Is more always better?: Outcomes of TIP versus platinum doublet neoadjuvant chemotherapy in high-risk penile cancer.

Abstract

e17032 Background: The optimal neoadjuvant chemotherapy (NACT) regimen for high-risk penile carcinoma (bulky, bilateral or pelvic nodes) is unclear. Although paclitaxel, ifosfamide and cisplatin (TIP) is used based on limited prospective data, platinum doublets are commonly used in real-world practice due to feasibility and toxicity concerns. Methods: We retrospectively analyzed patients with high-risk penile squamous carcinoma (clinical N2-N3) treated with NACT at Tata Memorial Centre between January 2016 and June 2025, comparing TIP with platinum doublet. Results: Among 58 patients (median age - 55 years), 31% were tobacco chewers, 15.5% were smokers, 22.4% were hypertensive and 13.8% were diabetic (Table 1). NACT regimens included paclitaxel carboplatin (60.3%), TIP (36.2%) and cisplatin 5-FU (3.4%). On histology, 8.6% were p16 positive and 37.9% were poorly differentiated. At a median follow-up of 10.5 months, TIP showed numerically longer DFS (8.9 vs 5.8 months, p = 0.55) and OS (12.6 vs 10.3 months, p = 0.564). Lung metastases occurred in 29.3%. Metronomic chemotherapy was offered to 22.4%; 41.4% were offered best supportive care. TIP had more grade 3/4 hematological toxicities (19% vs 8.1%) and hospitalizations (9.5% vs 8.1%), whereas platinum doublet had more gastro-intestinal toxicities (10.8% vs 0) and electrolyte disturbances (13.5% vs 4.8%), with rare serious events (encephalopathy, pneumonia and stroke) in both groups. Conclusions: In this real-world cohort, TIP showed numerically longer DFS and OS but higher hematologic toxicity, while platinum doublets were more feasible and better tolerated, underscoring the need for prospective studies in this rare disease. Characteristics TIP(n = 21) Platinum Doublet(n=37) p-value Age > 60 years 7 (33.3%) 14 (37.8%) 0.732 ECOG PS 0.863 0 9 (42.9%) 15 (40.5%) 1 12 (57.1%) 22 (59.5%) Clinical N stage 0.234 N2 4 (19%) 3 (8.3%) N3 17 (81%) 33 (91.7%) Completed > 3 cycles NACT 16 (76.2%) 29 (78.4%) 0.848 Response to NACT 0.273 Complete response 0 1 (2.7%) Partial response 12 (57.1%) 12 (32.4%) Stable disease 5 (23.8%) 11 (29.7%) Progressive disease 4 (19%) 13 (35.1%) Primary Surgery 0.487 Wide local excision 2 (9.5%) 4 (10.8%) Partial penectomy 13 (61.9%) 18 (48.6%) Total penectomy 5 (23.8%) 8 (21.6%) Not done 1 (4.8%) 7 (18.9%) Inguinal node dissection 0.049 Unilateral 0 1 (2.7%) Bilateral 18 (85.7%) 20 (54.1%) Pelvic node dissection 0.010 Unilateral 2 (9.5%) 3 (8.1%) Bilateral 15 (71.4%) 12 (32.4%) Pathological T stage 0.127 T1 5 (23.8%) 3 (8.1%) T2 7 (33.3%) 8 (21.6%) T3 5 (23.8%) 9 (24.3%) Pathological N stage 0.044 N0 2 (9.5%) 6 (16.2%) N1 1 (4.8%) 0 N3 15 (71.4%) 15 (40.5%) Extra-nodal extension 14 (66.7%) 14 (37.8%) 0.070 Adjuvant therapy 0.341 Radiation 2 (9.5%) 2 (5.4%) Chemoradiation 7 (33.3%) 7 (18.9%) Site of progression 0.947 Loco-regional 8 (38.1%) 15 (40.5%) Metastatic 10 (47.6%) 16 (43.2%)