Randomized trial of adjuvant 5-FU-platinum vs paclitaxel-platinum for high-risk penile cancer

Adjuvant chemotherapy is recommended for high-risk penile squamous cell carcinoma (SCC) metastatic to lymph nodes based on retrospective data, but no randomized trials have been conducted. We compared 5-fluorouracil (5-FU)-platinum with paclitaxel-platinum in this setting.

In this open-label, randomized trial at an Indian tertiary cancer center, men <70 years with resected node-positive penile SCC and ≥1 high-risk feature (perinodal extension, pelvic node involvement, >1 inguinal nodes, or ≥ 4 cm node) were assigned 1:1 to four 3-weekly cycles of 5-FU-platinum or paclitaxel-platinum, followed by cisplatin-based chemoradiotherapy. Primary endpoint was disease-free survival (DFS). Secondary endpoints were overall survival (OS), toxicity, and quality-of-life (QoL).

Between 2017 and 2024, 49 patients were randomized (5-FU-platinum: 25, paclitaxel-platinum: 24). At a median follow-up of 69 months, median DFS was 12.4 months (95% CI, 3.38-NR) vs 19.6 months (95% CI, 5.82-NR) (HR, 1.16; 95% CI, 0.55-2.45; P = 0.686) and median OS was 21.3 vs 36.7 months (HR, 1.13; 95% CI, 0.52-2.44; P = 0.754) for 5-FU-platinum and paclitaxel-platinum, respectively. Grade ≥3 toxicities occurred in 77.3% vs 40.9% (P = 0.014), grade ≥3 hematologic toxicities in 54.5% vs 4.5% (P < 0.001), and hospitalization for toxicity in 45.5% vs 9.1% (P = 0.016). Completion of all planned cycles was higher with paclitaxel-platinum (83.3% vs 48%; P = 0.009). QoL and sexual health were similar between the two treatment arms.

Adjuvant paclitaxel-platinum was associated with improved tolerability compared with fluorouracil-platinum in high-risk node positive penile cancer and warrants further evaluation in larger multicenter studies. Early termination precluded definitive efficacy comparisons.

Clinical Trials Registry of India (CTRI/2016/12/007567).

This work was supported by Indian Cooperative Oncology Network and Tata Memorial Center.