3 Background: For patients with cN2–N3 penile squamous cell carcinoma (SCC), multimodal therapy with chemotherapy and surgery is the standard of care. Although NCCN designates neoadjuvant cisplatin-based chemotherapy as preferred for bulky or fixed nodal disease, its real-world adoption and impact on survival are not well defined. To address this gap, we evaluated national outcomes to characterize the clinical benefit and utilization of perioperative chemotherapy in node-positive penile SCC. Methods: Using the National Cancer Database (2004–2022), we identified patients with any T, cN2–N3, and M0 penile SCC who received at least one definitive treatment modality. Patients were grouped as: lymph node dissection (LND) alone, adjuvant chemotherapy after LND, neoadjuvant chemotherapy followed by LND, LND with adjuvant radiation, or chemoradiation (CRT) without surgery. Overall survival (OS) was compared using multivariable Cox regression adjusting for age, comorbidity, race, insurance, income, and facility type. Results: Among 907 eligible patients, median age was 64 years, and 55% were treated at academic centers. Treatment distribution was: LND only (36.2%), adjuvant chemo (35.3%), neoadjuvant chemo (9.4%), LND + RT (3.8%), and CRT (15.4%). Median OS was 20.5 months for LND only, 31.6 for adjuvant chemo, 39.0 for neoadjuvant chemo, 25.6 for LND + RT, and 17.0 for CRT. On multivariable analysis, both adjuvant and neoadjuvant chemotherapy were independently associated with improved survival compared with surgery alone. Radiotherapy with or without surgery did not significantly improve outcomes. Treatment at academic centers was associated with longer survival. Conclusions: In node-positive penile SCC, integration of chemotherapy with lymph node dissection improves overall survival compared with surgery alone. Neoadjuvant chemotherapy provided the greatest survival benefit but remained markedly underused, administered in only 10 percent of patients with cN2–N3 disease. Radiotherapy without surgery offered no clear advantage. These population-level data validate NCCN-endorsed multimodal management, highlight gaps in the adoption of perioperative chemotherapy, and establish a real-world benchmark for implementing guideline-based multidisciplinary care in advanced penile cancer. Multivariable cox model for overall survival in node-positive penile SCC. Variable Comparator HR (95% CI) p-value Age ≥65 years vs <65 1.32 (1.08–1.61) 0.007 Facility: Academic vs Community 0.78 (0.64–0.96) 0.020 Adjuvant chemo + LND vs LND only 0.79 (0.65–0.98) 0.031 Neoadjuvant chemo + LND vs LND only 0.41 (0.27–0.62) <0.001 LND + RT vs LND only 0.75 (0.49–1.16) 0.193 CRT (no surgery) vs LND only 1.13 (0.89–1.44) 0.325 Charlson-Deyo ≥2 vs 0 1.17 (0.83–1.65) 0.365 Black race vs White 0.86 (0.66–1.14) 0.296
Kim et al. (Sun,) studied this question.