Genetic Factors Associated with Prostate Cancer Conversion from Active Surveillance to Treatment.
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ABSTRACT:
SUBMITTER: Jiang Y
PROVIDER: S-EPMC8725988 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Genetic Factors Associated with Prostate Cancer Conversion from Active Surveillance to Treatment.
Jiang Yu Y Meyers Travis J TJ Emeka Adaeze A AA Cooley Lauren Folgosa LF Cooper Phillip R PR Lancki Nicola N Helenowski Irene I Kachuri Linda L Lin Daniel W DW Stanford Janet L JL Newcomb Lisa F LF Kolb Suzanne S Finelli Antonio A Fleshner Neil E NE Komisarenko Maria M Eastham James A JA Ehdaie Behfar B Benfante Nicole N Logothetis Christopher J CJ Gregg Justin R JR Perez Cherie A CA Garza Sergio S Kim Jeri J Marks Leonard S LS Delfin Merdie M Barsa Danielle D Vesprini Danny D Klotz Laurence H LH Loblaw Andrew A Mamedov Alexandre A Goldenberg S Larry SL Higano Celestia S CS Spillane Maria M Wu Eugenia E Carter H Ballentine HB Pavlovich Christian P CP Mamawala Mufaddal M Landis Tricia T Carroll Peter R PR Chan June M JM Cooperberg Matthew R MR Cowan Janet E JE Morgan Todd M TM Siddiqui Javed J Martin Rabia R Klein Eric A EA Brittain Karen K Gotwald Paige P Barocas Daniel A DA Dallmer Jeremiah R JR Gordetsky Jennifer B JB Steele Pam P Kundu Shilajit D SD Stockdale Jazmine J Roobol Monique J MJ Venderbos Lionne D F LDF Sanda Martin G MG Arnold Rebecca R Patil Dattatraya D Evans Christopher P CP Dall'Era Marc A MA Vij Anjali A Costello Anthony J AJ Chow Ken K Corcoran Niall M NM Rais-Bahrami Soroush S Phares Courtney C Scherr Douglas S DS Flynn Thomas T Karnes R Jeffrey RJ Koch Michael M Dhondt Courtney Rose CR Nelson Joel B JB McBride Dawn D Cookson Michael S MS Stratton Kelly L KL Farriester Stephen S Hemken Erin E Stadler Walter M WM Pera Tuula T Banionyte Deimante D Bianco Fernando J FJ Lopez Isabel H IH Loeb Stacy S Taneja Samir S SS Byrne Nataliya N Amling Christopher L CL Martinez Ann A Boileau Luc L Gaylis Franklin D FD Petkewicz Jacqueline J Kirwen Nicholas N Helfand Brian T BT Xu Jianfeng J Scholtens Denise M DM Catalona William J WJ Witte John S JS
HGG advances 20211119 1
Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide asso ...[more]
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Project description:PurposeWe examined the demographic and clinicopathological parameters associated with the time to convert from active surveillance to treatment among men with prostate cancer.Materials and methodsA multi-institutional cohort of 7,279 patients managed with active surveillance had data and biospecimens collected for germline genetic analyses.ResultsOf 6,775 men included in the analysis, 2,260 (33.4%) converted to treatment at a median followup of 6.7 years. Earlier conversion was associated with higher Gleason grade groups (GG2 vs GG1 adjusted hazard ratio [aHR] 1.57, 95% CI 1.36-1.82; ≥GG3 vs GG1 aHR 1.77, 95% CI 1.29-2.43), serum prostate specific antigen concentrations (aHR per 5 ng/ml increment 1.18, 95% CI 1.11-1.25), tumor stages (cT2 vs cT1 aHR 1.58, 95% CI 1.41-1.77; ≥cT3 vs cT1 aHR 4.36, 95% CI 3.19-5.96) and number of cancerous biopsy cores (3 vs 1-2 cores aHR 1.59, 95% CI 1.37-1.84; ≥4 vs 1-2 cores aHR 3.29, 95% CI 2.94-3.69), and younger age (age continuous per 5-year increase aHR 0.96, 95% CI 0.93-0.99). Patients with high-volume GG1 tumors had a shorter interval to conversion than those with low-volume GG1 tumors and behaved like the higher-risk patients. We found no significant association between the time to conversion and self-reported race or genetic ancestry.ConclusionsA shorter time to conversion from active surveillance to treatment was associated with higher-risk clinicopathological tumor features. Furthermore, patients with high-volume GG1 tumors behaved similarly to those with intermediate and high-risk tumors. An exploratory analysis of self-reported race and genetic ancestry revealed no association with the time to conversion.
| S-EPMC8734323 | biostudies-literature
Project description:Many men diagnosed with localized prostate cancer can postpone definitive treatment without raising their risk of metastasis or death from disease. Active surveillance (AS) is a method of monitoring select men, with the option of switching to active treatment upon signs of progression, thereby avoiding the well-known side-effects of surgery and radiotherapy. This review analyzes the data from long-running AS cohorts to determine the safety and efficacy of AS. We conducted a narrative review of recently published data, including 14 articles from 13 AS cohorts. The cohorts used varying inclusion criteria, with reported differences in clinical T stage and Gleason Score (Grade Group), among other features. Some studies (n=5) limited their cohorts to low-risk patients, while others (n=8) also included intermediate-risk patients. The heterogeneity of the cohorts produced mixed results, with the risk of prostate cancer metastasis ranging from 0.1-1.0% at 10 years and the risk of prostate cancer mortality ranging from 0-1.9% at 10 years. However, the majority of studies reported risks of less than 0.5% at 10 years for both metastasis and death. For most cohorts, half of men remained untreated for 5-10 years, with estimates ranging from 37% receiving active treatment in the Toronto cohort to 73% in the Prostate Cancer Research International AS (PRIAS) study. Current data do not support the use of negative magnetic resonance imaging (MRI) to avoid scheduled biopsy. Taken together, the data collected from these AS cohorts suggests that AS is a safe approach for men with low-grade prostate cancer and some men with intermediate risk disease. AS should be more broadly implemented for eligible patients to avoid the decreases in quality of life from undergoing active treatment. Studies expanding the inclusion criteria and further defining a subset of men with favorable intermediate-risk prostate cancer who might safely benefit from AS are needed to assess the long-term outcomes of using AS in intermediate-risk groups.
| S-EPMC8261451 | biostudies-literature
Project description:BackgroundThe routine clinical use of serum prostatic specific antigen (PSA) testing has allowed earlier detection of low-grade prostate cancer (PCa) with more favourable characteristics, leading to increased acceptance of management by active surveillance (AS). AS aims to avoid over treatment in men with low and intermediate-risk PCa and multiple governing bodies have described several AS protocols. This study provides a descriptive profile of the Guy's and St Thomas NHS Foundation Trust (GSTT) AS cohort as a platform for future research in AS pathways in PCa.MethodsDemographic and baseline characteristics were retrospectively collected in a database for patients at the GSTT AS clinic with prospective collection of follow-up data from 2012. Seven hundred eighty-eight men being monitored at GSTT with histologically confirmed intermediate-risk PCa, at least 1 follow-up appointment and diagnostic characteristics consistent with AS criteria were included in the profile. Descriptive statistics, Kaplan-Meier survival curves and multivariable Cox proportion hazards regression models were used to characterize the cohort.DiscussionA relatively large proportion of the cohort includes men of African/Afro-Caribbean descent (22%). More frequent use of magnetic resonance imaging and trans-perineal biopsies at diagnosis was observed among patients diagnosed after 2012. Those who underwent trans-rectal ultrasound diagnostic biopsy received their first surveillance biopsy 20 months earlier than those who underwent trans-perineal diagnostic biopsy. At 3 years, 76.1% men remained treatment free. Predictors of treatment progression included Gleason score 3 + 4 (Hazard ratio (HR): 2.41, 95% Confidence interval (CI): 1.79-3.26) and more than 2 positive cores taken at biopsy (HR: 2.65, CI: 1.94-3.62). A decreased risk of progressing to treatment was seen among men diagnosed after 2012 (HR: 0.72, CI: 0.53-0.98).ConclusionAn organised biopsy surveillance approach, via two different AS pathways according to the patient's diagnostic method, can be seen within the GSTT cohort. Risk of patients progressing to treatment has decreased in the period since 2012 compared with the prior period with more than half of the cohort remaining treatment free at 5 years, highlighting that the fundamental aims of AS at GSTT are being met. Thus, this cohort is a good resource to investigate the AS treatment pathway.
| S-EPMC8135162 | biostudies-literature
Project description:Active surveillance is a strategy to delay or prevent treatment of indolent prostate cancer. The Prostate Cancer Research International: Active Surveillance (PRIAS) criteria were developed to select patients for prostate cancer active surveillance. The objective of this study was to compare pathological findings from PRIAS-eligible and PRIAS-ineligible clinically low-risk prostate cancer patients.A D'Amico low-risk cohort of 1512 radical prostatectomy patients treated at The Ottawa Hospital or Memorial Sloan Kettering Cancer Centre between January 1995 and December 2007 was reviewed. Pathological outcomes (pT3 tumours, Gleason sum ≥7, lymph node metastases, or a composite) and clinical outcomes (prostate-specific antigen [PSA] recurrence, secondary cancer treatments, and death) were compared between PRIAS-eligible and PRIAS-ineligible cohorts.The PRIAS-eligible cohort (n=945) was less likely to have Gleason score ≥7 (odds ratio [OR] 0.61; 95% confidence interval [CI] 0.49-0.75), pT3 (OR 0.41; 95% CI 0.31-0.55), nodal metastases (OR 0.37; 95% CI 0.10-1.31), or any adverse feature (OR 0.56; 95% CI 0.45-0.69) compared to the PRIAS-ineligible cohort. The probability of any adverse pathology in the PRIAS-eligible cohort was 41% vs. 56% in the PRIAS-ineligible cohort. At median follow-up of 3.7 years, 72 (4.8%) patients had a PSA recurrence, 24 (1.6%) received pelvic radiation, and 13 (0.9%) received androgen deprivation. No difference was detected for recurrence-free and overall survival between groups (recurrence hazard ratio [HR] 0.71; 95% CI 0.46-1.09 and survival HR 0.72; 95% CI 0.36-1.47).Low-risk prostate cancer patients who met PRIAS eligibility criteria are less likely to have higher-risk cancer compared to those who did not meet at least one of these criteria.
| S-EPMC5542829 | biostudies-other
Project description:ImportanceAlthough active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited.ObjectiveTo 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.Design, setting, and participantsThis 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.ExposureAt 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.Main outcomes and measuresOutcomes 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.ResultsA 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.Conclusions and relevanceIn 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.
| S-EPMC10582795 | biostudies-literature
Project description:PurposeActive surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS.Materials and methodsThis cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model.ResultsA total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL² predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17-2.88) and conversion (HR 1.56, 95% CI 1.05-2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to <50%: HR 1.41, 95% CI 0.91-2.18; ≥50%: HR 1.97, 95% CI 1.1453-3.40) compared with that of <15%. A Gleason grade group (GGG) of 3 tumor also predicted conversion (HR 2.69, 95% CI 1.06-6.79; GGG 3 vs 1). One patient developed metastasis, but none died of PC during the study period (2,141 person-years).ConclusionsAS is a viable option for Taiwanese men with non-high-risk PC, in terms of reclassification and conversion. High PSAD predicted reclassification, whereas high PSAD, MPCPC, and GGG predicted conversion.
| S-EPMC11216962 | biostudies-literature
Project description:PurposeWhile major prostate cancer active surveillance programs recommend repeat testing such as prostate specific antigen and prostate biopsy, to our knowledge compliance with such testing is unknown. We determined whether men in the community receive the same intensity of active surveillance testing as in prospective active surveillance protocols.Materials and methodsWe performed a retrospective cohort study of men 66 years old or older in the SEER (Surveillance, Epidemiology and End Results)-Medicare database. These men were diagnosed with prostate cancer from 2001 to 2009, did not receive curative therapy in the year after diagnosis and underwent 1 or more post-diagnosis prostate biopsies. We used multivariable adjusted Poisson regression to determine the association of the frequency of active surveillance testing with patient demographics and clinical features. In 1,349 men with 5 years of followup we determined the proportion who underwent testing as intense as that recommended by the Sunnybrook Health Sciences Centre and PRIAS (Prostate Cancer Research International Active Surveillance) programs, including 14 or more PSA tests and 2 or more biopsies, and The Johns Hopkins program, including 10 or more prostate specific antigen tests and 4 or more biopsies.ResultsAmong 5,192 patients undergoing active surveillance greater than 80% had 1 or more prostate specific antigen tests per year but fewer than 13% underwent biopsy beyond the first 2 years. Magnetic resonance imaging was rarely done during the study period. On multivariable analysis recent diagnosis and higher income were associated with a higher frequency of surveillance biopsy while older age and greater comorbidity were associated with fewer biopsies. African American men underwent fewer prostate specific antigen tests but a similar number of biopsies. During 5 years of active surveillance only 11.1% and 5.0% of patients met the testing standards of the Sunnybrook/PRIAS and The Johns Hopkins programs, respectively.ConclusionsIn the community few elderly men receive the intensity of active surveillance testing recommended in major prospective active surveillance programs.
| S-EPMC5010531 | biostudies-literature
Project description:BackgroundMaintaining men on active surveillance for prostate cancer can be challenging. Although most men who eventually undergo treatment have experienced clinical progression, a smaller subset elects treatment in the absence of disease reclassification. This study sought to understand factors associated with treatment in a large, contemporary, prospective cohort.MethodsThis study identified 1789 men in the Canary Prostate Cancer Active Surveillance Study cohort enrolled as of 2020 with a median follow-up of 5.6 years. Clinical and demographic data as well as information on patient-reported quality of life and urinary symptoms were used in multivariable Cox proportional hazards regression models to identify factors associated with the time to treatment RESULTS: Within 4 years of their diagnosis, 33% of men (95% confidence interval [CI], 30%-35%) underwent treatment, and 10% (95% CI, 9%-12%) were treated in the absence of reclassification. The most significant factor associated with any treatment was an increasing Gleason grade group (adjusted hazard ratio [aHR], 14.5; 95% CI, 11.7-17.9). Urinary quality-of-life scores were associated with treatment without reclassification (aHR comparing "mostly dissatisfied/terrible" with "pleased/mixed," 2.65; 95% CI, 1.54-4.59). In a subset analysis (n = 692), married men, compared with single men, were more likely to undergo treatment in the absence of reclassification (aHR, 2.63; 95% CI, 1.04-6.66).ConclusionsA substantial number of men with prostate cancer undergo treatment in the absence of clinical changes in their cancers, and quality-of-life changes and marital status may be important factors in these decisions.Lay summaryThis analysis of men on active surveillance for prostate cancer shows that approximately 1 in 10 men will decide to be treated within 4 years of their diagnosis even if their cancer is stable. These choices may be related in part to quality-or-life or spousal concerns.
| S-EPMC8738121 | biostudies-literature
Project description:BackgroundClinical consequences of active surveillance compared with immediate treatment have been evaluated in patients with low-risk prostate cancer; yet, its financial benefits have not been adequately studied in Canada or elsewhere. Our study objective was to evaluate the direct costs associated with active surveillance and immediate treatment in the Canadian context.MethodsWe developed a Markov model with Monte Carlo microsimulations to estimate the Canadian cost of prostate cancer associated with immediate treatment and active surveillance strategies. The patients receiving active surveillance were assumed to receive delayed treatment at a rate of 8.35%, 4.17% and 2.1% per year for the first 2 years, years 3 to 5, and years 6 to 10 of follow-up, respectively. All costs were assigned in Canadian dollars and reflect Quebec's health system.ResultsWith active surveillance, the mean cost of prostate cancer management over the first year and 5 years of follow-up was estimated at $6200 (95% confidence interval [CI] $6083-$6317) per patient. The mean cost corresponding to immediate treatment was estimated at $13 735 (95% CI $13 615-$13 855) per patient. We estimated that patients receiving active surveillance who received delayed treatment incurred higher costs of $16 257 per patient.InterpretationActive surveillance could offer important economic benefits to the Canadian health system, estimated at $96.1 million for each annual cohort of incident prostate cancer. These results add to the economic rationale advocating active surveillance for eligible men with low-risk prostate cancer.
| S-EPMC4084746 | biostudies-literature
Project description:BackgroundProstate cancer is the most common cancer in men and second leading cause of cancer-related deaths. Changes in screening guidelines, adoption of active surveillance (AS), and implementation of high-cost technologies have changed treatment costs. Traditional cost-effectiveness studies rely on clinical trial protocols unlikely to capture actual practice behavior, and existing studies use data predating new technologies. Real-world evidence reflecting these changes is lacking.ObjectiveTo assess real-world costs of first-line prostate cancer management.Design setting and participantsWe used clinical electronic health records for 2008-2018 linked with the California Cancer Registry and the Medicare Fee Schedule to assess costs over 24 or 60 mo following diagnosis. We identified surgery or radiation treatments with structured methods, while we used both structured data and natural language processing to identify AS.Outcome measurements and statistical analysisOur results are risk-stratified calculated cost per day (CCPD) for first-line management, which are independent of treatment duration. We used the Kruskal-Wallis test to compare unadjusted CCPD while analysis of covariance log-linear models adjusted estimates for age and Charlson comorbidity.Results and limitationsIn 3433 patients, surgery (54.6%) was more common than radiation (22.3%) or AS (23.0%). Two years following diagnosis, AS ($2.97/d) was cheaper than surgery ($5.67/d) or radiation ($9.34/d) in favorable disease, while surgery ($7.17/d) was cheaper than radiation ($16.34/d) for unfavorable disease. At 5 yr, AS ($2.71/d) remained slightly cheaper than surgery ($2.87/d) and radiation ($4.36/d) in favorable disease, while for unfavorable disease surgery ($4.15/d) remained cheaper than radiation ($10.32/d). Study limitations include information derived from a single healthcare system and costs based on benchmark Medicare estimates rather than actual payment exchanges.Patient summaryActive surveillance was cheaper than surgery (-47.6%) and radiation (-68.2%) at 2 yr for favorable-risk disease, which decreased by 5 yr (-5.6% and -37.8%, respectively). Surgery was less costly than radiation for unfavorable risk for both intervals (-56.1% and -59.8%, respectively).
| S-EPMC7751921 | biostudies-literature