Impact of bleomycin dose omissions on clinical outcomes in non-seminomatous germ cell tumors: A systematic review and meta-analysis.

612 Background: Non-seminomatous germ cell tumors (NSGCT) represent the most curable solid malignancies in young men with Bleomycin, Etoposide, and Cisplatin [BEP] ×3 as the cornerstone first-line regimen. Bleomycin-induced pulmonary toxicity often leads to dose omission or discontinuation, but its impact on treatment efficacy remains unclear. This study evaluates the effect of omission of one or more bleomycin doses from BEP ×3 on Clinical outcomes in patients with NSGCT. Methods: Following PRISMA guidelines, a literature search (PubMed, Google Scholar, Cochrane; through May 2025) identified 259 records, of which 3 studies met inclusion criteria. Adult NSGCT patients receiving BEP × 3 with or without ≥1 omitted bleomycin dose were analyzed. Primary outcomes were overall and relapse-free survival; secondary outcomes included salvage therapy and pulmonary toxicity. Data were pooled using a fixed-effects Mantel–Haenszel model to generate ORs with 95% CIs; heterogeneity was assessed via I². Study quality was appraised using the Newcastle–Ottawa Scale, and analyses were performed in RevMan 5.4. Results: Three studies encompassing a total of 514 patients were included in the final analysis; with 236 in intervention and 278 in comparator group. The population was predominantly male, with a median age ranging from 27 to 34 years across studies. In 2 of the studies average reduction in Bleomycin dose was about 20%. Reasons for omission of Bleomycin doses included; >25% reduction in DLCO, pulmonary symptoms, interstitial pneumonia on computed tomography without infection and an attempt at decreasing toxicity by simplifying the treatment regimen. No significant efficacy difference was reported by the included studies with omission of one or more bleomycin doses. When pooled, there was no statistically significant difference in efficacy as measured by the need for salvage therapy (OR 1.16, 95% CI: 0.80–1.68, p = 0.43; I² = 0%). In contrast, pulmonary toxicity was significantly lower among patients with omitted bleomycin doses (OR 0.33, 95% CI: 0.22–0.49, p < 0.00001; I² = 0%). These findings indicate that omitting bleomycin doses does not compromise efficacy while substantially reducing pulmonary risk. Conclusions: Bleomycin omission in BEP ×3 preserves treatment efficacy while markedly reducing pulmonary toxicity, supporting individualized chemotherapy adjustment for optimal safety and cure. While these findings are promising but data is very limited and, prospective studies are warranted to further confirm the safety and efficacy of bleomycin dose omission in NSGCT management.