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Cystoscopy with bladder biopsy. A: Cystoscopy showed diffuse redness of the bladder mucosa. B: Histopathological examination showed no evidence of malignancy and the absence of inclusion bodies in the epithelium.
Source publication
We report a case of non-bacterial cystitis that occurred after administration of atezolizumab, an antibody against programmed cell death ligand 1 (PD-L1). This cystitis was considered an immune-related adverse event (irAE). A 67-year-old woman with advanced breast cancer (cT4bN1M1, cStage IV) was treated with atezolizumab and nanoparticle albumin-b...
Contexts in source publication
Context 1
... urine cytology was negative for malignant cells. Cystoscopy showed diffuse redness of the bladder mucosa ( Figure 2A). A bladder biopsy was performed on day 112. ...
Citations
... irAEs represent a broad spectrum of dermatological, gastrointestinal and endocrine side effects and other organ system toxicities ranging from mild to life-threatening, which became a serious challenge for patients with the widespread use of ICIs [54]. Recently, few cases have described that ICIs including ipilimumab, atezolizumab, nivolumab, pembrolizumab and sintilimab are related to immune-related cystitis as an irAE [55][56][57][58]. ICIs-induced cystitis is generally manifested by irritative voiding symptoms and histological features of diffuse redness of bladder mucosa. ...
... Despite high efficacy of glucocorticoids, there are concerns about the use of glucocorticoids particularly as they are likely to affect negatively the therapeutic outcomes of ICIs due to immunosuppressive effects. Thus, unnecessary use of glucocorticoids should be avoided [58]. ...
Cystitis is an inflammatory condition of the urinary bladder with infectious or noninfectious aetiologies. Chemical-induced cystitis represents a relatively highly prevalent kind of noninfectious cystitis resulting from therapeutic agents or environmental chemicals. Drug-related cystitis is a type of urotoxicity of drugs, which is a commonly underreported condition leading to impaired quality of patients' life, discontinuation of medication and non-compliance. Drug-related cystitis can occur in several forms ranging from mild urinary symptoms to gross haematuria, which can be challenging for physicians to treat. Chemotherapeutic drugs, ketamine, tiaprofenic acid and several drugs have been reported to be associated with cystitis until now. Cyclophosphamide (CP) is an alkylating agent that leads to haemorrhagic cystitis with widespread awareness due to its high prevalence in patients under treatment intravenously. However, several currently available drugs have been also reported to induce cystitis, which may be usually ignored. Drug-related cystitis can cause emergency admissions and prolonged hospitalisation, leading to increased medical costs. Some cases of drug-related cystitis are clinically managed with established therapeutic interventions and/or prophylaxis, such as CP-induced haemor-rhagic cystitis. On the other hand, standard treatment is currently unavailable for most cases. This chapter will provide current knowledge regarding the drug-related cystitis that should be taken into consideration as a potential adverse effect of drugs by physicians.
... IrAEs can affect many organs throughout the body, and the probability of developing irAEs ranged from 54% to 76% in a meta-analysis. 1 Meanwhile, irAEs rarely affect the bladder, and only 12 cases of immune-related cystitis have been reported so far. [2][3][4][5][6][7][8][9][10][11][12] Steroids are recommended for the treatment of irAEs according to the guidelines, 13 and most cases of immune-related cystitis are also treated with steroids. However, whether steroids impair the therapeutic effect of ICIs remains controversial. ...
Introduction:
Although immune checkpoint inhibitors offer significant therapeutic benefits to patients with advanced cancer, they can also cause a variety of immune-related adverse events. As immune checkpoint inhibitors are being widely used, rare immune-related adverse events are being reported.
Case presentation:
A 70-year-old man with advanced salivary duct carcinoma was treated with pembrolizumab following radiotherapy. After receiving two doses of pembrolizumab, the patient experienced symptoms such as micturition pain and hematuria. Immune-related cystitis was suspected, and the patient underwent a bladder biopsy and bladder hydrodistension. Histological analysis revealed non-neoplastic bladder mucosa with CD8-positive lymphocyte-dominant inflammatory cell infiltration, consistent with immune-related cystitis. The patient's bladder symptoms improved postoperatively without steroid administration.
Conclusion:
Although steroids are commonly administered to treat immune-related adverse events, bladder hydrodistension may be a promising treatment option for immune-related cystitis to avoid administration of steroids, which may impair the therapeutic effect of immune checkpoint inhibitors.
... However, irAEs involving the urinary tract and bladder are rarely reported and often ignored by oncologists. To date, approximately ten cases with ICIinduced ureteritis/cystitis have been reported (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The symptoms of ICI-induced ureteritis/cystitis mainly include hematuria, pollakiuria, painful micturition, and sometimes acute kidney injury complications (4). ...
... IrAEs usually affect epithelial tissues (including those of the skin, lung, and gut) because these environmental interfaces are prone to large in ltrations of tissue-resident memory T cells (1,24). In ltration of T cells into the urothelial barrier have been observed in ICI-induced ureteritis/cystitis (3)(4)(5)10). We considered two molecular mechanisms as opportunities for therapeutic intervention and the prevention of irAE: (1) the recruitment of T cells to epithelial tissues; and (2) T cell activation. ...
... Histopathologic analysis has revealed the presence of CD8 + T cell expansions in multiple organs affected by ICI toxicity (1,4,10,18,29,30). Moreover, the expansion and activation of T cells also play a role in ICIinduced ureteritis/cystitis (3,4). ...
Common immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) include dermatological, gastrointestinal, pulmonary, or endocrine side effects. Although less common than other IrAEs, IrAEs involving the urinary tract and bladder are gradually being recognized by clinicians. However, the early diagnosis and optimal management of ICI-induced ureteritis/cystitis are challenging because the underlying mechanisms remain poorly understood. Here we report the results from a comprehensive single-cell analysis of cell populations implicated in ureteritis/cystitis induced by an anti-programmed-death-1 monoclonal antibody. We observed a striking expansion of T cells with highly cytotoxic state in the ureteritis/cystitis tissue, which was accompanied by a significant decrease in epithelial cell numbers. The proportion of macrophages was also increased in the ureteritis/cystitis tissue, compared with healthy tissue. Moreover, we identified changes in the molecular features of the CXCL, TNF, NF-κB, ITGB2, and GZMB signaling pathways. Collectively, our findings provide insights into the molecular mechanisms underlying ICI-induced ureteritis/cystitis and imply that modulating T cell, macrophage, epithelial cell, and endothelial cell functions by interfering with the identified signaling pathways could help guide new therapeutic strategies.
1例应用帕博利珠单抗联合化疗治疗的晚期肺腺癌患者在治疗14个周期后出现了尿频、尿急症状。经尿常规、肾功能、膀胱镜及计算机断层扫描（computed tomography, CT）检查考虑为免疫抑制剂相关性输尿管膀胱炎以及急性肾损伤。停用帕博利珠单抗联合化疗后症状缓解，再次应用帕博利珠单抗联合化疗尿路刺激症状明显加重，应用激素治疗后症状缓解。在使用免疫检查点抑制剂时，患者如出现泌尿系统症状，需考虑免疫相关输尿管膀胱炎，尽早识别和治疗。
Immune checkpoint inhibitor (ICI) is an up-to-date therapy for cancer with a promising efficacy, but it may cause unique immune-related adverse events (irAEs). Although irAEs could affect any organ, irAEs-induced whole urinary tract expansion was rarely reported. Herein, we reported a 27-year-old male patient with thymic carcinoma who received the treatment of tislelizumab, paclitaxel albumin and carboplatin. He was hospitalized for severe bellyache and lumbago after 6 courses of treatment. Antibiotic and antispasmodic treatment did not relieve his symptoms. The imaging examinations reported whole urinary tract expansion and cystitis. Therefore, we proposed that the patient’s pain was caused by tislelizumab-induced ureteritis/cystitis. After the discontinuation of tislelizumab and the administration of methylprednisolone, his symptoms were markedly alleviated. Herein, we reported a rare case of ICI-induced ureteritis/cystitis in the treatment of thymic cancer and reviewed other cases of immunotherapy-related cystitis and tislelizumab-related adverse events, which will provide a reference for the diagnosis and treatment of ICI-related irAEs.
Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4) and anti-programmed death cell protein 1 (anti-PD-1), are increasingly prescribed in metastatic carcinoma therapy. ICI-related kidney injury is gradually recognized by clinicians. However, immune-related ureteritis and cystitis easily go undiagnosed. We report three cases of PD-1 monoclonal antibody (mAb)-related ureteritis and cystitis. We further carried out a review of the literature about ICI-related ureteritis and cystitis. The cases in our reports manifest urinary irritation, sterile pyuria, gross hematuria, hydronephrosis, dilation of the ureters, and acute kidney injury. Urinary irritation improved effectively; urinalysis and renal function returned to normal after glucocorticoid therapy. During ICI therapy, urinalysis and renal function and urinary imaging examination are recommended to be monitored regularly. It contributes to identify immune-related ureteritis/cystitis earlier to efficiently alleviate urinary symptoms and immunologic urinary tract injury through glucocorticoid therapy while avoiding the abuse of antibiotics.
