Utility of periodic medical questionnaires and examinations for immune-related adverse event screening: A prospective observational study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) specific to the immunity-boosting activity of the drugs and may necessitate discontinuation of treatment depending on their severity. IrAEs may be difficult to diagnose in their early stages as they can occur in any organ. The present, prospective, observational study is the first to attempt to assess the utility of periodic medical questionnaires and laboratory, radiological, and physiological examinations in diagnosing irAEs. METHODS: We analyzed 51 patients who received immunotherapy for metastatic renal or urothelial carcinoma at Tokyo Metropolitan Tama Medical Center between 2016 and 2020. A medical questionnaire consisting of 41 questions and laboratory tests were administered to the patients on the day of each ICI administration and 1 week afterwards. A significant complaint was defined as a complaint not addressed in the questionnaire immediately prior to the first ICI administration. RESULTS: Fifty-one patients with metastatic renal or urothelial carcinoma were enrolled. The mean age was 72.1 years (range: 54-88 years). The male: female ratio was 32: 19. Of the total cohort, 26 (51%) patients had renal carcinoma, and 25 (49%) had urothelial carcinoma. The median follow-up time was 2.6 (range: 0.4-40.7) months. Thirty-three patients (65%) experienced irAEs. CONCLUSIONS: In our cohort, periodic medical questionnaires and examinations were effective for early diagnosis and prompt treatment of irAEs. Although periodic examinations led to a high irAE diagnosis rate, the attendant medical cost was high. Further study is needed to find ways of addressing this issue.

Nivolumab and Ipilimumab Combination Immunotherapy for Patients with Metastatic Collecting Duct Carcinoma.

Collecting duct carcinoma (CDC) is a rare, extremely aggressive form of renal cancer. Recently, immune checkpoint inhibitors (ICI), anti-programmed death-1 (PD-1) antibody, and anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody were approved for use against metastatic renal cell carcinoma. We herein described two cases of metastatic renal collecting duct carcinoma treated with a combination immunotherapy consisting of nivolumab and ipilimumab. In the first case, which included a bone metastasis, the best response achieved was stable disease (SD) for one year. In the second case, which was accompanied by a lung metastasis, the best response achieved was a partial response. The outcome of these cases suggested that the combination of nivolumab and ipilimumab is effective against renal collecting duct carcinoma.

Cerebral metastasis during remission after immunotherapy for metastatic urothelial carcinoma: A case report.

Central nervous system (CNS) metastasis of urothelial carcinoma (UC) is rare. Immune checkpoint inhibitors, which were developed for the treatment of patients with advanced cancer, have limited efficacy against CNS metastases due to the unique immune microenvironment of the brain. The brain is an immune-privileged organ and is protected by the blood-brain barrier. However, the management of CNS metastases of UC is crucial to improving the prognosis. The present report describes two cases of cerebral metastasis occurring in the context of systemic disease control using immunotherapy. To the best of our knowledge, the present report is the first to describe a CNS metastasis during remission induced by immunotherapy.

Submucosal urothelial bladder cancer: A case report.

Bladder tumors can be broadly divided into those of epithelial or mesodermal origin. Furthermore, 90% of bladder tumors arise from the epithelium of the bladder, and most cases of bladder cancer are histologically urothelial carcinomas. Mesodermal tumors are exceptionally rare and often benign. Of the mesenchymal tumors of the bladder, leiomyomas are the most common, and their prognosis depends on their histology. The present report describes a case of submucosal urothelial cancer in a patient with no past history of bladder cancer. To the best of our knowledge, there are no previous reports of urothelial cancer occurring in the submucosa. The present report was the first to document a case of submucosal urothelial cancer, whose diagnosis was made possible only by transurethral resection of bladder tumor. Although the precise pathomechanism of the present case was unclear, two hypotheses were considered. First, the urothelial cancer developed within a diverticulum, then the entrance of the diverticulum closed, sealing in the cancer. Second, the bladder cancer stemmed from aberrant urothelium in the submucosal tissue. If submucosal urothelial bladder carcinoma develops within the diverticular environment, its prognosis can be as poor as that of invasive bladder cancer due to the features of the diverticular environment. Even in a patient with a submucosal bladder tumor but no previous history of bladder cancer, bladder cancer should be considered in the differential diagnosis.

Safety of same-day administration of gemcitabine plus cisplatin chemotherapy for urothelial carcinoma.

The present study aimed to examine the safety of a gemcitabine and cisplatin (GC) combination chemotherapy regimen with short hydration for the treatment of urothelial cancer administered on the same day (same day regimen). Patients with locally advanced or metastatic urothelial cancer received the same-day GC regimen with short hydration every 4 weeks, and their serum creatinine (Cr) level was measured to assess renal function using linear mixed model analysis. A total of 20 patients receiving the same-day regimen exhibited no significant change in their serum Cr level; nor was there any significant change in the serum Cr level between patients who received the same day regimen and those who received the drugs on different days. The present study demonstrated that the same-day regimen was safe for patients with urothelial cancer.

Metastatic renal cell carcinoma regains sensitivity to tyrosine kinase inhibitor after nivolumab treatment: A case report.

Sequential therapy using tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors is the mainstay of treatment for metastatic renal cell carcinoma. Recently, anti-programmed death-1 (PD-1) antibody, a type of immune checkpoint inhibitor, was approved for use against metastatic renal cell carcinoma. In the present report, two cases of TKI-refractory metastatic renal cell carcinoma which regained sensitivity to TKI after immunotherapy with nivolumab were described. In one case, a third challenge with axitinib after nivolumab treatment resulted in tumor shrinkage, although the second challenge with axitinib immediately before nivolumab treatment had no effect. In another case, a second challenge with pazopanib after nivolumab slightly reduced lung metastasis, which was refractory to pazopanib before nivolumab treatment. These cases suggest that nivolumab can influence the response to subsequent TKI treatment.

Spontaneous regression of a renal mass and multiple lung nodules after methotrexate cessation.

INTRODUCTION: Methotrexate has been reported to increase the risk of lymphoproliferative disorders. We report a rare case who was clinically diagnosed with methotrexate-associated lymphoproliferative disorders of the kidney. CASE PRESENTATION: A 77-year-old patient with rheumatoid arthritis had taken low-dose methotrexate for 13 years. The patient developed left renal mass 3 cm in size and multiple pulmonary nodules. Initially, renal malignant tumor with lung metastases was considered and the renal biopsy was planned. However, under possible diagnosis of methotrexate-related lymphoproliferative disorder, we withdrew methotrexate treatment at first and then observed spontaneous regression of the tumorous lesions of the kidney and lungs. CONCLUSION: Although methotrexate-related lymphoproliferative disorder in kidneys is very rare, our case advocates the importance of a relevant differential diagnosis of methotrexate-related lymphoproliferative disorder under the setting of long-term treatment of methotrexate for rheumatoid arthritis.