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690 URINARY MARKERS FOR THE DETECTION OF UPPER URINARY TRACT UROTHELIAL CARCINOMA û THE VALUE OF INVASIVE URINE-SAMPLING
Vol. 189, No. 4S, Supplement, Sunday, May 5, 2013
THE JOURNAL OF UROLOGY姞
the site of original resection. Bladder recurrence data was available in 165 patients of whom 26 (15%) developed de novo bladder cancer following upper-tract surgery. A variety of salvage upper-tract therapies were utilized, although the majority of cases progressed to nephroureterectomy. 5-year cancer specific survival was dependent on primary tumor pathology and ranged between 50% and 100%. CONCLUSIONS: Pooled analysis of the literature highlights that approximately 15% of patients will suffer ipsilateral upper-tract or bladder recurrences after segmental resection of ureteral or renal pelvic tumors. These rates of recurrence should be discussed prior to surgery and underscore the need for vigilant post-operative surveillance. Published series of ipsilateral upper-tract and bladder recurrences following segmental resection of ureteral or renal pelvic tumors Ipsilateral upper-tract De novo recurrence bladder cancer Study (year) No. pts. Bin (2012) 17 35% (6/17) 23% (4/17) Giannarini (2007)
19
11% (2/19)
Lehman (2006)
51
10% (5/51)
Leitenberger (1996)
13
31% (4/13)
Zincke (1984)
27
15% (4/27)
26% (5/19) N/A 15% (2/13) N/A
Mazeman (1976)
116
12% (14/116)
13% (15/116)
Total
243
14% (35/243)
16% (26/165)
Source of Funding: None
689 FISH ANALYSIS OF WASHING URINE FROM THE UPPER URINARY TRACT IN THE DETECTION OF CORRESPONDING UROTHELIAL CANCERS Torsten Gruschwitz*, Marcus Horstmann, Mieczyslaw Gajda, Marc-Oliver Grimm, Jena, Germany; Kerstin Junker, Homburg/Saar, Germany INTRODUCTION AND OBJECTIVES: Fluorescence In Situ Hybridization (FISH) is approved for diagnosis and follow-up of patients with bladder cancer. Earlier studies have shown similarities between genetic alterations of urothelial cancer cells of the bladder and the upper urinary tract (UUT) The diagnostic value of FISH, however, in the detection of upper urinary tract transitional cell carcinoma (UUT TCC) remains under evaluation. METHODS: In 79 consecutive patients potentially harbouring UUT TCC, sampling of ureteral washing urine for FISH and cytology, retrograde ureteropyelography, ureterorenoscopy (URS) with or without endoscopic biopsy were performed. In case of endoscopically and/or histologically proven malignancy patients either underwent nephroureterectomy, partial ureterectomy or local treatment. Sensitivity and specificity were determined for FISH and cytology according to endoscopic findings and histological results. RESULTS: UUT TCC was found in 17 patients. 10 patients underwent nephroureterectomy, 4 partial ureterectomy and 2 endoscopic tumour ablation. One patient is still waiting for definitive surgery. Until now histological evaluation of these patients revealed 8x pTaG1-2, 3x pT1G1-3, 4x pT3G1-3 and 1x pT4G3 tumours. FISH detected 15 out of 17 tumours and was negative in 54 patients. Cytology was positive in 9 tumour patients and negative in 50 patients. This resulted in a sensitivity and specificity for FISH of 88.2% and 87.1%, and for cytology of 53% and 74 %, respectively. CONCLUSIONS: In the present study, FISH revealed to be a more sensitive and more specific marker in ureteral washing urine than cytology, which is the current reference standard in the detection of
e283
UUT TCC. Because of its high accuracy FISH positive ureteral washing urine should be considered a reason to further investigate the corresponding UUT. Source of Funding: None
690 URINARY MARKERS FOR THE DETECTION OF UPPER URINARY TRACT UROTHELIAL CARCINOMA uˆ THE VALUE OF INVASIVE URINE-SAMPLING Tilman Todenhöfer*, Jörg Hennenlotter, Michael Esser, Stefan Aufderklamm, Sarah Mohrhardt, Georgios Gakis, Ursula Ku¨hs, Arnulf Stenzl, Christian Schwentner, Tu¨bingen, Germany INTRODUCTION AND OBJECTIVES: Previous studies have shown a good performance of urine fluorescence in situ hybridization (FISH) for the detection of upper urinary tract (UUT) urothelial carcinoma (UUT-UC). Although not considered a standard procedure, several centers perform selective sampling of UUT urine with subsequent cytology and FISH. The additional value of this sampling method is widely unknown. The present study compares the performance of FISH and cytology in voided vs. UUT-derived urine samples in patients with suspect of UUT-UC. METHODS: 561 patients with suspect of UUT-UC receiving a complete workup (including imaging and ureterenoscopy (URS)) were included. 305 were analyzed by voided urine and 256 by UUT-derived samples. Cytology and FISH were performed as urine markers. Sensitivities, specificities, negative (NPVs) and positive predictive values (PPVs) were calculated by contingency analysis. RESULTS: 76 (13.5%) patients had UUT-UC (27 in the VU group and 49 in the UUT-derived urine group). For VU-samples, sensitivities, specificities, NPVs and PPVs of cytology were 59.3%, 84.0%, 95.3%, 27.6% versus 79.2%, 63.1%, 92.8% and 33.6% in UUT-derived samples. For FISH perfomed in VU samples, sensitivities, specificities, NPVs and PPVs were 52.9%, 87.6%, 95.8%, 25.7% versus 78.6%, 47.1%, 94.1% and 16.9% in UUT-derived samples. CONCLUSIONS: FISH and cytology showed a higher sensitivitiy in UUT-derived samples compared to VU. However, performing UUT-sampling is associated with a considerable decrease in specificity of these tests. The invasive method of UUT-sampling might therefore lead to an increased number of unnecessary diagnostic procedures. Due to a relatively high number of FISH and CYT negative tumors in the upper urinary tract, urine markers alone cannot replace endoscopic workup. Source of Funding: None
691 LIMITED SIGNIFICANCE OF ROUTINE EXCRETORY UROGRAPHY AS A SURVEILLANCE OF THE UPPER URINARY TRACT IN FOLLOW-UP OF PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER AFTER TRANSURETHRAL RESECTION Hideaki Miyake*, Ken-ichi Harada, Masato Fujisawa, Kobe, Japan INTRODUCTION AND OBJECTIVES: The primary objective of upper tract surveillance after transurethral resection (TUR) of nonmuscle invasive bladder cancer is to identify upper urinary tract cancers (UUTCs) at an early stage in asymptomatic patients, so that curative treatment can be offered. However, because of the lack of definitive guideline, there are several controversies associated with the surveillance of UUTC, including patient selection, type of imaging study and its frequency. The objective of this study was to evaluate the utility of routine excretory urography (IVP) for detecting subsequent UUTC during follow-up of patients with non-muscle invasive bladder cancer. METHODS: This study included 613 patients who underwent TUR of non-muscle invasive bladder cancer between January 1990 and December 2010, and followed for at least 1 year. After TUR,
THE JOURNAL OF UROLOGY姞
the site of original resection. Bladder recurrence data was available in 165 patients of whom 26 (15%) developed de novo bladder cancer following upper-tract surgery. A variety of salvage upper-tract therapies were utilized, although the majority of cases progressed to nephroureterectomy. 5-year cancer specific survival was dependent on primary tumor pathology and ranged between 50% and 100%. CONCLUSIONS: Pooled analysis of the literature highlights that approximately 15% of patients will suffer ipsilateral upper-tract or bladder recurrences after segmental resection of ureteral or renal pelvic tumors. These rates of recurrence should be discussed prior to surgery and underscore the need for vigilant post-operative surveillance. Published series of ipsilateral upper-tract and bladder recurrences following segmental resection of ureteral or renal pelvic tumors Ipsilateral upper-tract De novo recurrence bladder cancer Study (year) No. pts. Bin (2012) 17 35% (6/17) 23% (4/17) Giannarini (2007)
19
11% (2/19)
Lehman (2006)
51
10% (5/51)
Leitenberger (1996)
13
31% (4/13)
Zincke (1984)
27
15% (4/27)
26% (5/19) N/A 15% (2/13) N/A
Mazeman (1976)
116
12% (14/116)
13% (15/116)
Total
243
14% (35/243)
16% (26/165)
Source of Funding: None
689 FISH ANALYSIS OF WASHING URINE FROM THE UPPER URINARY TRACT IN THE DETECTION OF CORRESPONDING UROTHELIAL CANCERS Torsten Gruschwitz*, Marcus Horstmann, Mieczyslaw Gajda, Marc-Oliver Grimm, Jena, Germany; Kerstin Junker, Homburg/Saar, Germany INTRODUCTION AND OBJECTIVES: Fluorescence In Situ Hybridization (FISH) is approved for diagnosis and follow-up of patients with bladder cancer. Earlier studies have shown similarities between genetic alterations of urothelial cancer cells of the bladder and the upper urinary tract (UUT) The diagnostic value of FISH, however, in the detection of upper urinary tract transitional cell carcinoma (UUT TCC) remains under evaluation. METHODS: In 79 consecutive patients potentially harbouring UUT TCC, sampling of ureteral washing urine for FISH and cytology, retrograde ureteropyelography, ureterorenoscopy (URS) with or without endoscopic biopsy were performed. In case of endoscopically and/or histologically proven malignancy patients either underwent nephroureterectomy, partial ureterectomy or local treatment. Sensitivity and specificity were determined for FISH and cytology according to endoscopic findings and histological results. RESULTS: UUT TCC was found in 17 patients. 10 patients underwent nephroureterectomy, 4 partial ureterectomy and 2 endoscopic tumour ablation. One patient is still waiting for definitive surgery. Until now histological evaluation of these patients revealed 8x pTaG1-2, 3x pT1G1-3, 4x pT3G1-3 and 1x pT4G3 tumours. FISH detected 15 out of 17 tumours and was negative in 54 patients. Cytology was positive in 9 tumour patients and negative in 50 patients. This resulted in a sensitivity and specificity for FISH of 88.2% and 87.1%, and for cytology of 53% and 74 %, respectively. CONCLUSIONS: In the present study, FISH revealed to be a more sensitive and more specific marker in ureteral washing urine than cytology, which is the current reference standard in the detection of
e283
UUT TCC. Because of its high accuracy FISH positive ureteral washing urine should be considered a reason to further investigate the corresponding UUT. Source of Funding: None
690 URINARY MARKERS FOR THE DETECTION OF UPPER URINARY TRACT UROTHELIAL CARCINOMA uˆ THE VALUE OF INVASIVE URINE-SAMPLING Tilman Todenhöfer*, Jörg Hennenlotter, Michael Esser, Stefan Aufderklamm, Sarah Mohrhardt, Georgios Gakis, Ursula Ku¨hs, Arnulf Stenzl, Christian Schwentner, Tu¨bingen, Germany INTRODUCTION AND OBJECTIVES: Previous studies have shown a good performance of urine fluorescence in situ hybridization (FISH) for the detection of upper urinary tract (UUT) urothelial carcinoma (UUT-UC). Although not considered a standard procedure, several centers perform selective sampling of UUT urine with subsequent cytology and FISH. The additional value of this sampling method is widely unknown. The present study compares the performance of FISH and cytology in voided vs. UUT-derived urine samples in patients with suspect of UUT-UC. METHODS: 561 patients with suspect of UUT-UC receiving a complete workup (including imaging and ureterenoscopy (URS)) were included. 305 were analyzed by voided urine and 256 by UUT-derived samples. Cytology and FISH were performed as urine markers. Sensitivities, specificities, negative (NPVs) and positive predictive values (PPVs) were calculated by contingency analysis. RESULTS: 76 (13.5%) patients had UUT-UC (27 in the VU group and 49 in the UUT-derived urine group). For VU-samples, sensitivities, specificities, NPVs and PPVs of cytology were 59.3%, 84.0%, 95.3%, 27.6% versus 79.2%, 63.1%, 92.8% and 33.6% in UUT-derived samples. For FISH perfomed in VU samples, sensitivities, specificities, NPVs and PPVs were 52.9%, 87.6%, 95.8%, 25.7% versus 78.6%, 47.1%, 94.1% and 16.9% in UUT-derived samples. CONCLUSIONS: FISH and cytology showed a higher sensitivitiy in UUT-derived samples compared to VU. However, performing UUT-sampling is associated with a considerable decrease in specificity of these tests. The invasive method of UUT-sampling might therefore lead to an increased number of unnecessary diagnostic procedures. Due to a relatively high number of FISH and CYT negative tumors in the upper urinary tract, urine markers alone cannot replace endoscopic workup. Source of Funding: None
691 LIMITED SIGNIFICANCE OF ROUTINE EXCRETORY UROGRAPHY AS A SURVEILLANCE OF THE UPPER URINARY TRACT IN FOLLOW-UP OF PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER AFTER TRANSURETHRAL RESECTION Hideaki Miyake*, Ken-ichi Harada, Masato Fujisawa, Kobe, Japan INTRODUCTION AND OBJECTIVES: The primary objective of upper tract surveillance after transurethral resection (TUR) of nonmuscle invasive bladder cancer is to identify upper urinary tract cancers (UUTCs) at an early stage in asymptomatic patients, so that curative treatment can be offered. However, because of the lack of definitive guideline, there are several controversies associated with the surveillance of UUTC, including patient selection, type of imaging study and its frequency. The objective of this study was to evaluate the utility of routine excretory urography (IVP) for detecting subsequent UUTC during follow-up of patients with non-muscle invasive bladder cancer. METHODS: This study included 613 patients who underwent TUR of non-muscle invasive bladder cancer between January 1990 and December 2010, and followed for at least 1 year. After TUR,