Real-world outcomes of systemic therapy in penile cancer: A single-center experience from a tertiary referral hospital in Mexico.

7 Background: Systemic strategies for penile cancer remain poorly defined across heterogeneous stages. We report real-world outcomes from a single-institution retrospective cohort, focusing on progression-free survival (PFS), overall survival (OS), and response rates. Methods: We reviewed all penile cancer cases treated at the National Cancer Institute of Mexico (2013–2024). All clinical stages were eligible per the 2018 TNM classification. Patients who received chemotherapy in any setting and those who did not were included. Survival was estimated with Kaplan–Meier; prognostic factors for PFS/OS were assessed using Cox proportional hazards models. Objective response rate (ORR) and disease control rate (DCR) were abstracted from routine clinical documentation. Results: A total of 156 patients were included; mean age 56.5 years (range, 27–87). Squamous cell carcinoma predominated (98.7%); two patients (1.3%) had neuroendocrine tumors. Grade 2 was most common (n=119, 76.3%). Stage distribution: I (n=14, 9%), II (n=37, 23.7%), III (n=41, 26.3%), IV (n=62, 39.7%), and 0/is (n=2, 1.3%). HPV status was positive in 9 (5.8%), negative in 2.6%, and unknown in 91.7%. Neoadjuvant therapy was delivered to 26 patients (16.7%): PF was most common (n=13, 50%), followed by concurrent chemoradiotherapy (n=6, 23.1%) and TIP (n=4, 15.4%). In this subgroup, ORR was 50% (13/26), DCR 66% (17/26), and median PFS 13 months (95% CI, 11.2–14.7). Adjuvant treatment was given to 28 patients (17.9%): chemotherapy in 11 (39.3%), chemoradiotherapy in 9 (32.1%), and radiotherapy in 8 (28.6%). Among stage IV cases, 31 patients (19.9%) were M1; the most frequent metastatic sites were lung (n=18, 52.9%) and non-regional lymph nodes (n=16, 47.1%). In the overall cohort, median OS was 155 months (95% CI, 131–179). Comparing patients who received neoadjuvant therapy with those who did not showed no statistically significant OS difference (HR 0.59; 95% CI, 0.31–1.14; 18-month comparison). Among M1 patients who received at least one line of systemic therapy, median OS was 18.4 months (95% CI, 10.3–26.5). Conclusions: In this single-center cohort spanning all stages, squamous histology predominated and nearly 40% presented with stage IV disease. Neoadjuvant therapy achieved a 50% ORR and 13-month PFS but did not improve OS. Outcomes in M1 disease remain modest, underscoring the need for prospective trials to refine systemic strategies across stages.