Immune therapy-related hyperprogressive disease: Molecular mechanisms, biomarkers, and clinical strategies

Table 1 Incidence, key studies, and risk factors of hyperprogressive disease

Ref.	Cancer type	HPD incidence	Proposed risk factors
Ferrara et al[16], 2018	NSCLC	13.8%-26%	EGFR mutation, LDH > 250 U/L, liver metastasis, ≥ 2 metastatic sites
Lo Russo et al[14], 2020
Economopoulou et al[17], 2021	HNSCC	15.4%	11q13 chromosomal amplification (CCND1/FGF3), local recurrence
Kim et al[18], 2022	GC	9.2%-29.4%	EGFR/FGF4, MDM2 amplification, liver metastasis, high tumor burden, advanced age
Aoki et al[19], 2024
Hwang et al[22], 2020	Urothelial carcinoma	6.4%-8%	Elevated baseline NLR, high LDH levels
Abbas et al[10], 2019
Yamada et al[13], 2018	Melanoma	6%-42%	Advanced age, elevated baseline inflammatory markers (CRP/NLR)
Zhou et al[20], 2025
Şen et al[21], 2024	Bladder cancer	12.9%	Elevated baseline NLR, advanced age
	Renal cell carcinoma	4.8%

HPD: Hyperprogressive disease; NSCLC: Non-small cell lung cancer; HNSCC: Head and neck squamous cell carcinoma; GC: Gastric cancer; EGFR: Epidermal growth factor receptor; LDH: Lactate dehydrogenase; CCND1: Cyclin D1; FGF3: Fibroblast growth factor 3; FGF4: Fibroblast growth factor 4; MDM2: Mouse double minute 2 homolog; NLR: Neutrophil-to-lymphocyte ratio; CRP: C-reactive protein.