Here, we present a case of advanced bladder urothelial carcinoma. A 66-year-old female patient was diagnosed with bladder occupying mass, left hydronephrosis, and left ureter dilatation in a local hospital due to painless hematuria for 2 months. The patient was then hospitalized in Henan Cancer Hospital. The results of enhanced CT (2019.4.4) showed: 1. Thickening of the lower ureter and nodules at the entrance of the vesicoureter, about 25mm*22mm in size, with fluid in the dilated upper ureter and renal pelvis, and possible atypical cell carcinoma. 2. There are multiple lymph nodes in the retroperitoneum and between the liver and stomach. 3. Multiple metastases in both lungs. 4. There are multiple swollen lymph nodes in the running area of the left iliac vessels ( Figure 1A ). Renal dynamic imaging and glomerular filtration rate were measured with 99m-Tc-DTPA. Diagnostic considerations: 1. No obvious abnormality in blood perfusion of the right kidney. 2. The right glomerular filtration function is normal. 3. Poor excretion in the upper right urinary tract. 4. No function in the left kidney ( Figure 1B ). In order to relieve the symptoms of left kidney compression, a percutaneous external renal pelvic drainage tube was placed on April 11, 2019. Cystoscopy was performed, and the pathological results of biopsy showed urothelial carcinoma. There was no clear muscle infiltration in the submitted tissues( Figure 1C ). Immunohistochemistry: P63+,CK20+,CK7+, CyclinD1+, Ki-67: 80% ( Supplementary Figure 1 ). The final diagnosis was stage IV bladder urothelial carcinoma with multiple lung metastases. Because the patient has only one normal kidney left. According to the patient's age, physical fitness score and considering the nephrotoxicity of cisplatin, we choose gemcitabine (1000mg/m2, d1 8, q21d) as a single agent for the first-line treatment. After two cycles of gemcitabine treatment, the efficacy of chemotherapy was evaluated as SD (stable disease) ( Figure 2A ). The efficacy of chemotherapy remained as SD after four cycles of treatment ( Figure 2B ) and it became PD (progression disease) after six cycles of treatment ( Figure 2C ).
According to the patient's age, economic status, PD-1 donation policy and family's wishes, Sintilimab (200mg, on day1, q21d) was used for the second-line treatment for three cycles on 2019.9.20 2019.10.16 and 2019.11.12. The treatment efficacy is evaluated as PR (Partial response) ( Figure 3 ). Then Sintilimab was given for the fourth cycle of immunotherapy on 2019.12.04. One week later, on December 10, 2019, the patient developed chest tightness and shortness of breath, accompanied by gradual increase in dyspnea. The local hospital gave oxygen inhalation and anti-asthmatic treatment, but the symptoms did not alleviate. Chest CT examination considered infectious lesions of both lungs. Serological examination ruled out tuberculosis or Aspergillus infections. Subsequently, the patient was transferred to our hospital for further treatment. On admission, her blood oxygen saturation was 75%, and his skin was cyanotic. The breath sound of auscultation in both lungs is thick, and the wheezing sound can be heard. The results of chest CT examination on 2019.12.26 showed pneumonia in both lungs, that are more severe than earlier images ( Figure 4 ). The patient was suspected to had developed grade 3 immunotherapy-related pneumonia, and was given an intravenous infusion of methylprednisolone at 1 mg/(Kg.d) for 72 hours. After 3 days, the patient's chest tightness symptoms improved, and oxygen saturation reached 94%. The methylprednisolone was changed to oral administration and the dose was gradually reduced by 5-10mg per week. By March 23, 2020, methylprednisolone was reduced to 10mg/d orally, at which time the blood oxygen saturation had reached 96%. We performed chest CT to observe the changes of pneumonia, and the results showed that pneumonia of both lungs had improved significantly ( Figure 4B ). On January 14, 2021, the patient underwent whole-body enhanced CT evaluation. To our surprised, the results showed that the patient's lung metastases disappeared, and the local soft tissue shadow at the entrance of the ureter on the left side of the bladder disappeared completely ( Figure 5A ). The patient achieved progression-free survival for more than one year ( Figure 5B ). The current condition is generally good.