Complete Pathological Response to Neoadjuvant Pembrolizumab in a Patient With Chemoresistant Upper Urinary Tract Urothelial Carcinoma: A Case Report

Abstract

Treatment options as second-line therapy for advanced ureteral carcinoma are limited, and patients experiencing recurrence after first-line cisplatin-based chemotherapy have a poor prognosis. Recently, the programmed death-1 (PD-1) inhibitor pembrolizumab provided a better survival benefit with a complete response rate (9.2%) for chemoresistatant urothelial carcinoma. However, the dynamic changes of the cancer microenvironment about the cases of complete response are still unknown. We herein report a case of a 57-year-old man who had been diagnosed with localized, nonmuscle-invasive bladder cancer (pT1N0M0, high grade), for which he underwent transurethral resection of the bladder cancer twice. Given that gemcitabine plus carboplatin as first-line neoadjuvant chemotherapy was unable to control left vesicoureteral junction recurrence with muscle invasion (T3N0M0, high grade), the patient received the PD-1 inhibitor pembrolizumab as second-line neoadjuvant therapy in an attempt to stop tumor growth, which promoted dramatic tumor shrinkage without serious adverse effects and allowed subsequent nephroureterectomy and lymphadenectomy. To the best of our knowledge, this has been the first study to report that pembrolizumab administration before surgery for chemotherapy-resistant ureteral carcinoma promoted a pathological complete response, providing a better understanding of the cancer microenvironment after immunotherapy.

A case of neoadjuvant chemotherapy‐resistant muscle‐invasive bladder cancer that markedly responded to pembrolizumab before conversion radical cystectomy

“…To the best of our knowledge, there are no reports of preoperative pembrolizumab administration for progressive MIBC following NAC. One report compared pCR to pembrolizumab for chemotherapy‐resistant upper tract urothelial carcinoma 11 . In the present case, the LNM following neoadjuvant GC disappeared with pembrolizumab, which made it possible to perform conversion RC.…”

Camrelizumab monotherapy leading to partial remission for relapsed upper tract urothelial carcinoma after radical nephroureterectomy: a case report

“…During the treatment, the patient only experienced manageable toxicity and achieved a PR after eight cycles, which is consistent with those of previous investigations. Though there are currently no clinical trials focus on the effect of PD-1 in patients with UTUC, several single case studies have been reported in which durable response have been gained in patients with UTUC (18,19). The present study has several limitations, including a short follow-up time and being a single case.…”

Immunotherapy in synchronous MSI-H rectal adenocarcinoma and upper tract urothelial carcinoma: a case report

“…The trial found a significant improvement in DFS (HR 0.45, 95% CI: 0.30-0.68, P=0.0001) and 3-year event free survival (71%, 95% CI: 61-78% for chemotherapy group vs. 46%, 95% CI: 36-56% for surveillance group) (23). Without adjuvant chemotherapy, approximately one-third of patients recur and the 5-year survival rate is less than 50% (24,25). Neoadjuvant chemotherapy with cisplatin-based therapies has been effective in inducing pathological downstagingthe strongest prognostic factor for recurrence-free, cancerspecific and overall survival (24).…”

“…Similar to LARC, the data for neoadjuvant immunotherapy in UTUC is limited but appears promising (26). Ikarashi et al described a patient with UTUC who received neoadjuvant pembrolizumab after failing chemotherapy and subsequently achieved sustained complete remission (25). The NABUCCO trial examined the use of 2-3 cycles of neoadjuvant nivolumab and ipilimumab in 24 patients with locoregionally advanced urothelial cancer, including one patient with upper tract involvement (27).…”