Quantitative fluorescence determination of long-fragment DNA in stool as a marker for the early detection of colorectal cancer.

BACKGROUND: A variety of molecular markers have been evaluated for the development of a non-invasive approach to the diagnosis of colorectal cancer. We aimed to validate the diagnostic accuracy, using the same threshold as in the previous pilot study, of fluorescent long DNA test as a relatively simple and inexpensive tool for colorectal cancer detection. METHODS: A case-control study was conducted on 100 healthy subjects and 100 patients at first diagnosis of colorectal cancer. Human long-fragment DNA in stool was quantified by fluorescence primers and a standard curve and expressed in DNA nanograms. RESULTS: We validated the 25-ng value, which emerged as the most accurate cut-off in the pilot study, obtaining 79% (95% CI, 71-87%) sensitivity and 89% (95% CI, 83-95%) specificity. Specificity was very high for all cut-off values (15-40 ng) analyzed, ranging from 78 to 96%. Sensitivity was only slightly lower, reaching 84% at the lowest cut-off and maintaining a good level at the higher values. Diagnostic potential was independent of gender, age and tumor site. CONCLUSION: Fecal DNA analysis is a non-invasive and fairly simple test showing high diagnostic potential. These characteristics, together with the small amount of stool required, make it potentially suitable to be used alongside or as an alternative to current non-invasive screening approaches. Our next step will be to validate these results in a large-scale cohort study of a screening population, which is needed prior to implementation into clinical practice.

Receipt of adjuvant systemic therapy among patients with high-risk breast cancer detected by mammography screening.

BACKGROUND: Few studies have compared screen-detected (SD) breast cancer patients with symptomatic patients for the frequency and determinants of receipt of adjuvant systemic therapy according to accepted guidelines. METHODS: Depending on the date of diagnosis, adjuvant therapy guidelines from the 5th, 6th, and 7th St. Gallen International Conferences were used as standards to audit the treatment of 598 node-negative high-risk patients (59% SD) and 430 node-positive patients (40% SD) aged 50-69 years from an Italian cancer registry (1997-2001). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using backward stepwise logistic regression models. RESULTS: Among node-negative high-risk patients, SD cancers were smaller (P = 0.000) and of lower grade (P = 0.003). Downgrading was generally from grade 3 to grade 2, with an increased proportion of patients placed in the high-risk category due to grade 2 alone. The total rates of adjuvant systemic therapy were similar (58 vs. 60%) whereas SD patients were less often treated according to the guidelines (34 vs. 45%; OR = 0.61; 95% CI, 0.44-0.86). After adjustment for tumour size and other weaker confounders, the OR was 0.99 (95% CI, 0.67-1.46). Among node-positive patients, the OR of receiving the standard adjuvant systemic therapy did not differ between SD and symptomatic cancers. CONCLUSIONS: SD cancers amplified the prognostic heterogeneity of node-negative high-risk patients. Their lower likelihood of being treated according to the guidelines was largely explained by their lower risk profile. No evidence was found to suggest that physicians held a priori assumptions about the relative biological indolence of SD cancers.

Risk of cancer of the prostate and of the kidney parenchyma following bladder cancer.

AIMS AND BACKGROUND: A registry-based cohort study of male patients with bladder cancer was conducted to determine the relative risk of second primary cancer of the prostate and kidney, the uni-/multivariate differences in relative risk according to patient characteristics, the cumulative risk by duration of the follow-up, and the prevalence:incidence ratio of prostate and kidney cancer cases detected in the first 6 months after the diagnosis of bladder cancer. METHODS: The complete case records of all male patients (n = 2025) diagnosed with bladder cancer between 1986 and 2002 were extracted from the database of the Romagna Cancer Registry: 1539 patients were eligible for analysis of the incidence of following prostate and kidney cancers, of the relative risk and the standardized incidence ratio specific for the time interval of follow-up. RESULTS: A total of 108 prostate cancer cases and 23 kidney cancer cases were observed during the follow-up. The relative risk of second primary cancer of the prostate and kidney was respectively 3.52 (95% CI, 2.89-4.25) and 3.90 (95% CI, 2.47-5.85). The absolute excess risk was 11.8 x 1000 for prostate cancer and 2.5 x 1000 for kidney cancer. The number of prevalent cases of prostate and kidney cancer detected was approximately 10 times greater than the expected number based on incidence rates from the general population. During the follow-up, incidence of prostate cancer stabilized at a level that was 3- to 4-fold greater than that expected. Despite fluctuations, a decrease was also observed for incidence of kidney cancer. CONCLUSIONS: In summary, our study showed the relatively constant high incidence of prostate and kidney cancers in bladder cancer patients over time. The possibility of subsequent cancer implies that an appropriate long surveillance is required. The pertinence depends on the duration of the follow-up as well as the degree of surveillance.

Quality of life assessment of randomized controlled trials.

AIMS AND BACKGROUND: According to the USA Food and Drug Administration, quality of life (QOL) and/or survival are a priority for new anticancer drug approval. This study was performed to review approaches to QOL in randomized controlled clinical trials (RCCTs) and to survey the use of such measures in trials. MATERIAL AND METHODS: A literature survey was carried out using the Medline/Medscape, Embase, Cochrane Library, and Ovid databases. Included in the survey were all publications in the set period (from 1966 to June 2005) with "quality of life" in the title or in the abstract in the field of "randomized, controlled clinical trials". Each trial was evaluated according to the level of importance of QOL as a measure of outcome (primary, important and secondary) and was analyzed using the quality scoring system reported by Nicolucci et al. with some items regarding QOL. RESULTS: Four hundred and five RCCT articles in the oncology setting were found. Fifty-six of the 405 (13.8%) publications had QOL as primary end point. The overall quality score of these trials ranged from 40% to 100%, with a median overall score of 80%. The overall score was correlated with the year of publication (P = 0.007), the type of journal (P = 0.05), the presence of a biostatistician among the authors (P = 0.001), and the number of participating institutions (P = 0.009). CONCLUSIONS: More attention to QOL in all components of RCCTs (design, choice of instruments, data management and processing) is required from both clinicians and statisticians.

Relevance of urine telomerase in the diagnosis of bladder cancer.

CONTEXT: The identification of new molecular markers is one of the most challenging goals for the early detection of bladder cancer because available noninvasive methods have neither sufficient sensitivity nor specificity to be acceptable for routine use. OBJECTIVE: To develop a relatively simple, inexpensive, and accurate test that measures telomerase activity in voided urine to apply to large-scale screening programs for bladder cancer detection. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted in 218 men (84 healthy individuals and 134 patients at first diagnosis of histologically confirmed bladder cancer), frequency matched by age and recruited between March 2003 and November 2004 in Italy. Urine telomerase activity was determined using a highly sensitive telomeric repeat amplification protocol (TRAP) assay. Urine samples were processed for cytological diagnosis and TRAP assay. The diagnosis of bladder cancer was based on bioptic and cystoscopic examinations. The performance of the TRAP assay to detect urine telomerase activity was compared with urine cytology as an aid to early cancer detection. Quantification of urine telomerase activity was conducted in a blinded manner. MAIN OUTCOME MEASURE: Sensitivity and specificity of TRAP to detect bladder cancer. RESULTS: Using a 50 arbitrary enzymatic unit cutoff value, we validated the results obtained in the pilot study. In the overall series, sensitivity was 90% (95% confidence interval [CI], 83%-94%) and specificity was 88% (95% CI, 79%-93%). Specificity increased to 94% (95% CI, 85%-98%) for individuals aged 75 years or younger. The same predictive capacity of telomerase activity levels was observed for patients with low-grade tumors or with negative cytology results. CONCLUSIONS: The present validation study demonstrated the ability of urine telomerase activity levels to accurately detect the presence of bladder tumors in men. This test represents a potentially useful noninvasive diagnostic innovation for bladder cancer detection in high-risk groups such as habitual smokers or in symptomatic patients.