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EDITORIAL: IS THE ROLE OF CYSTOSCOPY IN THE DETECTION OF BLADDER CANCER REALLY DECLINING?
0022-5347/98/1592-0399$03.00/0 W E JOURNAL OF UROLOGY
Copyright 0 1998 by AMERICAN UROLOOICAL ASSOCIATION, INC.
Vol. 159, 399-400, February 1998 Printed in USA.
EDITORIAL: IS THE ROLE OF CYSTOSCOPY IN THE DETECTION OF BLADDER CANCER REALLY DECLINING? The current treatment of patients with hematuria or pre- 6 patients with invasive disease the sensitivity was 100%.A viously diagnosed bladder cancer is based primarily on the highly statistically significant difference was noted in the cystoscopic evaluation. The cystoscope is to the urologist as a median NMP22 level of those patients who did not have stethoscope is to a cardiologist. A cystoscope is an extension recurrence compared to those who did (5.45 units per ml. of our eyes just as a stethoscope enhances a cardiologist's versus 20.81 units per ml., respectively). hearing. The preceding 2 articles suggest that using Lewis X Stampfer et al studied 288 voided urine specimens in 231 antigen or nuclear matrix protein 22 (NMP22) as tumor patients with a history of transitional cell carcinoma. Cystomarkers on exfoliated urothelial cells in voided urine may scopic and conventional cytology findings were compared to replace cystoscopy for the detection of bladder cancer. Do the "22 values. Using a receiver operating characteristic authors of these manuscripts suggest that we approach these curve, the reference value of 6.4 units per ml. was identified patients blindly or are we, who hang on to our cystoscopes, as the optimum value for the detection of tumor. The sensilacking vision of the future? tivity and specificity of NMP22 were 68 and 80%, respecPode et a1 (page 389) from Hebrew University have built tively. Sensitivities increased with increasing tumor category upon the Memorial Sloan-Kettering Cancer Center (MSKCC) and grade. Defining a positive cytology as malignant, dysexperience using the Lewis X antigen to enhance bladder plastic and suspicious, the sensitivity of cytology was 43%. cancer detection.'" The Lewis X antigen is a cell surface Defining a negative cytology as atypical, reactive or nonmadifferentiation antigen carried on protein or lipid moieties. It lignant, the specificity was 92%. There was a highly signifiis not detectable in normal adult urothelial cells but is cant difference between median NMP22 values in the negapresent in more than 90% of transitional cell cancers regard- tive outcome group (3.0 units per ml.) compared to the less of grade, stage, blood group type or secretor status of the positive outcome group (9.8 units per ml.). The authors catindividual. Shienfeld et a1 examined 129 bladder wash spec- egorized 39 patients as low risk for progression (TaG1-2) and imens from 40 control and 89 bladder cancer patients.3 The 11 patients as high risk for progression (TaG3 or Tl). The sensitivity was 85%for immunocytological detection of Lewis sensitivity of NMP22 in these 2 groups was 59 and 90%, X antigen alone, 61% for conventional cytology alone and 93% respectively. when used in combination. The specificity of specimens negPode and Stampfer et al suggest that the tumor markers ative for Lewis X antigen was 85%and when prostate cancer investigated in their studies may be usea to modify cystopatients were excluded it was 96%. scopic followup among patients with superficial bladder canThe study by Pode et a1 differed from that of the MSKCC cer. They contend that if the urinary tumor marker is negainvestigators in several aspects. First, voided urine and not tive, then the interval between cystoscopies may be extended bladder wash specimens were used. Thus, the number of cells or eliminated. This tempting conclusion may ultimately examined was less than the earlier study. Second, a different prove to be correct. However, the ultimate question remains, monoclonal antibody (murine BG-7 IgM versus murine P-12 are these tumor markers really good enough to decrease IgM) was used. Third, the immunocytological and conven- traditional cystoscopic followup, or does this approach await tional cytological results were compared not only to cysto- future tumor markers with even more favorable sensitivity scopic and biopsy findings but also to ultrasonography. Fi- and specificity rates? nally, sensitivity and specificity were calculated when 2 DNA ploidy on voided urine specimens using image analimmunocytological specimens were analyzed. ysis has reported a sensitivity of 71% and specificity of 95%.6 Pode et a1 studied a total of 349 voided urine specimens Although similar to those reported for Lewis X antigen and from 180 patients. When a cutoff of 5% antigen positive cells NMP22, most urologists would not substitute deoxyribonuwas used the sensitivity was 80% and the specificity was cleic acid ploidy status for cystoscopy as the primary diag86%. It was surprising to discover that the sensitivity of nostic tool in the surveillance of patients with bladder cancer. bladder ultrasound was superior to conventional cytology (67 The authors of the 2 articles are to be congratulated for versus 48%, respectively) and that the specificity was virtu- conducting fine studies that help d e h e the clinical use of ally identical (98 versus 97%, respectively). Although 2 im- Lewis X antigen and NMP22 tumor markers. However, the munocytological specimens increased sensitivity to 95%, practitioner is cautioned not to approach the treatment of specificity decreased to 73%. In contrast to the MSKCC find- patients with hematuria or a history of bladder cancer in a ings, Lewis X antigen positive specimens were more frequent blind manner. Until randomized prospective clinical trials in higher grade tumors. This difference may be due to a comparing initial screening with a tumor marker from a larger sample or to the specimen collection technique (voided voided urine specimen demonstrate significant advantage urine compared to bladder wash specimen). When 1 immu- over traditional followup, cystoscopy remains the primary nocytological specimen was combined with ultrasound the mode of diagnosis of bladder cancer. At this time Lewis X sensitivity was 95% and the specificity was 82%. antigen and NMP22, like deoxyribonucleic acid ploidy status, The study by Stampfer et al (page 394) from Massachu- are supplemental tests. setts General Hospital, Boston University Medical Center Robert A. Badalament and M. D. Anderson Cancer Center examines the clinical use Rochester Urology, P.C. of NMP22 in the management of bladder cancer. Nuclear Rochester Hills,Michigan matrix protein is released from cells after apoptosis and is expressed at 10 to 25-fold higher levels in neoplastic cells than in normal cells.4 In an earlier multi-institutional study REFERENCES soloway et a1collectedvoided urine specimens at least 5 days 1. Cordon-Cardo,C.,Lloyd, K. O.,Finstad, C.L., McGroarty, M.E., postoperatively.6 Using a reference value of 10 units per ml. Reuter, V. E., Bander, N. E., Old, L. J. and Melamed, M. R: the sensitivity was 70% and specificity was 79%. Among the
400
ROLE OF CYSTOSCOPY IN DETECTION OF BLADDER CANCER
Immunoanatomic distribution of blood group antigens in the human urinary tract: influence of secretor status. Lab. Invest., 5 5 444,1986. Sheinfeld, J., Fair, 2. Cordon-Cardo, C., Reuter, V. E., Lloyd, K. 0.. W. R., Old, L. J. and Melamed, M. R.: Blood group related antigens in human urothelium: enhanced expression of precursor, Le X and Le Y determinants in urothelial carcinoma. Cancer Res., 48:4113, 1988. 3. Sheinfeld, J., Reuter, V. E., Melamed, M. R., Fair, W. R., Morse, M., Sogani, P. C., Herr, H. W., Whitmore, W. F., Jr. and Cordon-Cardo, C.: Enhanced bladder cancer detection with the
Lewis X antigen as a marker of neoplastic transformation. J. Urol., 143: 285, 1990. 4. Hoffman, M.: The cell's nucleus shapes up. Science, 2 5 9 1257, 1993. 5. Soloway, M. S., Buggman, J. V., Carpinib, G. A., Chodak, G. W., Church, P. A,, Lamm, D. L., Lange, P., Messing, E., Pasciak, R. M., Reservitz, G. B., Rukstalis, D. B., Sarosdy, M. F., Stadler, W. M., Thiel, R. P. and Hayden, C. L.: Use of a new tumor marker, urinary NMP22, in the detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment. J. Urol., 156: 1280, 1996.
Copyright 0 1998 by AMERICAN UROLOOICAL ASSOCIATION, INC.
Vol. 159, 399-400, February 1998 Printed in USA.
EDITORIAL: IS THE ROLE OF CYSTOSCOPY IN THE DETECTION OF BLADDER CANCER REALLY DECLINING? The current treatment of patients with hematuria or pre- 6 patients with invasive disease the sensitivity was 100%.A viously diagnosed bladder cancer is based primarily on the highly statistically significant difference was noted in the cystoscopic evaluation. The cystoscope is to the urologist as a median NMP22 level of those patients who did not have stethoscope is to a cardiologist. A cystoscope is an extension recurrence compared to those who did (5.45 units per ml. of our eyes just as a stethoscope enhances a cardiologist's versus 20.81 units per ml., respectively). hearing. The preceding 2 articles suggest that using Lewis X Stampfer et al studied 288 voided urine specimens in 231 antigen or nuclear matrix protein 22 (NMP22) as tumor patients with a history of transitional cell carcinoma. Cystomarkers on exfoliated urothelial cells in voided urine may scopic and conventional cytology findings were compared to replace cystoscopy for the detection of bladder cancer. Do the "22 values. Using a receiver operating characteristic authors of these manuscripts suggest that we approach these curve, the reference value of 6.4 units per ml. was identified patients blindly or are we, who hang on to our cystoscopes, as the optimum value for the detection of tumor. The sensilacking vision of the future? tivity and specificity of NMP22 were 68 and 80%, respecPode et a1 (page 389) from Hebrew University have built tively. Sensitivities increased with increasing tumor category upon the Memorial Sloan-Kettering Cancer Center (MSKCC) and grade. Defining a positive cytology as malignant, dysexperience using the Lewis X antigen to enhance bladder plastic and suspicious, the sensitivity of cytology was 43%. cancer detection.'" The Lewis X antigen is a cell surface Defining a negative cytology as atypical, reactive or nonmadifferentiation antigen carried on protein or lipid moieties. It lignant, the specificity was 92%. There was a highly signifiis not detectable in normal adult urothelial cells but is cant difference between median NMP22 values in the negapresent in more than 90% of transitional cell cancers regard- tive outcome group (3.0 units per ml.) compared to the less of grade, stage, blood group type or secretor status of the positive outcome group (9.8 units per ml.). The authors catindividual. Shienfeld et a1 examined 129 bladder wash spec- egorized 39 patients as low risk for progression (TaG1-2) and imens from 40 control and 89 bladder cancer patients.3 The 11 patients as high risk for progression (TaG3 or Tl). The sensitivity was 85%for immunocytological detection of Lewis sensitivity of NMP22 in these 2 groups was 59 and 90%, X antigen alone, 61% for conventional cytology alone and 93% respectively. when used in combination. The specificity of specimens negPode and Stampfer et al suggest that the tumor markers ative for Lewis X antigen was 85%and when prostate cancer investigated in their studies may be usea to modify cystopatients were excluded it was 96%. scopic followup among patients with superficial bladder canThe study by Pode et a1 differed from that of the MSKCC cer. They contend that if the urinary tumor marker is negainvestigators in several aspects. First, voided urine and not tive, then the interval between cystoscopies may be extended bladder wash specimens were used. Thus, the number of cells or eliminated. This tempting conclusion may ultimately examined was less than the earlier study. Second, a different prove to be correct. However, the ultimate question remains, monoclonal antibody (murine BG-7 IgM versus murine P-12 are these tumor markers really good enough to decrease IgM) was used. Third, the immunocytological and conven- traditional cystoscopic followup, or does this approach await tional cytological results were compared not only to cysto- future tumor markers with even more favorable sensitivity scopic and biopsy findings but also to ultrasonography. Fi- and specificity rates? nally, sensitivity and specificity were calculated when 2 DNA ploidy on voided urine specimens using image analimmunocytological specimens were analyzed. ysis has reported a sensitivity of 71% and specificity of 95%.6 Pode et a1 studied a total of 349 voided urine specimens Although similar to those reported for Lewis X antigen and from 180 patients. When a cutoff of 5% antigen positive cells NMP22, most urologists would not substitute deoxyribonuwas used the sensitivity was 80% and the specificity was cleic acid ploidy status for cystoscopy as the primary diag86%. It was surprising to discover that the sensitivity of nostic tool in the surveillance of patients with bladder cancer. bladder ultrasound was superior to conventional cytology (67 The authors of the 2 articles are to be congratulated for versus 48%, respectively) and that the specificity was virtu- conducting fine studies that help d e h e the clinical use of ally identical (98 versus 97%, respectively). Although 2 im- Lewis X antigen and NMP22 tumor markers. However, the munocytological specimens increased sensitivity to 95%, practitioner is cautioned not to approach the treatment of specificity decreased to 73%. In contrast to the MSKCC find- patients with hematuria or a history of bladder cancer in a ings, Lewis X antigen positive specimens were more frequent blind manner. Until randomized prospective clinical trials in higher grade tumors. This difference may be due to a comparing initial screening with a tumor marker from a larger sample or to the specimen collection technique (voided voided urine specimen demonstrate significant advantage urine compared to bladder wash specimen). When 1 immu- over traditional followup, cystoscopy remains the primary nocytological specimen was combined with ultrasound the mode of diagnosis of bladder cancer. At this time Lewis X sensitivity was 95% and the specificity was 82%. antigen and NMP22, like deoxyribonucleic acid ploidy status, The study by Stampfer et al (page 394) from Massachu- are supplemental tests. setts General Hospital, Boston University Medical Center Robert A. Badalament and M. D. Anderson Cancer Center examines the clinical use Rochester Urology, P.C. of NMP22 in the management of bladder cancer. Nuclear Rochester Hills,Michigan matrix protein is released from cells after apoptosis and is expressed at 10 to 25-fold higher levels in neoplastic cells than in normal cells.4 In an earlier multi-institutional study REFERENCES soloway et a1collectedvoided urine specimens at least 5 days 1. Cordon-Cardo,C.,Lloyd, K. O.,Finstad, C.L., McGroarty, M.E., postoperatively.6 Using a reference value of 10 units per ml. Reuter, V. E., Bander, N. E., Old, L. J. and Melamed, M. R: the sensitivity was 70% and specificity was 79%. Among the
400
ROLE OF CYSTOSCOPY IN DETECTION OF BLADDER CANCER
Immunoanatomic distribution of blood group antigens in the human urinary tract: influence of secretor status. Lab. Invest., 5 5 444,1986. Sheinfeld, J., Fair, 2. Cordon-Cardo, C., Reuter, V. E., Lloyd, K. 0.. W. R., Old, L. J. and Melamed, M. R.: Blood group related antigens in human urothelium: enhanced expression of precursor, Le X and Le Y determinants in urothelial carcinoma. Cancer Res., 48:4113, 1988. 3. Sheinfeld, J., Reuter, V. E., Melamed, M. R., Fair, W. R., Morse, M., Sogani, P. C., Herr, H. W., Whitmore, W. F., Jr. and Cordon-Cardo, C.: Enhanced bladder cancer detection with the
Lewis X antigen as a marker of neoplastic transformation. J. Urol., 143: 285, 1990. 4. Hoffman, M.: The cell's nucleus shapes up. Science, 2 5 9 1257, 1993. 5. Soloway, M. S., Buggman, J. V., Carpinib, G. A., Chodak, G. W., Church, P. A,, Lamm, D. L., Lange, P., Messing, E., Pasciak, R. M., Reservitz, G. B., Rukstalis, D. B., Sarosdy, M. F., Stadler, W. M., Thiel, R. P. and Hayden, C. L.: Use of a new tumor marker, urinary NMP22, in the detection of occult or rapidly recurring transitional cell carcinoma of the urinary tract following surgical treatment. J. Urol., 156: 1280, 1996.