Background: Immune checkpoint inhibitors targeting PD-L1 has recently been approved in locally advanced and metastatic urothelial bladder carcinoma patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience a very rapid tumor progression during immunotherapy.
Case presentation: The patient is a 58-year-old male with recurrent and metastatic urothelial bladder carcinoma. He was diagnosed as non-muscle-invasive bladder cancer 3 years ago, receiving transurethral resection of bladder tumor (TRUBT) and intravesical chemotherapy. One year later, TURBT was performed for recurrent and progressive urethral bladder tumors again. Following disease progression, he received radical cystectomy, pathologically staged as T2bN2M0, and adjuvant cisplatin-containing combination chemotherapy. When disease progressed to metastatic urothelial bladder carcinoma, the patient received anti-PD-L1 agent monotherapy and experienced unusually rapid disease progression within two months, which was confirmed by repeated CT scans to rule out pseudoprogression. The tumor growth rate (TGR) was used to estimate the increase in tumor volume over time. The TGR ratio was defined as the ratio of TGRPOSTto TGRPRE. The TGR ratio in the patient is 4.0-fold. Formalin-fixed paraffin embedded tissue following RC were obtained from Pathology Department Archives. Samples were analyzed to provide plausible rationale for hyperprogression after immunotherapy. In the present case, next-generation sequencing showed several alterations including MDM2 amplification, but not MDM4 amplification, EGFR aberrations, or DNMT3A alterations. Immunohistochemistry showed that PD-L1 percentage scoring of tumor cells and tumor-infiltrating immune cells was 2 (15-25%) and 2(5-10%), respectively.
Conclusions: In the presence of tumor PD-L1 expression, this patient with MDM2 family amplification could significantly accelerated tumor growth after immunotherapy. Genomic profiles might help to identify patients at risk for hyperprogression before immunotherapy. Further investigation is urgently needed.