Applying precision medicine to the active surveillance of prostate cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Reichard CA
PROVIDER: S-EPMC4758404 | biostudies-other | 2015 Oct
REPOSITORIES: biostudies-other
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Project description:Men on active surveillance (AS) face repeated biopsies. Most biopsy specimens will not show disease progression or change management. Such biopsies do not contribute to patient management and are potentially morbid and costly.To use a contemporary AS prospective trial to develop a tool to predict AS biopsy outcomes.Biopsy samples (median: 2; range: 2-9 per patient) from 859 men participating in the Canary Prostate Active Surveillance Study and with Gleason 6 prostate cancer (median follow-up: 35.8 mo; range: 3.0-148.7 mo) were analyzed.Logistic regression was used to predict progression, defined as an increase in Gleason score from ?6 to ?7 or increase in percentage of cores positive for cancer from <34% to ?34%. Fivefold internal cross-validation was performed to evaluate the area under the receiver operating characteristic curve (AUC).Statistically significant risk factors for progression on biopsy were prostate-specific antigen (odds ratio [OR]: 1.045; 95% confidence interval [CI], 1.028-1.063), percentage of cores positive for cancer on most recent biopsy (OR: 1.401; 95% CI, 1.301-1.508), and history of at least one prior negative biopsy (OR: 0.524; 95% CI, 0.417-0.659). A multivariable predictive model incorporating these factors plus age and number of months since last biopsy achieved an AUC of 72.4%.A combination of readily available clinical measures can stratify patients considering AS prostate biopsy. Risk of progression or upgrade can be estimated and incorporated into clinical practice.The Canary-Early Detection Research Network Active Surveillance Biopsy Risk Calculator, an online tool, can be used to guide patient decision making regarding follow-up prostate biopsy.
| S-EPMC4583313 | biostudies-literature
Project description:Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer.Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer.Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.
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Project description:Aided by developments in diagnostics and therapeutics, healthcare is increasingly moving toward precision medicine, in which treatment is customized to each individual. We discuss the relevance of precision medicine in prostate cancer, including gene targets, therapeutics and resistance mechanisms. We foresee precision medicine becoming an integral component of prostate cancer management to increase response to therapy and prolong survival.
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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.
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Project description:Despite advances in prostate cancer screening and treatment, available therapy options, particularly in later stages of the disease, remain limited and the treatment-resistant setting represents a serious unmet medical need. Moreover, disease heterogeneity and disparities in patient access to medical advances result in significant variability in outcomes across patients. Disease classification based on genomic sequencing is a promising approach to identify patients whose tumors exhibit actionable targets and make more informed treatment decisions. Here we discuss how we can accelerate precision oncology to inform broader genomically-driven clinical decisions for men with advanced prostate cancer, drug development and ultimately contribute to new treatment paradigms.
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Project description:Prostate cancer is the most common type of cancer in men and the second leading cause of cancer death in men in the United States. The recent surge of high-throughput sequencing of cancer genomes has supported an expanding molecular classification of prostate cancer. Translation of these basic science studies into clinically valuable biomarkers for diagnosis and prognosis and biomarkers that are predictive for therapy is critical to the development of precision medicine in prostate cancer. We review potential applications aimed at improving screening specificity in prostate cancer and differentiating aggressive versus indolent prostate cancers. Furthermore, we review predictive biomarker candidates involving ETS gene rearrangements, PTEN inactivation, and androgen receptor signaling. These and other putative biomarkers may signify aberrant oncogene pathway activation and provide a rationale for matching patients with molecularly targeted therapies in clinical trials. Lastly, we advocate innovations for clinical trial design to incorporate tumor biopsy and molecular characterization to develop biomarkers and understand mechanisms of resistance.
| S-EPMC3808235 | biostudies-literature
Project description:Prostate cancer is the second most common male cancer affecting Western society. Despite substantial advances in the exploration of prostate cancer biomarkers and treatment strategies, men are over diagnosed with inert prostate cancer, while there is also a substantial mortality from the invasive disease. Precision medicine is the management of treatment profiles across different cancers predicting therapies for individual cancer patients. With strategies including individual genomic profiling and targeting specific cancer pathways, precision medicine for prostate cancer has the potential to impose changes in clinical practices. Some of the recent advances in prostate cancer precision medicine comprise targeting gene fusions, genome editing tools, non-coding RNA biomarkers, and the promise of liquid tumor profiling. In this review, we will discuss these recent scientific advances to scale up these approaches and endeavors to overcome clinical barriers for prostate cancer precision medicine.
| S-EPMC6901987 | biostudies-literature
Project description:Prostate cancer is the most common cancer among men and the second leading cause of cancer-related death. For patients who develop metastatic disease, tissue-based and circulating-tumor-based molecular and genomic biomarkers have emerged as a means of improving outcomes through the application of precision medicine. However, the benefit is limited to a minority of patients. An additional approach to further characterize the biology of advanced prostate cancer is through the use of phenotypic precision medicine, or the identification and targeting of phenotypic features of an individual patient's cancer. In this review article, we will discuss the background, potential clinical benefits, and limitations of genomic and phenotypic precision medicine in prostate cancer. We will also highlight how the emergence of image-based phenotypic medicine may lead to greater characterization of advanced prostate cancer disease burden and more individualized treatment approaches in patients.
| S-EPMC9907055 | 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: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