[Show abstract][Hide abstract] ABSTRACT: The objective of this prospective study is to establish an appropriate cutoff value of urinary CYFRA 21.1 assay and to assess its utility combined with voided cytology and/or haemoglobin dipstick in the follow-up of patients with superficial bladder cancer.
From December 2000 to November 2003, 446 patients in follow-up for superficial bladder cancer (Ta-T1) after transurethral resection of the bladder (TURB) were included in a prospective study. Voided urine specimens were collected 7-14 d before cystoscopy and/or TURB for CYFRA 21.1 (one sample), haemoglobin dipstick (one sample), and cytology (three samples). All samples were processed for CYFRA 21.1 and haemoglobin dipstick according to manufacturer instructions. A control group (n=185) was obtained from patients in follow-up after transurethral resection of superficial disease (without recurrences within the following 6 mo). There were 125 recurrent transitional tumours detected by cystoscopy (34 TaG1; 53 TaG2/T1G1-2; 23 Ta-1G3/Tis, and 15 T2-4). Receiver operator characteristic (ROC) curves were constructed and cutoff values were chosen. Sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and their 95% confidence intervals were calculated.
ROC curve analysis based on the previously reported cutoff value of 4ng/ml for CYFRA 21.1 demonstrated a sensitivity and specificity of 43% and 68%, respectively. At a cutoff value of 1.5ng/ml, sensitivity was 73.8% with a low specificity (41%). Further lowering of the cutoff point below 1.5ng/ml did not demonstrate a significant increase in sensitivity. Therefore, this value was chosen as the most sensitive CYFRA 21.1 cutoff point during the rest of the study. Specificity increased when all the patients treated with pelvic radiotherapy or with UTI, urethral catheterisation, and intravesical instillations within 3 previous months were not included in our analysis. CYFRA 21.1 plus cytology and the combination of CYFRA 21.1, cytology, and haemoglobin dipstick demonstrated the highest overall sensitivities, and detected 91.3% of Ta-1G3 tumours and 93.3% of T2-4 tumours. However, there were one muscle-invasive tumour, two T1G3/Tis, three T1G2, and nine T1G1 neoplasms with negative combination of cytology and CYFRA 21.1 (1,5ng/ml). All these tumours were smaller than 2cm in size; most were single tumours. Nevertheless, there were 16 tumours larger than 0.5cm (0.5-2cm), and multiple neoplasms were endoscopically detected in 14 patients. Similar results were obtained through the combination of CYFRA 21.1 (cutoff: 1.5ng/ml), cytology, and haemoglobin dipstick.
In our experience the low sensitivity of urinary CYFRA 21.1, even using lower cutoff values and/or a combination with cytology and/or haemoglobin dipstick, makes its application not very useful as a surveillance tool for superficial bladder carcinoma.
No preview · Article · Jun 2007 · European Urology
[Show abstract][Hide abstract] ABSTRACT: The present study aimed to prospectively reassess the cut-off value of the urinary BTAtrak assay in order to optimize the detection of high and middle risk recurrent tumors during the follow-up of superficial bladder cancer. Patients and Methods: We prospectively investigated sensitivity and specificity values of BTAtrak (cut-off: 8 U/ml), cytology, hemoglobin dipstick and their combinations in 956 patients monitored for bladder cancer recurrence. All of the patients (n = 2) with upper urinary tract tumours (UUTT) showed a positive BTAtrak and were not included in the study. We found 215 bladder neoplasms, 149 were papillary and the remaining 66 were solid tumors. There were 115 (53.5%) single tumors and 100 (46.5%) multiple tumors. The mean size of the tumors was 1.78 ± 1.8 cm with 80 (37.2%) minor than 0.5 cm, 103 (47.9%) from 0.5 to 3 cm and 32 (14.9%) tumors greater than 3 cm. Results: BTAtrak (cut-off: 8 U/ml) plus cytology demonstrated the highest overall sensitivity and detected all high-risk tumors (Ta-1G3/Tis and T2-4). Specificity increased considerably when radiotherapy, urinary tract infection (UTI), urethral catherization as well as intravesical instillations within 3 months before BTAtrak determination were not included. The combinations of cytology and BTAtrak resulted negative in 42.6% of cases with a BTAtrak cut-off of 8 U/ml. Conclusion: The combination of cytology and BTAtrak using a lower cut-off level (8 U/ml) demonstrated to be a very sensitive marker to detect most of dangerous tumors in the follow-up of superficial bladder cancer.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study was to evaluate the length of telomeres in patients with bladder cancer using a quantitative flow cytometry (flow-FISH) technique.
Bladder washing samples from 51 patients with bladder cancer were obtained immediately before transurethral resection. The average length of telomere repeats was measured by flow-FISH, as previously reported. Results were expressed in molecular equivalents of soluble fluorochrome (MESF) units.
Bladder washing specimens provided adequate cell numbers for flow-FISH in 49 cases. The TEL means were 1014.71, 2343.36, 5567 and 18267.57 for Ta, T1, T2 and T3/4 tumors, respectively. Regarding grade it was obtained a mean MESF value of 1379.46, 3391.29 and 15925.11 for G1, G2 and G3, respectively. ANOVA demonstrated statistically significant differences in stage (p: 0.014) and tumor grades (p: 0.012). In relation to ploidy, we found a mean MESF value of 2701.37 and 16085.44 MESF units for diploid and aneuploid cells, respectively. Significant difference (p: 0.003) was observed between both groups.
To date, this is the first report wherein telomere length was measured using flow-FISH method in exfoliated cells in urine from patients with bladder cancer. Further investigations are required to demonstrate whether flow-FISH technique might be considered as a tumor marker of bladder cancer.
No preview · Article · Oct 2005 · European Urology