First-Line PD-1 Blockade Combined With Chemotherapy for Stage IV Penile Squamous Cell Carcinoma: A Multicenter Retrospective Study

Background: The purpose of this study was to evaluate the efficacy and safety of PD-1 blockade combined with cisplatin and paclitaxel (TP)–based chemotherapy as first-line treatment for advanced penile squamous cell carcinoma (PSCC). Patients and Methods: A retrospective review was performed of 32 eligible patients with high-risk stage IV (cN3M0–1) PSCC who received first-line PD-1 blockade combined with TP-based chemotherapy at 5 medical centers (2019–2023). Clinical responses were assessed using RECIST version 1.1. Treatment-related adverse events (TrAEs) and postsurgical complications were graded according to CTCAE version 5.0. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Multiplex immunofluorescence was used to explore potential biomarkers and to present the tumor microenvironment landscape before and after treatment. Results: After a median treatment duration of 4 cycles (range, 2–6), the overall objective response rate was 78.1% (25/32). Among 27 patients with locally advanced PSCC, 13 (48.1%) subsequently underwent consolidative surgery and 6 (22.2%) achieved a pathologic complete response (pCR). Additionally, 8 (25.0%) patients in the overall cohort underwent consolidated radiotherapy. Median follow-up was 21.1 months (95% CI, 14.1–42.7). Median PFS and OS were 15.0 months (95% CI, 11.4–not available [NA]) and 19.3 months (95% CI, 16.7–NA), respectively. All patients experienced TrAEs, with 50% (16/32) of them having grade ≥3 TrAEs. Higher intratumoral CD8+ T-cell infiltration was observed in pretreatment samples of responders compared with nonresponders ( P =.03). CD4+ T-cells, natural killer cells, and macrophages, among others, exhibited significant changes after treatment (all P <.05), suggesting their potential involvement in the antitumor response to immunochemotherapy. Conclusions: PD-1 blockade plus TP-based chemotherapy was effective and well tolerated, with favorable survival outcomes for patients with stage IV PSCC. High pretreatment intratumoral CD8+ T-cell infiltration may help to identify potential responders.