Introduction/Background
Standard 1st-line therapy for urothelial cancer (UC) is cisplatin based combination chemotherapy (CT). This is also true for patients with upper urinary tract urothelial cell carcinoma (UTUC). Alternatively, carboplatin based chemotherapy is used for patients ineligible for cisplatin. Gemcitabine/Carboplatin (GCa) showed an objective response rate (ORR) of 38% and less severe acute toxicity compared to methotrexate/carboplatin/vinblastine (M-CAVI).
In 2017, pembrolizumab and atezolizumab were approved also for cisplatin ineligible patients in the first line setting based on ORRs of 23-24% and promising overall survival in two uncontrolled phase II trials. Recently, the indication for both checkpoint inhibitors (CPI) in the first line was restricted to patients with a positive PD-L1 status (“high levels of PD-L1”) based on preliminary and still unpublished results from ongoing phase III trials.
Patient information
B is a 61 year old male bus driver who is spending much of his leisure time with his wife on the canary islands, where she recently moved to for a new business. Work up of gross hematuria showed UC of the right upper urinary tract. Surgery was performed externally. Pathological review of the nephroureterectomy specimen showed urothelial cancer, G3, pT3b, pN1.
Diagnosis
B first presented at Charité in January 2019 for consultation concerning adjuvant CT. Renal function was low (GFR 35-40ml/min) and performance status was good (PS1). Thus, 4 cycles of GCa were recommended. Five days later the patient presented at our emergency department with an acute abdomen. Laparoscopic appendectomy revealed local pelvic reccurrence of UC and further imaging showed a central necrotic liver metastasis which was rapidly progressing.
Treatment
For the treatment of first line metastatic UC in this cisplatin unfit patient the PD-L1 status was requested. Surprisingly, the result showed IC 0% and CPS 100. In the meantime the patient had a performance status of 2-3 and treatment was to be started urgently. The contradictory PD-L1 results, the lower response rate of CPI compared to GCa and the presumably better tolerability of immunotherapy were weighted against each other. Finally, pembolizumab was started in 02/2019.
Outcome & Follow-up
The patient showed an immediate clinical improvement, PS 0 at 3 months and a complete response 6 months after CPI initiation.
