Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study

SIMPLE SUMMARY: To investigate the organ-specific responses and clinical outcomes of mixed responses (MRs) to treatment with pembrolizumab for unresectable or metastatic urothelial carcinoma (ur/mUC), 136 patients were analyzed retrospectively. The total objective response rate (ORR) and organ-specific ORR were determined according to RECIST version 1.1 as follows: (i) CR, (ii) PR, (iii) SD, and (ⅳ) PD. MR was defined as when PD occurred in one lesion plus either CR or PR in other lesion simultaneously, and 12 cases were applicable. Most of the organ-specific ORR was 30–40%, but bone metastasis was only 5%. Compared to non-responders, responders to locally advanced lesions and lymph node, lung, or liver metastases were involved in OS, but local recurrence and bone metastases were not involved in OS. In MR, patients who continued pembrolizumab experienced longer survival times compared to patients who discontinued pembrolizumab and received standard treatment. ABSTRACT: To investigate the organ-specific response and clinical outcomes of mixed responses (MRs) to immune checkpoint inhibitors (ICIs) for unresectable or metastatic urothelial carcinoma (ur/mUC), we retrospectively analyzed 136 patients who received pembrolizumab. The total objective response rate (ORR) and organ-specific ORR were determined for each lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 as follows: (i) complete response (CR), (ii) partial response (PR), (iii) stable disease (SD), and (iv) progressive disease (PD). Most of the organ-specific ORR was 30–40%, but bone metastasis was only 5%. There was a significant difference in overall survival (OS) between responders and non-responders with locally advanced lesions and lymph node, lung, or liver metastases (HR 9.02 (3.63–22.4) p < 0.0001; HR 3.63 (1.97–6.69), p < 0.0001; HR 2.75 (1.35–5.59), p = 0.0053; and HR 3.17 (1.00–10.0), p = 0.049, respectively). MR was defined as occurring when PD happened in one lesion plus either CR or PR occurred in another lesion simultaneously, and 12 cases were applicable. MR was significantly associated with a poorer prognosis than that of the responder group (CR or PR; HR 0.09 (0.02–0.35), p = 0.004). Patients with bone metastases benefitted less. Care may be needed to treat patients with MR as well as patients with pure PD. Further studies should be conducted in the future.