Early detection of pancreatic cancer

Pancreatic adenocarcinoma is a low-incident but highly mortal disease. It accounts for only 3% of estimated new cancer cases each year but is currently the fourth common cause of cancer mortality. By 2030, it is expected to be the 2nd leading cause of cancer death. There is a clear need to diagnose and classify pancreatic cancer at earlier stages in order to give patients the best chance at a definitive cure through surgery. Three precursor lesions that distinctly lead to pancreatic adenocarcinoma have been identified, and we have increasing understanding the non-genetic and genetic risk factors for the disease. With increased understanding about the risk factors, the familial patters, and associated accumulation of genetic mutations involved in pancreatic cancer, we know that there are mutations that occur early in the development of pancreatic cancer and that improved genetic risk-based strategies in screening for pancreatic cancer may be possible and successful at saving or prolonging lives. The remaining challenge is that current standards for diagnosing pancreatic cancer remain too invasive and too costly for widespread screening for pancreatic cancer. Furthermore, the promises of noninvasive methods of detection such as blood, saliva, and stool remain underdeveloped or lack robust testing. However, significant progress has been made, and we are drawing closer to a strategy for the screening and early detection of pancreatic cancer.

A double constrained robust capon beamforming based imaging method for early breast cancer detection

Ultra-wideband （UWB） microwave images are proposed for detecting small malignant breast tumors based on the large contrast of electric parameters between a malignant tumor and normal breast tissue. In this study, an antenna array composed of 9 antennas is applied to the detection. The double constrained robust capon beamforming （DCRCB） algorithm is used for reconstructing the breast image due to its better stability and high signal-to-interference-plus-noise ratio （SINR）. The successful detection of a tumor of 2 mm in diameter shown in the reconstruction demonstrates the robustness of the DCRCB beamforming algorithm. This study verifies the feasibility of detecting small breast tumors by using the DCRCB imaging algorithm.

Advancements in Barrett's esophagus detection:The role of artificial intelligence and its implications

Artificial intelligence(AI)is making significant strides in revolutionizing the detection of Barrett's esophagus(BE),a precursor to esophageal adenocarcinoma.In the research article by Tsai et al,researchers utilized endoscopic images to train an AI model,challenging the traditional distinction between endoscopic and histological BE.This approach yielded remarkable results,with the AI system achieving an accuracy of 94.37%,sensitivity of 94.29%,and specificity of 94.44%.The study's extensive dataset enhances the AI model's practicality,offering valuable support to endoscopists by minimizing unnecessary biopsies.However,questions about the applicability to different endoscopic systems remain.The study underscores the potential of AI in BE detection while highlighting the need for further research to assess its adaptability to diverse clinical settings.

Applications of artificial intelligence in, early detection of cancer, clinical diagnosis and personalized medicine

Artificial intelligence(AI)refers to the simulation of human intelligence in machines programmed to convert raw input data into decision-making actions,like humans.AI programs are designed to make decisions,often using deep learning and computer-guided programs that analyze and process raw data into clinical decision making for effective treatment.New techniques for predicting cancer at an early stage are needed as conventional methods have poor accuracy and are not applicable to personalized medicine.AI has the potential to use smart,intelligent computer systems for image interpretation and early diagnosis of cancer.AI has been changing almost all the areas of the medical field by integrating with new emerging technologies.AI has revolutionized the entire health care system through innovative digital diagnostics with greater precision and accuracy.AI is capable of detecting cancer at an early stage with accurate diagnosis and improved survival outcomes.AI is an innovative technology of the future that can be used for early prediction,diagnosis and treatment of cancer.

Novel automated non-invasive detection of ocular surface squamous neoplasia using artificial intelligence

Ocular surface squamous neoplasia(OSSN)is a common eye surface tumour,characterized by the growth of abnormal cells on the ocular surface.OSSN includes invasive squamous cell carcinoma(SCC),in which tumour cells penetrate the basement membrane and infiltrate the stroma,as well as non-invasive conjunctival intraepithelial neoplasia,dysplasia,and SCC in-situ thereby presenting a challenge in early detection and diagnosis.Early identification and precise demarcation of the OSSN border leads to straightforward and curative treatments,such as topical medicines,whereas advanced invasive lesions may need orbital exenteration,which carries a risk of death.Artificial intelligence(AI)has emerged as a promising tool in the field of eye care and holds potential for its application in OSSN management.AI algorithms trained on large datasets can analyze ocular surface images to identify suspicious lesions associated with OSSN,aiding ophthalmologists in early detection and diagnosis.AI can also track and monitor lesion progression over time,providing objective measurements to guide treatment decisions.Furthermore,AI can assist in treatment planning by offering personalized recommendations based on patient data and predicting the treatment response.This manuscript highlights the role of AI in OSSN,specifically focusing on its contributions in early detection and diagnosis,assessment of lesion progression,treatment planning,telemedicine and remote monitoring,and research and data analysis.

Acceptance on colorectal cancer screening upper age limit in South Korea

BACKGROUND The Korea National Cancer Screening Program currently provides screening for colorectal cancer(CRC)for adults older than 50 years with no upper age limit.In general,people are likely to only pay attention to the benefits of cancer screening and to neglect its risks.Most consider the benefits of cancer screening as being far greater than the risks and are unaware that any potential benefits and harms can vary with age.AIM To report acceptance of an upper age limit for CRC screening and factors associated therewith among cancer-free individuals in Korea.METHODS The present study analyzed data from the Korea National Cancer Screening Survey 2017,a nationally representative random sample of 4500 Korean individuals targeted for screening for the five most common types of cancer.A total of 1922 participants were included in the final analysis.The baseline characteristics of the study population are presented as unweighted numbers and weighted proportions.Both univariate and multivariate logistic regression models were developed to examine factors related with acceptance of an upper age limit for CRC screening;subgroup analysis was also applied.RESULTS About 80%(1554/1922)of the respondents agreed that CRC screening should not be offered for individuals older than 80 years.Specifically,those who had never been screened for CRC had the highest acceptance rate(91%).Overall,screening history for CRC[screened by both fecal occult blood test and colonoscopy,adjusted odds ratio(aOR)=0.33,95%CI:0.22-0.50]and other cancers(aOR=0.55,95%CI:0.34-0.87),as well as a family history of cancer(aOR=0.66,95%CI:0.50-0.87),were negatively associated with acceptance of an upper age limit for CRC screening.In contrast,metropolitan residents(aOR=1.86,95%CI:1.29-2.68)and people who exercised regularly(aOR=1.42,95%CI:1.07-1.89)were more likely to accept an upper age limit.After subgrouping,we found gender,marital status,and lifetime smoking history among never-screened individuals and residential region,family history of cancer,and physical activity among never-screened individuals to be associated with acceptance of an upper age limit.CONCLUSION This study describes acceptance of an upper age limit for CRC screening and factors associated with it,and provides perspectives that should be considered,in addition to scientific evidence,when developing population-based cancer screening policies and programs.

Usefulness of CA 19–9 for pancreatic cancer screening in patients with new-onset diabetes

Background： Generally, carbohydrate antigen 19–9 （CA 19–9） is not useful for screening pancreatic cancerin the asymptomatic general population. This study aimed to evaluate the utility of CA 19–9 level as a screening indicator of pancreatic cancer in asymptomatic patients with new-onset diabetes.

Cancer/testis antigen, Kita-Kyushu lung cancer antigen-1 and ABCD stratification for diagnosing gastric cancers

BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk of developing gastric cancer(GC).The Kita–Kyushu lung cancer antigen-1(KK-LC-1)is a Cancer/Testis antigen frequently expressed in GC.AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors.The levels of serum PG I/PG II and IgG against H.pylori were measured.According to their serological status,the patients were classified into the four groups of the ABCD stratification.RESULTS Of the 77 examined patients,63(81.8%)expressed KK-LC-1.The IgG titers of H.pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1(P=0.0289 and P=0.0041,respectively).The expression of KK-LC-1 in group C[PG method(+)/H.pylori infection(+)]was as high as 93.9%high.KK-LC-1 was also detected in group A[-/-].CONCLUSION The KK-LC-1 expression in GC was associated with H.pylori infection and atrophic status,so that,KK-LC-1 may be a useful marker for the diagnosis of GC.

Colorectal cancer screening in the COVID-19 era

Colorectal cancer(CRC)is the third most diagnosed form of cancer and second most deadly cancer worldwide.Introduction of better screening has improved both incidence and mortality.However,as the coronavirus disease 2019(COVID-19)pandemic began,healthcare resources were shunted away from cancer screening services resulting in a sharp decrease in CRC screening and a backlog of patients awaiting screening tests.This may have significant effects on CRC cancer mortality,as delayed screening may lead to advanced cancer at diagnosis.Strategies to overcome COVID-19 related disruption include utilizing stool-based cancer tests,developing screening protocols based on individual risk factors,expanding telehealth,and increasing open access colonoscopies.In this review,we will summarize the effects of COVID-19 on CRC screening,the potential longoutcomes,and ways to adapt CRC screening during this global pandemic.

Impact of colorectal cancer screening participation in remote northern Canada:A retrospective cohort study

BACKGROUND Screening provides earlier colorectal cancer(CRC)detection and improves outcomes.It remains poorly understood if these benefits are realized with screening guidelines in remote northern populations of Canada where CRC rates are nearly twice the national average and access to colonoscopy is limited.AIM To evaluate the participation and impact of CRC screening guidelines in a remote northern population.METHODS This retrospective cohort study included residents of the Northwest Territories,a northern region of Canada,age 50-74 who underwent CRC screening by a fecal immunohistochemical test(FIT)between January 1,2014 to March 30,2019.To assess impact,individuals with a screen-detected CRC were compared to clinically-detected CRC cases for stage and location of CRC between 2014-2016.To assess participation,we conducted subgroup analyses of FIT positive individuals exploring the relationships between signs and symptoms of CRC at the time of screening,wait-times for colonoscopy,and screening outcomes.Two sample Welch t-test was used for normally distributed continuous variables,Mann-Whitney-Wilcoxon Tests for data without normal distribution,and Chi-square goodness of fit test for categorical variables.A P value of<0.05 was considered to be statistically significant.RESULTS 6817 fecal tests were completed,meaning an annual average screening rate of 25.04%,843(12.37%)were positive,629 individuals underwent a follow-up colonoscopy,of which,24.48%had advanced neoplasia(AN),5.41%had CRC.There were no significant differences in stage,pathology,or location between screen-detected cancers and clinically-detected cancers.In assessing participation and screening outcomes,we observed 49.51%of individuals referred for colonoscopy after FIT were ineligible for CRC screening,most often due to signs and symptoms of CRC.Individuals were more likely to have AN if they had signs and symptoms of cancer at the time of screening,waited over 180 d for colonoscopy,or were indigenous[respectively,estimated RR 1.1895%CI of RR(0.89-1.59)];RR 1.523(CI:1.035,2.240);RR 1.722(CI:1.165,2.547)].CONCLUSION Screening did not facilitate early cancer detection but facilitated higher than anticipated AN detection.Signs and symptoms of CRC at screening,and long colonoscopy wait-times appear contributory.

Practical considerations for colorectal cancer screening in older adults

Recent guidelines recommend that colorectal cancer(CRC)screening after age 75 be considered on an individualized basis,and discourage screening for people over 85 due to competing causes of mortality.Given the heterogeneity in the health of older individuals,and lack of data within current guidelines for personalized CRC screening approaches,there remains a need for a clearer framework to inform clinical decision-making.A revision of the current approach to CRC screening in older adults is even more compelling given the improvements in CRC treatment,post-treatment survival,and increasing life expectancy in the population.In this review,we aim to examine the personalization of CRC screening cessation based on specific factors influencing life and health expectancy such as comorbidity,frailty,and cognitive status.We will also review screening modalities and endoscopic technique for minimizing risk,the risks of screening unique to older adults,and CRC treatment outcomes in older patients,in order to provide important information to aid CRC screening decisions for this age group.This review article offers a unique approach to this topic from both the gastroenterologist and geriatrician perspective by reviewing the use of specific clinical assessment tools,and addressing technical aspects of screening colonoscopy and periprocedural management to mitigate screening-related complications.

Current and future opportunities for liquid biopsy of circulating biomarkers to aid in early cancer detection

Early diagnosis of cancer can significantly improve treatment and survival outcomes.Imaging and tissue biopsy are the gold standard diagnostic approaches but are costly,invasive,and often unable to detect early-stage tumors.The past decade has marked an acceleration in the discovery and development of liquid biopsy tests for aiding in the detection of various types of tumor markers in non-tissue samples,such as blood.Liquid biopsy markers include circulating tumor cells,as well as tumor cell fragments,nucleic acids,and proteins.Liquid biopsy may be useful in screening patients considered to be at high risk of developing cancer,for refining diagnosis when combined with other test results,and for early detection of recurrence.Advances in big data analytics,informatics,and artificial intelligence will make it possible to combine patient history,clinical data,and liquid biopsy marker profiles to achieve more accurate and earlier diagnosis.In this review,we summarize the current use of liquid biopsy in cancer care,including the development of multi-analyte panels to improve diagnostic accuracy and detect several cancer types in a single assay.We highlight recent advances for potential future applications of liquid biopsy to aid in the diagnosis of early-stage lung cancer.We also discuss the opportunities and challenges of integrating liquid biopsy into current algorithms for cancer screening and diagnosis.

Survey of hepatitis B virus infection for liver cancer screening in China:A population-based,cross-sectional study

Background:Hepatitis B virus(HBV)infection is the primary cause of hepatocellular carcinoma(HCC)in China.The target population for HCC screening comprises individuals who test positive for hepatitis B surface antigen(HBsAg).However,current data on the prevalence of HBV infection among individuals who are eligible for HCC screening in China are lacking.We aimed to assess the seroepidemiology of HBV infection among Chinese individuals eligible for HCC screening to provide the latest evidence for appropriate HCC screening strategies in China.Methods:Questionnaires including information of sex,age,ethnicity,marital status,educational level,source of drinking water,as well as smoking and alcohol consumption history and serum samples were collected from females aged 45-64 years and males aged 35-64 years in 21 counties from 4 provinces in eastern and central China between 2015 and 2023.Enzyme-linked immunosorbent assay methods were used to detect the serum HBV marker HBsAg.Results:A total of 603,082 individuals were enrolled,and serum samples were collected for analysis from January 1,2015 to December 31,2023.The prevalence of HBsAg positive in the study population was 5.23%(31,528/603,082).The prevalence of HBsAg positive was greater in males than in females(5.60%[17,660/315,183]vs 4.82%[13,868/287,899],χ^(2)=187.52,P<0.0001).The elderly participants exhibited a greater prevalence of HBV infection than younger participants(χ^(2)=41.73,P<0.0001).Birth cohort analysis revealed an overall downward trend in HBV prevalence for both males and females.Individuals born in more recent cohorts exhibited a lower prevalence of HBV infection as compared to those born earlier.Conclusions:The current prevalence of HBV infection remains above 5%in populations eligible for HCC screening in China.Further efforts should be made to increase the accessibility of HCC screening among individuals with HBV infection.

Socioeconomic inequalities in cancer incidence and mortality:An analysis of GLOBOCAN 2022

Background:Given the recent updates in cancer burden estimates by GLOBOCAN 2022,this study was undertaken to provide pertinent perspectives within the context of the Human Development Index(HDI)and major world economies.Methods:Datasets sourced from GLOBOCAN encompassed cancer cases and deaths across all cancer types in 2022,alongside projections up to 2050.Cancer incidences and deaths of the top 10 cancers within China and four distinct HDI-classified regions were compared using descriptive analyses.Age-standardized incidence rates(ASIRs)and mortality rates(ASMRs)worldwide for the most prevalent cancers in 2022 across ten largest economies and four-tier HDIs were examined.The top five cancer types concerning both incidence and mortality in China were delineated by sex and age group.Results:In males,prostate cancer predominated in countries with low,high(except China),and very high HDI.Prostate and liver cancers were prominent causes of death in countries with low HDI.In females,breast and cervical cancers predominated in countries with low-to-medium HDI.Lung and colorectal cancer incidence and deaths increased with high HDI for both sexes.ASIRs and ASMRs for breast,prostate,lung,and colorectal cancers in the top 10 economies were higher than the global average.However,liver,stomach,and cervical cancers in most Western countries exhibited lower rates.In China,hematologic malignancies(43%)were prevalent among children aged 0-14 years,whereas thyroid cancer led among adolescents and young adults aged 15-39 years.Regarding incidence and mortality,lung cancer predominated for individuals over 40 years,except for females aged 40-59 years,in whom breast cancer predominated.Projected trends indicated substantial increases in new cancer cases(76.6%)and deaths(89.7%)over the next three decades.Conclusions:Infection-and poverty-related cancer burdens are offset by increased prostate,breast,colorectal,and lung cancer incidence associated with rapid societal and economic transitions.Cancer incidence and mortality patterns in China feature characteristics of developed and developing countries,necessitating tailored,evidence-based,and comprehensive strategies for effective cancer prevention and control.

Application of an artificial intelligence system for endoscopic diagnosis of superficial esophageal squamous cell carcinoma

BACKGROUND Upper gastrointestinal endoscopy is critical for esophageal squamous cell carcinoma(ESCC)detection;however,endoscopists require long-term training to avoid missing superficial lesions.AIM To develop a deep learning computer-assisted diagnosis(CAD)system for endoscopic detection of superficial ESCC and investigate its application value.METHODS We configured the CAD system for white-light and narrow-band imaging modes based on the YOLO v5 algorithm.A total of 4447 images from 837 patients and 1695 images from 323 patients were included in the training and testing datasets,respectively.Two experts and two non-expert endoscopists reviewed the testing dataset independently and with computer assistance.The diagnostic performance was evaluated in terms of the area under the receiver operating characteristic curve,accuracy,sensitivity,and specificity.RESULTS The area under the receiver operating characteristics curve,accuracy,sensitivity,and specificity of the CAD system were 0.982[95%confidence interval(CI):0.969-0.994],92.9%(95%CI:89.5%-95.2%),91.9%(95%CI:87.4%-94.9%),and 94.7%(95%CI:89.0%-97.6%),respectively.The accuracy of CAD was significantly higher than that of non-expert endoscopists(78.3%,P<0.001 compared with CAD)and comparable to that of expert endoscopists(91.0%,P=0.129 compared with CAD).After referring to the CAD results,the accuracy of the non-expert endoscopists significantly improved(88.2%vs 78.3%,P<0.001).Lesions with Paris classification type 0-IIb were more likely to be inaccurately identified by the CAD system.CONCLUSION The diagnostic performance of the CAD system is promising and may assist in improving detectability,particularly for inexperienced endoscopists.

Global burden and trends of lung cancer incidence and mortality

Background:Lung cancer has been the leading cause of cancer-related deaths worldwide for many years.This study aimed to investigate the global patterns and trends of lung cancer.Methods:Lung cancer incidence and mortality were derived from the GLOBOCAN 2020 database.Continuous data from Cancer Incidence in Five Continents Time Trends were used to analyze the temporal trends from 2000 to 2012 using Joinpoint regression,and average annual percent changes were calculated.The association between the Human Development Index and lung cancer incidence and mortality was assessed by linear regression.Results:An estimated 2.2 million new lung cancer cases and 1.8 million lung cancer-related deaths occurred in 2020.The age-standardized incidence rate(ASIR)ranged from 36.8 per 100,000 in Demark to 5.9 per 100,000 in Mexico.The age-standardized mortality rate(ASMR)varied from 32.8 per 100,000 in Poland to 4.9 per 100,000 in Mexico.Both ASIR and ASMR were approximately twice higher in men than in women.The ASIR of lung cancer showed a downward trend in the United States of America(USA)between 2000 and 2012,and was more prominent in men.The age-specific incidence rates of lung cancer for ages of 50 to 59 years showed an upward trend in China for both men and women.Conclusions:The burden of lung cancer is still unsatisfactory,especially in developing countries like China.Considering the effectiveness of tobacco control and screening in developed countries,such as the USA,there is a need to strengthen health education,accelerate the establishment of tobacco control policies and regulations,and improve early cancer screening awareness to reduce the future burden of lung cancer.

RAMAN SPECTROSCOPY FOR IN VIVO TISSUE ANALYSIS AND DIAGNOSIS,FROM INSTRUMENT DEVELOPMENT TO CLINICAL APPLICATIONS

Raman spectroscopy is a noninvasive,nondestructive analytical method capable of determining the biochemical constituents based on molecular vibrations.It does not require sample preparation or pretreatment.However,the use of Raman spectroscopy for in vivo clinical applications will depend on the feasibility of measuring Raman spectra in a relatively short time period(a few seconds).In this work,a fast dispersive-type nearinfrared(NIR)Raman spectroscopy system and a skin Raman probe were developed to facilitate real-time,noninvasive,in vivo human skin measurements.Spectrograph image aberration was corrected by a parabolic-line fiber array,permitting complete CCD vertical binning,thereby yielding a 16-fold improvement in signal-to-noise ratio.Good quality in vivo skin NIR Raman spectra free of interference from fiber fluorescence and silica Raman scattering can be acquired within one second,which greatly facilitates practical noninvasive tissue characterization and clinical diagnosis.Currently,we are conducting a large clinical study of various skin diseases in order to develop Raman spectroscopy into a useful tool for non-invasive skin cancer detection.Intermediate data analysis results are presented.Recently,we have also successfully developed a technically more challenging endoscopic Laser-Raman probe for early lung cancer detection.Preliminary in vivo results from endoscopic lung Raman measurements are discussed.

Hepatocellular carcinoma surveillance and quantile regression for determinants of underutilisation in at-risk Australian patients

BACKGROUND While clinical guidelines recommend hepatocellular carcinoma(HCC)surveillance for at-risk individuals,reported surveillance rates in the United States and Europe remain disappointingly low.AIM To quantify HCC surveillance in an Australian cohort,and assess for factors associated with surveillance underutilisation.METHODS All patients undergoing HCC surveillance liver ultrasounds between January 1,2018 to June 30,2018 at a tertiary hospital in Melbourne,Australia,were followed until July 31,2020,or when surveillance was no longer required.The primary outcome was the percentage of time up-to-date with HCC surveillance(PTUDS).Quantile regression was performed to determine the impact of factors associated with HCC surveillance underutilisation.RESULTS Among 775 at-risk patients followed up for a median of 27.5 months,the median PTUDS was 84.2%(IQR:66.3%-96.3%).85.0%of patients were followed up by specialist gastroenterologists.Amongst those receiving specialist care,quantile regression demonstrated differential associations at various quantile levels of PTUDS for several factors.Older age at the 25th quantile(estimate 0.002 per percent,P=0.03),and cirrhotic status at the 75th quantile(estimate 0.021,P=0.017),were significantly associated with greater percentage of time up-to-date.African ethnicity(estimate-0.089,P=0.048)and a culturally and linguistically diverse(CALD)background(estimate-0.063,P=0.01)were significantly associated with lower PTUDS at the 50th quantile,and again for CALD at the 75th quantile(estimate-0.026,P=0.045).CONCLUSION While median PTUDS in this Australian cohort study was 84.2%,awareness of the impact of specific factors across PTUDS quantiles can aid targeted interventions towards improved HCC surveillance.

Two-photon microscopy in pre-clinical and clinical cancer research

The applications of two-photon microscopy （TPM） on pre-clinical and clinical study of human cancer and diseases are reviewed in this paper. First, the principle of two-photon excitation （TPE） is introduced. The resulting advantages of TPM for imaging studies of animal models and human samples are then elaborated. Subsequently, the applications of TPM on various aspects of tumor studies, including tumor angiogenesis, invasion and metastasis, tumor microenvironment and metabolism are introduced. Furthermore, studies of TPM on clinical human skin biopsy and the development of two-photon microendoscopy are reviewed. Finally, potential future directions are discussed.

PSA density in the diagnosis of prostate cancer in the Chinese population: results from the Chinese Prostate Cancer Consortium

We performed this study to investigate the diagnostic performance of prostate-specific antigen density(PSAD)in a multicenter cohort of the Chinese Prostate Cancer Consortium.Outpatients with prostate-specific antigen(PSA)levels≥4.0 ng ml^(-1) regardless of digital rectal examination(DRE)results or PSA levels<4.0 ng ml^(-1)and abnormal DRE results were included from 18 large referral hospitals in China.The diagnostic performance of PSAD and the sensitivity and specificity for the diagnosis of prostate cancer(PCa)and high-grade prostate cancer(HGPCa)at different cutoff values were evaluated.A total of 5220 patients were included in the study,and 2014(38.6%)of them were diagnosed with PCa.In patients with PSA levels ranging from 4.0 to 10.0 ng ml^(-1),PSAD was associated with PCa and HGPCa in both univariate(odds ratio[OR]=45.15,P<0.0001 and OR=25.38,P<0.0001,respectively)and multivariate analyses(OR=52.55,P<0.0001 and OR=26.05,P<0.0001,respectively).The areas under the receiver operating characteristic curves(AUCs)of PSAD in predicting PCa and HGPCa were 0.627 and 0.630,respectively.With the PSAD cutoff of 0.10 ng ml^(-2),we obtained a sensitivity of 88.7%for PCa,and nearly all(89.9%)HGPCa cases could be detected and biopsies could be avoided in 20.2%of the patients(359/1776 cases).Among these patients who avoided biopsies,only 30 cases had HGPCa.We recommend 0.10 ng ml^(-2) as the proper cutoff value of PSAD,which will obtain a sensitivity of nearly 90%for both PCa and HGPCa.The results of this study should be validated in prospective,population-based multicenter studies.