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Contemporary impact of transrectal ultrasound lesions for prostate cancer detection.

PURPOSE: Transrectal ultrasound (TRUS) guided systematic biopsy of the prostate is the gold standard diagnostic modality for prostate cancer. Consequently, the value of discrete hypoechoic lesions on TRUS lesions considered suspicious for cancer deserves meticulous reevaluation, specifically in the prostate specific antigen era when the majority of tumors diagnosed are nonpalpable. We studied whether the predictability of a biopsy core changes if the tissue comes from an isoechoic vs hypoechoic lesion. MATERIALS AND METHODS: Prospective data were collected on 3,912 consecutive patients referred to our medical center between 1993 and 1999 for biopsy of the prostate. A sextant technique (apex, mid gland and base) with an additional core biopsy from the transitional zone was used. If a hypoechoic lesion was identified, the biopsy was taken from the lesion. Correlation between hypoechoic lesions, isoechoic areas and cancer detection for each core was performed. RESULTS: A total of 31,296 cores were obtained from the cohort. Overall 2,642 (68%) cores had at least 1 hypoechoic lesion ultrasonographically. Cancer was detected in 675 (25.5%) and 323 (25.4%) patients with or without hypoechoic lesions (p = 0.97). The per core cancer detection was fairly uniform and averaged 9.3% and 10.4% for hypoechoic and isoechoic areas, respectively. The difference was not statistically significant (p = 0.3). Gleason scores were less than 7, 7 and greater than 7 in 46%, 34% and 20% of cases, respectively. CONCLUSIONS: Despite the higher prevalence of cancers discovered in prostates with hypoechoic areas, the hypoechoic lesion itself was not associated with increased cancer prevalence compared with biopsy cores from isoechoic areas. For impalpable tumors TRUS findings are not contributory for staging.

Adult↗

Surgical treatment of gastric cancer detected by mass screening.

BACKGROUND/AIMS: It is crucial to improve the postoperative prognosis of patients with gastric cancer in geographic regions where the incidence of gastric cancer is high. This study compared the efficacy of surgical treatment in patients with gastric cancer detected by a mass screening survey with that of patients diagnosed in accordance with standard medical practice. METHODOLOGY: The subjects included 189 patients with gastric cancer detected by a mass screening survey (screening group) who underwent surgical treatment from 1988 to 1995, and 517 patients who underwent a standard medical work-up (non-screening group). RESULTS: The incidence of early gastric cancer, curative resectability rate, and 5-year survival rates between the screening and non-screening groups were 73.0% versus 48.4% (p < 0.01), 90.5% versus 66.7% (p < 0.01), and 86.2% versus 61.0% (p < 0.01), respectively. CONCLUSIONS: Surgical treatment for patients with gastric cancer identified by mass screening is effective in saving lives and reduces the mortality from gastric cancer in the target population of mass screening. However, a further prospective randomized controlled study of this screening method will be necessary in the future.

Adult↗

A protein chip system for parallel analysis of multi-tumor markers and its application in cancer detection.

BACKGROUND: Tumor markers are routinely measured in clinical oncology. However, their value in cancer detection has been controversial largely because no single tumor marker is sensitive and specific enough to meet strict diagnostic criteria. One strategy to overcome the shortcomings of single tumor markers is to measure a combination of tumor markers to increase sensitivity and look for distinct patterns to increase specificity. This study aimed to develop a system for parallel detection of tumor markers as a tool for tumor detection in both cancer patients and asymptomatic populations at high risk. MATERIALS AND METHODS: A protein chip was fabricated with twelve monoclonal antibodies against the following tumor markers respectively: CA125, CA15-3, CA19-9, CA242, CEA, AFP, PSA, free-PSA, HGH, beta-HCG, NSE and ferritin. Tumor markers were captured after the protein chip was incubated with serum samples. A secondary antibody conjugated with HRP was used to detect the captured tumor markers using chemiluminescence technique. Quantification of the tumor markers was obtained after calibration with standard curves. RESULTS: The chip system showed an overall sensitivity of 68.18% after testing 1147 cancer patients, with high sensitivities for liver, pancreas and ovarian tumors and low sensitivities for gastrointestinal tumors, and a specificity of 97.1% after testing 793 healthy individuals. Application of the chip system in physical checkups of 15,867 individuals resulted in 16 cases that were subsequently confirmed as having cancers. Analysis of the detection results with a Support Vector Machine algorithm considerably increased the specificity of the system as reflected in healthy individuals and hepatitis/cirrhosis patients, but only modestly decreased the sensitivity for cancer patients. CONCLUSION: This protein chip system is a potential tool for assisting cancer diagnosis and for screening cancer in high-risk populations.

Antibodies, Monoclonal↗

A narrative analysis: a black woman's perceptions of breast cancer risks and early breast cancer detection.

The oncology nurse's role in breast cancer management is enhanced by knowledge of the patient's perceptions of risks. This case study elucidates the process by which perceived risks of breast cancer are embedded in sequences of biographic experiences including childhood sexual abuse, childhood injuries, and an abusive marriage. The case study shows that risk perceptions and subsequent delayed breast cancer detection is related to (a) a belief that breast cancer results from "bad luck, or fate"; (b) lack of cancer-related symptoms; (c) belief that a higher power determines ill health; (d) reluctance to turn to others for help while in an abusive marriage; (e) family history of cancer invulnerability since generations of family members died of diabetes, heart disease, and pregnancy-related illnesses; and (f) fear of gynecologic exams resulting from childhood sexual abuse. Furthermore, nonapplicability of traditional breast cancer risk factors such as heredity, age older than 30 years at first full-term pregnancy, early menarche, and late menopause prohibit an accurate assessment of self-risk. This case study suggests that breast cancer risk perception often differs from that of biomedical factors, and that an understanding of risk judgments is essential for appropriate therapeutic responses.

Adult↗

The risks of prostate cancer detection by transrectal ultrasound guide biopsy in Thai men with abnormal prostatic-specific antigen or abnormal digital rectal examination.

OBJECTIVE: To determine the risks of prostate cancer detection in Thai men with abnormal prostatic-specific antigen (PSA) or abnormal digital rectal examination (DRE). MATERIAL AND METHOD: One hundred and forty four Thai men with abnormal PSA or abnormal DRE or both were biopsied at the prostate gland with the use of transrectal ultrasound guide biopsy (TRUSBX). The risks of prostate cancer detection were evaluated. RESULTS: Mean age was 65.7 years old (S.D. = 9.88). The risks of positive biopsy according to the PSA levels of 0-4 ng/ml, 4.1-10 ng/ml, 10.1-20 ng/ml, 20.1-50 ng/ml, 50.1-100 ng/ml and more than 100 ng/ml were 6.25 per cent, 6.67 per cent, 10.8 per cent, 33.3 per cent, 60 per cent and 100 per cent, respectively. The risks of positive biopsy according to DRE appearances of total hard consistency, nodule, induration and benign prostatic hyperplasia were 57.1 per cent, 23.5 per cent, 34.6 per cent and 10 per cent, respectively. Of 144 men, 32 had adenocarcinoma of prostate. Radical prostatectomy was performed on 15 patients with clinically localized disease. Ten patients (66.6%) had free margin on their pathological specimens and 6 (40%) had organ confined disease. CONCLUSION: PSA testing alone or DRE alone is not a perfect test to diagnose prostate cancer since prostate cancer may present in men with normal PSA or men with no suspicious cancer DRE. For early detection of prostate cancer, both PSA testing and DRE need to be performed. When either PSA testing or DRE or both is abnormal, TRUSBX should be carried out.

Adenocarcinoma↗

Prostate cancer detection at low prostate specific antigen.

PURPOSE: At low prostate specific antigen (PSA) the indication for prostate biopsy is usually an abnormal digital rectal examination. We evaluate the diagnostic value of PSA, digital rectal examination, transrectal ultrasonography and tumor characteristics at low PSA (0 to 4.0 ng./ml.). We confirm and add to recent evidence that digital rectal examination has a low predictive value and that many significant cancers at this PSA range may be missed. MATERIALS AND METHODS: From 1994 to 1997 a total of 10,523 participants 54 to 74 years old were randomized to screening in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. Of the participants 9,211 (87.5%) had PSA less than 4.0 ng./ml., and underwent digital rectal examination and transrectal ultrasonography. Expected rates of prostate cancer detection were calculated using logistic regression analysis. Radical prostatectomy was performed in about half of the 478 men diagnosed with prostate cancer. Tumors were characterized by pT category, Gleason score and cancer volume in 166 processed radical prostatectomy specimens. In 50 of these cases PSA was 0 to 4.0 ng./ml. RESULTS: The positive predictive value of digital rectal examination and transrectal ultrasonography at PSA 0 to 4.0 ng./ml. was only 9.7%. Positive predictive value strongly depended on PSA. Sensitivity was calculated by using estimates of the prevalence of sextant biopsy detectable prostate cancers. Of 760 detectable cancers 478 (67%) were diagnosed irrespective of PSA in men screened with digital rectal examination, transrectal ultrasonography and PSA. Only 127 of 348 detectable prostate cancers (36.5%) were actually diagnosed in men with PSA 2 to 4 mg./ml. The importance of these missed cancers was evaluated with parameters of tumor aggressiveness within PSA ranges. CONCLUSIONS: Approximately half of the tumors missed with PSA 0 to 4 ng./ml. had aggressive characteristics (Gleason score 7 or greater, Gleason 4-5 components) and were organ confined. These tumors should be diagnosed and treated according to the present understanding of their natural history. More sensitive and selective screening strategies are needed. Presently a wrong "window of opportunity" is used for early detection of prostate cancer.

Aged↗

Complexed PSA performance for prostate cancer detection in an African-American population.

OBJECTIVES: Complexed prostate-specific antigen (cPSA) has been shown to improve the differentiation of benign and malignant disease compared with total PSA (tPSA) in studies evaluating predominantly white populations of men. We sought to evaluate the diagnostic performance of cPSA relative to tPSA in a population of African-American men. METHODS: Consecutive African-American men scheduled for prostate biopsy were enrolled prospectively at the Louisiana State University Medical Center, New Orleans. Serum was collected before the biopsy procedure and tested with the Immuno 1 tPSA and cPSA methods. Receiver operating characteristic curve analysis was performed and the area under the curve was calculated for tPSA and cPSA. RESULTS: A total of 156 patients were evaluated, 51 (32.7%) of whom were diagnosed with prostate cancer. The median PSA value for men with prostate cancer was 4.96 ng/mL and for those with benign disease was 3.93 ng/mL. The receiver operating characteristic analysis indicated that the area under the curve for cPSA (0.679) was statistically greater than that achieved for tPSA (0.642, P = 0.004). Using cutoff values for cPSA of 2.3 ng/mL and for tPSA of 2.85 ng/mL provided a specificity of 31.4% and 26.7%, respectively, at a sensitivity for prostate cancer detection of 95%. This was not statistically significant (P = 0.18). CONCLUSIONS: cPSA offers modest improvement in prostate cancer detection compared with tPSA in African-American men, but not at the clinically relevant 95% sensitivity level. Additional work is needed to improve prostate cancer detection in this high-risk cohort of patients.

Adenocarcinoma↗

The pathological features and prognosis of prostate cancer detectable with current diagnostic tests.

The discrepancy between the high prevalence of prostate cancer found at autopsy and the low incidence of clinical cancer prompted a study to determine whether the new diagnostic tests, that is ultrasonography and serum prostatic specific antigen (PSA) levels, detect prostate cancer at an earlier stage than the traditional test, digital rectal examination, without detecting a larger proportion of clinically unimportant cancer. Clinically detected cancer treated by radical prostatectomy (306 cases) and incidental cancer found in cystoprostatectomy specimens (90) were categorized into 3 groups by the volume, grade, extent of the cancer and outcome of treatment: clinically unimportant tumor (0.5 cm.3 or less, Gleason grades 1 to 3 and confined to the prostate), clinically important curable cancer (more than 0.5 cm.3 or grade 4 or 5 and confined, or with microscopic extracapsular extension) or advanced disease (extensive extracapsular extension, seminal vesicle invasion or lymph node metastases). Of 306 clinically detected tumors 9% were unimportant and 29% were advanced. In contrast, incidental cystoprostatectomy disease was either unimportant (78%) or curable (22%) and no tumor was advanced (p < 0.0005). Cancer detectable by digital rectal examination, ultrasonography or PSA was distributed similarly among the 3 groups. Impalpable cancer detected by PSA was less likely to be advanced (11%) than cancer detected by digital rectal examination (34%, p = 0.01) but no more likely to be unimportant (13% versus 8%). Of 29 tumors detected only by systematic biopsies because of an elevated PSA level only 4% were advanced, while 17% were unimportant. Cancer detectable with each of the available diagnostic tests was similar and differed distinctly from that found incidentally in cystoprostatectomy specimens. The detection of impalpable cancer by PSA or ultrasound decreased the proportion of advanced tumor detected without increasing significantly the detection of unimportant disease.

Adult↗

Second reading of screening mammograms increases cancer detection and recall rates. Results in the Florence screening programme.

OBJECTIVE: To assess double reading effectiveness in mammography screening. DESIGN: Retrospective study of 177,631 consecutive mammograms double read during 1998-2003. SETTING: The Florence screening programme, involving 11 trained radiologists. Abnormalities reported by at least one reader prompted assessment. RESULTS: The referral rate was 2.89% for the first reader, 3.15% for the second reader, and 3.59% for either reader. Of 713 total cancers detected, 43 were suspected only by the second reader (6.4% relative, 0.024% increase in absolute detection rate) and had a lower stage compared to the first reader (pTis-pT1b = 65.7 versus 52.0%): 41 were reviewed and classified (error type) as "minimal sign" in six, and "screening error" in 35 cases, or as BI-RADS 3 in one, 4a in 20, 4b in 13, and 4c in three cases. The second reading cost was 2.70 per woman examined, or 11,168 per additional cancer detected (versus 11,585 at a single reading). DISCUSSION: Second reading is effective in detecting a limited number of additional cancer cases. Tumour stage (one-third over 1 cm in diameter) and review findings (high rate of "screening errors" and BI-RADS R4b-c categories) suggest that second reading detects small "difficult cases" as well as larger cancers missed due to fatigue or loss of attention. Second reading reduces screening specificity to a minor extent, and since cancer detection at second reading seems cost-effective the procedure is recommendable in routine practice.

Aged↗

Prostate cancer detection with two sets of ten-core compared with two sets of sextant biopsies.

OBJECTIVES: To compare the cancer detection of two consecutive sets of prostate biopsies using either the sextant or the 10-core technique. METHODS: Ninety-one specimens after radical prostatectomy were used and consecutive sets of biopsies were performed ex vivo on each prostate after the operation. The sextant biopsies were taken paramedian and midlobular, three per side. For the 10-core biopsies, two cores per side from the lateral areas of the prostate were added. We developed a realistic simulation of a transrectal sonographic biopsy procedure. RESULTS: In the first set of sextant biopsies, 55 prostate cancers (60.4%) were found; in the second set, 13 additional tumors were detected. Two consecutive sets of sextant biopsies thus found 68 tumors (74.7%). Using one 10-core biopsy led to cancer detection in 71 of the prostates (78%). A second 10-core biopsy revealed 11 additional tumors, for a cumulative cancer detection rate of 90.1%. We found that 9 (9.9%) of all the cancers were not diagnosed by two consecutive sets of this extended biopsy protocol. Eight of these cancers (88.9%) were clinically significant as determined by a tumor volume larger than 0.5 cm(3). CONCLUSIONS: Although the 10-core protocol is far superior to the commonly used sextant protocol, a significant number of prostate cancers can still be found on a second similar set of prostate biopsies. Even after two consecutive sets of 10-core biopsies, approximately 10% of the prostate tumors remained undetected. Most of them were clinically significant.

Biopsy, Needle↗

[Quality of the Early Cervical Cancer Detection Program in the State of Nuevo León].

OBJECTIVE: To determine the quality of the Early Cervical Cancer Detection Program in the state of Nuevo León. MATERIAL AND METHODS: A random selection of 4791 cytologic reports were analyzed, emitted by the State Ministry of Health, the University Hospital and the Mexican Institute for Social Security early cervical cancer detection modules. Pap tests of women with hysterectomy, current pregnancy, menopause or positive result were excluded. Quality was measured with previously defined standards. Analysis included, besides univariate statistics, tests of significance for proportions and means. RESULTS: The quality of the program was fairly satisfactory at the level of the State. The quality of the sampling procedure was low; 39.9% of the tests contained endocervical cells. Quality of coverage was low; 15.6% were women 25+years with first time Pap test. Quality of opportunity was high; 8.5 +/- 7 weekdays between the date of the pap smear and the interpretation date. CONCLUSIONS: Strategies are needed to increase the impact of the state program, such as improving the sampling procedure and the coverage quality levels.

Adult↗

Breast cancer detection with sonography and mammography: comparison using state-of-the-art equipment.

This prospective study, involving 1,000 women referred for routine mammography, compares the breast cancer detecting abilities of state-of-the-art mammography and sonography using an automated water-path scanner. Mammography was found to be the superior technique, detecting 62 (97%) of the 64 pathologically proven cancers, while sonography detected only 37 (58%). When considering those cancers most amenable to cure, mammography detected over 90% in all categories, but sonography detected only 48% of the cancers that had not yet spread to axillary lymph nodes, only 30% of the nonpalpable malignancies, and only 8% of the cancers smaller than 1 cm. These data indicate that sonography is not an acceptable substitute for mammography in the detection and diagnosis of breast cancer. The data further suggest that radiologists who wish to improve the cancer-detecting ability of their current breast imaging operation should upgrade their mammography to state-of-the-art status before adding an automated whole-breast ultrasound scanner.

Breast Neoplasms↗

[Counseling protocol for early cancer detection at the Women's Health Center in Ruma].

INTRODUCTION: Women's health care office in Ruma Health Center provides health care for women of Ruma and Irig communities. According to census in 1991, Ruma community has 55.063 inhabitants; 28.266 women out of which 13.149 are of reproductive age. Irig community, has 11.696 inhabitants, 6.072 women and 2.526 are of reproductive age. PROTOCOL: According to protocol each woman who consults her gynecologist, is thoroughly examined. The overall examination included the following: anamnesis in regard to risk factors for malignant diseases of female genital organs and breast, speculum examination, cytologic smear, colposcopy, palpatory examination of breast gynecological palpatory examination. On the basis of gathered results, further examinations, if necessary, were carried out: cervical biopsy, endocervical curettage, ultrasound examination, mammography and so on. Two groups of patients were formed on the basis of gathered results--high-risk group and "no-risk" group of patients with no risk from malignant disease. The high-risk group of patients has a separate file and is actively controlled; if necessary this group is called for check-ups at intervals from six months to a year periods. The group of "no-risk" patients is controlled once in a three-year period. FORMING THE HIGH-RISK GROUP: High-risk group in regard to a malignant disease of the cervix is formed on the basis of the following findings: 1. Positive family history (mother, aunt, sister, etc.). 2. Positive personal history (positive sexual factor, early sexual relations, early marriage, more sexual partners, more marriages, bad sexual hygiene, human papilloma virus infection (HPV), herpes simplex virus infection, bad living and social conditions, smoking, intra-uterine and oral contraception, immune suppression, and human immune deficiency virus infection (HIV). 3. Positive clinical findings: chronic cervicitis, condylomas. 4. Positive laboratory findings: positive cytological smear, all atypical colposcopic findings, all histopathological findings of precancerous, high oncogenes groups of HPV. 5. Detected cases of malignant disease of the cervix uleri. Cervical biopsy is performed in each woman with positive cytologic and colposcopic findings. Histopathological findings are done according to Bethesda system. HPV classification according to type is done with LSIL changes, and if a high oncogenes HPV type is obtained, women require conisation of the cervix uteri. With HSIL changes, women require cervix conisation. Invasive forms of cervix uteri malignant disease, require treatment in Oncology Institute. High-risk group for endometrial and breast carcinomas is formed on the basis of positive family and personal history, positive clinical and laboratory findings. High-risk women have separate files (marked with "R") and if necessary they are asked for additional check-up. RESULTS: In the framework of the Office for early cancer detection the Cancer Registry (2,3) contains the following: personal data, address, date of disease detection, diagnosis and the disease stage, way of treatment, outcome and a questionnaire on risk factors. Morbidity of precancerous and malignant diseases of female genitalia and breast as well as mortality will be monitored in the forthcoming period. CONCLUSION: We consider the Protocol of work of the Office for early detection of cancer to be an acceptable and compulsory model for protection of women by existing public health services. 1. Each woman who comes to see her gynecologist for examination, should be systematically examined; the risk of malignant disease and necessary further examinations also must be determined. 2. An accurate file on high-risk group must be kept and women should be actively called to come for check-ups, unless they do it in an appointed period--one year at the latest. 3. Women should be kept informed, through local media, about the importance of overall examinations and risk factors for malignant diseases in women. 4.

Breast Neoplasms↗

Extended peripheral zone biopsy schemes increase cancer detection rates and minimize variance in prostate specific antigen and age related cancer rates: results of a community multi-practice study.

PURPOSE: We assessed the impact of age and prostate specific antigen (PSA) on extended systematic biopsy schemes for detecting prostate carcinoma and better characterized these tumors as a function of patient age and PSA. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,299 consecutive patients who underwent initial systematic biopsy performed by 167 community based urologists. A total of 12 systematic biopsies of the peripheral zone were obtained in all patients. Various biopsy schemes were then created and cancer detection rates were calculated. Data analyses were stratified by patient age and PSA. RESULTS: On biopsy 1,020 patients (44.4%) had cancer. Detection rates increased with increasing patient age. Increasing age and PSA were associated with larger, higher grade tumors. Overall and unique site specific cancer detection rates were highest for laterally directed biopsies and the apical biopsy of the standard sextant scheme. The 12 site biopsy scheme outperformed all other schemes in patients with PSA 7 ng./ml. or less and in those 60 years or younger. The variation in age related and PSA related detection rates was greatest for the standard sextant scheme and this variability decreased for extended biopsy schemes. CONCLUSIONS: This multi-practice community based study confirms the inadequacy of sextant biopsies and emphasizes the need for extended peripheral zone sampling of the lateral aspect of the prostate. Generally increasing patient age and PSA were associated with larger, higher grade tumors. Extended biopsy schemes minimize PSA and age related detection rates.

Age Factors↗

[Two cases of breast cancer detected by 99mTc-tetrofosmin myocardial scintigraphy].

Breast cancer ranks the second position among the cancer of women in Japan. We report two cases of breast cancer detected by 99mTc-tetrofosmin. First case was 51 years old female with breast cancer (invasive papillotubular carcinoma) and dextrocardia. She received 99mTc-tetrofosmin myocardial scintigraphy to evaluate dextrocardia and suspicious coronary artery disease. A planar image of 99mTc-tetrofosmin myocardial scintigraphy showed myocardium at the right side, gall bladder at the left lower side and abnormal uptake on the left chest wall. Transaxial images of 99mTc-tetrofosmin myocardial SPECT showed myocardium at the right side and abnormal uptake on the left chest wall. Second case was 78 years old female with breast cancer (intracystic papillary carcinoma) and arrhythmia. 99mTc-tetrofosmin myocardial scintigraphy was performed to evaluate arrhythmia and suspicious coronary artery disease. A planar image of 99mTc-tetrofosmin myocardial scintigraphy shows hot nodule at the lateral side of the myocardium. Transaxial images of 99mTc-tetrofosmin myocardial SPECT showed abnormal uptake at the left lateral side on the chest wall. Both cases appeared illed foci as abnormal uptake with 99mTc-tetrofosmin scintigraphy, although histological diagnosis was different. We conclude that 99mTc-tetrofosmin scintigraphy is helpful for evaluating breast cancer.

Aged↗

Comparative pathology of prevalent and incident cancers detected by breast screening. Edinburgh Breast Screening Project.

In the Edinburgh Breast Screening Project 210 cancers were detected from commencement in 1979 up to December, 1984. By this time the full initial cohort had completed at least 3 visits and a proportion had attended for up to 5 visits, so pathological characteristics for prevalent and incident cancers could be compared. The main differences are in distribution of histological type of cancer, detection of occult invasive disease, and lymph-node positivity among incident tumours. Only the first of these was statistically significant. This evaluation shows that cancer detection by screening in Edinburgh conforms with screening theory, in which detection of good prognosis tumours is favoured at the prevalence screens, and faster growing, aggressive tumours are found at the incidence screens. Qualitative histopathology may provide a better measure than standard quantitative judgments of size and lymph node status to compare the varieties of cancer detected by screening programmes and to understand the biology of the disease.

Aged↗

Molecular biomarkers for cancer detection in blood and bodily fluids.

Cancer is a major and increasing public health problem worldwide. Traditionally, the diagnosis and staging of cancer, as well as the evaluation of response to therapy have been primarily based on morphology, with relatively few cancer biomarkers currently in use. Conventional biomarker studies have been focused on single genes or discrete pathways, but this approach has had limited success because of the complex and heterogeneous nature of many cancers. The completion of the human genome project and the development of new technologies have greatly facilitated the identification of biomarkers for assessment of cancer risk, early detection of primary cancers, monitoring cancer treatment, and detection of recurrence. This article reviews the various approaches used for development of such markers and describes markers of potential clinical interest in major types of cancer. Finally, we discuss the reasons why so few cancer biomarkers are currently available for clinical use.

Antibodies, Neoplasm↗

Biomarker risk assessment and bladder cancer detection in a cohort exposed to benzidine.

BACKGROUND: Cancer screening with highly sensitive, specific biomarkers that reflect molecular phenotypic alterations is an attractive strategy for cancer control. We examined whether biomarker profiles could be used for risk assessment and cancer detection in a cohort of Chinese workers occupationally exposed to benzidine and at risk for bladder cancer. METHODS: The cohort consisted of 1788 exposed and 373 nonexposed workers, followed from 1991 through 1997. We assayed urothelial cells from voided urine samples for DNA ploidy (expressed as the 5C-exceeding rate [DNA 5CER]), the bladder tumor-associated antigen p300, and a cytoskeletal protein (G-actin). Workers were stratified into different risk groups (high, moderate, and low risk) at each examination based on a predefined biomarker profile. For workers who developed bladder cancer, tumor risk assessment was analyzed from samples collected 6-12 months before the cancer diagnosis. The associations between risk group and subsequent development of bladder cancer were analyzed by Cox proportional hazards regression analysis and logistic analysis, after adjustment. All statistical tests were two-sided. RESULTS: Twenty-eight bladder cancers were diagnosed in exposed workers and two in nonexposed workers. For risk assessment, DNA 5CER had 87.5% sensitivity, 86.5% specificity, an odds ratio (OR) of 46.2 (95% confidence interval [CI] = 8.1 to 867.0), and a risk ratio (RR) of 16.2 (95% CI = 7.1 to 37.0); p300 had 50.0% sensitivity, 97.9% specificity, an OR of 40.0 (95% CI = 9.0 to 177.8), and an RR of 37.9 (95% CI = 16.8 to 85.3). The risk of developing bladder cancer was 19.6 (95% CI = 8.0 to 47.9) times higher in workers positive for either the DNA 5CER or p300 biomarkers than in workers negative for both biomarkers and 81.4 (95% CI = 33.3 to 199.3) times higher in workers positive for both biomarkers. G-actin was a poor marker of individual risk. CONCLUSIONS: Occupationally exposed workers at risk for bladder cancer can be individually stratified, screened, monitored, and diagnosed based on predefined molecular biomarker profiles.

Actins↗