Adjuvant pembrolizumab in genomically selected high-risk patients with muscle-invasive bladder cancer

Patients with muscle-invasive urothelial bladder cancer post neoadjuvant cisplatin-based chemotherapy with pathologic advanced disease (ypT3, ypT4, ypN+) at radical cystectomy have a significantly worse five-year overall survival. There is currently no preferred adjuvant therapy to reduce risk of cancer recurrence in this high-risk patient cohort and surveillance remains the standard-of-care.

We present a case series of two patients who received cisplatin-based neoadjuvant chemotherapy and had pathologic node-positive urothelial carcinoma at the time of radical cystectomy. Tumor next generation sequencing revealed high mutational burden in both patients and positive PD-L1 in one patient.Management and outcome: Patients were treated with adjuvant pembrolizumab and experienced long-term disease free intervals.

Use of adjuvant checkpoint inhibitors in patients post neoadjuvant cisplatin-based chemotherapy with pathologic advanced disease at the time of radical cystectomy at high-risk of cancer recurrence sounds appealing. Careful patient selection based on tumor-specific genomic alterations may be key. Large trials addressing this question are ongoing.