PSA-based prostate cancer screening： the role of active surveillance and informed and shared decision making

Since the first publication describing the identification of prostate-specific antigen （PSA） in the 1960s, much progress has been made. The PSA test changed from being initially a monitoring tool to being also used as a diagnostic tool. Over time, the test has been heavily debated due to its lack of sensitivity and specificity. However, up to now the PSA test is still the only biomarker for the detection and monitoring of prostate cancer. PSA-based screening for prostate cancer is associated with a high proportion of unnecessary testing and overdiagnosis with subsequent overtreatment. In the early years of screening for prostate cancer, high rates of uptake were very important. However, over time the opinion on PSA-based screening has shifted towards the notion of informed choice. Nowadays, it is thought to be unethical to screen men without them being aware of the pros and cons of PSA testing, as well as the fact that an informed choice is related to better patient outcomes. Now, as the results of three major screening studies have been presented and the downsides of screening are becoming better understood, informed choice is becoming more relevant.

The active surveillance management approach for patients with low risk papillary thyroid microcarcinomas: is China ready?

Due to exponential increases in incidences,low risk papillary thyroid microcarcinoma(PTMC)has become a clinical and social issue in recent years.An active surveillance(AS)management approach is an alternative to immediate surgery for patients with low risk PTMC.With decreased doubts about the safety and validity due to evidence from a large number of studies,the AS approach has become increasingly popular worldwide.However,Chinese thyroid surgeons still lag behind other countries in their knowledge of clinical practices and research related to AS.To promote the implementation of AS in China,thyroid surgeons should understand the implications,advantages,and disadvantages of management approaches for AS,and should also consider the willingness of Chinese patients,the impact on the medical billing system,and the enthusiasm of doctors.Thus,a management approach for AS based on the Chinese population should be developed to reduce the risk of disease progression and enhance patient adherence.Herein,we summarize the recent research achievements and deficiencies in AS approaches,and describe the initial experiences regarding AS in the Chinese population,in order to assist Chinese thyroid surgeons in preparing for AS management in the era of PTMC precision medicine.

Active surveillance as a management strategy for papillary thyroid microcarcinoma

Active surveillance(AS)can be considered as a treatment strategy for low risk papillary thyroid microcarcinoma(PTMC),with the absence of clinically apparent lymph nodes,extrathyroidal extensions,and distant metastasis.After reviewing the reports on AS of low risk PTMCs worldwide,we introduced AS,and discussed the selection criteria for active surveillance candidates based on different guidelines and the follow-up schedules.Moreover,the requirement of cytological diagnosis,progression evaluation methods,necessity of thyrotropin suppression,and medical costs were issues that both clinicians and patients considered.The usefulness of AS for low risk PTMC patients depended on accurate and confidential evaluation of patient risk.Clinicians may adopt measures like dynamic monitoring,risk stratification,and making personal follow-up schedules to minimize these potential risks.By appropriately selecting PTMC patients,AS can be an effective alternative treatment to immediate surgery.

Contemporary approach to active surveillance for favorable risk prostate cancer

The approach to favorable risk prostate cancer known as“active surveillance”was first described explicitly in 2002.This was a report of 250 patients managed with a strategy of expectant management,with serial prostate-specific antigen and periodic biopsy,and radical intervention advised for patients who were re-classified as higher risk.This was initiated as a prospective clinical trial,complete with informed consent,beginning in 2007.Thus,there are now 20 years of experience with this approach,which has become widely adopted around the world.In this chapter,we will summarize the biological basis for active surveillance,review the experience to date of the Toronto and Hopkins groups which have reported 15-year outcomes,describe the current approach to active surveillance in patients with Gleason score 3þ3 or selected patients with Gleason score 3þ4 with a low percentage of Gleason pattern 4 who may also be candidates,enhanced by the use of magnetic resonance imaging,and forecast future directions.

Active chinese mistletoe lectin-55 enhances colon cancer surveillance through regulating innate and adaptive immune responses

AIM:To investigate the potential role of Active Chinese mistletoe lectin-55 (ACML-55) in tumor immune surveillance. METHODS: In this study, an experimental model was established by hypodermic inoculating the colon cancer cell line CT26 (5 × 105 cells) into BALB/c mice. The experimental treatment was orally administered with ACML-55 or PBS, followed by the inoculation of colon cancer cell line CT26. Intracellular cytokine staining was used to detect IFN-γ production by tumor antigen specific CD8+ T cells. FACS analysis was employed to profi le composition and activation of CD4+, CD8+, γδ T and NK cells. RESULTS: Our results showed, compared to PBS treated mice, ACML-55 treatment signifi cantly delayed colon cancer development in colon cancer -bearingBalb/c mice in vivo. Treatment with ACML-55 enhanced both Ag specifi c activation and proliferation of CD4+ and CD8+ T cells, and increased the number of tumor Ag specific CD8+ T cells. It was more important to increase the frequency of tumor Ag specific IFN-γ producing-CD8+ T cells. Interestingly, ACML-55 treatment also showed increased cell number of NK, and γδT cells, indicating the role of ACML-55 in activation of innate lymphocytes. CONCLUSION: Our results demonstrate that ACML-55 therapy can enhance function in immune surveillance in colon cancer-bearing mice through regulating both innate and adaptive immune responses.

Active surveillance in low risk papillary thyroid carcinoma

In recent decades,while the incidence of thyroid cancer has increased exponentially around the world,mortality has remained stable.The vast majority of this increase is attributable to the identification of intrathyroidal papillary microcarcinomas,which exhibit slow growth rates with indolent courses.A diagnosis of thyroid cancer based upon the presence of these small tumors could be considered as an overdiagnosis,as the majority of these tumors would not likely result in death if left untreated.Although surgical resection was the classical standard therapy for papillary microcarcinomas,active surveillance(AS)has emerged over the last three decades as an alternative approach that is aimed to recognize a minority group of patients who will clinically progress and would likely benefit from rescue surgery.Despite the encouraging results of AS,its implementation in clinical practice is strongly influenced by psychosocial factors.The aim of this review is to describe the epidemiology,clinical evolution,prognostic factors,and mortality of papillary thyroid microcarcinomas.We also summarize the AS strategy according to published evidence,characterize the criteria for selecting patients for AS according to risk factors and environmental characteristics,as well as analyze the current limitations for AS implementation.

Active surveillance as a practical strategy to differentiate lethal and non-lethal prostate cancer subtypes

Differentiation between lethal and non-lethal prostate cancer subtypes has become a very important issue in avoiding excessive treatment in an era when prostate-specific antigen （PSA） screening has reduced the rate of prostate cancer deaths by more than 20%. However, it is difficult to determine the patients who may or may not benefit from immediate treatment interventions at the time of the initial diagnosis. The selection of candidate patients who can postpone immediate treatment and undergo follow-ups with a specific surveillance program, or ＇active surveillance,＇ is a practical way to minimize overtreatment. In this review, the benefits and risks of active surveillance are discussed. Future perspectives, including imaging and new biomarkers for improving the outcomes of active surveillance programs, are also discussed.

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance

AIM:To examine whether addition of 3T multiparametric magnetic resonance imaging(mp MRI)to an active surveillance protocol could detect aggressive or progressive prostate cancer.METHODS:Twenty-three patients with low risk disease were enrolled on this active surveillance study,all of which had Gleason score 6 or less disease.All patients had clinical assessments,including digital rectal examination and prostate specific antigen(PSA)testing,every 6 mo with annual 3T mp MRI scans with gadolinium contrast and minimum sextant prostate biopsies.The MRI images were anonymized of patient identifiers and clinical information and each scan underwentradiological review without the other results known.Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mp MRI to identify prostate cancer and progressive disease were calculated.RESULTS:During follow-up(median 24.8 mo)11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment.Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years.All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mp MRI scans at baseline(43.5% sensitivity).Aggressive disease prediction from baseline mpM RI scans had satisfactory specificity(81.8%)but low sensitivity(58.3%).Twentytwo patients had serial mp MRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy(30% specificity and 100% sensitivity).CONCLUSION:Addition of mp MRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods.

Outcomes of combination MRI-targeted and transperineal template biopsy in restaging low-risk prostate cancer for active surveillance

Objective:Active surveillance(AS)offers a strategy to reduce overtreatment and now is a widely accepted treatment option for low-risk prostate cancer.An ideal tool for risk-stratification would detect aggressive cancers and exclude such men from taking up AS in the first place.We evaluate if a combination of transperineal template biopsy with magnetic resonance imaging(MRI)-targeted biopsy identifies significant prostate cancer amongst men initially diagnosed with low-risk prostate cancer.Methods:This prospective,single-blinded study included men with low-risk prostate cancer(D’Amico’s Criteria)diagnosed on conventional transrectal ultrasound-guided biopsy.Patients first underwent multiparametric MRI of the prostate
6 weeks after initial biopsy.Each suspicious lesion is mapped and assigned a Prostate Imaging Reporting and Data System(PIRADS)score.Template biopsy is first performed with the surgeon blinded to MRI findings followed by MRI-targeted biopsy using a robotic transperineal biopsy platform.Results:The age of the 19 men included is 65.4±4.9 years(mean±SD).Prostate specific antigen(PSA)at diagnosis and at the time of transperineal biopsy were comparable(7.3±1.7 ng/mL and 7.0±1.8 ng/mL,p Z 0.67),so were prostate volumes(34.2±8.9 mL and 32.1±13.4 mL,p Z 0.28).MRI-targeted biopsy had a higher percentage of cancer detection per core compared to template biopsy(11.7%vs.6.5%,p Z 0.02),this was more than 3 times superior for Gleason 7 disease(5.9%vs.1.6%,p<0.01).Four of 18(22.2%)patients with MRI lesions had significant disease with MRI-targeted biopsy alone.Three of 19 patients(15.8%)had significant disease with template biopsy alone.In combination,both techniques upclassified five patients(26.3%),all of whom underwent radical prostatectomy.Whole mount histology confirmed tumour location and grade.All six patients with PIRADS 5 lesions had cancer detected(66.6%significant disease).Conclusion:A combination of MRI-targeted and template biopsy may optimally risk-classify“low-risk”patients diagnosed on initial conventional transrectal ultrasonography(TRUS)prostate biopsy.

Expending the Paradigm: Active Surveillance for Intermediate Risk Prostate Cancer

Prostate cancer is the leading male cancer worldwide. There remains a controversy as to which patients have indolent disease and which patients present an aggressive disease needing treatment with intent to cure. Because of quality of life impairment associated with treatment by radiation or surgery, active surveillance (AS) is a valid management option to avoid or differ aggressive treatment. Traditionally, AS was reserved for men with low risk prostate cancer, however intermediate risk patients are more and more found in AS cohorts. The aim of this review is to describe the place of AS in intermediate risk patients and the perspectives offered by such a treatment modality.

Active surveillance in metastatic pancreatic neuroendocrine tumors:A 20-year single-institutional experience

BACKGROUND Pancreatic neuroendocrine tumors(PanNETs)are heterogeneous and indolent;systemic therapy is not essential for every patient with metastatic PanNET.The National Comprehensive Cancer Network guidelines state that delaying treatment is an option for PanNET with distant metastasis,if the patient has stable disease.However,specific factors that influence surveillance were not mentioned.In addition,data regarding the period of active surveillance in patients with metastatic PanNET are lacking.AIM To specifically determine factors influencing active surveillance in patients with liver metastatic nonfunctioning PanNETs(NF-PanNETs).METHODS Seventy-six patients with liver metastatic NF-PanNETs who received active surveillance from a high-volume institution were enrolled.Time to disease progression(TTP)and time to initiation of systemic therapy were determined.RESULTS Thirty-one(40.8%)patients had recurrent liver disease after R0 resection;45(59.2%)were diagnosed with liver metastasis.The median follow-up period was 42 mo and 90.7%patients were observed to have disease progression.The median TTP(mTTP)was 10 mo.Multivariate analysis showed that the largest axis of the liver metastasis>5 mm(P=0.04),non-resection of the primary tumor(P=0.024),and T3-4 stage(P=0.028)were associated with a shorter TTP.The mTTP in patients with no risk factors was 24 mo,which was significantly longer than that in patients with one(10 mo)or more(6 mo)risk factors(P<0.001).A nomogram with three risk factors showed reasonable calibration,with a C-index of 0.603(95%confidence interval:0.47-0.74).CONCLUSION Active surveillance may only be safe for metastatic NF-PanNET patients with favorable risk factors,and other patients progressed rapidly without treatment.Further studies with a larger sample size and a control group are needed.

Anomaly Based Camera Prioritization in Large Scale Surveillance Networks

Digital surveillance systems are ubiquitous and continuously generate massive amounts of data,and manual monitoring is required in order to recognise human activities in public areas.Intelligent surveillance systems that can automatically identify normal and abnormal activities are highly desirable,as these would allow for efficient monitoring by selecting only those camera feeds in which abnormal activities are occurring.This paper proposes an energy-efficient camera prioritisation framework that intelligently adjusts the priority of cameras in a vast surveillance network using feedback from the activity recognition system.The proposed system addresses the limitations of existing manual monitoring surveillance systems using a three-step framework.In the first step,the salient frames are selected from the online video stream using a frame differencing method.A lightweight 3D convolutional neural network(3DCNN)architecture is applied to extract spatio-temporal features from the salient frames in the second step.Finally,the probabilities predicted by the 3DCNN network and the metadata of the cameras are processed using a linear threshold gate sigmoid mechanism to control the priority of the camera.The proposed system performs well compared to state-of-theart violent activity recognition methods in terms of efficient camera prioritisation in large-scale surveillance networks.Comprehensive experiments and an evaluation of activity recognition and camera prioritisation showed that our approach achieved an accuracy of 98%with an F1-score of 0.97 on the Hockey Fight dataset,and an accuracy of 99%with an F1-score of 0.98 on the Violent Crowd dataset.

A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong,China:what did we learn?

This study aimed to report the outcomes of active surveillance(AS)in the management of low-risk prostate cancer(PCa).It recruited87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance(PRIAS)protocol with local adaptation at SH Ho Urology Centre,Prince of Wales Hospital,Hong Kong,China.We investigated the predictorsof disease progression and found that baseline prostate-specific antigen density(PSAD)and the presence of the highest ProstateImaging-Reporting and Data System(PI-RADS)score 5 lesion on magnetic resonance imaging(MRI)are significantly correlatedwith disease progression.Moreover,men with PSAD>0.2 ng ml^(−2)or PI-RADS 4 or 5 lesions had significantly worse upgradingfree survival compared to those with PSAD≤0.2 ng ml−2 and PI-RADS 2 or 3 lesions.The study concludes that AS is a safe andeffective management strategy for selected patients to defer radical treatment and that most disease progression can be detectedafter the first repeated biopsy.The combination of PSAD>0.2 ng ml^(−2)and PI-RADS 4 or 5 lesions may serve as a useful predictorof early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

Treatment of intermediate-risk prostate cancer with active surveillance in the routine care—Long-term outcomes of a prospective noninterventional study(HAROW)

Background:We report here the long-term outcomes of patients with intermediate-risk prostate cancer(PCa)treated with active surveillance(AS)in a daily routine setting.Material andmethods:HAROW(2008–2013)was a noninterventional,health service research study investigating themanagement of localized PCa in a community setting.A substantial proportion of the study centers were office-based urologists.A follow-up examination of all intermediate-risk patients with AS was conducted.Overall,cancer-specific,metastasis-free,and treatment-free survival rates,as well as reasons for discontinuation,were determined and discussed.Results:Of the 2957 patients enrolled,52 with intermediate-risk PCa were managed with AS and were available for evaluation.The median follow-up was 6.8 years(interquartile range,3.4–8.6 years).Seven patients(13.5%)died of causes unrelated to PCa,of whom 4 were under AS or under watchful waiting.Two patients(3.8%)developed metastasis.The estimated 8-year overall,cancer-specific,metastasis-free,and treatment-free survival rates were 85%(95%confidence interval[CI],72%–96%),100%,93%(95%CI,82%–100%),and 31%(95%CI,17%–45%),respectively.Onmultivariable analysis,prostate-specific antigen density of≥0.2 ng/mL2 was significantly predictive of receiving invasive treatment(hazard ratio,3.29;p=0.006).Reasons for discontinuation were more often due to patient's or physician's concerns(36%)than due to observed clinical progression.Conclusions:Although survival outcome data for intermediate-risk patients managed with AS in real-life health care conditions were promising,rates of discontinuation were high,and discontinuation was often a patient's decision,even when the signs of disease progression were absent.This might be an indication of higher levels of mental burden and anxiety in this specific subgroup of patients,which should be considered when making treatment decisions.From a psychological perspective,not all intermediate-risk patients are optimal candidates for AS.

Can testosterone therapy be offered to men on active surveillance for prostate cancer？ Preliminary results

This report presents our experience with T therapy in a cohort of T-deficient men on active surveillance （AS） for Gleason 3 ＋ 3 and Gleason 3 ＋ 4 prostate cancer （PCa）. A retrospective chart review identified 28 men with T deficiency who underwent T therapy （T group） for at least 6 months while on AS for PCa. A comparison group of 96 men on AS for PCa with untreated T deficiency （no-T group） was identified at the same institution. The AS protocol followed a modified Epstein criteria and allowed inclusion of men with a single core of low-volume Gleason 3 ＋ 4 PCa. Mean age was 59.5 and 61.3 years, and mean follow-up was 38.9 and 42.4 months for the T and no-T groups, respectively. Of all 28 men in the T group, 3 （10.7%） men developed an increase in Gleason score while on AS. Of 22 men in the T group with Gleason 3 ＋ 3 disease, 7 （31.8%） men developed biopsy progression including 3 men （13.6%） who developed Gleason 3 ＋ 4 PCa. Of 6 men with Gleason 3 ＋ 4 disease at baseline, 2 （33.3%） men developed an increase in tumor volume, and none developed upgrading beyond Gleason 3 ＋ 4. All 96 men in the no-T group had Gleason 3 ＋ 3 disease at baseline and, 43 （44.7%） developed biopsy progression, including 9 men （9.38%） with upgrading to Gleason 7 （3 ＋ 4）. Biopsy progression rates were similar for both groups and historical controls. Biopsy progression in men on AS appears unaffected by T therapy over 3 years. Prospective placebo-controlled trials of T therapy in T-deficient men on AS should be considered given the symptomatic benefits experienced by treated men.

Applicability of Wireless Activity Sensor Network to Avian Influenza Monitoring System in Poultry Farms

Since there are cases that chickens infected with highly pathogenic avian influenza (HPAI) viruses die with almost no fever, body-temperature sensing cannot be effective for the early detection of avian influenza (AI) infection in these cases. In addition, sensors directly attached to the body surface are easily affected by their surroundings, therefore it is not easy to measure the body-temperature of chickens. This paper proposes a new method to detect abnormal states of chickens with only their activity data obtained by wearable wireless sensor nodes. The method is that if its state that the present average activity of a chicken in one hour is smaller than 0.6 times minimum average daytime activity in its life continues for 3 hours, a judgment that the chicken is abnormal state is made. This method can detect the abnormal states twice as early as that with body-temperature sensing does. Since the activity sensor nodes are easily attached to chickens and hardly affected by their surroundings, this system can be reliable.

The comparison of survival between active surveillance or watchful waiting and focal therapy for low-risk prostate cancer:a real-world study from the SEER database

To reduce treatment-related side effects in low-risk prostate cancer(PCa),both focal therapy and deferred treatments,including active surveillance(AS)and watchful waiting(WW),are worth considering over radical prostatectomy(RP).Therefore,this study aimed to compare long-term survival outcomes between focal therapy and AS/WW.Data were obtained and analyzed from the Surveillance,Epidemiology,and End Results(SEER)database.Patients with low-risk PCa who received focal therapy or AS/WW from 2010 to 2016 were included.Focal therapy included cryotherapy and laser ablation.Multivariate Cox proportional hazards models were used to compare overall mortality(OM)and cancer-specific mortality(CSM)between AS/WW and focal therapy,and propensity score matching(PSM)was performed to reduce the influence of bias and unmeasured confounders.A total of 19292 patients with low-risk PCa were included in this study.In multivariate Cox proportional hazards model analysis,the risk of OM was higher in patients receiving focal therapy than those receiving AS/WW(hazard ratio[HR]=1.35,95%confidence interval[CI]:1.02–1.79,P=0.037),whereas no significant difference was found in CSM(HR=0.98,95%CI:0.23–4.11,P=0.977).After PSM,the OM and CSM of focal therapy and AS/WW showed no significant differences(HR=1.26,95%CI:0.92–1.74,P=0.149;and HR=1.26,95%CI:0.24–6.51,P=0.782,respectively).For patients with low-risk PCa,focal therapy was no match for AS/WW in decreasing OM,suggesting that AS/WW could bring more overall survival benefits.

Automatic Unusual Activities Recognition Using Deep Learning in Academia

In the current era,automatic surveillance has become an active research problem due to its vast real-world applications,particularly for maintaining law and order.A continuous manual monitoring of human activities is a tedious task.The use of cameras and automatic detection of unusual surveillance activity has been growing exponentially over the last few years.Various computer vision techniques have been applied for observation and surveillance of real-world activities.This research study focuses on detecting and recognizing unusual activities in an academic situation such as examinationhalls,which may help the invigilators observe and restrict the students from cheating or using unfairmeans.To the best of our knowledge,this is the first research work in this area that develops a dataset for unusual activities in the examination and proposes a deep learning model to detect those unusual activities.The proposed model has been named Automatic Unusual Activity Recognition(AUAR),which employsmotion-based frame extraction approaches to extract key-frames and then applies advanced deep learning Convolutional Neural Network algorithm with diverse configurations.The evaluation using standard performancemeasures confirmthat theAUARmodel outperforms the already proposed approaches for unusual activity recognition.Apart from evaluating the proposed model on the examination dataset,we also apply AUAR on Violent and Movies datasets,widely used in the relevant literature to detect suspicious activities.The results reveal that AUAR performs well on various data sets compared to existing state-of-the-art models.

A critical review of national physical activity policies relating to children and young people in England

Background:There has been an increasing focus on the importance of national policy to address population levels of physical inactivity.It has been suggested that the 4 cornerstones of policy comprise(1)national guidelines on physical activity(PA),(2)setting population goals and targets,(3)surveillance or health-monitoring systems,and(4)public education.The current study aimed to review the policy actions that have addressed each of these elements for children and youth in England and to identify areas of progress and remaining challenges.Methods:A literature search was undertaken to identify past and present documents relevant to PA policy for children and youth in England.Each document was analyzed to identify content relevant to the 4 cornerstones of policy.Results:Physical activity guidelines(Cornerstone 1)for children and youth have been in place since 1998 and reviewed periodically.Physical activity targets(Cornerstone 2)have focussed on the provision of opportunities for PA,mainly through physical education in schools rather than in relation to the proportion of children meeting recommended PA levels.There has been much surveillance(Cornerstone 3)of children’s PA,but this has been undertaken infrequently over time and with varying inclusions of differing domains of activity.There has been only 1 campaign(Cornerstone 4)that targeted children and their intermediaries,Change4Life,which was an obesity campaign focussing on dietary behavior in combination with PA.Most recently,a government infographic supporting the PA guidelines for children and young people was developed,but details of its dissemination and usage are unknown.Conclusion:There have been many developments in national PA policy in England targeted to children and young people.The area of most significant progress is national PA guidelines.Establishing prevalence targets,streamlining surveillance systems,and investing in public education with supportive policies,environments,and opportunities would strengthen national policy efforts to increase PA and reduce sedentary behavior.