Neoadjuvant and/or adjuvant immune checkpoint inhibitors combined with chemotherapy for locally advanced resectable penile squamous cell carcinoma.

[BACKGROUND] The efficacy of immune checkpoint inhibitors (ICI) combined with chemotherapy as a neoadjuvant/adjuvant therapy for locally advanced penile squamous-cell carcinoma (PSCC) remains unclear.

[METHODS] A prospective, non-randomized, two-cohort study was designed to evaluate the efficacy of sintilimab combined with chemotherapy in this setting. Based on preoperative assessment, Patients were assigned to either undergo surgery following neoadjuvant therapy plus adjuvant therapy or to proceed directly to surgery followed by adjuvant therapy. Outcomes included progression-free survival (PFS), objective response rate (ORR), pathological complete response (pCR), major pathological response (MPR), overall survival (OS), disease control rate (DCR), and adverse events (AEs). The study has been registered with the Chinese Clinical Trial Registry (ChiCTR2400094629) and is currently ongoing.

[RESULTS] A preliminary analysis was performed on 25 enrolled patients. With a median follow-up of 20 months, among the 17 patients who received neoadjuvant therapy, the ORR was 52.9% (including 2 complete responses and 7 partial responses), and the DCR was 76.5%. Notably, in the treatment-naive subgroup, the ORR reached 66.7%. Of the 12 patients who underwent surgery, 2 achieved pCR and 3 achieved MPR. The 18-month PFS and OS rates for the entire cohort were 71.4% and 90.0%, respectively. Stratified by treatment modality, the neoadjuvant-adjuvant group showed an 18-month PFS rate of 68.8% and an OS rate of 85.7%, while the adjuvant-only group had 18-month PFS and OS rates of 75.0% and 100.0%, respectively. Patients who attained a radiological CR/PR after neoadjuvant therapy had significantly better PFS compared to those with SD/PD ( = 0.005). No significant association was observed between PD-L1 expression (CPS ≥20) and PFS. Grade ≥3 treatment-related adverse events occurred in 20% of patients.

[CONCLUSION] This preliminary analysis demonstrates that ICI combined with chemotherapy provides durable antitumor activity and a manageable safety profile as neoadjuvant and/or adjuvant therapy for locally advanced PSCC. These results warrant further validation in larger cohorts.