Stepwise Application of Urine Markers to Detect Tumor Recurrence in Patients Undergoing Surveillance for Non-Muscle-Invasive Bladder Cancer

Table 3

Performance of marker combinations in detecting recurrences in patients undergoing surveillance of non-muscle-invasive bladder cancer (NMIBC). Values are given in %. Two ways of considering marker combinations as positive were applied. In the first analysis, every positive marker led to a positive combination. In the second analysis, all markers had to be positive for considering a combination positive. High-risk tumors were defined as tumors showing at least one of the following features: pT1 or higher, G3, carcinoma in situ (Cis). Pos: positive, Sens: sensitivity, Spec: specificity, PPV: positive predictive value, NPV: negative predictive value, FISH: fluorescence in situ hybridization, and NMP22: nuclear matrix protein 22.

Combination	Criteria for positive combination	pos	Sensitivity total (sensitivity high risk tumors)	Spec	PPV	NPV total (NPV high risk tumors)	Accuracy
2-Test combinations
Cytology & FISH	≥1 marker pos	230	80.5 (94.0)	64.2	44.7	90.1 (98.8)	68.5
	2 markers pos	149	63.3 (82.0)	80.8	54.3	85.9 (89.6)	76.2
Cytology & uCyt	≥1 marker pos	252	84.4 (92.0)	59.5	42.8	91.3 (98.2)	66.1
	2 markers pos	115	51.6 (66.0)	86.2	57.4	82.3 (95.3)	77.0
Cytology & NMP22	≥1 marker pos	318	86.7 (98.0)	40.8	34.6	89.5 (97.7)	53.0
	2 markers pos	123	53.1 (68.0)	84.5	55.3	83.3 (95.0)	76.2
FISH & uCyt	≥1 marker pos	269	86.7 (96.0)	56.5	41.5	92.1 (98.2)	63.7
	2 markers pos	125	53.9 (66.0)	84.3	55.2	83.5 (95.2)	76.2
FISH & NMP22	≥1 marker pos	330	88.3 (96.0)	39.2	33.2	90.2 (98.6)	51.9
	2 markers pos	141	56.3 (74.0)	80.6	51.1	83.6 (96.1)	74.1
uCyt & NMP22	≥1 marker pos	335	89.8 (92.0)	38.1	34.3	91.2 (97.2)	51.8
	2 markers pos	124	46.8 (60.0)	82.0	48.4	81.1 (94.4)	72.7
3-Test combinations
Cytology & FISH & uCyt+	≥1 marker pos	282	87.5 (96.0)	52.1	39.7	92.0 (99.0)	61.4
	3 markers pos	101	46.1 (62.0)	88.2	58.4	81.9 (95.0)	77.0
Cytology & FISH & NMP22	≥1 marker pos	338	90.6 (98.0)	37.5	34.3	91.7 (99.3)	51.5
	3 markers pos	104	49.2 (66.0)	88.5	60.0	82.8 (95.5)	78.1
Cytology & uCyt & NMP22	≥1 marker pos	352	93.8 (100.0)	34.7	34.1	93.8 (100.0)	50.3
	3 markers pos	79	39.1 (56.0)	91.2	63.3	80.7 (94.5)	77.8
FISH & uCyt & NMP22	≥1 marker pos	356	94.5 (100.0)	33.8	36.0	94.5 (100.0)	49.9
	3 markers pos	84	40.6 (58.0)	91.0	61.9	80.9 (94.7)	77.6
4-Test combination
Cytology & FISH & uCyt+ & NMP22	≥1 marker pos	359	94.5 (100.0)	33.1	33.7	94.4 (100.0)	49.3
	4 markers pos	68	35.9 (54.0)	93.3	65.7	80.1 (94.4)	78.1