a median of 4.6 h/day away from home. Movement was widespread within and outside the study area, with participants traveling up to 500 km from their homes. Indices of mobility were higher in the dry season than the rainy season (median km traveled/day = 3.5 vs. 2.2, P = 0.03), among male compared to female participants (median km traveled/day = 3.8 vs. 2.0, P = 0.0008), and among adults compared to adolescents (median total km traveled = 104.6 vs. 59.5, P = 0.05). Half of participants traveled outside the study area, and 30% traveled into Mozambique, including 15 who stayed in Mozambique overnight.ConclusionsStudy participants in Mutasa District, Zimbabwe, were highly mobile throughout the year. Many participants traveled long distances from home, including overnight trips into Mozambique, with clear implications for malaria control. Interventions targeted at mobile populations and cross-border transmission may be effective in preventing malaria introductions in this region.

SC10 - Drop-out rates from active surveillance for disease progression remain consistent and not negligible over time. A plea for long-term assessment based on a large, prospectively collected active surveillance cohort

SC10 - Drop-out rates from active surveillance for disease progression remain consistent and not negligible over time. A plea for long-term assessment based on a large, prospectively collected active surveillance cohort