Referral for “Neoadjuvant Chemotherapy” for Muscle-Invasive Bladder Cancer to a Multidisciplinary Board: Patterns, Management and Outcomes

Figures & data

Table 1 Baseline (Pre-Chemotherapy) Characteristics of 46 Patients with Muscle-Invasive Bladder Cancer Treated with Chemotherapy

Characteristic	Total	Chemotherapy Alone (n=8)	Chemotherapy + Surgery (n=30)	Chemotherapy + Radiotherapy (n=8)	p- value
Median (25th −75th percentile)
Age (at date of diagnosis of MIBC)	67.6 (60.6–72.6)	68.2 (64.1–71.6)	67.9 (59.8–73.3)	65.7 (61.2–72.9)	0.761
Age (at first course)	68.1 (60.6–72.7)	68.5 (64.2–71.9)	68 (59.9–73.5)	66.2 (61.3–73)	0.743
Creatinine clearance	93.4 (65–109)	88.2 (56.9–99.5)	99.5 (65–110)	87.8 (76.2–110.1)	0.624
N (%)
ECOG PS					0.535 ᶘ
0	37 (80.4)	7 (87.5)	25 (83.4)	5 (62.5)
1	8 (17.4)	1 (12.5)	4 (13.3)	3 (37.5)
3	1 (2.2)	0 (0)	1 (3.3)	0 (0)
Gender					0.854 ᶘ
Female	8 (17.4)	2 (25)	5 (16.7)	1 (12.5)
Male	38 (82.6)	6 (75)	25 (83.3)	7 (87.5)
Clinical T					0.720 ᶘ
T1	1 (2.2)	0 (0)	1 (3.3)	0 (0)
T2	32 (69.5)	4 (50)	22 (72.4)	6 (75)
T3	12 (26.1)	4 (50)	6 (20)	2 (25)
T4a	1 (2.2)	0 (0)	1 (3.3)	0 (0)
Hydronephrosis					0.587 ᶘ
No	34 (73.9)	5 (62.5)	22 (73.3)	7 (87.5)
Yes	10 (21.7)	3 (37.5)	6 (20)	1 (12.5)
Unknown	2 (4.4)	0 (0)	2 (6.7)	0 (0)
Clinical LN involvement					0.196 ᶘ
N0	36 (78.3)	5 (62.5)	23 (76.7)	8 (100)
N1	1 (17.4)	1 (37.5)	0 (0)	0 (0)
N2	2 (4.4)	0 (0)	2 (6.7)	0 (0)
N3	2 (4.4)	1 (12.5)	1 (3.3)	0 (0)
M1a	3 (6.5)	1 (12.5)	2 (6.7)	0 (0)
Unknown	2 (4.4)	0 (0)	2 (6.7)	0 (0)
Histology					0.148 ᶘ
TCC	43 (93.5)	8 (100)	29 (96.7)	6 (75)
Mixed*	3 (6.5)	0 (0)	1 (3.3)	2 (25)
Grade					>0.999 ᶘ
1	3 (6.5)	0 (0)	3 (10)	0 (0)
2	2 (4.4)	0 (0)	2 (6.7)	0 (0)
3	41 (89.1)	8 (100)	25 (83.3)	8 (100)
Tis					0.807 ᶘ
No	39 (84.8)	8 (100)	24 (80)	7 (87.5)
Yes	5 (10.9)	0 (0)	4 (13.3)	1 (12.5)
Missing	2 (4.3)	0 (0)	2 (6.7)	0 (0)
Clinical TNM					0.956 ᶘ
II	28 (60.9)	4 (50)	18 (60)	6 (75)
IIIA	9 (19.6)	2 (25)	5 (16.6)	2 (25)
IIIB	4 (8.7)	1 (12.5)	3 (10)	0 (0)
IVA	3 (6.5)	1 (12.5)	2 (6.7)	0 (0)
Missing	2 (4.3)	0 (0)	2 (6.7)	0 (0)

Notes: ANOVA; ᶘ Fisher’s exact. *Sarcomatoid, neuroendocrine, squamous.

Abbreviations: ECOG, Eastern Co-operative Oncology Group; PS, performance status; TCC, transitional-cell carcinoma; MIBC, muscle-invasive bladder cancer; LN, lymph node.

Figure 1 Type of post chemotherapy management of 46 patients with muscle-invasive bladder cancer referred for “neoadjuvant” chemotherapy to the multidisciplinary tumor board. Colours correspond to the initial clinical stage.

Table 2 Toxicities Associated with Chemotherapy, Surgery, Radiotherapy. Percentages are Shown in Parentheses

Toxicity	Grade
	1	2	3	4	5
Chemotherapy (n=46)
Neutropenia	1 (2.2)
Anemia	6 (13)	3 (6.7)
Thrombocytopenia	4 (8.7)		1 (2.2)	1 (2.2)
Fatigue	2 (4.4)	6 (13)
Non-neutropenic infection					1 (2.2)
Renal function	3 (6.5)
Diarrhea	2 (4.4)
Constipation	3(6.7)
Nausea – Vomiting	8 (17.4)	2 (4.4)
Stomatitis	1 (2.2)
Neurotoxicity	2 (4.4)
Ototoxicity	1 (2.2)	1 (2.2)
Bleeding (gastric)			1 (2.2)
Hypokalaemia		1 (2.2)	1 (2.2)
Hyponatraemia		1 (2.2)		1 (2.2)
Venous thromboembolic event			1 (2.2)
Surgery (n=30)
Ureteroenteric anastomosis stricture			1 (3.4)
Infection		4 (13.8)
Hernia	1 (3.4)
Anaemia	1 (3.4)	6 (20)
Septisaemia		2 (6.9)
Acute coronary syndrome				1 (3.4)
Atrial fibrillation		2 (6.9)
Transient ischemic attack	1 (3.4)
Pulmonary embolism		2 (6.9)
Pulmonary oedema	1 (3.4)
Hypertension		2 (6.9)
Inferior Vena Cava rupture					1 (3.4)
Mycetaemia			1 (3.4)
Hypokalaemia		1 (3.4)
Wound dehiscence				1 (3.4)
Wound infection			1 (3.4)
Bowel obstruction				1 (3.4)
Radiotherapy (n=8)
Urinary		5 (62.5)	3 (37.5)
Rectal	4 (50)	4 (50)

Table 3 3-Year Disease Free Survival and 5-Year Overall Survival and Cancer Specific Survival Rates (%) from 1st Course of Chemotherapy for All Patients and According to Subsequent Management. 95% Confidence Interval in Parentheses

	n	Total	p^ᶂ	Chemotherapy+Surgery (n=30)	p^ᶘ	Chemotherapy (n=8)	Chemotherapy+Radiotherapy (n=8)	p^¶
3-year Disease Free Survival rate
All patients	45	67.3 (51–79.2)		65.2 (44.9–79.6)		66.7 (19.5–90.4)	75 (31.5–93.1)	0.644
PS			0.617		0.455			0.411
0	37	68.6 (50.4–81.2)		62.3 (40–78.4)		66.7 (19.5–90.4)	100
≥1	8	60 (19.6–85.2)		80 (20.4–96.9)		No patients	33.3 (0.9–77.4)
Clinical T			0.185		0.311			0.423
T1+T2	32	71.9 (52.9–84.3)		69.6 (46.6–84.2)		66.7 (5.4–94.5)	83.3 (27.3–97.5)
T3+T4a	13	54.6 (22.9–78)		50 (11.1–80.4)		66.7 (5.4–94.5)	50 (0.6–91)
Clinical N			0.185		0.002			0.428
N0	35	70.2 (51.7–82.8)		72.1 (48.1–86.4)		50 (5.8–84.5)	75 (31.5–93.1)
N1+N2+N3+M1a	8	43.8 (10.1–74.2)		20 (0.8–58.2)		100	No patients
Tis			0.718		0.419			0.625
No	38	72 (54.2–83.9)		73.5 (50.2–87.2)		66.7 (19.5–90.4)	71.4 (25.8–92)
Yes	5	60 (12.6–88.2)		50 (5.8–84.5)		No patients	100
Clinical TNM			0.051		0.066			0.146
II	27	74.1 (53.2–86.7)		72.2 (45.6–87.4)		66.7 (5.4–94.5)	83.3 (27.3–97.5)
IIIA+IIIB+IVA	16	50.5 (23.2–72.6)		45 (13.9–72.4)		66.7 (5.4–94.5)	50 (0.6–91)
ypT*					0.004
T0+Ta+Tis+T1	12			100
T2+T3+T4a	18			44.4 (21.6–65.1)
ypTNM*					0.004
0+0a+0is+I	12			100
II+IIIA+IIIB	18			44.4 (21.6–65.1)
ypN*					0.011
N0	20			69.6 (44.5–85.1)
N1 + N2	5			20 (0.8–58.2)
pCR*					0.151
No	25			59.4 (37.6–75.8)
Yes	5			100
pDS*					0.009
No	16			43.8 (19.8–65.6)
Yes	14			92.3 (56.6–98.9)
tnmDS*					0.303
No	13			53.9 (24.8–76)
Yes	17			75 (46.3–89.8)
	5-year Overall Survival rate
All patients	46	45.3 (27.8–61.4)		46.7 (23.7–66.8)		37.5 (8.7–67.4)	54.7 (13.7–83.2)	0.542
PS			0.498		0.297			0.44
0	37	48.9 (28.8–66.3)		39.5 (15.7–62.8)		42.9 (9.8–73.4)	100
≥1	9	33.3 (5.3–66.4)		80 (20.4–96.9)		0	0
Tis			0.754		0.419			0.516
No	39	48.2 (29.3–64.9)		52.6 (26.1–73.5)		37.5 (8.7–67.4)	53.6 (13.2–82.5)
Yes	5	NR		NR		No patients	NR
Clinical T			0.086		0.049			0.181
T1/T2	33	51.4 (29.6–69.5)		52 (25.7–73)		25 (0.9–66.5)	80 (20.4–96.9)
Other	13	29.9 (6.2–59.3)		NR		50 (5.8–84.5)	0
Clinical N			0.083		<0.001			0.172
N0	36	48.2 (27.5–66.1)		57.2 (29.7–77.4)		20 (0.8–58.2)	54.7 (13.7–83.2)
N1,N2,N3,M1a	8	25 (3.7–55.8)		0		66.7 (5.4–94.5)	No patients
Clinical TNM			0.011		0.004			0.031
II	28	56.6 (32.7–74.8)		60.6 (30.5–81)		25 (0.9–66.5)	80 (20.4–96.9)
IIIA+IIIB+IVA	16	21.4 (4–47.9)		0		50 (5.8–84.5)	0
ypT*					0.03
Tis+T0+Ta+T1	12			73.3 (24.3–93.4)
T2+T3+T4a	18			31.3 (9.6–56.1)
ypN*					0.049
N0	20			51 (22.9–73.6)
N1+N2	5			NR
ypTNM*					0.03
0+I	12			73.3 (24.3–93.4)
Other	18			31.3 (9.6–56.1)
pCR*					0.387
No	25			41.3 (18–63.4)
Yes	5			80 (20.4–96.9)
pDS*					0.049
No	16			31.3 (9.3–56.6)
Yes	14			68.6 (25.3–90.2)
tnmDS*					0.575
No	13			38.5 (11.1–66)
Yes	17			56.5 (23.3–79.9)
	5-year Cancer Specific Survival rate
All patients	45	52.9 (33–69.3)		57.1 (31.2–76.3)		50 (11.1–80.4)	54.7 (13.7–83.2)	0.919
PS			0.422		0.486			0.415
0	37	57.6 (34.9–74.9)		51 (21.9–74.2)		50 (11.1–80.4)	100 (NR)
≥1	8	37.5 (5.6–71.7)		80 (20.4–96.9)		No patients	0
Tis			0.379		0.183			0.269
No	38	57.1 (35.4–74)		65.2 (34.5–84.2)		50 (11.1–80.4)	85.7 (33.4–97.9)
Yes	5	NR		NR		No patients	NR
Clinical T			0.13		0.082			0.247
T1/T2	32	58.8 (34.6–76.7)		61.9 (32.9–81.3)		33.3 (0.9–77.4)	80 (20.4–96.9)
Other	13	35.4 (6.9–66.8)		NR		66.7 (5.4–94.5)	0
Clinical TNM			0.029		0.013			0.071
II	27	61.3 (35.5–79.4)		64.9 (32.7–84.7)		33.3 (0.9–77.4)	80 (20.4–96.9)
IIIA+IIIB+IVA	16	32.7 (7–62.4)		NR		66.7 (5.4–94.5)	0
Clinical N			0.229		<0.001			0.319
N0	35	53 (30.3–71.3)		63.4 (32.7–83)		25 (0.8–66.5)	54.7 (13.7–83.2)
N1,N2,N3,M1a	8	42.9 (9.8–73.4)		NR		100	No patients
ypT*					0.005
Tis+T0+Ta+T1	12			100
T2+T3+T4a	18			34.7 (10.8–60.5)
ypN*					0.013
N0	20			62.5 (30.3–83.1)
N1+N2	5			NR
ypTNM*					0.005
0+I	12			100
II,IIIA,IIIB	18			34.7 (10.8–60.5)
pCR*					0.171
No	25			51.2 (25–72.4)
Yes	5			100
pDS*					0.013
No	16			35.2 (10.6–61.4)
Yes	14			92.3 (56.6–98.9)
tnmDS*					0.449
No	13			43.3 (12.5–71.4)
Yes	17			75 (46.3–89.8)

Notes: ᶂ Log rank test; ᶘLog rank test for surgery patients; ¶ Stratified Log rank test for all three modalities; *only for patients who underwent surgery.

Abbreviations: PS, performance status; NR, not reached.

Figure 2 Disease-free survival, overall survival and cancer-specific survival for the 46 patients included in the study.

Figure 3 Disease-free survival according to post-chemotherapy treatment type.