Control computerized tomography in neoadjuvant chemotherapy for muscle invasive urinary bladder cancer has no value for treatment decisions and low correlation with nodal status

Figures & data

Figure 1. Patient flow chart. From four participating cystectomy centres, a total of 244 patients with MIBC planned for neoadjuvant chemotherapy undergoing cystectomy (RC) 2008–2019 were identified. Two patients were excluded due to cN+. 139/242 (57%) underwent control computerized tomography (cCT) before the final NAC cycle and were finally analyzed for the study. 65 patients underwent RC following NAC without cCT and 38 patients underwent CT after the final NAC cycle and just before RC - none of these two subgroups entered analysis.

Table 1. Patient characteristics of the main cohorts.

			Treatment alterations due to control-CT (cCT)
	Total cohort	No cCT	No cCT performed	Yes
Variables	(n = 242)	(n = 103)	(n = 134)	(n = 5)
Age mean (SD)	67.6 (7.3)	67.1 (7.2)	68.4 (7.0)	57.8 (10.8)
BMI mean (SD)	26.0 (3.9)	25.9 (3.6)	26.0 (4.2)	26.7 (2.5)
CACI score mean (SD)	5.1 (1.3)	4.8 (1.2)	5.1 (1.3)	3.6 (1.7)
Sex n (%)
Female	54 (22.3)	30 (29.1)	22 (16.4)	2 (40.0)
Male	188 (77.7)	73 (70.9)	112 (83.6)	3 (60.0)
Histopathology n (%)
Urothelial	217 (89.7)	91 (89.2)	122 (91.0)	4 (80.0)
Uroth. w. squamous diff.	23 (9.5)	11 (10.8)	11 (8.2)	1 (20.0)
Small cell carcinoma	1 (0.4)	0 (0.0)	1 (0.7)	0 (0.0)
cT stage n (%)
cT2	147 (60.7)	71 (68.9)	75 (56.0)	1 (20.0)
cT3	82 (33.9)	27 (26.2)	51 (38.1)	4 (80.0)
cT4a	13 (5.34)	5 (4.9)	8 (6.0)	0 (0.0)
cN stage n (%)
cN0	242 (100.0)	103 (100.0)	134 (100.0)	5 (100.0)
cN+	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
cM stage n (%)
cM0	242 (100.0)	103 (100.0)	134 (100.0)	5 (100.0)
cM+	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
pT stage n (%)
pT0	80 (33.1)	30 (29.1)	48 (35.8)	2 (40.0)
pTis	20 (8.3)	8 (7.8)	12 (9.0)	0 (0.0)
pTa	6 (2.5)	1 (1.0)	5 (3.7)	0 (0.0)
pT1	15 (6.2)	9 (8.7)	6 (4.5)	0 (0.0)
pT2	55 (22.7)	20 (19.4)	35 (26.1)	0 (0.0)
pT3	47 (19.4)	29 (28.2)	17 (12.7)	1 (20.0)
pT4a	12 (5.0)	5 (4.9)	6 (4.5)	1 (20.0)
pT4b	7 (2.9)	1 (1.0)	5 (3.7)	1 (20.0)
pN stage n (%)
pN0	189 (78.0)	76 (73.8)	109 (81.3)	4 (80.0)
pN1	22 (9.1)	10 (9.7)	12 (9.0)	0 (0.0)
pN2	14 (5.8)	8 (7.8)	5 (3.7)	1 (20.0)
pNx	17 (7.0)	9 (8.7)	8 (6.0)	0 (0.0)
pM stage n (%)
pM0	242 (100.0)	103 (100.0)	134 (100.0)	5 (100.0)
pM1	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)

Table 2. Differences in cCT-practices between the study centres.

	Control-CT Performed
	No	Yes
Cystectomy center
Umeå	12 (11.7)	115 (82.7)
Sundsvall-Härnösand	32 (31.1)	5 (3.6)
Västmanland	32 (31.1)	6 (4.3)
Linköping	27 (26.2)	13 (9.4)
Total	103 (42.5)	139 (57.5)

Data are shown as n (%).

Most of the patients that had undergone control CT (cCT) were treated at NUS in Umeå, Sweden. The other three centres had previously had the same routine of performing cCT, but during the last years have abandoned the procedure.

Table 3. Groups based on the result of control CT imaging compared to baseline CT.

	Status of control-CT	n = 139	%
Group 1	Complete response	4	2.9
Group 2	Partial response	70	50.4
Group 3	Stable disease	38	27.3
Group 4	Progressive disease	6	4.3
Group 5	Incompletely filled bladder	15	10.8
Group 6	Unclear/difficult to interpret	6	4.3

The radiological data were categorized into six different groups based on RECIST criteria.

Table 4. Total patients who showed progress on control CT compared with total examined with control CT (%).

	Treatment change due
	to progress on control-CT
cCT result	Yes	No	Total
Progress	4 (67.0)	2 (33.0)	6 (100.0)
No progress	0 (0.0)	133 (100.0)	133 (100.0)
Total examined	4 (2.9)	135 (97.1)	139 (100.0)

Data are shown as n (%).

Totally 6/139 patients showed suspicious progress on control CT, yet 2/6 had no change of treatment and proceeded according to original plans, for radical cystectomy.

Table 5. Descriptive statistics over treatment alterations.

	Control CT	Total cohort
Treatment alteration
No	104 (74.8)	176 (72.7)
No, even though progress on cCT	2 (1.4)	2 (0.8)
Yes, due to progress on cCT	4 (2.9)	4 (1.6)
Yes, hard to interpret cCT	1 (0.7)	1 (0.4)
Yes, due to NAC side effects	26 (18.7)	59 (24.3)
Yes, due to other reasons	2 (1.4)	2 (0.8)
Total	139	242

Data are shown as n (%).

Most NAC-treatments were prematurely ended due to side effects and not due to suspicious progression at control CT (cCT).

Clear suspicious progression led to quick cystectomy in only four patients and one patient had poorly interpreted CT images in which progression was not clear, but could not be excluded, which led to a change of previously planned treatment and quick cystectomy. Two patients had other reasons for quick cystectomy; one had a fistula between the bowel and the urinary bladder and in the second, the rational for quick cystectomy was unclear/undefined and cannot be deducted from the results of the cCT-report.

Table 6. Patient characteristics in the six patients who had suspicious progression at cCT.

cCT-progressing patients	RC- center	Sex	Age	BMI	CACI	Histopathology	cTNM	pTNM	NAC combination	No. of NAC cycles	Decision at at second MDT
Susp.Progress 1	NUS	M	75	25.5	6	Urothelial	cT3N0M0	pT0N0M0	Other	6	Continue NAC
Susp. Progress 2	NUS	M	46	24.4	2	Uroth/squamous	cT3N0M0	pT0N0M0	MVAC HD	2	Quick RC
Susp. Progress 3	NUS	M	72	26.5	5	Urothelial	cT2N0M0	pT0N0M0	MVAC HD	3	Continue NAC
Susp. Progress 4	NUS	M	73	29.1	6	Urothelial	cT3N0M0	pT4aN2M0	MVAC HD	2	Quick RC
Susp. Progress 5	NUS	M	61	24.1	4	Urothelial	cT3N0M0	pT3N0M0	MVAC HD	2	Quick RC
Susp. Progress 6	NUS	F	60	29.4	4	Urothelial	cT2N0M0	pT4bN0M0	MVAC HD	2	Quick RC

The table describes the characteristics of the six patients in the finally analysed cohort in which cCT had suggested progression, yet only one of six (17%) was found to be progressive at histopathological analysis post-RC (a patient with pT4b). Thus, the cCT was inaccurate in predicting correct outcomes. Further, due to the lack of internationally standardized guidelines for cCT and algorithm-based actions to be taken, 2/6 had been recommended to discontinue NAC and undergo a quick RC while 4/6 received MDT recommendations of continuing planned NAC and forthcoming RC.

Table 7. Displaying progress in pTNM-staging compared with assessed progress on cCT.

	pTNM progress		Total
	Yes	No
Control-CT progress
Yes	1 (16.7)	5 (83.3)	6 (100.0)
No	28 (21.1)	105 (78.9)	133 (100.0)
Total	29	110	139

Data are shown as n (%).

Real-life clinical activity for the reported cohort of 139 CT-controlled patients was incongruent with finally verified outcomes, in which only 1/6 cCT-progressing patients had true progress with nodal dissemination and 28/29 patients with final pN+, never were discovered with the examination.

Data Availability statement

On reasonable request, the corresponding author can make available all codified data from the data base used for this study.