Immunotherapy-Related Cystitis: Case Report and Review of the Literature

Figures & data

Table 1 Laboratory Testing Results

Test	Result	Reference Range
WBC ×10^9/L	7.18	4.00–10.00
PLT ×10^12/L	189	100–300
CRP (mg/L)	10.90	<5.0
Glucose (mmol/L)	4.7	3.8–6.1
Creatine (μmol/L)	32	44–123
Uric acid (μmol/L)	293	208–428
LDH (U/L)	298	109–245
CK (U/L)	173	25–200
γGT (U/L)	173	0–40
T3 (nmol/L)	1.78	1.3–3.1
T4 (nmol/L)	105.3	59–154

Abbreviations: WBC, white blood cells; PLT, platelet count; LDH, lactate dehydrogenase; CRP, C-reactive protein; CK, creatine kinase; γGT, gamma-glutamyl transferase; T3, triiodothyronine; T4, Thyroxine.

Table 2 IHC Staining for the Patient’s Tissue Samples

Sample	PD-L1	PD-1	CD3	CD4	CD8	CD19	CD56
Squamous carcinoma	60% (weak to medium)	5% (medium)	30% (medium)	8% (weak)	10% (strong)	8% (strong)	<1%
Small cell lung cancer	<1%	<1%	3–4% (medium)	<1%	3% (strong)	<1%	80% (medium to strong)
Bladder urothelium	0	<1%	5% (strong)	1% (weak)	3% (strong)	1% (weak)	20% (stromal, medium)

Abbreviations: IHC, Immunohistochemistry; PD-L1, programmed death-ligand 1; PD-1, programmed death 1.

Table 3 Cases of Immune-Related Cystitis Following ICI: Clinical Characteristics and Malignancy Status

Patient No.	Reference	Sex	Age	Malignancy	ICI	Onset from ICI	Best Response	ICI Discontinuation
1	Current paper	M	51	SCLC	Nivolumab	15 weeks	CR	Yes
2	Ueki^Citation16	F	78	NSCLC	Pembrolizumab	51 weeks	PR	Yes
3	Shimatani^Citation23	M	50	NSCLC	Nivolumab	14 weeks	NR	Rechallenge
		M	60	NSCLC	Nivolumab	24 weeks	NR	Yes
4	Ozaki^Citation24	M	62	NSCLC	Nivolumab	6 weeks	NR	Yes

Abbreviations: NR, not reported; CR, complete remission; PR, partial remission; M, male; F, female.

Figure 1 (A) Preoperative chest CT scan (captured on March 19th, 2018). (B) Histology revealed squamous carcinoma of the lung (x100). (C) Postoperative chest CT follow-up (captured on April 11th, 2018). (D) PET-CT scan (captured on July 18th, 2019). (E) Histology findings indicated SCLC. (F) PET-CT scan (captured on September 11th, 2019). Significant abnormal findings were noted (arrow).

Figure 2 (A) Hepatic metastatic lesion and (B) bone metastases on PET-CT (captured on Nov. 11th, 2019). (C and D) Confirmation of CR after second line nivolumab and paclitaxel (captured on April 8th, 2020). (E) Cystoscopy showed that the entire bladder mucosa was edematous. (F) Histology of urothelium. Significant abnormal findings were noted (arrow).

Figure 3 Radiotherapy planning to be delivered to bone metastases for this patient.

Figure 4 IHC staining for the patient’s tissue samples. (A–E) Lung squamous carcinoma staining for CD3, CD4, CD8, PD-1 and PD-L1, respectively. (F–J) Small cell lung cancer biopsy sample staining for CD3, CD4, CD8, PD-1 and PD-L1, respectively. (K–O) Urothelium biopsy staining for CD3, CD4, CD8, PD-1 and PD-L1, respectively.

Figure 5 Clinical course of the patient. *means “times” (for 6 weeks).

Ueki Y, Matsuki M, Kubo T, et al. Non-bacterial cystitis with increased expression of programmed death-ligand 1 in the urothelium: an unusual immune-related adverse event during treatment with pembrolizumab for lung adenocarcinoma. IJU Case Rep. 2020;3(6):266–269. doi:10.1002/iju5.12211

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Shimatani K, Yoshimoto T, Doi Y, Sonoda T, Yamamoto S, Kanematsu A. Two cases of nonbacterial cystitis associated with nivolumab, the anti-programmed-death-receptor-1 inhibitor. Urol Case Rep. 2018;17:97–99. doi:10.1016/j.eucr.2017.12.006

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Ozaki K, Takahashi H, Murakami Y, Kiyoku H, Kanayama H. A case of cystitis after administration of nivolumab. Int Cancer Conf J. 2017;6:164–166. doi:10.1007/s13691-017-0298-6

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